Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
NATIONAL LIBRARY OF MEDICINE service for health professionals and consumers. It links extensive information from the National Institutes of Health and other reviewed sources of information on specific diseases and conditions.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
Inanimate objects that become enclosed in the body.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.
The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.
Conditions or pathological processes associated with pregnancy. They can occur during or after pregnancy, and range from minor discomforts to serious diseases that require medical interventions. They include diseases in pregnant females, and pregnancies in females with diseases.
A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Cytosolic signaling adaptor proteins that were initially discovered by their role in the innate immunity (IMMUNITY, INNATE) response of organisms that lack an adaptive immune system. This class of proteins contains three domains, a C-terminal ligand recognition domain, an N-terminal effector-binding domain, and a centrally located nuclear-binding oligomerization domain. Many members of this class contain a C-terminal leucine rich domain which binds to PEPTIDOGLYCAN on the surface of BACTERIA and plays a role in pathogen resistance.
A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
A spectrum of disorders characterized by clonal expansions of the peripheral blood LYMPHOCYTE populations known as large granular lymphocytes which contain abundant cytoplasm and azurophilic granules. Subtypes develop from either CD3-negative NATURAL KILLER CELLS or CD3-positive T-CELLS. The clinical course of both subtypes can vary from spontaneous regression to progressive, malignant disease.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Organic compounds which contain tin in the molecule. Used widely in industry and agriculture.
Organometallic compounds which contain tin and three alkyl groups.
An industrial fungicide with low mammalian toxicity, although it does possess an irritant capacity for skin and mucous membranes.
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups.

Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. (1/9720)

BACKGROUND: Since 1968 it has been known that bone marrow transplantation can ameliorate severe combined immunodeficiency, but data on the long-term efficacy of this treatment are limited. We prospectively studied immunologic function in 89 consecutive infants with severe combined immunodeficiency who received hematopoietic stem-cell transplants at Duke University Medical Center between May 1982 and September 1998. METHODS: Serum immunoglobulin levels and lymphocyte phenotypes and function were assessed and genetic analyses performed according to standard methods. Bone marrow was depleted of T cells by agglutination with soybean lectin and by sheep-erythrocyte rosetting before transplantation. RESULTS: Seventy-seven of the infants received T-cell-depleted, HLA-haploidentical parental marrow, and 12 received HLA-identical marrow from a related donor; 3 of the recipients of haploidentical marrow also received placental-blood transplants from unrelated donors. Except for two patients who received placental blood, none of the recipients received chemotherapy before transplantation or prophylaxis against graft-versus-host disease. Of the 89 infants, 72 (81 percent) were still alive 3 months to 16.5 years after transplantation, including all of the 12 who received HLA-identical marrow, 60 of the 77 (78 percent) who were given haploidentical marrow, and 2 of the 3 (67 percent) who received both haploidentical marrow and placental blood. T-cell function became normal within two weeks after transplantation in the patients who received unfractionated HLA-identical marrow but usually not until three to four months after transplantation in those who received T-cell-depleted marrow. At the time of the most recent evaluation, all but 4 of the 72 survivors had normal T-cell function, and all the T cells in their blood were of donor origin. B-cell function remained abnormal in many of the recipients of haploidentical marrow. In 26 children (5 recipients of HLA-identical marrow and 21 recipients of haploidentical marrow) between 2 percent and 100 percent of B cells were of donor origin. Forty-five of the 72 children were receiving intravenous immune globulin. CONCLUSIONS: Transplantation of marrow from a related donor is a life-saving and life-sustaining treatment for patients with any type of severe combined immunodeficiency, even when there is no HLA-identical donor.  (+info)

Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors. (2/9720)

The crystal structure of the extracellular domain of CD94, a component of the CD94/NKG2 NK cell receptor, has been determined to 2.6 A resolution, revealing a unique variation of the C-type lectin fold. In this variation, the second alpha helix, corresponding to residues 102-112, is replaced by a loop, the putative carbohydrate-binding site is significantly altered, and the Ca2+-binding site appears nonfunctional. This structure may serve as a prototype for other NK cell receptors such as Ly-49, NKR-P1, and CD69. The CD94 dimer observed in the crystal has an extensive hydrophobic interface that stabilizes the loop conformation of residues 102-112. The formation of this dimer reveals a putative ligand-binding region for HLA-E and suggests how NKG2 interacts with CD94.  (+info)

Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations. (3/9720)

Daidzein and genistein glucuronides (DG and GG), major isoflavone metabolites, may be partly responsible for biological effects of isoflavones, such as estrogen receptor binding and natural killer cell (NK) activation or inhibition. DG and GG were synthesized using 3-methylcholanthrene-induced rat liver microsomes. The Km and Vmax for daidzein and genistein were 9.0 and 7.7 micromol/L, and 0.7 and 1.6 micromol/(mg protein. min), respectively. The absence of ultraviolet absorbance maxima shifts in the presence of sodium acetate confirmed that the synthesized products were 7-O-glucuronides. DG and GG were further purified by a Sephadex LH-20 column. DG and GG competed with the binding of 17beta-(3H) estradiol to estrogen receptors of B6D2F1 mouse uterine cytosol. The concentrations required for 50% displacement of 17beta-(3H) estradiol (CB50) were: 17beta-estradiol, 1.34 nmol/L; diethylstilbestrol, 1.46 nmol/L; daidzein, 1.6 micromol/L; DG, 14.7 micromol/L; genistein, 0.154 micromol/L; GG, 7.27 micromol/L. In human peripheral blood NK cells, genistein at <0.5 micromol/L and DG and GG at 0.1-10 micromol/L enhanced NK cell-mediated K562 cancer cell killing significantly (P < 0.05). At > 0.5 micromol/L, genistein inhibited NK cytotoxicity significantly (P < 0.05). The glucuronides only inhibited NK cytotoxicity at 50 micromol/L. Isoflavones, and especially the isoflavone glucuronides, enhanced activation of NK cells by interleukin-2 (IL-2), additively. At physiological concentrations, DG and GG were weakly estrogenic, and they activated human NK cells in nutritionally relevant concentrations in vitro, probably at a site different from IL-2 action.  (+info)

Enhanced tumor growth and invasiveness in vivo by a carboxyl-terminal fragment of alpha1-proteinase inhibitor generated by matrix metalloproteinases: a possible modulatory role in natural killer cytotoxicity. (4/9720)

Matrix metalloproteinases (MMPs) are believed to contribute to the complex process of cancer progression. They also exhibit an alpha1-proteinase inhibitor (alphaPI)-degrading activity generating a carboxyl-terminal fragment of approximately 5 kd (alphaPI-C). This study reports that overexpression of alphaPI-C in S2-020, a cloned subline derived from the human pancreas adenocarcinoma cell line SUIT-2, potentiates the growth capability of the cells in nude mice. After stable transfection of a vector containing a chimeric cDNA encoding a signal peptide sequence of tissue inhibitor of metalloproteinase-1 followed by cDNA for alphaPI-C into S2-020 cells, three clones that stably secrete alphaPI-C were obtained. The ectopic expression of alphaPI-C did not alter in vitro cellular growth. However, subcutaneous injection of the alphaPI-C-secreting clones resulted in tumors that were 1.5 to 3-fold larger than those of control clones with an increased tendency to invasiveness and lymph node metastasis. These effects could be a result of modulation of natural killer (NK) cell-mediated control of tumor growth in nude mice, as the growth advantage of alphaPI-C-secreting clones was not observed in NK-depleted mice, and alphaPI-C-secreting clones showed decreased NK sensitivity in vitro. In addition, production of alphaPI and generation of the cleaved form of alphaPI by MMP were observed in various human tumor cell lines and in a highly metastatic subline of SUIT-2 in vitro. These results provide experimental evidence that the alphaPI-degrading activity of MMPs may play a role in tumor progression not only via the inactivation of alphaPI but also via the generation of alphaPI-C.  (+info)

Human uterine lymphocytes. (5/9720)

During the luteal phase and the early months of pregnancy, there is a dense mucosal infiltration of CD56+ natural killer (NK) cells. These uterine NK cells have a phenotype (CD56bright, CD16-, mCD3-) which distinguishes them from peripheral blood NK cells (CD56dim, CD16bright, mCD3-). The uterine NK cells are in close association with extravillous trophoblast (EVT) cells which infiltrate into the decidua and maternal spiral arteries. This subpopulation of trophoblast expresses two human leukocyte antigen (HLA) class I molecules, HLA-G and HLA-C. Circulating NK cells express receptors for HLA class I molecules. We have recently found evidence that similar receptors are present on decidual NK cells belonging to both the Killer Inhibitory Receptor (KIR) and CD94 families. The repertoire of NK receptors expressed varies between different women. The findings indicate that decidual NK cells do have receptors for trophoblast HLA class I molecules. Experiments are underway to determine the effects of this interaction on NK cell function.  (+info)

Phenotypic and functional studies of leukocytes in human endometrium and endometriosis. (6/9720)

The aetiology of endometriosis, a common and disabling disorder, is presently unknown, although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity. These studies investigate the relationship between leukocyte populations, steroid hormone receptor expression, proliferative activity, bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle. Significantly increased oestrogen receptor expression, bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis, and CD56+ endometrial granulated lymphocytes (eGLs) were significantly reduced in ectopic endometrium. Apoptotic cells were rarely found in control and subject endometria. In contrast with endometriosis, adenomyotic lesions showed identical steroid hormone receptor expression, proliferative activity, bcl-2 expression and leukocyte subpopulations to eutopic endometrium, indicating different aetiologies for these disorders. The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified (>98%) by immunomagnetic separation. Except for a negligible cytotoxic activity of eGLs from early proliferative samples, cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood, predominantly CD56+ CD16+ natural killer cells. eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses. eGLs are evidently functionally important in the eutopic endometrium. Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis.  (+info)

Endometriotic disease: the role of peritoneal fluid. (7/9720)

Peritoneal fluid and the intraovarian milieu are a specific microenvironment. Peritoneal fluid originates mainly as an ovarian exudation product caused by increased vascular permeability, with cyclic variation in volume and steroid hormones which are always higher than in plasma. It contains large amounts of macrophages and their secretion products, and has a large exchange area with plasma through the peritoneum, which is highly permeable for small molecules. Diffusion becomes virtually zero for molecules with a molecular weight of >100000 Da. In women with the luteinized unruptured follicle (LUF) syndrome, concentrations of oestrogens and progesterone are much lower in the luteal phase. Endometriosis is associated with sterile low-grade inflammation, increased concentrations of activated macrophages and many of their secretions, such as cytokines, growth factors and angiogenic factors. Concentrations of CA-125 and of glycodelins are also increased, secreted locally by the endometrial cells. Natural killer (NK) cell function declines, possibly mediated by glycodelins or local intercellular adhesion molecule (ICAM) -1 shedding. The ovary is also a specific microenvironment, with steroid hormone concentrations 1000-fold higher in follicles than in plasma. Endometrial and superficially implanted cells are influenced by peritoneal fluid concentrations so that local environment, rather than inherent cellular differences could explain differences between superficial endometriosis and eutopic endometrium. Differences between superficial implants and endometriotic disease, deep infiltrating or cystic ovarian endometriosis, may thus arise via different endocrine environments. Superficial endometrial implants are regulated by peritoneal fluid factors, whereas deep endometriosis and cystic ovarian endometriosis are influenced by blood or ovarian factors. The endometriotic disease theory considers superficial endometriotic implants and their remodelling as a physiological process in most women, and concentrates on the causes of severe endometriosis such as differences in the eutopic endometrium from women with and without endometriosis (which may indicate hereditary differences), the invasiveness of some endometriotic cells in vitro, focal 'shielding' of endometriotic foci by adhesions, and inhibition of NK activity by ICAM-1 and glycodelins. Endometriotic disease is thus seen as a benign tumour. The type of cellular lesion, hereditary and immunological environments and local hormone concentrations in the ovary and in peritoneal fluid, will decide expression as cystic ovarian endometriosis, deep endometriosis or adenomyosis externa, and whether the latter is associated with adhesions.  (+info)

Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta. (8/9720)

We determined whether the IFN-beta gene can be used to suppress angiogenesis, tumor growth, and metastasis of human prostate cancer cells growing in the prostate of nude mice. Highly metastatic PC-3M human prostate cancer cells were engineered to constitutively produce murine IFN-beta subsequent to infection with a retroviral vector containing murine IFN-beta cDNA. Parental (PC-3M-P), control vector-transduced (PC-3M-Neo), and IFN-beta-transduced (PC-3M-IFN-beta) cells were injected into the prostate (orthotopic) or subcutis (ectopic) of nude mice. PC-3M-P and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastases, whereas PC-3M-IFN-beta cells did not. PC-3M-IFN-beta cells also suppressed the tumorigenicity of bystander nontransduced prostate cancer cells. PC-3M-IFN-beta cells produced small tumors (3-5 mm in diameter) in nude mice treated with anti-asialo GM1 antibodies and in severe combined immunodeficient/Beige mice. Immunohistochemical staining revealed that PC-3M-IFN-beta tumors were homogeneously infiltrated by macrophages, whereas control tumors contained fewer macrophages at their periphery. Most tumor cells in the control tumors were stained positive by an antibody to proliferative cell nuclear antigen; very few were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, PC-3M-IFN-beta tumors contained fewer proliferative cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3M-IFN-beta tumors. PC-3M-IFN-beta cells were more sensitive to lysis mediated by natural killer cells in vitro or to cytostasis mediated by macrophages than control transduced cells. Conditioned medium from PC-3M-IFN-beta cells augmented splenic cell-mediated cytolysis to control tumor cells, which could be neutralized by antibody against IFN-beta. Collectively, the data suggest that the suppression of tumorigenicity and metastasis of PC-3M-IFN-beta cells is due to inhibition of angiogenesis and activation of host effector cells.  (+info)

In the context of kidney transplantation, little is known about the involvement of natural killer (NK) cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e., calcineurin-inhibitors like Cyclosporin A vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on
Insufficient natural killer cell responses against retroviruses: how to improve NK cell killing of retrovirus-infected cells. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Sharma, S D.; Tsai, V; and Proffitt, M R., Enhancement of mouse natural killer cell activity by thyroxine. (1982). Subject Strain Bibliography 1982. 1180 ...
TY - JOUR. T1 - Stage-dependent gene expression profiles during natural killer cell development. AU - Kang, Hyung Sik. AU - Kim, Eun Mi. AU - Lee, Sanggyu. AU - Yoon, Suk Ran. AU - Kawamura, Toshihiko. AU - Lee, Young Cheol. AU - Kim, Sangsoo. AU - Myung, Pyung Keun. AU - San, Ming Wang. AU - Choi, Inpyo. PY - 2005/11/1. Y1 - 2005/11/1. N2 - Natural killer (NK) cells develop from hematopoietic stem cells (HSCs) in the bone marrow. To understand the molecular regulation of NK cell development, serial analysis of gene expression (SAGE) was applied to HSCs, NK precursor (pNK) cells, and mature NK cells (mNK) cultured without or with OP9 stromal cells. From 170,464 total individual tags from four SAGE libraries, 35,385 unique genes were identified. A set of genes was expressed in a stage-specific manner: 15 genes in HSCs, 30 genes in pNK cells, and 27 genes in mNK cells. Among them, lipoprotein lipase induced NK cell maturation and cytotoxic activity. Identification of genome-wide profiles of gene ...
Abstract Natural killer (NK) cells are considered to be critical players in anticancer immunity. However, cancers are able to develop mechanisms to escape NK cell attack or to induce defective NK cells. Current NK cell-based cancer immunotherapy is aimed at overcoming NK cell paralysis through several potential approaches, including activating autologous NK cells, expanding allogeneic NK cells, usage of stable allogeneic NK cell lines and genetically modifying fresh NK cells or NK cell lines. The stable allogeneic NK cell line approach is more practical for quality-control and large-scale production. Additionally, genetically modifying NK cell lines by increasing their expression of cytokines and engineering chimeric tumor antigen receptors could improve their specificity and cytotoxicity. In this review, NK cells in tumor immunotherapy are discussed, and a list of therapeutic NK cell lines currently undergoing preclinical and clinical trials of several kinds of tumors are reviewed.. ...
CHAPTER 85 FUNCTIONS OF NATURAL KILLER CELLS Williams Hematology CHAPTER 85 FUNCTIONS OF NATURAL KILLER CELLS GIORGIO TRINCHIERI LEWIS L. LANIER Identification and Definition of Natural Killer Cells Definition Morphology Origin and Tissue Distribution Mechanisms of Natural Killer Cell Functions Cell-Mediated Cytotoxicity Production of Cytokines Physiologic Roles of Natural Killer Cells Natural Resistance Regulation of…
Now, results from a new study carried out using a mouse model, show that modified cells called super natural killer cells are able to seek out cancer cells in lymph nodes to destroy them, thus halting the process of metastasis. Michael King, senior author of the study, said in a press release: We want to see lymph node metastasis become a thing of the past.. The super natural killer cells find the cancerous cells in the lymph nodes and induce apoptosis - in other words, the cancer cells self-destruct and disintegrate, thus averting their further lymphatic spread. But what are these super natural killer cells? They are a modified version of the so-called natural killer cells - or NK cells for short.. NK cells are a type of lymphocytes that play a major role in the killing of cancer cells and virus-infected cells by inducing apoptosis. To obtain the super version of these lymphocytes, scientists attached nanoparticles to the NK cell surface. These nanoparticles contain a protein dubbed TRAIL ...
This sensitivity allows natural killer cells to vigorously initiate natural killer cytotoxicity (by emptying granules of porforin and granzyme) and inflammation as soon as pathogenesis is detected, and is essential to protection against viruses and tumors. Natural killer cells have genomic (not needed recombination, or RAG-independent) cell surface receptors which recognize classical Class I MHC molecules (and structural relatives like MICA, RAE-1 and H-60).. Natural killer cells lack TcRs, CD4s and CD8; instead, they have: cell-surface activating receptors, which bind noncovalently to molecules with ITAMs; and on the cytoplasmic side, inhibitory receptors with ITIM(s) which -- upon phosphorylation -- recruit and activate SHP-1 & -2, which inhibit the activating receptors. The balance between activating signals and inhibitory signals is what determines whether a natural killer cell will destroy or bypass a microbe it encounters. ...
TY - JOUR. T1 - Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells. AU - Itoh, Kyogo. AU - Platsoucas, Chris D.. AU - Balch, Charles M.. PY - 1987. Y1 - 1987. N2 - Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (, 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 11b and ...
Definition of Natural killer cells in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is Natural killer cells? Meaning of Natural killer cells as a legal term. What does Natural killer cells mean in law?
TY - JOUR. T1 - Expression of CD94 and 56bright on Natural Killer Lymphocytes - the Influence of Exercise. AU - Horn, Peggy. AU - Leeman, K. AU - Gore, Christopher. PY - 2002. Y1 - 2002. M3 - Article. VL - 23. SP - 595. EP - 599. JO - International Journal of Sports Medicine. JF - International Journal of Sports Medicine. SN - 0172-4622. IS - 8. ER - ...
TY - JOUR. T1 - Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. AU - Ayello, Janet. AU - van de Ven, Carmella. AU - Fortino, Weiwei. AU - Wade-Harris, Cheryl. AU - Satwani, Prakash. AU - Baxi, Laxmi. AU - Simpson, Lynn L.. AU - Sanger, Warren G. AU - Pickering, Diana. AU - Kurtzberg, Joanne. AU - Cairo, Mitchell S.. PY - 2006/6/1. Y1 - 2006/6/1. N2 - Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free ...
Natural Killer Cells are the most aggressive white cells in the immune system. They make up about 5% to 15% of the total lymphocyte circulating population. They target tumor cell and protect against a wide variety of infectious microbes. Natural Killer Cells are a very important factor in the fight against cancer. Immune Stimulation is the key to keeping the white blood cell count high and giving the Natural Killer Cells a chance to fight cancer and other diseases.. ...
NK cell lytic activity is often inhibited by MHC class I molecules expressed by target cells. It is believed that this mechanism allows the immune system to destroy cells that downregulate class I expression due to infection or transformation ((1)). Most or all natural killer cells in mice express one or more members of the Ly49 receptor family, a group of closely related and genetically linked MHC class I-specific inhibitory receptors ((2)). The capacity of NK cells to attack target cells that lack MHC class I expression, while sparing cells that express self-MHC class I molecules, depends in large part on inhibitory recognition of MHC molecules by Ly49 receptors.. mAb reagents to some Ly49 receptors have been used to show that they are expressed on overlapping subsets of natural killer cells ((3)-(5)). An NK cell can express multiple Ly49 receptors, including Ly49 receptors that do not recognize self-MHC class I molecules. The overall pattern of expression of different Ly49 receptors suggests ...
Natural killer (NK) cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. NK cells show a broad array of tissue distribution and phenotypic variability. NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells and control the cytolytic function. NK cells have been used in several clinical trials to control tumor growth. However, the results are encouraging only in hematological malignancies but not very promising in solid tumors. Increasing evidence suggests that tumor microenvironment regulate the phenotype and function of NK cells. In this review, we discussed the NK cell phenotypes and its effector function and impact of the tumor microenvironment on effector and cytolytic function of NK cells. We also summarized various NK cell-based immunotherapeutic strategies used in the past, and the possibilities to improve the function of NK cell
Background: A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8(+) T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings: In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any ...
Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further
TY - JOUR. T1 - Adhesion and activation molecules expressed by human natural killer cells. AU - Santoni, Angela. AU - Gismondi, Angela. AU - Paolini, Rossella. AU - Procopio, Antonio. AU - Morrone, Stefania. AU - Mainiero, Fabrizio. AU - Santoni, Giorgio. AU - Piccoli, Mario. AU - Frati, Luigi. PY - 1991/2. Y1 - 1991/2. N2 - Our study concerns the expression and the regulation of adhesion and activation receptors on human NK cells. In particular we provide evidence on: a) the expression on fresh human NK cells of VLA-4, VLA-5 and VLA-6, extracellular matrix (ECM) receptors of integrin family capable of mediating their adhesion to FN and LM; b) the role of PKC on the regulation of CD16, a differentiation antigen associated with FcγR type III expressed by all NK cells, which mediate ADCC activity and trigger lymphokine production.. AB - Our study concerns the expression and the regulation of adhesion and activation receptors on human NK cells. In particular we provide evidence on: a) the ...
Ulm C, Saffarzadeh M, Mahavadi P, Müller S, Prem G, Saboor F, Simon P, Middendorff R, Geyer H, Henneke I, Bayer N, Rinné S, Lütteke T, Böttcher-Friebertshäuser E, Gerardy-Schahn R, Schwarzer D, Mühlenhoff M, Preissner KT, Günther A, Geyer R, Galuska SP., Cell Mol Life Sci 70(19), 2013 ...
Hence, the hypothesis that UL18 replaces class I MHC molecules to prevent NK cell lysis does not seem to apply to hCMV-infected HFFs and transfected epithelial and ovary cells (293, COS-7, and CHO-K1). It was recently reported that UL18 inhibits NK cell lysis of 721.221 B lymphoblastoid targets, mediated through CD94 ((11)). In repeated studies, we never observed inhibition of NK cell killing against UL18 expressing targets using clones with functional CD94 or KIR. In view of this discrepancy, several aspects of the previous report should be highlighted. First, in the prior study UL18 was transfected into 721.221 targets; however, transfectants were isolated on the basis of surface β2M expression, not UL18. Second, we have failed to generate stable UL18 transfectants in 721.221 or in 15 other human or mouse lines, because it seems that prolonged expression (,2 wk) of UL18 results in cell death. We could only generate UL18 transfectants in high efficiency transient transfection systems such as ...
Brunda, M J.; Taramelli, D; Holden, H T.; and Varesio, L, Effects of resting and activated macrophages on natural killer cell activity and lymphoproliferation. Abstr. (1981). Subject Strain Bibliography 1981. 551 ...
A low affinity receptor for IgG immune complexes, Fc gamma RIII(CD16), is expressed on human NK cells as an integral membrane glycoprotein anchored through a tr
In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation ...
NK cells have important functions in cancer immunosurveillance, bone marrow allograft rejection, fighting infections, tissue homeostasis and reproduction. NK cell-based therapies are promising treatments for blood cancers. Overcoming their currently limited efficacy requires a better understanding of the molecular mechanisms controlling NK cell development and dampening their effector functions. NK cells recognize the loss of self-antigens or upregulation of stress-induced ligands on pathogen-infected or tumor cells through invariant NK cell receptors (NKR), and then kill such stressed cells. Two second-messenger pathways downstream of NKRs are required for NK cell maturation and effector responses: PIP3-generation by PI3K, and generation of diacylglycerol and IP3 by PLCγ. Here, we identify a novel role for the phosphorylated IP3 metabolite inositol(1,3,4,5)tetrakisphosphate (IP4) in NK cells. IP4 promotes NK cell terminal differentiation and acquisition of a mature NKR repertoire. However, in ...
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Background: Human peripheral blood NK cells constitutively express CD56 and CD16 antigens. Peripheral blood NK cells seem to be strongly related with decidual NK cells, and may reflect the decidual NK cell functional status. There are varied reports concerning the relationship between NK cell cytotoxicity in women with recurrent spontaneous abortion. Objective: To study NK activity in women with history of RSA by using a non-radioactive cytotoxicity assay. Methods: Peripheral blood lymphocytes from RSA and healthy multiparous women were obtained. Lymphocytes were isolated and mixed with K562 NK-sensitive cell line. A non-radioactive method for NK cell cytotoxicity assessment was utilized. Dead K562 cell populations were detected by FACS Calibur flow cytometry, and the data obtained was analysed on cell-Quest software. The proportion of CD16+ /CD56+ cells was then calculated. Results: The proportion of NK cells were 9.21% ± 3.06 and 13.48% ± 4.09 in healthy women and RSA, respectively. The percentage
Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3 from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction with an activating receptor ...
Compared to GEA, AEA appears to preserve perioperative NKCC. This effect may be related to an attenuated stress hormone response associated with AEA. Cancer patients may have improved killing of embolized tumor cells during surgery performed under AEA.
treatment add-ons, you may be interested in some impartial and expert advice in two new scientific opinion papers published by the Royal College of Obstetricians and Gynaecologists (RCOG). They call for more high quality research into the role of natural killer cells in fertility and the effect of endometrial scratching on pregnancy outcomes.. Scientific Impact Papers (SIP), are up-to-date reviews of emerging or controversial scientific issues. The first paper looks at the role of uterine natural killer (uNK) cells, how they are measured, the role of testing and the evidence behind any links to improving implantation rates and early placental development. The paper clarifies that uNK cells are completely different from peripheral blood natural killer cells (which you would be testing in the blood tests some fertility clinics currently offer).. The paper makes it clear that there is no evidence to offer routine tests for NK cells as part of fertility treatment or testing, and that there is ...
TY - JOUR. T1 - An Ets element regulates the transcription of the human 2B4 gene in natural killer cells. AU - Vaidya, Swapnil V.. AU - Mathew, Porunelloor A.. PY - 2005/5/1. Y1 - 2005/5/1. N2 - 2B4 (CD244) acts as an activation receptor on human NK cells, whereas it sends inhibitory signals in murine NK cells. A previous study indicated a prominent role for AP-1 in the transcription of 2B4 gene. To further understand the transcriptional regulation we analyzed the upstream positive regulatory region (-1151 to -704) of the 2B4 promoter. We have identified an Ets element that regulates the 2B4 gene transcription in an AP1 dependent manner.. AB - 2B4 (CD244) acts as an activation receptor on human NK cells, whereas it sends inhibitory signals in murine NK cells. A previous study indicated a prominent role for AP-1 in the transcription of 2B4 gene. To further understand the transcriptional regulation we analyzed the upstream positive regulatory region (-1151 to -704) of the 2B4 promoter. We have ...
Natural killer (NK) cells are innate immune system lymphocytes with an integral role in host defense against HIV infection. and promote the cytotoxic features that Rabbit polyclonal to JAK1.Janus kinase 1 (JAK1), is a member of a new class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain.The second phosphotransferase domain bears all the hallmarks of a protein kinase, although its structure differs significantly from that of the PTK and threonine/serine kinase family members. kill focus CBR 5884 on cells. Once older, NK cells circulate in the tissue and bloodstream even though surveying for contaminated or malignant cells. Although NK cells are formidable players in the immune system response against infections, genetically modifying NK cells expressing CARs could improve NK cell targeting of malignant and infected cells. Within this review, the function is certainly talked about by us of NK ...
Natural killer cell An innate effecter cells of immune system limits viremia and tumor burden Natural killer cell, also called NK cell, is a cell with large particles in the cytoplasm. NK cell is developed from bone marrow lymphoid stem cells, and its differentiation and development depend on bone marrow or thymus microenvironment, mainly distributed in peripheral blood and spleen, and a small amount in lymph nodes and other tissues. It is named because of its non-specific cytotoxicity. Without the receptors of T cells and B cells, there will be no genetic recombination of the recipient. But it still has some special receptors called "Killer cell immunoglobulin-like receptors (KIR)". KIR are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of NK cell function. NK cell is accounted about 5~10% of all lymphocytes, but NK cell can eliminate many kinds of pathogens and many kinds of tumor cells. NK cell contact with
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The T- and B-Lymphocyte and Natural Killer Cell Profile includes the following tests:. Percentage CD3+; absolute CD3+; percentage CD3+CD4+; absolute CD3+CD4+; percentage CD3+CD8+; absolute CD3+CD8+; percentage CD3-CD56+ natural killer (NK) cells; absolute CD3-CD56+ natural killer (NK) cells; percentage CD19+; absolute CD19+; CD4:CD8 ratio; CBC. .. HIV-1 infection results in a decrease of CD4 T cells, an increase in CD8 T cells, a decrease in the CD4:CD8 ratio, and a progressive destruction of immune function. Enumeration of CD4 and CD8 T cells in HIV-1 seropositive patients may be used for prognostic purposes and to monitor disease progression and retroviral therapy. Natural killer (NK) cells are large granular lymphocytes that mediate MHC-unrestricted cytotoxicity against virus-infected and malignant cells and manufacture a number of cytokines following stimulation of the immune system.. ...
A key mechanism of tumor resistance to immune cells is mediated by expression of peptide-loaded HLA class I molecule (HLA-E) in tumor cells, which suppresses NK cell activity via ligation of the NK inhibitory receptor CD94/NK group 2 member A (NKG2A). Gene expression data from approximately 10,000 tumor samples showed widespread HLAE expression, with levels correlating with those of KLRC1 (NKG2A) and KLRD1 (CD94). To bypass HLA-E inhibition, we developed a way to generate highly functional NK cells lacking NKG2A. Constructs containing a single-chain variable fragment derived from an anti-NKG2A antibody were linked to endoplasmic reticulum-retention domains. After retroviral transduction in human peripheral blood NK cells, these NKG2A protein expression blockers (PEBLs) abrogated NKG2A expression. The resulting NKG2Anull NK cells had higher cytotoxicity against HLA-E-expressing tumor cells. Transduction of anti-NKG2A PEBL produced more potent cytotoxicity than interference with an anti-NKG2A ...
The skin condition atopic dermatitis (AD) is driven by a type 2 immune response. Mack et al. performed high-dimensional immune profiling of patients with AD and revealed deficiencies in certain subsets of natural killer (NK) cells. NK cells showed signs of activation-induced cell death and were restored in patients that responded to immunotherapy. Circulating NK cells were also decreased in a mouse AD model; boosting NK cells with an IL-15 superagonist ameliorated symptoms in the mice. These results suggest that strategies to restore NK cells could help rebalance immunity in AD. ...
Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures.
TY - JOUR. T1 - Natural killer cells in cancer immunotherapy. AU - Miller, Jeffrey S.. AU - Lanier, Lewis L.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Natural killer (NK) cells have evolved to complement T and B cells in host defense against pathogens and cancer. They recognize infected cells and tumors using a sophisticated array of activating, costimulatory, and inhibitory receptors that are expressed on NK cell subsets to create extensive functional diversity. NK cells can be targeted to kill with exquisite antigen specificity by antibody-dependent cellular cytotoxicity. NK and T cells share many of the costimulatory and inhibitory receptors that are currently under evaluation in the clinic for cancer immunotherapy. As with T cells, genetic engineering is being employed to modify NK cells to specifically target them to tumors and to enhance their effector functions. As the selective pressures exerted by immunotherapies to augment CD8+ T cell responses may result in loss of MHC class I, NK cells may ...
Consecutive serum samples were obtained from patients with syphilis before and on three occasions after treatment. The sera contained immunosuppresive factors associated with the immunoglobulin fraction, which could depress the natural killer cell activity of healthy controls. There was no evidence that allogeneic or lymphocytotoxic antibodies played a role in immuno-suppression, which could be reproduced with both soluble and insoluble antigen-IgG-antibody complexes.. ...
Natural killer (NK) cells are innate immune cells with the ability to recognize and eliminate virally infected cells and cancer cells without prior sensitization. There is a functional heterogeneity between individual NK cells, where some NK cells are more efficient at killing cancer cells than others. Methods that allow studies of single NK cells are required to understand the functional differences and how they correlate with the activation and development status of the NK cell.. This thesis focuses on the development and implementation of microchip- based imaging of NK cells, which is covered in five papers. Paper I presents a microchip screening platform for assessment of the cytotoxic potential of individual NK cells, by confining single NK cells together with target cells in microwells, followed by microscopy screening over extended time periods and automated image analysis. In paper II, the microchip platform was applied to test the ability of a novel trispecific killer engager (TriKE) to ...
Natural killer (NK) cells take up chylomicrons (CM), very low density (VLDL), low density (LDL), high density (HDL) and acetyl-modified low density (AcLDL) lipoproteins through different receptors, VLDL being the lipoprotein with the highest uptake and HDL the lowest. The uptake of LDL can be selectively blocked by the anti-LDL receptor, which does not affect the uptake of CM, VLDL, HDL and AcLDL. Although the uptake of lipoproteins assessed by flow cytometry using DiI is not very high, the lipoproteins are able to induce an increase in proliferative responses, VLDL, AcLDL and HDL being the most important ones with 12- and 17-fold increments, respectively. CM, VLDL and LDL at low concentrations increase NK cytotoxic activity, while HDL and AcLDL inhibit, in a dose-dependent fashion, the killing of NK cells against K562. These results suggest the presence of four different receptors that are responsible for the cytotoxic and proliferative responses observed ...
Definition of NATURAL KILLER CELL: NK cell. A lymphoid cell which kills a range of tumour cell targets in the absence of prior immunization and without evident antigen specificity. Morpholog
The anti-HIV activity of natural killer (NK) cells could be induced fast enough to potentially prevent the establishment of HIV infection. Epidemiological studies identified two genotypes encoding NK receptors that contribute to NK cell function, that were more frequent in people who remained uninfected despite multiple HIV exposures than in HIV-susceptible subjects. NK cells from carriers of the *h/*y+B*57 genotype have higher NK cell functional potential and inhibit HIV replication in autologous HIV-infected CD4+ T cells (iCD4) more potently than those from carriers of non-protective genotypes. HIV suppression depends on the secretion of CC-chemokines that block HIV entry into CD4+ cells. NK cell education and the effect of HIV infection on iCD4 cell surface expression of MHC-I antigens both influenced NK cell responses to autologous iCD4. The second KIR3DS1 homozygous protective genotype encodes an activating receptor that upon interacting with its HLA-F ligand on iCD4 induces anti-viral activity.
Human NK cells bear surface receptors that inhibit their cytolytic activity upon specific recognition of MHC class Ia Ags; little is known about the capacity of class Ib molecules to regulate NK cell function. We have studied the roles of different NK inhibitory receptors in recognition of the class Ib HLA-G. To this end, we analyzed the ability of an HLA-defective tumor cell line (721.221) transfected with the membrane form of HLA-G1, which contains the three external domains, to inhibit the cytolytic activity mediated by a panel of NK clones from several donors. A substantial proportion of peripheral blood NK clones appeared to be significantly inhibited by the HLA-G1-transfected cell line (referred to as .221-G1); nevertheless, no relation was observed between the expression and the function of serologically identifiable Ig-SF receptors (p58/p70) and specific recognition of .221-G1 cells. Moreover, p58 killer cell inhibitory receptor-IgG soluble fusion proteins specifically bound to 721.221 ...
Natural Killer Cell Activation Structures小鼠单克隆抗体[ANK61](ab36392)可与大鼠样本反应并经IP, IHC, Flow Cyt实验严格验证,被1篇文献引用。
TY - JOUR. T1 - Effect of Whole-Body Hyperthermia and Cyclophosphamide on Natural Killer Cell Activity in Murine Erythroleukemia. AU - Shen, Rong Nian. AU - Hornback, Ned B.. AU - Shidnia, Homayoon. AU - Lu, Li. AU - Broxmeyer, Hal E.. AU - Brahmi, Zacharie. PY - 1988/8/15. Y1 - 1988/8/15. N2 - Mice infected with the polycythemia-inducing strain of Friend virus complex (FVC-P) develop a fatal erythroid disease similar in some respects to leukemia. Six- to eight-week-old DBA/2 female mice were injected i.v. with 0.5 ml of a virus suspension containing approximately 5 x 104 plaque-forming units and 5 x 103 spleen focus-forming units. Four treatment regimens were begun 3 days postinjection: (a) no treatment; (b) whole-body hyperthermia (WBH) alone; (c) cyclophosphamide (CY) alone; (d) WBH combined with CY. WBH treatment utilized a microwave generator operating at 2450 MHz. The i.p. temperature of the mice receiving WBH was maintained at 39.5-40°C for 30 min. The CY was given i.p. at a dosage of 20 ...
Background: Although there is convincing data in support of the effectiveness of hyperthermia in tumor therapy, the molecular mechanisms underlying the clinical effects of hyperthermia are still poorly understood. Objective: To investigate natural killer (NK) cell cytotoxicity against heat-treated SW-872 and HeLa tumor cell lines. Methods: NKG2D ligands and HLA class I transcription were examined using quantitative real-time PCR in treated tumor cell lines at 0, 2, 4, 6 and 12 h following thermal treatment at 39C and 42C for 1 h. The expression of MICA/B, ULBP1 and ULBP2 were also determined by flow cytometry. NK92-MI cytotoxic activity against heat-treated target cell lines was assessed by LDH release as well as annexin-V and 7-AAD assays. Results: Our results showed that heat treatment at 39C improved the cytolytic activity of NK cells against SW-872 cells without increasing NKG2D ligand concentration or decreasing HLA class I levels. Conclusion: The observed increase in the cytotoxicity of
Polymorphisms in cell surface receptors of natural killer cells and their ligands on target cells can affect susceptibility to viral infections including human immunodeficiency virus (HIV)-1. We found that the carriage of the human leukocyte antigen (HLA)-G minus 14-bp polymorphism, LILRB1 single nucleotide polymorphism rs1061680, and activating and inhibitory killer immunoglobulin-like receptors (KIRs) were different when data were compared between Caucasian, African Americans and Asian populations. However, carriage was similar when HIV-1 patients were compared with control donors, with the exception of the African American cohort.. ...
Emerging evidence suggests that NK cells could be important in the early effector response induced by vaccination, supported by vaccine antigen-specific CD4 IL-2 production and antigen-antibody immune complexes. Memory-like NK cells, with heightened responsiveness can be also generated by pre-activation with cytokines. I found that NK cell differentiation is accelerated in Africans in The Gambia compared to age-matched UK residents and that this is linked to reduced functional NK cell responses to cytokines. This effect may also relate to a high burden of human cytomegalovirus (HCMV) infection in this population, with all Gambian study subjects infected by 3 years of age. There is also significant variation in lymphoid and myeloid cell populations with increasing age. Additionally, I found that a deletion of the NKG2C gene, a receptor important for recognition of HCMV infected cells, results in delayed NK cell differentiation. Furthermore, the allele frequency of the NKG2C gene deletion is ...
Rabinowich H., Manciulea M., Metes D., Sulica A., Herberman R.B., Corey S.J., Whiteside T.L.. We recently reported that Fc mu R on NK cells is a signal transducing protein that stimulates a rapid increase in the level of cytoplasmic free calcium upon binding of IgM. This study was designed to examine signal transduction via the Fc mu R on NK cells and to characterize intracellular second messengers activated by IgM. Immunoprecipitation of IgM-bound Fc mu R by IgM-specific Ab coimmunoprecipitated the zeta- and Fc epsilon RI gamma-chains. Furthermore, engagement and clustering of Fc mu R by polyclonal IgM induced tyrosine phosphorylation of the zeta- and Fc epsilon RI gamma-chains, indicating their functional association with the Fc mu R-induced signal transduction cascade. Ligand-induced clustering of the Fc mu R also induced activity of src family kinases, Lck, Fyn, Lyn, and Src, as well as their physical interaction with the receptor. Triggering via Fc mu R also induced the activity of Syk and ...
TY - JOUR. T1 - Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. AU - Sojka, Dorothy K.. AU - Plougastel-Douglas, Beatrice. AU - Yang, Liping. AU - Pak-Wittel, Melissa A.. AU - Artyomov, Maxim N.. AU - Ivanova, Yulia. AU - Zhong, Chao. AU - Chase, Julie M.. AU - Rothman, Paul B.. AU - Yu, Jenny. AU - Riley, Joan K.. AU - Zhu, Jinfang. AU - Tian, Zhigang. AU - Yokoyama, Wayne M.. PY - 2014/4/8. Y1 - 2014/4/8. N2 - Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a ...
Bridging innate and adaptive immunity, the NK cell is an important effector lymphocyte that participates in the early immune response to pathogens through the production of cytokines and chemokines (1). Furthermore, the NK cell has also been found to mediate cytolytic activity against virally infected cells and malignant cells (1, 2). Following the principle of the missing self hypothesis, NK recognition of self MHC Ags on putative target cells leads to inhibition of effector functions. Accordingly, target cell loss of self-MHC class I expression releases NK cell effector functions by removing the MHC-mediated inhibition (3). Regulation of NK cell function is accomplished through a diverse complement of receptors mediating, activating, and inhibiting signals in response to ligand interactions.. In humans, receptors that signal activation include the NK cytotoxicity receptors (4), whose ligands remain unclear, and NKG2D, which has been shown to recognize MHC class I chain-related proteins A ...
The researchers used an animal model to show that the loss of innate immune control by young natural killer cells can lead to infectious mononucleosis. Young natural killer cells, which small children in particular have in abundance, seem to be especially suited to killing off the cells that multiply EBV, according to Christian Münz, Professor of Experimental Immunology at the University of Zurich. This weakens the primary infection and infectious mononucleosis does not break out.. Without the defense of the natural killer cells, EBV multiplies so dramatically during the primary infection phase that the aggressive response of the adaptive immune system - chiefly of the T killer cells - makes the infected person sick with infectious mononucleosis. In the animal model we also observed weight loss and the increased occurrence of EBV-associated lymphomas. Consequently, natural killer cells seem to play a key role in the development of the primary infection with Epstein-Barr Virus. This is how ...
Horowitz, A., Strauss-Albee, D.M., Leipold, M. et al.. Natural killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in the donor panel. Genetics largely determined inhibitory receptor expression, whereas activation receptor ...
TY - JOUR. T1 - Tumor necrosis factor alpha (TNF-α) blockade improves natural killer cell (NK) activation, hypertension, and mitochondrial oxidative stress in a preclinical rat model of preeclampsia. AU - Cunningham, Mark W.. AU - Jayaram, Aswathi. AU - Deer, Evangeline. AU - Amaral, Lorena M.. AU - Vaka, Venkata Ramana. AU - Ibrahim, Tarek. AU - Cornelius, Denise C.. AU - LaMarca, Babbette. N1 - Funding Information: This study was supported by NIH grant RO1HD067541 (BL), NIH grants R00HL130456 and P20GM104357 (DCC), NIH P20GM121334 (BL, LMA), American heart association (AHA) early career award 19CDA34670055 (LMA), and the AHA early career grant award 18CDA34110264 (MWCJr). Publisher Copyright: © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.. PY - 2020. Y1 - 2020. N2 - The RUPP rat model of Preeclampsia exhibits hypertension (MAP), cytolytic natural killer (cNK) cells, tumor necrosis factor alpha (TNF-α) and mitochondrial Reactive Oxygen Species (mt ROS). Objective: ...
Gellert, Ginelle C. uPAR Interaction and Regulation of Natural Killer Cell Integrins: Implications for the Modulation of NK Cell Migration and Invasion. Doctor of Philosophy (Biomedical Sciences), May 2003; pp. 118, 2 tables; 12 figures; bibliography 163. The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor, devoid of an intracellular domain, but nevertheless initiates signaling, possibly through lateral interactions with integrins. Since adoptively transferred interleuking-2 (IL-2) activated natural killer (A-NK) cells can accumulate within established cancer metastases, these A-NK cells may integrate components of adhesion and proteolysis to facilitate their infiltration into tumors. The work in this dissertation investigates the hypothesis that uPAR directly interacts with and regulates the expression of integrins on the surface of NK cells in the potential modulation of NK cell migration and invasion. Crosslinking studies have revealed a relationship between the
In the present study, we provide evidence that freshly isolated neuroblastoma cells are susceptible to NK-mediated lysis. More importantly, we show that a key role in the lytic process is played by PVR, a molecule expressed at the tumor cell surface that is recognized by the DNAM-1 receptor. We analyzed highly purified, fresh neuroblastoma cells isolated from bone marrow aspirates (22) . As compared with cultured neuroblastoma cell lines (20) , freshly isolated neuroblasts were generally more resistant to lysis. Remarkably, a certain degree of variability existed among different tumors. In particular, we show that tumor cells displaying maximal susceptibility to lysis were characterized by high surface expression of PVR. This molecule was recently recognized as a ligand for DNAM-1, a surface receptor mediating NK cell activation and tumor cell killing (17) . In line with these findings, we now demonstrate that mAb-mediated disruption of DNAM-1-PVR interactions inhibits NK-mediated killing of ...
Natural killer (NK) cells play key roles in innate and adaptive immune responses against virus and tumor cells. Their function relies on the dynamic balance between activating and inhibiting signals through receptors that bind ligands expressed on target cells. The absence of inhibitory receptor engagement with their ligands and the presence of activating signals transmitted by activating receptors interacting with specific ligands, leads to NK cell activation (Lanier, 2005; Raulet et al., 2001). Thus, the balance of the ligands expressed for inhibitory and activating receptors determines whether NK cells will become activated to kill the target cells. This protocol allows to assign a precise ligand specificity to any given receptor on NK cells. Thus, if a tumor cell expresses the ligand, this protocol will allow to evaluate its interaction with the specific receptor. In particular, killer cell immunoglobulin (Ig)-like receptors (KIR) recognize their ligands (HLA class I molecules) through the direct
TY - JOUR. T1 - Use of natural killer cells as immunotherapy for leukaemia. AU - Grzywacz, Bartosz J. AU - Miller, Jeffrey S. AU - Verneris, Michael R. N1 - Funding Information: This work was funded by the Childrens Cancer Research Fund, Leukemia Research Fund, P01 CA111412 and P01 CA65493. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2008/9. Y1 - 2008/9. N2 - Natural killer (NK) cells potentially play a significant role in eradicating residual disease following allogeneic haematopoietic cell transplantation, and have been explored as tools for adoptive immunotherapy for chemotherapy-refractory patients. NK cell cytotoxicity is modulated by multiple activating and inhibitory receptors that maintain a balance between self-tolerance and providing surveillance against pathogens and malignant transformation. The functional characteristics of NK cells are dictated by the strength of inhibitory receptor signalling. Major histocompatibility complex (MHC)-specific inhibitory ...
Author: Niemeyer, Marcus et al.; Genre: Journal Article; Published in Print: 2008-01; Keywords: transcriptomics; T helper cells; regulatory T cells; natural killer T cells; natural killer cells; Title: Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses
In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell that has been stimulated to kill tumor cells. If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells. It has been shown that lymphocytes, when exposed to Interleukin 2, are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic. LAK cells respond to these lymphokines, particularly IL-2, by lysing tumor cells that were already known to be resistant to NK cell activity. The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot. LAK cells are also capable of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors. LAK cells are specific to tumor cells and do not display activity against normal cells. ...
In this study, profoundly depressed NK cell activity was observed in a large subgroup of patients with sJRA and in only 1 of 20 patients with the polyarticular form of the disease. The extent of NK dysfunction in this group of patients was similar to that seen in patients with MAS [17] or HLH [12, 13]. The two study groups (sJRA versus other JRA subtypes) were well matched in terms of age, duration of the disease, and treatment regimens with the exception of a slightly higher proportion of patients with sJRA receiving steroids. Steroids have been reported to suppress the cytolytic activity of NK cells [22], and this might potentially have contributed to the observed differences in NK function. However, the logistic regression analysis did not show significant differences between groups defined on the basis of treatment regimens. In addition, several patients with sJRA who demonstrated profoundly depressed NK cell cytolytic activity were receiving only non-steroidal anti-inflammatory drugs. Owing ...
Natural killer (NK) cells play a key role in non-specific immune response in different cancers, including pancreatic cancer. However the anti-tumor effect of NK cells decreases during pancreatic cancer progression. The regulatory pathways by which NK cells facilitate tumor immune escape are unclear, therefore our purpose was to investigate the roles of the contributory factors. NK cells isolated from fresh healthy peripheral blood were co-cultured with normal human pancreatic ductal cells hTERT-HPNE and human pancreatic cancer cell lines SW1990 and BxPc-3 in vitro. Then NK cell function was determined by Flow cytometric analysis of surface receptors and cytotoxic granules in NK cells, NK cell apoptosis and cytotoxicity, and Enzyme-linked immunosorbent assay of cytokines. Expression level of MMP-9, IDO and COX-2 in hTERT-HPNE and SW1990 cells were detected by quantitative RT-PCR. Statistical differences between data groups were determined by independent t-tests using SPSS 19.0 software. Our results
Faculty of Engineering and Natural Sciences. SEMINAR. Natural Killer Cell Therapy in Multiple Myeloma: Towards a Phase I/II Clinical Trial. Tolga Sutlu, Karolinska Institute, Sweden. Abstract:. Despite the advances in autologous stem cell transplantation and chemotherapy, multiple myeloma (MM) remains an incurable disease. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy and immunotherapy. Cell-based immunotherapy after hematopoietic stem cell transplantation has been attempted but, with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied.. We have primarily attempted to determine if NK cells provide anti-MM activity following interleukin-2 (IL-2) administration, and if ex vivo activated and intravenously (i.v.) administered NK cells prolong survival in MM bearing C57BL/KaLwRij mice. IL-2 ...
Natural killer (NK) cells were first described 16 years ago. Studies with athymic or neonatally thymectomized mice showed they had relatively low incidences of carcinogen-induced tumors and good resistance during the initial encounter with viral infection. These mice lacked mature T cells, but had normal or elevated numbers of cells able to lyse certain tumor cell lines without prior stimulation. Subsequent studies have shown that NK activity can be enhanced by cytokines, specifically by interferons (IFN) and interleukin-2 (IL_2). A second type of unrestricted tumor cell killing has been described. Lymphocytes, incubated overnight with IL-2, acquire the ability to kill both fresh tumor cells and tumor cell lines resistant to killing by NK cells. These cells are known as lymphokine-activated (LAK) cells. This thesis will discuss the properties of LAK and NK cells, their unclear relationship with each other, and the regulatory effects of IFN and IL-2 on their activity.
Natural Killer (NK) cells contribute to the control of cancer through immunosurveillance and may influence phenotypic sculpting of cancer through immunoediting. NK cells may also contribute to the control of hematological malignancies such as acute myeloid leukemia (AML) following allogeneic stem cell transplantation. However, no studies have shown direct clinical evidence that supports immunoediting by NK cells in AML at presentation, or whether activating ligand expression at diagnosis serves as a prognostic indicator of survival. We now show that at diagnosis, expression of NK cell ligands on AML blast populations is heterogeneous. Furthermore, expression of multiple activating ligands is associated with favorable cytogenetics and improved leukemia-free survival. In analyses of paired diagnostic and relapse samples, AML blasts exhibiting lower expression of activating ligands were selectively increased at relapse, indicating that NK cell-mediated blast immunoediting occurred prior to AML ...
A first-in-human Phase I study of multiple myeloma patients combined expanded cord blood-derived natural killer cells with transplantation of a patients own stem cells and high-dose chemotherapy with little or none of the side effects seen with current treatments. Nina Shah, M.D. Multiple myeloma is a cancer that forms from white blood cells that are found in the bone marrow and are normally vital to a healthy immune system. Natural killer (NK) cells are white blood cells that roam through the blood stream, attacking infections and potentially cancer-causing cells. The technology to grow NK cells from umbilical cord blood was developed by Nina Shah, M.D., assistant professor and Elizabeth J. Shpall, M.D., professor in the department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. Results from the clinical study, led by Shah and Shpall, were presented today at the 57th Annual Meeting of the American Society of Hematology (ASH) annual ...
The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon γ (IFNγ) and tumour necrosis factor α. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1β treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFNγ in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells
In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögrens syndrome (pSS) and to identify predictors of response to treatment. Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögrens Syndrome Disease Activity Index score of ≥3 points at W28. After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D-positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score |1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5-0.67) to 0.50 (0.5-0.5) (p=0.06). B-cell activating
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (n = 21), patients with asthma (n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (n = 29) had a marked increase in the ratios of CD4+ T cells to NK cells and neutrophils to NK cells. BAL NK cells in severe asthma were skewed toward the cytotoxic CD56dim subset, with significantly increased BAL fluid levels of the cytotoxic mediator granzyme A. The numbers of BAL CD56dim NK cells and CCR6−CCR4− T helper 1-enriched CD4+ T cells correlated inversely with lung function [forced expiratory volume in 1 s (FEV1) % predicted] in asthma. Relative to cells from healthy ...
The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16 ?
The purpose of work described in this thesis was to (i) determine the contribution of innate immune responses to the early pro-inflammatory cytokine response to Plasmodium falciparum, (ii) describe the kinetics and cellular sources ofIFN-y production by human PBMC in response to activation by intact, infected erythrocytes (iRBC) or freeze-thawed schizont lysate (PfSL) and (iii) determine the activation requirements for innate immune cells responding to P. falciparum. Infected erythrocytes induce a more rapid and intense IFN-y response from malaria naive PBMC than does PfSL, correlating with rapid iRBC activation of CD3-CD56+ natural killer (NK) cells to produce IFN-y. There is marked heterogeneity between donors in the magnitude of the NK-IFN-y response not correlating with mitogen or cytokine-induced NK activation or prior malaria exposure. The NK-IFN-y response is highly IL-I2 dependent, partly IL-I8 dependent and highly dependent on direct contact between the NK cell and the parasitized ...
Alterations in natural killer (NK) cell number and function were examined in cigarette smokers and nonsmokers with silicosis, silica dust exposure without silicosis, or no exposure to rock dust. Blood NK cell number, percentage, and tumoricidal activity were measured in 120 hardrock miners, 57 of whom had radiographic evidence of silicosis, and in 33 community referents. There was a significant in
Cross-linking of FcγRIIIA (CD16) receptor on natural killer (NK) cells induces receptor-associated tyrosine kinase activation and tyrosine phosphorylation of numerous intracellular proteins, including phospholipase C (PLC)-γ1, PLC-γ2 and the associated ζ chain. Here we report that Vav, a proto-oncogene, also became tyrosine phosphorylated upon stimulation of CD16 in interleukin 2-activated NK cells (LAK-NK) as well as in an NK cell line, NK3.3. In addition, we observed that in LAK-NK cells, Vav was associated with a 70 kDa protein that also became tyrosine phosphorylated upon CD16 cross-linking. The association of this 70 kDa protein with Vav was disrupted by ionic detergent treatment. Tyrosine phosphorylation of Vav was inhibited by herbimycin A, a specific tyrosine kinase inhibitor. In vitro kinase assays with Vav immunoprecipitates derived from NK3.3 cells or LAK-NK cells resulted in the appearance of a phosphorylated 58 kDa protein, suggesting the presence of a kinase within the Vav ...
1. ReddehaseMJ. 2002 Antigens and immunoevasins: opponents in cytomegalovirus immune surveillance. Nat Rev Immunol 2 831 844. 2. LanierLL. 2008 Evolutionary struggles between NK cells and viruses. Nat Rev Immunol 8 259 268. 3. LodoenMB. LanierLL. 2006 Natural killer cells as an initial defense against pathogens. Curr Opin Immunol 18 391 398. 4. BironCA. ByronKS. SullivanJL. 1989 Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320 1731 1735. 5. JonjicS. BabicM. PolicB. KrmpoticA. 2008 Immune evasion of natural killer cells by viruses. Curr Opin Immunol 20 30 38. 6. PowersC. DeFilippisV. MalouliD. FruhK. 2008 Cytomegalovirus immune evasion. Curr Top Microbiol Immunol 325 333 359. 7. WilkinsonGW. TomasecP. StantonRJ. ArmstrongM. ProdhommeV. 2008 Modulation of natural killer cells by human cytomegalovirus. J Clin Virol 41 206 212. 8. LodoenMB. LanierLL. 2005 Viral modulation of NK cell immunity. Nat Rev Microbiol 3 59 69. 9. LjunggrenHG. KarreK. 1990 In ...
Therapeutic natural killer (NK) cell-mediated alloreactivity towards acute myeloid leukemia (AML) has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B cell precursor leukemia (BCP-ALL) appears to be resistant to NK cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. We here demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity towards pediatric BCP-ALL in vivo. Notably, not only adoptively transferred mature, KIR(+) NK cells but also immature, KIR- NK cells arising early post transplantation in humanized NSG mice (huNSG) exerted substantial anti-leukemic activity. Low-dose and long-term treatment of huNSG mice with the DNA-demethylating agent 5-Aza-cytidine distinctly enhanced the anti-tumor response, interestingly ...
Researchers observed a marked increase in natural killer cells in HIV - positive children receiving massage therapy than those who did not receive massage. Natural killer cells are unique in that they attack only cells infected by a microbe. The children who did not receive massage had a steady decrease of these important immune cells, while those receiving treatment either remained stable or had an increase in natural killer cells ...
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The NK killing activity is regulated by activating and inhibitory NK receptors. All of the activating ligands identified so far are either viral or stress-induced proteins. The class I MHC proteins are the ligands for most of the inhibitory NK receptors. However, in the past few years, several receptors have been identified that are able to inhibit NK killing independently of class I MHC recognition. We have previously demonstrated the existence of a novel inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic Ag (CEA)-related cell adhesion molecule 1 (CEACAM1) interactions. In this study, we demonstrate that CEACAM1 also interacts heterophilically with the CEA protein. Importantly, we show that these heterophilic interactions of CEA and CEACAM1 inhibit the killing by NK cells. Because CEA is expressed on a wide range of carcinomas and commonly used as tumor marker, these results represent a novel role for the CEA protein enabling the escape of tumor cells from NK
Background Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures.. Methods HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells.. Results In general, high ...
Cell surface proteins major histocompatibility complex (MHC) class I-related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein-tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for
The antitumor activities of cytolytic T lymphocytes and natural killer cells are being increasingly investigated and exploited in cancer immunotherapy. One mechanism by which these cells recognize tumor cells is by engagement of NKG2D, an activating receptor on cytolytic T lymphocytes and natural killer cells, by MICA/B and ULBP family stress antigens.. In a study reported in Science Translational Medicine, Vantourout and colleagues showed that activation of EGFR is responsible for surface upregulation of NKG2D ligands in human epithelial cells in response to ultraviolet irradiation, osmotic shock, oxidative stress, and growth factor exposure. EGFR activation results in intracellular relocalization of adenylate-uridylate (AU)-rich element RNA-binding protein 1 (AUF1); AUF1 proteins normally destabilize NKG2D ligand mRNAs by targeting an AU-rich element that is conserved in the 3′ ends of most human, but not murine, NKG2D ligand genes. NKG2D ligand expression was positively correlated with EGFR ...
Immunodeficiency with natural killer cell deficiency (MCM4) Test Cost INR 30000.00 Surat Pune Jaipur Lucknow Kanpur Nagpur Visakhapatnam Indore Thane Bhopal Patna Vadodara Ghaziabad Ludhiana Coimbatore Madurai Meerut Ranchi Allahabad Trivandrum Pondicherry Mysore Aligarh best offer discount price
A first-in-human Phase I study of multiple myeloma patients combined expanded cord blood-derived natural killer cells with transplantation of a patients own stem cells and high-dose chemotherapy with little or none of the side effects seen with current treatments.. View article ...
Killer Cell Lectin Like Receptor D1 Human Recombinant, Killer Cell Lectin Like Receptor D1, Killer Cell Lectin-Like Receptor Subfamily D, Member 1, NK Cell Receptor, CD94 Antigen, CD94, KP43, Killer Cell Lectin-Like Receptor Subfamily D Member 1, Natural Killer Cells Antigen CD94, KLRD1.
Are natural killer cells the explanation for unexplained infertility, IVF failure, and repeated miscarriage? Learn what you need to know here.
Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated.
Defects in NK and NKT cell activities have been implicated in the etiology of type 1 (autoimmune) diabetes in NOD mice on the basis of experiments performed using surrogate phenotypes for the identification of these lymphocyte subsets. Here, we have generated a congenic line of NOD mice (NOD.b-Nkrp1(b)) which express the allelic NK1.1 marker, enabling the direct study of NK and NKT cells in NOD mice. Major deficiencies in both populations were identified when NOD.b-Nkrp1(b) mice were compared with C57BL/6 and BALB.B6-Cmv1(r) mice by flow cytometry. The decrease in numbers of peripheral NK cells was associated with an increase in their numbers in the bone marrow, suggesting that a defect in NK cell export may be involved. In contrast, the most severe deficiency of NKT cells found was in the thymus, indicating that defects in thymic production were probably responsible. The deficiencies in NK cell activity in NOD mice could only partly be accounted for by the reduced numbers of NK cells, and fewer ...
INTRODUCTION. Human exposure to cadmium due to environmental factors is known to affect several tissues in the body.The major sources of exposure to cadmium are contaminated food and water, tobacco, and industrial fumes and dusts (Goyer & Cherian, 1995). Toxic effects of Cd have also been demonstrated on the bone formation and immune system (Nordberg, 1996) and (Waalkes et al., 1999). Cadmium causes damage both to humoral immune response and cell mediated immunity (Descotes, 1992; Dan et al., 2000). Cifone et al. (1989) demonstrated that the exposure to 200 and 400 ppm Cd of adult rats caused both inhibitory and stimulatory effects on natural killer cells activity and cytotoxic activity. Moreover, Hemdan et al. (2006) reported that Cd treatment exerted differential effects on cytokine production in human immunocompetent cells. Immunotoxic properties of most heavy metals is not well lit, and the underlying mechanisms are not fully understood. Therefore, the aim of this study, an important ...
article{9e6ef65e-280f-480c-95c2-8ec585bac8f7, abstract = {Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. cDNAs for both soluble and transmembrane (tm) proteins were expressed in the human YT-Indy NK-cell line. Targeting of a soluble TNF receptor (sTNFR1) was achieved by expressing a cDNA construct with a transmembrane sequence to facilitate ER-export and by incorporating a cytosolic sorting signal (Y) from CD63 to overcome constitutive secretion. The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with subcellular fractionation, immunoelectron microscopy, and immunofluorescence microscopy. A soluble sTNFR1 form was generated in the secretory lysosome by endogenous proteolytic activity. Expression of ...
... and natural killer cell and helper T cell activity; in other words, consuming the proteins of the robust sea cucumber had a ... Natural Killer cells are cytotoxic; they help eliminate tumors and fight infectious diseases. In addition, C. robustus has been ... It was reported that C. robustus was capable of fission, but there was no evidence of asexual reproduction in natural ... It is likely asexual reproduction was not found in natural populations because the conditions were not stressful enough. ...
Natural killer cells[change , change source]. Natural killer (NK) cells are a part of the immune system a person is born with. ... T and B cells[change , change source]. T cells (thymus cells) and B cells (bone cells) are the main cells of the adaptive ... Natural killer cells can tell the difference between infected cells, tumours, and normal cells. They recognise changes in the ... Natural killer cells Lysis of virally infected cells and tumour cells 7% (2-13%) ...
Natural killer cells[edit]. Main article: Natural killer cell. NK cells are a part of the innate immune system and play a major ... Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell- ... Main articles: T cell and B cell. T cells (thymus cells) and B cells (bone marrow- or bursa-derived cells[a]) are the major ... Natural killer cells Lysis of virally infected cells and tumour cells 7% (2-13%) CD16 CD56 but not CD3 ...
"Focus on Natural Killer Cells: Classics". Nature Immunology. 9 (5). 2008. "Fellow Professor Daniel Davis". The Academy of ... Davis DM, Chiu I, Fassett M, Cohen GB, Mandelboim O, Strominger JL (Dec 1999). "The human natural killer cell immune synapse". ... Working with Jack Strominger at Harvard University, Davis showed structured immune synapses for the Natural Killer cell. Davis ... His research, using microscopy to study immune cell biology has helped understand how immune cells interact with each other. He ...
... that a cell was diseased, and should be killed by a Natural Killer (NK) cell. 8. Sex and Smelly T-shirts The chapter describes ... "Focus on Natural Killer Cells: Classics". Nature Immunology. 9 (5). 2008. "Fellow Professor Daniel Davis". The Academy of ... Alan Townsend found that killer T-cells destroyed cells that carried an HLA protein and small fragments of viral protein. Those ... and the way the body distinguishes self from not-self via natural killer cells. The compatibility mechanism contributes also to ...
... tumor cells or cells infected with viruses. Klein named them "natural killer cells". Klein has had a longstanding interest in ... killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer ... In the 1960s, she led the discovery of natural killer cells and developing Burkitt's lymphoma cell lines. In 1975, the U.S. ... malignant behavior can be suppressed by genes in normal cells. In the 1960s, Eva Klein developed cell lines from Burkitt's ...
"Effects of prolactin and cortisol on natural killer (NK) cell surface expression and function of human natural cytotoxicity ... Natural killer cells are affected by cortisol. Cortisol stimulates many copper enzymes (often to 50% of their total potential ... and T helper cells (Th1 cells), but upregulates interleukin 4, interleukin 10, and interleukin 13 by Th2 cells. This results in ... The suppressor immune cells are not affected by GRMF, so the immune cells' effective setpoint may be even higher than the ...
Other innate leukocytes include natural killer cells, mast cells, eosinophils, basophils, macrophages, and dendritic cells. ... dendritic cells) and Lymphoid lineage cells (T-cells, B-cells, NK-cells). The chemorepulsion of immune cells was first ... Farrell, HE; Degli-Esposti, Davis-Poynter NJ (1999). "Cytomegalovirus evasion of natural killer cell responses". Immunology ... Cancer cells leverage the chemorepulsion of immune cells to evade recognition and destruction by immune cells. Without a ...
Sun JC, Beilke JN, Lanier LL (January 2009). "Adaptive immune features of natural killer cells". Nature. 457 (7229): 557-61. ... Evidence of trained immunity is found mainly at monocytes/macrophages and NK cells and, less at γδ T cells and innate lymphoid ... because there is development of at least partially-specific clones of NK cells. These cells have receptors on their surface ... This shows that the immune memory is created at the level of progenitor cells, but so far it is not known how this memory is ...
These two events allow for immune evasion by suppressing the cell-mediated immune response and natural killer cell response, ... This prevents the natural killer cell response.[citation needed] Below are the distinct viruses in this family known to cause ... When the virus enters a cell, the cellular immune response is to protect the cell. The cell does so by wrapping the viral DNA ... clinical signs such as swollen or tender lymph nodes and immunological findings such as reduced levels of natural killer cells ...
Smyth, Mark J.; Martinet, L. (March 2015). "Balancing natural killer cell activation through paired receptors". Nature Reviews ... The protein may play a role in the adhesion of activated T and NK cells to their target cells during the late phase of the ... CD96 is a receptor protein which is expressed on T cells and NK cells and shares sequence similarity with CD226 (also known as ... Fuchs A, Cella M, Giurisato E, Shaw AS, Colonna M (April 2004). "Cutting edge: CD96 (tactile) promotes NK cell-target cell ...
Natural killer cell granule protein 7 is a protein that in humans is encoded by the NKG7 gene. GRCh38: Ensembl release 89: ... "Entrez Gene: Natural killer cell granule protein 7". Retrieved 2016-02-23. CS1 maint: discouraged parameter (link) v t e. ...
"Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, ... To this end, lymphoid leukemias can also be divided by the type of cells affected: B-cell leukemia T-cell leukemia NK-cell ... Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally ... Oshimi K (July 2003). "Leukemia and lymphoma of natural killer lineage cells". Int. J. Hematol. 78 (1): 18-23. doi:10.1007/ ...
... and immature natural killer cells. These Natural Killer cells have a reduced lytic function; which can be improved with regular ... but are not as vulnerable to opportunistic pathogens as patients with true Natural Killer cell deficiency-type SCID. Netherton ...
"Recognition of bacterial glycosphingolipids by natural killer T cells". Nature. 434 (7032): 520-525. Bibcode:2005Natur.434.. ... Cell. 165 (4): 813-826. doi:10.1016/j.cell.2016.04.010. PMC 5543418. PMID 27114034. Shivatare, Vidya S.; Shivatare, Sachin S.; ... "Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells". Proceedings of the National Academy of ...
Beaulieu AM, Madera S, Sun JC (2015). "Molecular Programming of Immunological Memory in Natural Killer Cells". Advances in ... The expression of ZBTB32 is induced by inflammatory cytokines and promotes proliferation of natural killer cells. Zbtb32 ... ZBTB32 is highly expressed spermatogonial stem cells, in hematopoietic stem and progenitor cells (please also refer to the RNA ... Cell. 125 (4): 801-14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685. Ikeda R, Yoshida K, Inoue I (May 2007). " ...
This case demonstrated the rare association between Natural Killer cell lymphoma and PNP, suggesting that Natural Killer cells ... The underlying tumors are almost exclusively of B-cell lineage. However, T-cells and CD56+ Natural Killer cells have also been ... "Paraneoplastic pemphigus due to natural-killer/T-cell lymphoma". British Journal of Haematology. 154 (2): 160. doi:10.1111/j. ... This is followed by transplanting peripheral blood stem cells. If the lesions are mild, the patient will be subject to a good ...
Mendenhall WM, Olivier KR, Lynch JW, Mendenhall NP (April 2006). "Lethal midline granuloma-nasal natural killer/T-cell lymphoma ... Cytoplasmic-staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils (a type of white blood cell) are ... Due to a high frequency of abnormally low white blood cell counts seen with cyclophosphamide treatment, Pneumocystis jirovecii ... and many giant cells. Bacterial colonization with Staphylococcus aureus has been hypothesized as an initiating factor of the ...
Some cells are specially designed to phagocytize. These cells include Natural Killer cells, macrophages, and neutrophils. All ... Endocytosis is when a cell absorbs a molecule, such as a protein, from outside the cell by engulfing it with the cell membrane ... The vesicles fuse with the cell membrane and their content, usually protein, is released out of the cell. There are two types ... Methods of cytosis not only move substances in, out of, and through cells, but also add and subtract membrane from the cell's ...
"LabCentral resident Conkwest treats Cancer with Natural Killer Cells". LabCentral. Archived from the original on 4 December ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... "Multiple transcripts of the killer cell immunoglobulin-like receptor family, KIR3DL1 (NKB1), are expressed by natural killer ... 1996). "The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory ... A natural killer cell receptor for HLA-B allotypes". J. Immunol. 155 (5): 2306-10. PMID 7650366. Litwin V, Gumperz J, Parham P ...
... has a very specialized role in cell recognition by natural killer cells (NK cells). HLA-E binds a restricted subset of ... "Human natural killer cells: their origin, receptors and function". European Journal of Immunology. 32 (5): 1205-11. doi:10.1002 ... "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C". Nature. 391 (6669): 795-9. Bibcode:1998Natur.391..795B. doi: ... "Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells". Nature Immunology. 19 (5 ...
Chinese scientists to pioneer first human CRISPR trial Cerwenka, Adelheid; Lanier, Lewis L. (2016). "Natural killer cell memory ... Targeted therapy Natural killer cells can induce immunological memory. Research is being developed to modify their action ... are assayed on cultures of bacteria and mammalian cells. The goal of oncogenomics is to identify new oncogenes or tumor ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... G-specific receptor expressed on all natural killer cells". J. Exp. Med. 189 (7): 1093-100. doi:10.1084/jem.189.7.1093. PMC ... "DNA methylation maintains allele-specific KIR gene expression in human natural killer cells". J. Exp. Med. 197 (2): 245-55. doi ... induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells ...
Park S, Ko YH (January 2014). "Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders". The Journal ... The bite sites are infiltrated with T helper cells, CD8+ T cells, and CD16+ NK cells. In this mixture of infiltrates, most of ... cell leukemia (also termed aggressive NK-cell leukemia/lymphoma), and extranodal NK/T-cell lymphoma, nasal type. MBA in ... Lympoid cells at the bite site may also express the EBV1 viral gene, BZLF1; this gene promotes the lyses of its infected cell ...
It is also known as Natural Killer Cell Receptor 2B4 This gene encodes a cell surface receptor expressed on natural killer ... natural killer cell receptor 2B4". Online Mendelian Inheritance in Man (OMIM): 605554 "CD244 molecule, natural killer cell ... 1999). "2B4, the Natural Killer and T Cell Immunoglobulin Superfamily Surface Protein, Is a Ligand for CD48". J. Exp. Med. 188 ... Kumaresan PR, Mathew PA (2000). "Structure of the human natural killer cell receptor 2B4 gene and identification of a novel ...
Natural killer cell receptors. This can cause PVR to possibly be transferred to NK cells and cause fratricide of Natural killer ... The poliovirus receptor plays a role in cell motility during tumor cell invasion and migration. PVR binds to CD96 and CD226 - ... it has been found that C1orf142 has larger expression rates in cell line of giant cell lung carcinoma they have high metastatic ... and COTL1 in Non-Small Cell Lung Cancer Cell Lines With Different Tumor Metastatic Potential". Journal of Investigative ...
Kibakaya, EC; Stephen K; Whalen MM (2009). "Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells ... and by reducing natural killer cell activity. A 2013 literature review on TBBPA concludes that TBBPA does not produce "adverse ... TBBPA likely also suppresses immune responses by inhibiting expression of CD25 receptors on T cells, preventing their ...
This research has shown that Natural Killer cells have receptors (TDAG8) for certain glycosphingolipids that build up in an ... Maghazachi, Azzam A. (February 5, 2013). "On the Role of Natural Killer Cells in Neurodegenerative Diseases". Toxins (Basel). 5 ... cell leukodystrophy may be distinct disease entities due to the secretion of inflammatory mediators by natural killer cells in ... target the Natural Killer cells for destruction thereby preventing their cytotoxic effects. These sphingolipids have been ...
Natural killer T cell. NK cells. *Cytokine-induced killer cell. *Lymphokine-activated killer cell ... Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that secrete ... In humans, CD27 is a good marker for plasma cells, naive B cells are CD27-, memory B-cells are CD27+ and plasma cells are ... Germinal center B cells may differentiate into memory B cells or plasma cells. Most of these B cells will become plasmablasts ( ...
Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis. Immunology Letters. March 2017 ... Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine ... 细胞毒性T细胞(CTLs, killer T cells)负责杀伤被病毒感染的细胞和癌细胞,在对器官移植的免疫排斥中也有参与。其特点在于细胞表面的CD8蛋白质。它通过识别所有有核细胞表面的MHC-
... the proportion of trees with a high level of natural resistance seemed to be very low, probably less than 5%.[24] A Lithuanian ... perforating the middle lamella but damage to either the plasmalemma or cell walls was not observed.[29] The disease is often ... "Trees that thrive amid killer fungus hold secret to saving threatened ash". London: The Telegraph. Retrieved 4 November 2012 ... mature trees would not be removed because of the implications for wildlife who depend on the trees for their natural habitat. ...
The presence of the cap changes the effectiveness of natural killer (NK) cells in destroying these B cells. When an NK cell ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... It induces apoptosis of CD20+ cells.. The combined effect results in the elimination of B cells (including the cancerous ones) ... ocrelizumab, humanized (90%-95% human) B cell-depleting agent.. *ofatumumab (HuMax-CD20) a fully human B cell-depleting agent.[ ...
Multiple tornadoes produced by the same storm cell are referred to as a "tornado family".[21] Several tornadoes are sometimes ... "Natural Disasters: Tornadoes". BBC Science and Nature. BBC. Archived from the original on 2002-10-14. Retrieved 2009-12-13 ... "Tornado factory - giant simulator probes killer twisters". Popular Science. 213 (1): 76-78. ... Tornadic storms do not contain more lightning than other storms and some tornadic cells never produce lightning at all. More ...
... killer, false killer, pilot, pygmy killer, and melon-headed whales) in the Indian Ocean Sanctuary, 1772-1986 in Cetaceans and ... Odontocetes, such as the sperm whale, possess teeth with cementum cells overlying dentine cells. Unlike human teeth, which are ... Gormley, Gerard (1990). Orcas of the Gulf: A Natural History. Lincoln, NE: toExcel. p. 10. ISBN 978-0-595-01118-6.. ... the pygmy killer whale, the false killer whale, and the two species of pilot whales, all of which are classified under the ...
The cytotoxicity of Natural Killer (NK) cells and the antigen-presenting function of dendritic cells is known to diminish with ... Bruunsgaard, H.; A. N. Pedersen; M. Schroll; P. Skinhoj; B. K. Pedersen (2001). "Decreased natural killer cell activity is ... diversity cytotoxic activity of Natural Killer T-cells (NKTs) decreases impaired proliferation in response to antigenic ... "Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1 ...
"The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line ... 1997). "CD2 induced apoptosis of peripheral T cells.". Transplant. Proc. 29 (5): 2377-8. PMID 9270771. doi:10.1016/S0041-1345( ... Peterson A, Seed B (1987). "Monoclonal antibody and ligand binding sites of the T cell erythrocyte receptor (CD2).". Nature 329 ... Yang J, Ye Y, Carroll A, Yang W, Lee H (2001). "Structural biology of the cell adhesion protein CD2: alternatively folded ...
His interest in immunology has led to publications in HIV disease, cellular activation and natural killer cell function, tumor ... The staging and prognostic value of subset markers on CD8 cells in HIV disease. In Janossy G, Autran B. Miedema F (eds): ... Enumeration of CD4+ T-cells in the peripheral blood of HIV-infected patients: interlaboratory study of the FACSCount system. ... platelet activation in vascular disease and stem cell transplantation in cancer patients. As an endocrinologist he has an ...
... killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T ... The natural endogenous ligand with the greatest efficacy for a given receptor is by definition a full agonist (100% efficacy). ... In biochemistry and pharmacology, a receptor is a protein molecule that receives chemical signals from outside a cell.[1] When ... Cells can increase (upregulate) or decrease (downregulate) the number of receptors to a given hormone or neurotransmitter to ...
"Escape is the unlikely link between The Shawshank Redemption and Natural Born Killers". The A.V. Club. Archived from the ... Andy passes through a hole in his cell hidden by a movie poster to escape both his cell and ultimately Shawshank.[33] ... and Riot in Cell Block 11.[90][91] Gene Siskel said that like One Flew Over the Cuckoo's Nest, The Shawshank Redemption is an ... At the next day's roll call, the guards find Andy's cell empty. An irate Norton throws a rock at a poster of Raquel Welch ...
... natural history study - natural killer cells (NK cells) - NCI - New Drug Application - nebulized - Nef - neoplasm - nephrotoxic ... T suppressor cells - T4 cell - T4 cells (T-helper cells) - T8 cells - Tanner staging - TAT - TB - template - TeachAIDS - ... B-cell lymphoma - B cells - B lymphocytes (B cells) - bactericidal - bacteriostatic - bacterium - baculovirus - baseline - ... cells - CDC National Prevention Information Network (CDC-NPIN) - cell lines - cell-mediated immunity (CMI) - cellular immunity ...
Sidney Cooke, child molester and serial killer, was born in Stroud.[112] ... The Cotswold Area of Outstanding Natural Beauty surrounds the town, and the Cotswold Way path passes by it to the west. It lies ... from which there was access to a simple square chamber of one cell containing disarticulated human remains. Traces of the ...
Natural killer cells: virus-infected and tumor cells.. Deeply staining, eccentric. NK-cells and cytotoxic (CD8+) T-cells. Years ... T cells: *CD4+ helper T cells: T cells displaying co-receptor CD4 are known as CD4+ T cells. These cells have T-cell receptors ... γδ T cells share characteristics of helper T cells, cytotoxic T cells, and natural killer cells. ... Natural killer cells are able to kill cells of the body that do not display MHC class I molecules, or display stress markers ...
... natural killer cells and monocytes (CD15+), as well as activation markers (HLA-DR, CD25, CD80 (B cells). Tests for T cell ... cell responses to mitogens and allogeneic cells, cytokine production by cells Tests for B cell function: antibodies to routine ... Normal numbers of B cells with decreased IgG and IgA and increased IgM: Hyper-IgM syndromes Normal numbers of B cells with ... VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or ...
Mendenhall WM, Olivier KR, Lynch JW, Mendenhall NP (April 2006). "Lethal midline granuloma-nasal natural killer/T-cell lymphoma ... a type of white blood cell) are associated with GPA.[11] Involvement of the ears, nose, and throat is more common in ... and many giant cells.[16] Bacterial colonization with Staphylococcus aureus has been hypothesized as an initiating factor of ... and decreases the incidence of abnormally low white blood cell counts by one-third.[8] However, pulsed intravenous ...
Natural killer cells[change , change source]. Main article: Natural killer cell. Natural killer cells, or NK cells, are a part ... The innate leukocytes include: Natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells including ... Instead, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells. It recognises such cells by a ... Gets immune cells (such as natural killer cells) to the infection by producing cytokines. ...
স্বভাবগত ঘাতক কোষ (Natural killer cell). *বৃক্ষরূপী কোষ (Denditric cell). *প্রতিজন বা প্রত্যুৎপাদক (Antigen) ...
... produced mainly by T lymphocytes and natural killer (NK) cells, necessary for eliciting reaction against these antigens. The ... TI-1 antigens are classified as B-cell mitogens, because they induce numerous cell divisions. In higher concentrations, TI-1 ... Immature B cells are anergized, so they do not elicit any immune response. That may explain why children up to 5 years are not ... TI-1 antigen, which has an activity that can directly activate B cells and TI-2 antigen, which has highly repetitive structure ...
positive regulation of natural killer cell mediated cytotoxicity. • adaptive immune response. • T-helper 17 cell lineage ... 2 and reduces adherence of natural killer cells, thereby protecting HTLV-1-infected primary CD4+ T cells from autologous ... natural killer cell proliferation. • immune system process. • positive regulation of interferon-gamma production. • positive ... surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked ...
... beginning with cleaning out their own cell after eating through their capped brood cell): feed brood, receive nectar, clean ... Bevan, E. The Honey-bee: Its Natural History, Physiology and Management. London: Baldwin, Cradock & Joy, 1827. ... Africanized bees (known colloquially as "killer bees") are hybrids between European stock and one of the African subspecies A. ... Eggs are laid singly in a cell in a wax honeycomb, produced and shaped by the worker bees. Using her spermatheca, the queen can ...
Natural killer cells[edit]. Main article: Natural killer cell. Natural killer cells (NK cells) are a component of the innate ... T cell subsets bearing invariant T cell receptors (TCRs), such as CD1d-restricted Natural Killer T cells, γδ T cells exhibit ... The innate leukocytes include: natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells include ... Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a ...
... distributes readily in high concentrations into immune cells, has antimicrobial and natural killer cell activities, ... "Natural food-Fruit Vitamin C Content". The Natural Food Hub. Archived from the original on March 7, 2007. Retrieved March 7, ... Cell. 132 (6): 1039-48. doi:10.1016/j.cell.2008.01.042. PMID 18358815. Lay summary - Science Daily (March 21, 2008).. ... Stone, Irwin (1972), The Natural History of Ascorbic Acid in the Evolution of Mammals and Primates. ...
Kaur, Jaskaran; Sukhman Dhami (October 2007), Protecting the Killers: A Policy of Impunity in Punjab, India (PDF), 19 (14), New ... opened a cell within ISI with the objective of supporting the "[Sikhs']...freedom struggle against India". Rahman's colleagues ... passed a resolution proclaiming the natural association of Punjab and Sikh religious community.[25] ... "Protecting the Killers: A Policy of Impunity in Punjab, India: I. Summary". Human Rights Watch. 9 October 2006. Retrieved 11 ...
Main article: Killer Bob. Frank Silva was a set decorator who worked on the pilot episode. One day, when he was moving ... while she is visiting his cell to ask for a divorce. Hank coldly replies: "you give me my alibi, and I'll give you a divorce". ... who married the decoy Cooper replaces in his return to the natural realm. ... She and Laura Palmer were both kidnapped and violently beaten by the serial killer BOB during the crime that drives much of the ...
... it has been detected in natural killer cells, platelets, and monocytes. T cell activation is accompanied by a strong up- ... cell cycle arrest. • learning or memory. • cellular copper ion homeostasis. • cellular response to copper ion. • cell cycle. • ... cell surface. • endoplasmic reticulum. • membrane raft. • anchored component of membrane. • extracellular exosome. • cell ... PrP immune cells include hematopoietic stem cells, mature lymphoid and myeloid compartments, and certain lymphocytes; also, ...
NK (Natural killer) limfocīti: vīrus inficētās un audzējšūnas. Ekscentrisks, labi iekrāsojas. Vairāki gadi atmiņas šūnām, ... Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9. ...
"Natural History, Science, &c". The Friend. 54: 223. 1881.. *^ Boswell, Victor R. "Improvement and Genetics of Tomatoes, Peppers ... Meiosis is central to the processes by which diploid microspore mother cells within the anther give rise to haploid pollen ... "Killer Tomatoes". The East Hampton Star. Archived from the original on 29 May 2009. ... University of California Agriculture and Natural Resources (21 May 1994). "California Agriculture Online". California ...
... peripheral blood mononuclear cell), of which a small percentage are NK cells (Natural Killer cell); less often they are ... ADCC requires an effector cell which classically is known to be natural killer (NK) cells that typically interact with ... NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface, indicating a non-self cell. ... By NK cells[edit]. The typical ADCC involves activation of NK cells by antibodies. An NK cell expresses Fc receptors, mostly ...
Th1 type cytokine release of IFN-γ and IL-2 that further stimulates clonal T cell proliferation and natural killer cell ... They have also been shown to cause dose dependent G0/G1 cell cycle arrest in leukemia cell lines where the analogs showed 100 ... Orphan indications include diffuse large B-cell lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma. Lenalidomide ... is induced in the presence of TNF-α and the adhesion of MM cells to BMSC. In vitro proliferation of MM cell lines and ...
Not to be confused with Natural killer T cell.. Natural killer cells, or NK cells, are a type of cytotoxic lymphocyte critical ... Tumor cell surveillance[edit]. Natural killer cells often lack antigen-specific cell surface receptors, so are part of innate ... Pyzik M, Vidal SM (2009). "Natural killer cells: NK cells stroll down the memory lane". Immunology and Cell Biology. 87 (4): ... NK cells are thought to be an important cell type in this process.[17] These cells are known as "uterine NK cells" (uNK cells) ...
... cells are the leading maternal immune cells which act as a natural defense system and help in fighting infections. During ... pregnancy, NK cells aid in supplying blood to the fetus, essential for its growth and development. It also protects the fetus ... Natural Killer (NK) cells are the leading maternal immune cells which act as a natural defense system and help in fighting ... Natural Killer Cells During Pregnancy. News-Medical. 09 April 2020. , ...
Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination?: Natural Killer Cells in Vaccination ... 2006) T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol 7:507-516. ... Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination?: Vaccination Strategies Based on NK Cell and ILC ... 2007) Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26:503-517. ...
Malaria-infected red blood cells trigger the immune systems first line of defense by releasing small vesicles that activate a ... Natural killer cells that responded to Plasmodium-infected red blood cells had higher levels of MDA5, which was activated by ... Natural killer cells are important immune cells that provide the first line of defense against malaria infection but show ... "The study reveals how natural killer cells recognize parasite-infected red blood cells and possible approaches to treat malaria ...
NK cells, co-cultured with K562 and renal cell carcinoma tumor Cancer immunotherapy involving natural killer (NK) cell ... cells. Cell Immunol 1991;135:454Á70. natural killer cells. Blood 1990;76:2421Á38. 17 Igarashi T, Wynberg J, Srinivasan R, ... cells was significantly higher with expanded NK cells T cells, no CD56/CD3 cells, no CD19 B cells and (27.699.3%) compared with ... Expanded Introduction receptors expressed on target cells. They can also mediate Natural killer (NK) cells are innate immune ...
... and comprise the third kind of cells other than B and T Lymphocytes. They usually... ... Natural Killer Cells are also defined as large granular lymphocytes (LGL) ... Importance of Natural killers cells: Natural killer cells are derived from Pluripotent Hematopoietic stem cells and are ... Introduction to Natural Killer cells: Natural Killer cells was discovered in the year 1970. It is a type cytotoxic lymphocyte ...
... and natural killer cell deficiency and MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency ... Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol. 2006;6(6):399-409.. View this article via: PubMed ... Human natural killer cell development. Immunol Rev. 2006;214:56-72.. View this article via: PubMed CrossRef Google Scholar ... Unraveling human natural killer cell deficiency. Jordan S. Orange University of Pennsylvania School of Medicine, Department of ...
... they produce cytokines that attract NK cells. The massive recruitment of NK cells allows killing cancer cells and lets the ... They found that if autophagy -- the intracellular recycling process -- is blocked in tumor cells, ... Bringing natural killer cells to the tumor battlefield LIH scientists discover a mechanism that inhibits tumor growth in skin ... Natural Killer (NK) cells, lymphocytes of the innate immune system with strong cytotoxic activity, play a major role in the ...
... aiming to understand the mechanisms by which tumour cells are eliminated by the immune system. ... Natural Killer T cells & cancer progression? Lead researcher. Prof Jamie Rossjohn, Prof James McCluskey ... Our project, focussed on tumour immunology, aims to understand the mechanisms by which tumour cells are eliminated by the ... Cancer is a disease of the cells, which are the bodys basic building blocks. ...
Kits for Primary Blood Cells Products at ... Kits for Human Natural Killer Cells along with other ... Cells were analyzed by flow cytometry 24 hours post Nucleofection™. eGFP expression in natural killer cells is shown after ... Nucleofection™ of primary human NK cells Primary human natural killer cells were transfected by Nucleofection™ with a plasmid ... Natural killer (NK), human (Nucleofector Kits) , Optimized Protocol , PDF. *Primary Cell Optimization (96-well Nucleofector ...
Two reports address how natural killer (NK) cells help prevent rejection (see the Perspective by Kärre). Rugerri et al. ... Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295, 2097-2100 (2002 ... Activation of NK cells can also be prevented by ligands that bind inhibitory receptors on the NK cell surface. Wang et al. ... Host-reactive NK cells may ablate antigen-presenting cells in the host and, in so doing, prevent them from inducing anti-host T ...
Human natural killer (NK) cells comprise approximately 15% of all circulating lymphocytes. Owing to their early production of ... The biology of human natural killer-cell subsets.. Cooper MA1, Fehniger TA, Caligiuri MA. ... NK cells are crucial components of the innate immune system. Human NK cells can be divided into two subsets based on their cell ... but has low natural cytotoxicity and is CD16(dim) or CD16(-). In addition, we will discuss other cell-surface receptors ...
Natural killer (NK) cells which belong in innate immunity, play an important role for defense against invading pathogens and ... Novel Animal Model for Analyzing Human Natural Killer Cell Functions In Vivo. ... NK cells make up around 5-20% of the white blood cells circulating in the bloodstream and are also critical cells for ... which supports the proliferation of T-cells. Unexpectedly, they found that human NK cells predominantly developed in the mice ...
... which destroys the virus along with the infected cell. ... which destroys the virus along with the infected cell. ... Natural killer cells are a specific type of white blood cell; they induce apoptosis, ... Natural killer cells are a specific type of white blood cell; they induce apoptosis, ... Natural killer (NK) cells are a specific type of white blood cell. Theyre an important component of your cell-mediated (innate ...
Stem cell research: Natural Born Killers?. April 10, 2007 7:07 PM Subscribe. Stem Cell Research: An interesting argument on why ... If a stem cell has a soul, does destroying that stem cell condemn that soul to hell? (For the sake of argument, limit the scope ... Bushs stem cell policy makes perfect sense.. He worries that democrats will use stem cells to grow spine.. posted by hortense ... No credit: What would that stem cell be like in heaven/hell? A 6-year old child? A grown adult? Or... still just a stem cell? ( ...
NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver ... NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver ... In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid ... Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects. ...
The utility of NK cells in human health has been underscored by a growing number of persons who are deficient in NK cells and/ ... cells are part of the innate immune defense against infection and cancer and are especially useful in combating certain viral ... Natural killer; Natural killer cell deficiency; Natural killer cells; PID; Primary immunodeficiency; VZV; Varicella zoster ... Keywords: ADCC; Antibody-dependent cell-mediated cytotoxicity; CMV; CNKD; CTL; Classical natural killer cell deficiency; ...
Here, we review the role of NK cells against hepatitis C virus (HCV) and hepatitis B virus (HBV), two agents that cause acute ... cells are traditionally regarded as first-line effectors of the innate immune response, but they also have a distinct role in ... Natural Killer Cells in Viral Hepatitis Cell Mol Gastroenterol Hepatol. 2015 Nov;1(6):578-588. doi: 10.1016/j.jcmgh.2015.09.004 ... Natural killer (NK) cells are traditionally regarded as first-line effectors of the innate immune response, but they also have ...
Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells ( ... Natural killer cells acquire CD73 expression upon exposure to mesenchymal stem cells. Blood 123:594-595PubMedCrossRefGoogle ... Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant ... Adenosinergic signaling Cancer Natural killer cell immunotherapy Immunometabolism This is a preview of subscription content, ...
Because many cell types, including natural killer (NK) cells, T cells and macrophages, may be involved in tumour resistance in ... leads to a complete and selective impairment of naturally occurring killer lymphocytes, whereas all other forms of cell- ... The defective gene product may lie within the lytic pathway subsequent to tumour cell contact. ... vivo1, these mice will provide a critical test of the hypothesis that it is NK cells which provide a first line of defence ...
Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, ... Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, ... natural killer (NK) cells have a regulatory role and interactions between NK cells and dendritic cells (DCs) aid DC maturation ... natural killer (NK) cells have a regulatory role and interactions between NK cells and dendritic cells (DCs) aid DC maturation ...
... called Natural Killers, target and kill diseased tissue. ... resolution than ever before exactly how white blood cells, ... Discuss: Scientists view natural killer cells in super 3D Sign in to comment. Be respectful, keep it civil and stay on topic ... Scientists view natural killer cells in super 3D. Researchers in England are able to see in greater resolution than ever ... Natural Killer] cells are important in our immune response to viruses and rogue tissues like tumors," said Professor Daniel ...
... these tumor cells lacking normal expression of HLA class I molecules should be destroyed by natural killer (NK) cells, ... these tumor cells lacking normal expression of HLA class I molecules should be destroyed by natural killer (NK) cells, ... inhibitory tumor cell surface molecules, or even RNA transfer during cell-cell contact between NK and target cells. ... NK cells, at the frontier of innate and adaptive immune system, have a central role in tumor cells surveillance as demonstrated ...
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centers RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.. ...
Natural killer (NK) cells are innate lymphoid cells that have been increasingly recognised as important in lung allograft ... NK cells can promote tolerance, such as through the depletion of donor antigen-presenting cells. Alternatively, these cells can ... via killer cell immunoglobulin-like receptor (KIR) or NKG2D receptor ligation, respectively. NK cells likely mediate complement ... Here, we review NK cells, their diverse receptors and the mechanisms through which NK cells are postulated to mediate important ...
natural killer cell synonyms, natural killer cell pronunciation, natural killer cell translation, English dictionary definition ... of natural killer cell. n. A large granular lymphocyte that kills virus-infected, cancerous, or abnormal cells without first ... nat′ural kill′er cell`. n. a small killer cell that destroys virus-infected cells or tumor cells without activation by an ... Natural killer cell - definition of natural killer cell by The Free Dictionary ...
... This article or section may require restructuring to meet Wikipedias .Please discuss this issue on the ... Natural Killer T cell. B cells: Plasma, Memory. Natural killer cells (Lymphokine-activated killer cell). ... Natural Killer cell activity is tightly regulated. Natural Killer cells must receive an activating signal, which can come in a ... This allows Natural Killer cells to target cells against which a humoral response has been mobilized and to lyse cells through ...
For the first time the functions of natural killer cells in the womb have been identified. Researchers at the University of ... The natural killer cells perform the role of targeting and clearing inflammatory stressed cells, thereby making space for the ... The new study Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium which is ... Tags: Cycling, Embryo, Endometrium, Inflammation, IVF, Medical School, Miscarriage, Natural Killer Cells, Pregnancy, Research, ...
NKT is developing biological treatments to interact with natural killer T cells (or NKT cells), a class of white blood cells, ... One response to "NKT Therapeutics Aims For Severe Asthma, Targeting Natural Killer T Cells". ... a lack of them make the B-cells attack body tissue. This clearly indicates that removing the NKT cells will increase the risk ... "Invariant NKT cells limit activation of autoreactive CD1d-positive B cells", Fredrik Wermeling, Sara M. Lind, Emilie Domange ...
... Hideki Takahashi, Tatsuo Yamamoto, ... NK cells and CD56bright CD16- NK cells, known as uterine NK cells, which make up 70-80% of NK cells in the decidua [18]. In our ... K. S. Campbell and J. Hasegawa, "Natural killer cell biology: an update and future directions," The Journal of Allergy and ... C. D. Gregory, L. P. Shah, H. Lee, I. V. Scott, and P. R. Golding, "Cytotoxic reactivity of human natural killer (NK) cells ...
  • In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors , but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, NK1.1 or NK1.2 in C57BL/6 mice . (
  • In addition to the knowledge that natural killer cells are effectors of innate immunity , recent research has uncovered information on both activating and inhibitory NK cell receptors which play important functional roles, including self tolerance and the sustaining of NK cell activity. (
  • NK cell receptors can also be differentiated based on function. (
  • Natural cytotoxicity receptors directly induce apoptosis after binding to Fas ligand that directly indicate infection of a cell. (
  • The MHC-dependent receptors (described above) use an alternate pathway to induce apoptosis in infected cells. (
  • NCR (natural cytotoxicity receptors), a type of type 1 transmembrane proteins of the immunoglobulin superfamily, upon stimulation, mediate NK killing and release of IFNγ. (
  • Human uNKs share many of the surface receptors and proteins of circulating Natural Killer (cNK) cells, exhibiting high levels of CD94 and CD56. (
  • However, they possess a unique expression profile of certain proteins, specifically CD9, CD103 (an integrin) and killer immunoglobulin-like receptors (KIRs). (
  • As with cNKs, uNKs also express ILT genes (immunoglobulin-like transcripts) and the recently discovered NCRs (natural cytotoxicity receptors). (
  • These cells are attracted to the uterus during pregnancy independent of chemokine receptors CCR-2 and CCR-5 in spite of these being important in recruitment of other inflammatory responses, and the exact method of their homing is yet to be understood. (
  • Whereas adaptive immune cells have rearranged receptor genes to recognize the universe of antigens, natural killer (NK) cells are innate immune lymphocytes with a limited repertoire of germ-line encoded receptors for target recognition. (
  • Unlike adaptive T and B lymphocytes, NK cells do not somatically rearrange their receptor genes, but rely upon a finite number of germ line-encoded inhibitory and activating NK receptors capable of recognizing MHC class I and class I-like molecules ( 8 , 9 ). (
  • Engagement of self-MHC class I by inhibitory NK receptors prevents NK cell killing of normal cells, and NK cell activity is dictated by a complex integration of signals from both inhibitory and activating NK receptors ( 10 ). (
  • The CD56(dim) NK-cell subset is more naturally cytotoxic and expresses higher levels of Ig-like NK receptors and FCgamma receptor III (CD16) than the CD56(bright) NK-cell subset. (
  • In addition, we will discuss other cell-surface receptors expressed differentially by human NK-cell subsets and the distinct functional properties of these subsets. (
  • Natural Killer Cell includes two types of surface receptors (activating receptor and inhibitory receptor) to control their cytotoxic activity. (
  • These receptors recognize MHC class l alleles that could explain the killing process of NK cells for low level of MHC class l molecule. (
  • Adenosinergic signaling heavily implicates natural killer cells through both direct and indirect effects on their cytolytic activity, expression of cytotoxic granules, interferon-γ, and activating receptors. (
  • Activation of NK cells can also be prevented by ligands that bind inhibitory receptors on the NK cell surface. (
  • Natural killer (NK) cell immune responses are regulated by a balance of activating and inhibitory signals transmitted by cell surface receptors. (
  • Interaction between Toll-like receptors and natural killer cells in the destruction of bile ducts in primary biliary cirrhosis," Hepatology, vol. (
  • NK-cells are defined as large granular lymphocytes that do not express T-cell antigen receptors (TCR) or Pan T marker CD3 or surface immunoglobulins (Ig) B cell receptor but that usually express the surface markers CD16 (FcγRIII) and CD56 in humans, and NK1.1/NK1.2 in certain strains of mice. (
  • Aside from the Fc receptor, Natural Killer cells express a variety of receptors that serve to either activate or suppress their cytolytic activity. (
  • These receptors bind to various ligands on target cells, both endogenous and exogenous, and have an important role in regulating the NK-cell response. (
  • Most of these receptors are not unique to NK cells and can be present in other T cell subsets as well. (
  • These inhibitory receptors recognize MHC class I alleles , which could explain why NK cells kill cells possessing low levels of MHC class I molecules. (
  • NK cell cytotoxicity is regulated by activating and inhibitory surface receptors and is additionally modulated by cytokines ( 2 ). (
  • Inhibitory NK cell receptors include killer cell Ig-like receptors (KIR) in humans and Ly49 family members in mice, both of which interact with MHC I to ensure the self-tolerance against healthy cells. (
  • NK cell activation can be mediated by a variety of different surface receptors, such as NKG2D, NKp46, and NKp30 ( 3 ). (
  • The synergistic activity of NK cell activation receptors in licensed NK cells couples the release of cytotoxic granules to TNFSF14 production. (
  • TNFSF14 protein expression was induced by three primary mechanisms of NK cell activation, namely, via the engagement of CD16, by the synergistic activity of multiple target cell-sensing NK-cell activation receptors, and by the cytokines IL-2 and IL-15. (
  • For antitumor responses, TNFSF14 was preferentially produced by the licensed NK-cell population, defined by the expression of inhibitory receptors specific for self-MHC class I molecules. (
  • The coupling of TNFSF14 production to tumor-sensing NK-cell activation receptors links the tumor immune surveillance function of NK cells to DC maturation and adaptive immunity. (
  • Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. (
  • Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections. (
  • Some of the scientists are engineering NK cells to express chimeric antigen receptors (CARs), emulating the development of CAR T cells. (
  • Nevertheless, the nervous and immune systems can influence each other's activity because immune cells express neurotransmitter receptors, and neurons express cytokine receptors. (
  • They were first named in an article in 1976 [3] and later categorized as part of the innate immune system due to their morphology, origin (bone marrow), and lack of antigen-specific receptors (such as those on T and B-cells' surfaces) and their respective genes. (
  • After NK cells form bindings of their membranal receptors with ligands on the surfaces of their neighboring cells, if the binding cells are recognized as alien, "stressed" or "infected" (target cells), cytolytic granules in NK cells are transported to the site of cell contacts and fuse with NK cells' membrane to release the cytolytic enzymes into the space between the cells' synapses. (
  • NK role in tumor-cells clearance is proved by allogenic stem cells transplantation, since a better engraftment and a low relapse rate are observed when the graft NK inhibitory receptors mismatch with recipient HLA molecules ( 3 ) (Figure 1 ). (
  • The triggering event of NK-cells activation and killing of target cells results from a balance between activating and inhibitory signals sent by membrane receptors that either enhance or block the NK-mediated cytotoxicity ( 4 ). (
  • Inhibitory signals arise from interaction between HLA-specific inhibitory receptors, as the killer immunoglobulin-like receptors (KIR), NK group protein 2A (NKG2A), or Immunoglobulin-like transcript 2 (ILT-2) with HLA class I molecules, whereas the absence or abnormal expression of the later molecules induces NK-cells cytotoxicity ( 5 ). (
  • The natural cytotoxicity receptors (NCR) NKp46/NCR1, NKp30/NCR3, and NKp44/NCR2 ( 7 ), NKG2D, DNAM-1 and also co-receptors such as 2B4/CD244 and NTBA, play a central role in NK activation. (
  • These cells evolved to recognise alterations in self through a diverse set of germline-encoded activating and inhibitory receptors and display a broad range of effector functions that play important roles in responding to infections, malignancies and allogeneic tissue. (
  • Here, we review NK cells, their diverse receptors and the mechanisms through which NK cells are postulated to mediate important lung transplant clinical outcomes. (
  • To investigate the changes in the maternal immune system at term pregnancy, we studied the expression of natural cytotoxicity receptors (NCRs) and the cytokine production of NK cells in term placenta decidua and peripheral blood. (
  • It has been reported that the killer inhibitory receptors (KIR) in uterine NK cells play a role in maintaining a normal pregnancy. (
  • The receptors that are responsible for NK cell activation during the process of natural cytotoxicity are collectively termed natural cytotoxicity receptors (NCRs). (
  • NK cells are now recognized to express a repertoire of activating and inhibitory receptors that is calibrated to ensure self-tolerance while allowing efficacy against assaults such as viral infection and tumor development. (
  • The distinctive features of innate immunity commonly refer to a broadly distributed variety of myeloid and lymphoid cells that can exert rapid effector function through a limited repertoire of germline-encoded receptors. (
  • In contrast, adaptive immunity in mammals is characterized by two types of lymphocytes, T and B cells, clonally expressing a large repertoire of antigen receptors that are produced by site-specific somatic recombination, that is, T cell receptor (TCR) and antibody/B cell receptor (BCR). (
  • FcγRIIIa/CD16a, one of the low-affinity receptors for IgG Fc, is involved in antibody-dependent cell-mediated cytotoxicity (ADCC). (
  • Natural killer cells are part of our immune system's rapid-response team against cancer cells, taking them out through the activation of cancer cell suicide via "death receptors. (
  • Approved cell therapies for cancer also rely on modifying T cells, in those cases to produce cancer cell-binding chimeric antigen receptors (CARs), and have been effective in treating certain cancers such as leukemia, Patel tells The Scientist . (
  • Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. (
  • Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. (
  • However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. (
  • Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), which confer cytotoxicity against tumors. (
  • NK cell activity is regulated by the cumulative effects of multiple activating and inhibitory signals that are transmitted through the receptors on the NK cell surface. (
  • Further, expression of anti-CD19 chimeric antigen receptors (CARs) containing 41BB and CD3ζ signal domains on NK cells enhanced the activating signals originating from CD19 antigen engagement, leading to cytotoxicity specifically against B-cell leukemia [4] . (
  • The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. (
  • The identity and specificity of both inhibitory and stimulatory receptors for class I MHC molecules on NK cells has been intensely studied, and much is known about the role of these receptors in dictating NK functional activity ( 8 - 10 ). (
  • The formation of the repertoire of mouse natural killer (NK) cell receptors for major histocompatibility complex (MHC) class I molecules was investigated by determining the developmental pattern of Ly49 receptor expression. (
  • During the first days after birth, few or no splenic NK cells express Ly49A, Ly49C, Ly49G2, or Ly49I receptors. (
  • After in vivo transfer, NK cells not expressing specific Ly49 receptors can give rise to NK cells that do, and cells expressing one of these four Ly49 receptors can give rise to cells expressing others. (
  • Interestingly, expression of one of the receptors tested, Ly49A, did not occur after in vivo transfer of Ly49A − cells. (
  • The capacity of NK cells to attack target cells that lack MHC class I expression, while sparing cells that express self-MHC class I molecules, depends in large part on inhibitory recognition of MHC molecules by Ly49 receptors. (
  • An NK cell can express multiple Ly49 receptors, including Ly49 receptors that do not recognize self-MHC class I molecules. (
  • One possibility is that all Ly49 receptors to be expressed by an individual NK cell are initially expressed more or less simultaneously at a specific stage of differentiation. (
  • These cells do possess Fc receptors for IgG and can kill target cells using antibody-dependent cell-mediated cytotoxicity. (
  • Recent studies have shown that ADCC, mediated through certain receptors on the surface of many of the body's immune system cells such as white blood cells and natural killer cells , can be activated by the use of IgG1 monoclonal antibodies. (
  • NK cells have special proteins on their surface - so-called death ligands - which dock to corresponding receptors on the target cells and thus activate their self-destruction. (
  • Natural killer (NK) cells, which play an important role in tumor surveillance, offer a key advantage over T cells in that they kill some cancer cells without requiring tumor-specific cell-surface receptors, meaning they can work in many patients, explains Dan Kaufman , lead author of the study and the director of cell therapy at the University of California, San Diego, School of Medicine. (
  • CAR-T cell therapies are built by harvesting a patient's T cells and genetically modifying them to produce so-called chimeric antigen receptors (CARs) that direct them to destroy cancer cells. (
  • NK cell activation by leukemic dendritic cells involves NKG2D activating receptors and is blocked by imatinib mesylate. (
  • A type of T cell that does not express markers of either T or B-cell lineage , but may possess fc receptors for immunoglobulin g. (
  • After LT, recipient NK cells exhibit a tolerant phenotype, with downregulation of activating receptors, reduced cytotoxicity and cytokine production. (
  • To become licensed, i.e. functionally competent to be triggered through its activation receptors, an NK cell must engage host MHC class I via at least one of its MHC class I-specific inhibitory receptors, such as the Ly49 family of receptors in the mouse. (
  • These findings suggest that NK cell licensing is modulated by the strength of the interaction of inhibitory receptors with host MHC class I. (
  • This effect is achieved through a complex mosaic of inhibitory and activating receptors expressed by NK cells that ultimately determine the magnitude of the NK-cell response. (
  • NK-cell activity is regulated by an intricate balance of signals transmitted by inhibitory and activating receptors. (
  • 3 CD56 bright CD16 − NK cells produce abundant IFN-γ in response to stimulation with interleukin (IL)-12 and proliferate robustly when cultured in IL-2, whereas CD56 dim CD16 + NK cells are more cytolytic and produce significant amounts of cytokine when their activating receptors are engaged. (
  • This is further supported by recent data demonstrating the dynamics of expression of the killer immunoglobulin-like receptors (KIR), CD57, CD94, and CD62L expression on the CD56 dim CD16 + NK cells as they mature from CD56 bright CD16 - NK-cell precursors. (
  • T-cell immunoglobulin- and mucin domain-containing (Tim)-3 is a member of Tim family of receptors of which there are 3 in humans (Tim-1, Tim-3, and Tim-4). (
  • CD56 bright NK cells constitutively express the high- and intermediate-affinity IL-2 receptors and expand in vitro and in vivo in response to low (picomolar) doses of IL-2. (
  • All resting CD56 bright NK cells have high expression of CD94/NKG2 C-type lectin receptors. (
  • 14 A small percentage (less than 10%) expresses killer cell immunoglobulin-like receptors (KIR), 15 while most (more than 85%) resting CD56 dim NK cells are KIR + and have low expression of CD94/NKG2. (
  • NK cells constitutively express receptors for monocyte-derived cytokines (monokines) and produce critical cytokines, such as IFN-γ, in response to monokine stimulation. (
  • NK cell-activating receptors play an important role in the recognition of targets, which transduce the signals necessary for cellular machinery to induce target injury and cytokine production. (
  • Lanier, L. L. NK cell receptors. (
  • and Chimeric Antigen Receptor directed killing using the taNK® platform, which includes NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells. (
  • Virus-driven evolution of natural killer cell receptors. (
  • that is, a certain population of cells seemed to be able to lyse tumor cells without having been previously sensitized to them. (
  • Kiessling's research involved the well-characterized ability of T lymphocytes to lyse tumor cells against which they had been previously immunized. (
  • Natural killer (NK) cells contain enzymes that can kill other cells, especially tumor cells and cells infected by viruses. (
  • However, tumor cells can circumvent this immune defense by establishing a surrounding microenvironment that prevents the infiltration of NK cells and thus promotes tumor survival and growth. (
  • They found that if autophagy - the intracellular recycling process - is blocked in tumor cells, they produce cytokines that attract NK cells. (
  • This occurs through the ability of tumor cells to develop an immunosuppressive microenvironment preventing cytotoxic immune cells such as NK cells to infiltrate tumors and kill cancer cells. (
  • Autophagy can be blocked in tumor cells and mouse models pharmacologically and genetically, the latter by inhibiting the expression of genes involved in the initiation of autophagy, for example BECN1 coding for the protein Beclin-1. (
  • They found that, when the autophagy process is blocked in tumor cells by inhibiting the expression of BECN1, a large amount of functional NK cells infiltrated into the tumor. (
  • The research team revealed that autophagy-defective tumor cells produced an increased amount of CCL5, a small cytokine with chemotactic properties, able to attract NK cells to the tumor bed. (
  • Targeting autophagy in tumor cells is a promising strategy to reinforce the immune system to fight cancer", he claims. (
  • Hoskin DW, Mader JS, Furlong SJ et al (2008) Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (review). (
  • a small killer cell that destroys virus-infected cells or tumor cells without activation by an immune system cell or antibody. (
  • We show that tumor cells induce rapid production of the cytokine TNF superfamily member 14 (TNFSF14) in human NK cells and that these NK cells induce DC maturation in a TNFSF14-dependent manner. (
  • Thus, NK cell activation by tumor cells is linked to the initiation of adaptive immunity via TNFSF14-mediated NK-DC cross-talk. (
  • Here, we have analyzed the response of human NK cells to tumor cells, and we identify a pathway by which NK-DC interactions occur. (
  • CAR T cells have demonstrated success in leukemia because the tumor cells, and their antigens, are available in blood," notes Robin Parihar, MD, PhD, an assistant professor of pediatric hematology-oncology at Baylor College of Medicine. (
  • Natural cytotoxicity refers to the fact that they can rapidly cause tumor cells' lyses in the absence of any previous stimulation [1] , [2] . (
  • Nonetheless, tumor-cells evade the specific T-lymphocyte mediated immune surveillance using many mechanisms but especially by the down-regulation of the expression of HLA class I antigens. (
  • In theory, these tumor-cells lacking normal expression of HLA class I molecules should be destroyed by natural killer (NK) cells, according to the missing-self hypothesis. (
  • NK cells, at the frontier of innate and adaptive immune system, have a central role in tumor-cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. (
  • The down-regulation of HLA class I molecules is an immune escape mechanism frequently used by tumor cells ( 6 ) that, accordingly, should not be recognized by the T-lymphocyte receptor (TCR). (
  • The absence of normal HLA class I molecule on tumor cells should lead to NK-cells activation, more efficiently when co-stimulatory molecules and ligands for NK activating receptor are present at tumor cell surface. (
  • Once activated, NK lymphocytes kill tumor cells via FcgRIIIA (CD16) which can trigger antibody-dependent cellular cytotoxicity (ADCC) on encountering target cells opsonized with IgG, via the Fas/Fas-L pathway and via cytotoxic granules (perforin/granzyme) secretion ( 1 , 8 ). (
  • Checkpoint inhibitors have revolutionized cancer treatment by unleashing the immune system on tumor cells. (
  • Natural killer (NK) cells have the ability to recognize and eliminate tumor cells, making them ideal candidates for tumor immunotherapy [1] , [2] . (
  • Similarly, T cells captured NKG2D and NKp46 ligands on tumor cells through trogocytosis and promoted NK cell activity [12] . (
  • Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. (
  • Compared to healthy cells, tumor cells are more sensitive to TRAIL stimulation. (
  • It is therefore believed that the binding of TRAIL to the TRAIL receptor triggers the death of tumor cells without affecting healthy cells. (
  • The results of this work may be important in the fight against cancer, since the discovered signaling pathway regulates the function of NK cells, which in turn are important for the control of tumor cells. (
  • There are several new cancer therapies that aim to reactivate the immune system in order to remove tumor cells, including studies aiming at reactivating NK cells in tumor patients. (
  • From Book News, Inc. A collection of readily reproducible methods designed to study natural killer cells (a subset of lymphocytes that can directly lyse some tumor cells and certain virally affected cells without prior sensitization). (
  • CAR-expressing, stem-cell-derived natural killer cells destroy mesothelin-expressing tumor cells from mice, programmed to fluoresce red when they're intact and green when they are killed. (
  • My NK cells will kill your tumor cells, and vice versa," he says. (
  • This type of cell attacks tumor cells and infected cells by releasing chemicals that are toxic to the cell , resulting to cell death of the target cell . (
  • Natural killer (NK) cells are considered innate lymphocytes that are able to kill pathogenic microorganisms, including bacteria, parasites and fungi as well as virus-infected cells and tumor cells without prior stimulation. (
  • Known as natural killer cells, they're a part of the immune system normally associated with eliminating tumor cells and cells infected by viruses. (
  • AbstractPurpose of ReviewWe aim to review the most recent findings in the use of NK cells in childhood cancers.Recent FindingsNatural killer cells are cytotoxic to tumor cells. (
  • NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine storm. (
  • NK cells (belonging to the group of innate lymphoid cells ) are defined as large granular lymphocytes (LGL) and constitute the third kind of cells differentiated from the common lymphoid progenitor -generating B and T lymphocytes . (
  • Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of innate lymphoid cells (ILC) and represent 5-20% of all circulating lymphocytes in humans. (
  • NK cells (belonging to the group of innate lymphoid cells) are one of the three kinds of cells differentiated from the common lymphoid progenitor, the other two being B and T lymphocytes. (
  • Uterine natural killer (uNK) cells make up approximately 70% of maternal lymphocytes during pregnancy, occupying both the decidua basalis of the endometrium at the implantation site and the mesometrial lymphoid aggregate of pregnancy (MLAp) that surrounds the blood vessels supplying the placenta. (
  • NK cells are innate lymphocytes capable of recognizing and killing target cells and producing immunoregulatory cytokines, especially IFN-γ ( 4 ). (
  • Human natural killer (NK) cells comprise approximately 15% of all circulating lymphocytes. (
  • Natural Killer Cells are also defined as large granular lymphocytes (LGL) and comprise the third kind of cells other than B and T Lymphocytes. (
  • Natural Killer (NK) cells, lymphocytes of the innate immune system with strong cytotoxic activity, play a major role in the immune response against tumors. (
  • We report here that a mutant gene in the mouse called beige ( bg J ), leads to a complete and selective impairment of naturally occurring killer lymphocytes, whereas all other forms of cell-mediated lysis are apparently normal. (
  • NK cells are effector lymphocytes of the innate immune system that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage … NK cells are also regulatory cells engaged in reciprocal interactions with dendritic cells, macrophages, T cells and endothelial cells. (
  • In the 40 years since the discovery of natural killer (NK) cells, it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. (
  • Non-hepatocytes include about 20% lymphocytes, 20% Kupffer cells, 40% endothelial cells, 20% stellate cells, and biliary cells ( 5 ). (
  • This is in contrast to the frequency of NK cells in peripheral blood, where they only account for 5-15% of lymphocytes. (
  • Natural killer (NK) cells are innate lymphocytes that are important for early and effective immune reactions against infections and cancer. (
  • Natural killer cells (NK cells) are a type of granular cytotoxic lymphocytes that are non-adherent and non-phagocytic. (
  • NK cells were originally defined as a subset of lymphocytes that have natural cytotoxic activity against certain types of tumorous cells and endogenous type-C viruses in mice. (
  • Natural Killer (NK) cells are large granular lymphocytes of the innate immune system. (
  • There were fewer cells positive for NKG2D, NKp46, and NKp30 among CD56+CD3- cells in deciduas than in peripheral blood, but the percentages of NKp44-positive cells in CD56+CD3- lymphocytes in deciduas tended to be higher. (
  • Natural killer (NK) cells are innate immune lymphocytes that are identified by the expression of the CD56 surface antigen and the lack of CD3. (
  • Natural killer (NK) cells were originally defined as effector lymphocytes of innate immunity endowed with constitutive cytolytic functions. (
  • Natural killer (NK) cells are lymphocytes, immune cells which have a powerful arsenal of cytotoxic weaponry that they can use against tumors. (
  • The peripheral blood and bone marrow show atypical large granular lymphocytes, which exhibit an immunophenotype similar to that of extranodal NK/T-cell lymphoma. (
  • Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. (
  • Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. (
  • A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. (
  • large granular lymphocytes that do not express markers of either T or B cell lineage. (
  • A class of large, granular lymphocytes that bind directly to cells bearing foreign ANTIGENS and kill them. (
  • Pre-clinical studies conducted at Sweden's Karolinska Institute have demonstrated that Vycellix's molecules significantly enhance cancer targeting cytotoxic lymphocytes such as cytotoxic T cells and natural killer cells (NK cells). (
  • Natural Killer (NK) cells are large granular lymphocytes readily distinguished from thymus derived (T) and bursa-equivalent (B) lymphocytes on the basis of cellular morphology, surface markers and function. (
  • Although NK cells comprise a low percentage of circulating lymphocytes, they can be rapidly and accurately quantitated using flow cytometry and labelled monoclonal antibodies directed at specific cell surface antigens. (
  • Abstract Natural killer T (NKT) cells are important regulatory lymphocytes that have been shown in mouse studies, to have a crucial role in promoting immunity to tumours, bacteria and viruses, and in suppressing cell-mediated autoimmunity. (
  • Natural killer (NK) cells are innate lymphocytes that play an important role against viral infections and cancer. (
  • Human NK cells transcribe the highest amounts of Tim-3 among lymphocytes. (
  • 1-4 Human NK cells comprise approximately 10% of all peripheral blood lymphocytes and are characterized phenotypically by the presence of CD56 and the lack of CD3. (
  • Induced pluripotent stem (iPS) cells, "all-purpose" cells capable of differentiating into any type of cell, present a potential solution to this shortage of NKT cells, but with a catch: in lymphocytes, rearrangement of genes during differentiation drastically diminishes the effectiveness of conventional iPS cell generation techniques, resulting in only a small portion of cells with the desired antitumor function. (
  • The BCMA protein is important in B cell development and preferentially expressed in mature B lymphocytes. (
  • The small differences observed in the number of CD8+-T lymphocytes and natural killer cells are only of questionable physiological relevance. (
  • Association of depression with viral load, CD8 T lymphocytes, and natural killer cells in women with HIV infection. (
  • Natural killer cell activation is determined by the balance of inhibitory and activating receptor stimulation. (
  • Pross and Jondal were studying cell-mediated cytotoxicity in normal human blood and the effect of the removal of various receptor-bearing cells on this cytotoxicity. (
  • Malaria-infected red blood cells trigger the immune system's first line of defense by releasing small vesicles that activate a pathogen recognition receptor called MDA5, according to a study published October 4 in the open-access journal PLOS Pathogens by Peter Preiser of Nanyang Technological University in Singapore and Jianzhu Chen of the Massachusetts Institute of Technology, and colleagues. (
  • Beavis PA, Milenkovski N, Henderson MA, John LB, Allard B, Loi S, Kershaw MH, Stagg J, Darcy PK (2015) Adenosine receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced antitumor T-cell responses. (
  • In addition, recent studies of gene-deficient animals, in particular Syk and ZAP70 double-deficient mice, suggest that NK cells possess a robust and potentially redundant receptor system to ensure their development and function. (
  • This natural killer cell interacts with the CD94/ NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years. (
  • Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice. (
  • NK-cells, along with macrophages and several other cell types, express the FcR molecule, an activating biochemical receptor that binds the Fc portion of antibodies . (
  • Valuable techniques for specific applications include vaccinia virus protein expression, soluble KIR-Fc fusions for HLA class I binding assays, calcium mobilization in cell conjugates, and identification of heterodimeric receptor complexes using cDNA library expression cloning. (
  • It took a while to figure out how to engineer NK cells outside of the body," he laments, but his lab found a way to make CAR NK cells, NK cells that express a chimeric protein that consists of two linked components: the activating receptor, NKG2D, and the cytotoxic ζ-chain of the T-cell receptor. (
  • The researchers first observed that a fraction of NK cells that had been recruited into tumors in mice expressed PD-1, the checkpoint receptor targeted by the inhibitors, suggesting that the drugs could affect the cells' behavior. (
  • Alternatively, these cells can drive rejection through cytotoxic effects on allograft tissue recognised as 'non-self' or 'stressed', via killer cell immunoglobulin-like receptor (KIR) or NKG2D receptor ligation, respectively. (
  • NK cells likely mediate complement-independent antibody-mediated rejection of allografts though CD16A Fc receptor-dependent activation induced by graft-specific antibodies. (
  • Finally, NK cells play an important role in response to infections, particularly by mediating cytomegalovirus infection through the CD94/NKG2C receptor. (
  • OCIL inhibits NK cell function via binding to the receptor NKRP1D. (
  • MAFA clusters with the type I Fc epsilon receptor (FcepsilonRI) and inhibits the mast cells secretory response to FcepsilonRI stimulus [ PMID: 9765598 , PMID: 12217400 ]. (
  • CD72 is a regulator of B cell receptor signaling [ PMID: 11999169 ]. (
  • LOX-1 is the major receptor for OxLDL in endothelial cells and thought to play a role in the pathology of atherosclerosis [ PMID: 15695803 , PMID: 27160316 ]. (
  • An unusual inhibitory receptor--the mast cell function-associated antigen (MAFA). (
  • Specifically, the startup has an antibody that is designed to home in on a cellular receptor-a type of protein marker on the surface of cells-it believes is unique to many NKT cells. (
  • heterodimers) - a C-type lectin family receptor, conserved in both rodents and primates and identifies non-classical (also non-polymorphic) MHC I molecules like HLA E . Though indirect, this is a way to survey the levels of classical (polymorphic) HLA molecules, however, because expression of HLA-E at the cell surface is dependent upon the presence of classical MHC class I leader peptides. (
  • We have previously genetically modified in vitro expanded NK cells to express DAP10 and the chimeric NKG2D receptor containing the CD3ζ signal domain, which altered the balance between the activating and inhibitory signals of NK cells and enhanced the cytotoxicity against NKG2D ligand-bearing tumors [3] . (
  • The chemokine receptor CCR7 has been shown to be transferred from donor cells onto the surface of NK cells via trogocytosis, and this transfer stimulated NK cell migration, leading to enhanced lymph node homing [10] , [11] . (
  • In allogeneic NK cell therapy, the mismatch between the killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) can be harnessed to increase the antitumor activity. (
  • That's led to a healthy amount of research into NK immunotherapies, which could boast significant advantages over first-generation immunotherapies based on chimeric antigen receptor T-cells (CAR-T). Unfortunately, biopharma companies have been largely unable to replicate the inherent seek-and-destroy capability of NK cells in early stage clinical trials. (
  • B cell survival requires a functional B cell receptor ( 27 ), and exposure to soluble factors ( 28 ). (
  • One possible explanation for these data is that the order of Ly49 receptor expression by NK cells is nonrandom. (
  • A central issue in murine NK cell development concerns how Ly49 receptor expression is coupled to NK cell maturation and education processes. (
  • 10 ) have recently shown that ABL/ABL directly alters the function of NK cells (i.e., induces partial IL-2 independent growth and increases killer immunoglobulin-like receptor expression in primary CD56 bright NK cell subsets). (
  • Natural killer T (NKT) cells are a specialized population of T cells that express a semi-invariant T cell receptor (TCR alpha beta) and surface antigens typically associated with natural killer cells. (
  • The T-cell immunoglobulin- and mucin domain-containing (Tim)-3 receptor was initially identified as a T-helper 1-specific type I membrane protein involved in regulating T-cell responses. (
  • 6-8 These NK cells also express the c- kit receptor tyrosine kinase whose ligand enhances IL-2-induced proliferation. (
  • 9 10 In contrast, resting CD56 dim NK cells express only the intermediate affinity IL-2 receptor, are c- kit neg , and proliferate weakly in response to high doses of IL-2 (1 to 10 nM) in vitro, even after induction of the high-affinity IL-2 receptor. (
  • NK cell subsets have differential natural killer receptor (NKR) repertoires. (
  • 16 CD56 dim NK cells lack this receptor but have recently been found to express PEN5, an NK cell-restricted sulfated lactosamine epitope that partially mediates the binding of L-selectin, 15 thus suggesting the potential for differential trafficking of human NK cell subsets in vivo. (
  • We determined that NKp30 is the activating pattern recognition receptor that mediates NK cell killing of these fungi, and that β-1,3-glucan is the ligand for NKp30. (
  • To achieve this objective, haNK cells have been engineered to express IL-2 and the high-affinity variant of the CD16 receptor (V158 FcγRIIIa). (
  • Dr. Soon-Shiong added, "As only about 10% of patients are born with the high affinity CD16 receptor, we believe the potential for haNK cell therapy to improve patient outcomes for the other 90% of the patient population and become part of the standard-of-care for cancer patients is very compelling. (
  • Raulet, D. H., Vance, R. E. and McMahon, C. W., Regulation of the natural killer cell receptor repertoire. (
  • Tormo, J., Natarajan, K., Margulies, D. H. and Mariuzza, R. A., Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. (
  • Additionally, I found that a deletion of the NKG2C gene, a receptor important for recognition of HCMV infected cells, results in delayed NK cell differentiation. (
  • This receptor is found on a number of tumor types, including T cell and Natural Killer cell lymphomas, as well as multiple myeloma. (
  • It functions by killing target cell through antibody-dependent cell-mediated cytotoxicity or through perforin formation, killing cells without prior sensitization (hence, the name). (
  • NantKwest's haNK cell therapy platform, developed to be an allogeneic, off-the-shelf therapy, is focused on optimizing the key role that natural killer cells play in mediating innate immunity, enhancing adaptive immune responses, and, specifically in the case of haNK, improving anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC). (
  • The first published study to assert that untreated lymphoid cells were able to confer a natural immunity to tumors was performed by Dr. Henry Smith at the University of Leeds School of Medicine in 1966, leading to the conclusion that the "phenomenon appear[ed] to be an expression of defense mechanisms to tumor growth present in normal mice. (
  • and administration of therapeutic agents modulating the susceptibility fgjhd, IFN-g, GM-CSF, TNF-a, MIP-1a and MIP-1b compared of tumors to NK-cell lysis has been proposed recently. (
  • Researchers affiliated with the Kawasaki INnovation Gateway at SKYFRONT, have successfully developed a humanized mouse model showing that so-called NK cells that directly attacking tumors, can survive and maintain function in vivo. (
  • They are self-activated and play an important role in elimination of tumors and virus-affected cells. (
  • The massive recruitment of NK cells allows killing cancer cells and lets the tumors shrink. (
  • When CCL5 is depleted, the infiltration of NK cells and the subsequent regression of tumor volume were no longer observed, thus confirming the crucial role of CCL5 in driving NK cells into autophagy-defective tumors. (
  • The more CCL5 is produced, the stronger tumors are infiltrated with NK cells. (
  • NK cells play a major role in the rejection of tumors and cells infected by viruses . (
  • Among the advanced methods covered are those for in vitro transendothelial migration, in vivo detection of cells migrating into tumors, immunofluorescence staining of intracellular cytokines, and in vitro NK cell development. (
  • As our understanding of the innate immune system catches up with our understanding of the adaptive immune system, natural killer (NK) cells are emerging as an alternative to T cells in eliciting an immune response to tumors. (
  • All cell therapy lags behind in solid tumors, where the antigen is hidden. (
  • And of course the tumor microenvironments surrounding solid tumors contain immunosuppressive cells like myeloid-derived suppressor cells, inhibitory macrophages, and regulatory T cells (Tregs) that all conspire to inhibit the activity of T cells-including any CAR T cells that doctors might want to use to destroy the tumor. (
  • NKG2D.ζ cells may do more than enhance the efficacy of CAR T cells delivered to tumors. (
  • They may help recruit the CAR T cells to the tumors. (
  • Understanding the effects of neuroendocrine factors on NK cell activities during physiological and pathophysiological conditions may result in novel therapeutic strategies to enhance NK cell functions against tumors. (
  • Natural Killer] cells are important in our immune response to viruses and rogue tissues like tumors," said Professor Daniel Davis, from the Department of Life Sciences at Imperial College London. (
  • The natural killer (NK) cells are central players in innate immunity particularly regarding the surveillance against malignant tumors ( 1 , 2 ). (
  • These drugs' effects have been almost exclusively attributed to responses from antitumor T cells, yet they also work in certain tumors that T cells cannot recognize, suggesting other types of cells may be at play. (
  • What dose of NK cells can be given safely to subjects with metastatic solid tumors or leukemia. (
  • New research out of the Raulet lab suggests a mechanism explaining why Natural Killer cells are sometimes rendered ineffective, and even more excitingly, suggests a therapeutic approach for re-awakening them to attack tumors. (
  • Unfortunately, tumors protect themselves using a protective microenvironment that shields them from attack from NK cells. (
  • NaturalNews) Researchers have discovered breakthrough advances in antitumor immunotherapy in the wake of an eye-opening study showing how spirulina extract activates natural killer cells to destroy tumors. (
  • These unique cells can recognize viruses and tumors in the absence of antibodies and signal molecules, making them a potent innate immune system defender. (
  • Learning how to make these cells work is critical for helping people control inflammation, autoimmune disorders and tumors. (
  • The cells, derived from induced pluripotent stem cells, are in testing as an immunotherapy for cancer patients with solid tumors. (
  • I n a first-of-its-kind clinical trial, a natural killer cell immunotherapy derived from induced pluripotent stem cells is being tested for safety in 64 patients with a variety of solid tumors. (
  • Those approaches have had limited success against solid tumors, but NK cells have the potential to be a better treatment option if those cancer cells have lost MHC. (
  • Natural killer (NK) cells have the capacity to target tumors and are ideal candidates for immunotherapy. (
  • This novel strategy could be a potential valuable therapeutic approach for the treatment of B-cell tumors. (
  • In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. (
  • In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. (
  • Overall, it is clear that NK cell therapy is safe and promises a new paradigm for the treatment of solid tumors. (
  • NK cells are thought to play an important role in immune defense against pathogens ( 1 - 3 ) and tumors ( 4 - 7 ). (
  • The study found that during pregnancy, a decline in the number of natural killer cells that are a type of immune system cell, ripens conditions in the body for existing tumors to spread to new locations, reports Live Science. (
  • They noted that the mice treated with the iPSC-derived CAR-NK cells and those treated with CAR-T cells both had shrunken tumors after 21 days compared to control mice, which had received infusions of NK cells without CAR constructs. (
  • Sandip Patel, MD, principal investigator for the FT500 trial at Moores Cancer Center and lead physician for Ruff's NK cell therapy treatment, is excited by the prospect of cell-based immunotherapy in solid tumors. (
  • We are interested in expanding our armamentarium of immune cell types we target in solid tumors, which to date have mainly been T-cell directed therapies, and expanding to other cell types, such as natural killer cells, which may have unique advantages in treating certain cancer types," said Patel, who specializes in cancer immunotherapy and early phase clinical trials. (
  • Dendritic cell-mediated NK cell activation can lead to the control of ( a ) viral replication ( 12 ) and ( b ) the growth of NK cell-sensitive tumors ( 11 , 13 ). (
  • NK cell therapy is currently being investigated as a treatment for various liquid and solid tumors, but also has the demonstrated potential to be effective against virally infected cells. (
  • Through their production of TH1 cytokines, NKT cells play an essential role in innate immune responses, protecting against tumors and virus-infected cells. (
  • The primary objective of the study is to determine the safety of haNK cell monotherapy administered intravenously once per week in up to 16 patients with metastatic or locally advanced solid tumors. (
  • This phase I trial studies the side effects and best dose of expanded natural killer cells in treating younger patients with brain tumors that have come back or do not respond to treatment. (
  • Infusing a particular type of a patient's own white blood cells called natural killer cells that have been through a procedure to expand (increase) their numbers may work in treating patients with recurrent/refractory brain tumors. (
  • I. To establish the safety, feasibility, efficacy, and maximum tolerated dose (MTD) of administering autologous natural killer (NK) cells that have been propagated ex vivo with artificial antigen-presenting cells (aAPC) and administered directly into the ventricle in recurrent /refractory malignant posterior fossa tumors. (
  • Phase I Study of Intraventricular Infusions of Autologous Ex Vivo-Expanded NK Cells in Children With Recurrent/Refractory Malignant Posterior Fossa Tumors of the Central Nervous System. (
  • Production of Type 2 cytokines is vital in a successful pregnancy, whereas growth factors produced by NK cells play a vital role in the angiogenic (new blood cells) activity. (
  • NK cells also produce cytokines such as IFN-gamma (IFN-γ) to protect the host during the innate response to infection. (
  • Owing to their early production of cytokines and chemokines, and ability to lyse target cells without prior sensitization, NK cells are crucial components of the innate immune system. (
  • Secretion of the above cytokines and NK-cell method for expanding highly cytotoxic clinical-grade NK cells in vitro cytolytic function were IL-2 dose dependent. (
  • Natural Killers cell's are activated in response interferons or macrophages derived cytokines. (
  • A large granular lymphocyte that kills virus-infected, cancerous, or abnormal cells without first having been exposed to specific antigens and that also produces a variety of cytokines. (
  • 2 NK cells also help regulate your immune system by producing cytokines, signaling molecules that stimulate and regulate other immune system cells. (
  • The cytokines Interferon play a crucial role in NK-cell activation. (
  • NK cells are activated in response to interferons or macrophage -derived cytokines. (
  • Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. (
  • This communication is mediated by direct cellular contacts (e.g., synapse formation between neurons or between immune cells) and by soluble mediators (neurotransmitters or cytokines). (
  • Such responses are mediated through two major effector functions, the direct cytolysis of target cells and the production of cytokines and chemokines. (
  • To kill off cancer, the NK cells secrete cytokines and chemokines. (
  • Kaufman was surprised to find that, compared to the mice treated with CAR NKs, the animals that had received the CAR-T cell treatment appeared to be in worse shape: they had damage in organs such as the liver, lungs, and kidneys and an increase in inflammatory cytokines. (
  • NK cells don't seem to have the toxicity as the CAR-T cells," he adds, speculating that NK immunotherapies may be safer than CAR-T therapies, which sometimes cause adverse side effects that involve increased levels of cytokines in the blood of patients. (
  • NKT cells can have either protective or deleterious effects due to their abilities to produce cytokines that promote either inflammation or immune tolerance. (
  • During the innate immune response to infection, monocyte-derived cytokines (monokines), stimulate natural killer (NK) cells to produce immunoregulatory cytokines that are important to the host's early defense. (
  • In this report, it is shown that CD56 bright NK cells produce significantly greater levels of interferon-γ, tumor necrosis factor-β, granulocyte macrophage-colony-stimulating factor, IL-10, and IL-13 protein in response to monokine stimulation than do CD56 dim NK cells, which produce negligible amounts of these cytokines. (
  • It is proposed that human CD56 bright NK cells have a unique functional role in the innate immune response as the primary source of NK cell-derived immunoregulatory cytokines, regulated in part by differential monokine production. (
  • Natural killer (NK) cells are innate immune effectors that produce immunoregulatory cytokines, such as interferon (IFN)-γ and granulocyte macrophage-colony-stimulating factor GM-CSF, critical to early host defense against a variety of viral, bacterial, and parasitic pathogens. (
  • 17-20 In the current study we examine CD56 bright and CD56 dim NK cell production of multiple cytokines-including IFN-γ, tumor necrosis factor (TNF)-β, IL-10, IL-13, TNF-α, and GM-CSF-in response to stimulation with monokines. (
  • Memory-like' NK cells, with heightened responsiveness can be also generated by pre-activation with cytokines. (
  • I found that NK cell differentiation is accelerated in Africans in The Gambia compared to age-matched UK residents and that this is linked to reduced functional NK cell responses to cytokines. (
  • However, vaccination resulted in intrinsic changes to NK cells with enhancement of NK cell IFN-γ responsiveness to exogenous cytokines. (
  • Natural killer (NK) cells recognize ligands such as viral proteins on the surface of infected cells and mount an immune response to remove them from circulation. (
  • [21] The cytolytic granules also contain Fas ligands, which facilitate the Fas-medicated cytotoxicity of NK cells coexisting with the granule-exocytosis pathway [22] , and granulysin but knowledge about its biochemical pathways and significance within the cytolytic granules are limited. (
  • The protein TRAIL is one of these death ligands that NK cells use to kill their target cells. (
  • Indeed, ABL/ABL translocation enhances the expression levels of the NKG2D ligands on dendritic cells, which is counteracted by imatinib mesylate. (
  • Here we show that the BCR/ABL translocation specifically confers to dendritic cells a selective NK cell stimulatory function by up-regulating the expression of NKG2D ligands in both mouse and human models. (
  • Previous studies have provided conflicting data on the effect of HLA matching for NK cell ligands in LT. (
  • These findings suggest that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3. (
  • Because many cell types, including natural killer (NK) cells, T cells and macrophages, may be involved in tumour resistance in vivo 1 , these mice will provide a critical test of the hypothesis that it is NK cells which provide a first line of defence against neoplasia 2 . (
  • One of NK cells' originally-described morphological characteristics was the granules inside their cytoplasm, similar to what seen in macrophages. (
  • [1] [2] However, later research revealed that these granules bear more similarity to those in stimulated killer T-cells than those in macrophages, and are the effector organelles of cytolysis caused by killer T-cells and NK cells. (
  • CD56dim natural killer (NK) cells, a fraction of monocyte/macrophages, and a fraction of T cells, and activates these effector cells. (
  • Macrophages phagocytose (or 'gobble up') diseased cells, antibodies are required for ADCC, and T-cells produce slow-starting, long-lasting memory responses. (
  • Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. (
  • Other investigators have developed related recombinant fusion proteins to recruit effectors, such as NK-cells and macrophages. (
  • NT cells are also great communicators, regulating interactions with macrophages and dendritic, endothelial and T cells. (
  • Later that same year, Ronald Herberman published similar data with respect to the unique nature of the mouse effector cell. (
  • Continuing work has uncovered multiple checkpoints linked to adenosine within the purinergic signaling cascade as contributing to immune evasion from NK cell effector function. (
  • The authors focus here on the nature of recognition events by NK cells and address how these events are integrated to trigger these distinct and graded effector functions. (
  • Functionally, naive T and B cells encounter antigens in specialized lymphoid organs and undergo a process of cell division and maturation before exerting their effector function. (
  • Another way to empower abs is the design of bispecific abs and related fusion proteins allowing a narrower choice of effector cells. (
  • Here we review frequently chosen classes of effector cells, as well as common trigger molecules. (
  • cytotoxic granules are released onto the surface of the bound target cell, and the effector proteins they contain penetrate the cell membrane and induce programmed cell death. (
  • We described in 1999 that dendritic cells have unique capacities to trigger NK cell effector functions in vitro ( 11 ). (
  • When given alone, DMSO activated hepatic NKT and NK cells in vivo as evidenced by increased NKT cell numbers and higher intracellular levels of the cytotoxic effector molecules interferon-γ (IFN-γ) and granzyme B in both cell types. (
  • Emerging evidence suggests that NK cells could be important in the early effector response induced by vaccination, supported by vaccine antigen-specific CD4 IL-2 production and antigen-antibody immune complexes. (
  • The biology of human natural killer-cell subsets. (
  • Human NK cells can be divided into two subsets based on their cell-surface density of CD56--CD56(bright) and CD56(dim)--each with distinct phenotypic properties. (
  • Now, there is ample evidence to suggest that these NK-cell subsets have unique functional attributes and, therefore, distinct roles in the human immune response. (
  • Furthermore, studies into the immunological reactions against cytomegalovirus in mice and human has generated evidences that certain subsets of NK cells can be activated and stimulated to multiply in response to specific pathogens. (
  • Lansdorp, "Telomere length in human natural killer cell subsets," Annals of the New York Academy of Sciences, vol. (
  • 1 , 2 Functionally distinct NK-cell subsets can be defined based on the level of CD56 and CD16 coexpression. (
  • Human NK cell subsets can be distinguished by CD56 surface density expression (ie, CD56 bright and CD56 dim ). (
  • 1 There are 2 distinct subsets of human NK cells identified by cell surface density of CD56. (
  • These data support a model whereby CD56 bright and CD56 dim NK cells represent functionally distinct subsets of mature human NK cells. (
  • Heterogeneity of natural killer cell subsets in NK‐1.1+ and NK‐1.1− inbred mouse strains and their progeny. (
  • Therefore, a key issue in the field of anti-cancer immunotherapy is to develop strategies capable of driving cytotoxic immune cells into the tumor bed. (
  • Our study provides a cutting edge advance in the field of cancer immunotherapy and could specifically pave the way for more effective NK cell-based immunotherapies. (
  • Guillerey C, Huntington ND, Smyth MJ (2016) Targeting natural killer cells in cancer immunotherapy. (
  • Carotta S (2016) Targeting NK cells for anticancer immunotherapy: clinical and preclinical approaches. (
  • Wang W, Erbe AK, Hank JA et al (2015) NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. (
  • Although NK cells might appear to be redundant in several conditions of immune challenge in humans, NK cell manipulation seems to hold promise in efforts to improve hematopoietic and solid organ transplantation, promote antitumor immunotherapy and control inflammatory and autoimmune disorders. (
  • In oncology, this has largely meant immunotherapy with T cells, both engineered and not. (
  • I'm currently researching how natural killer cells can be put to work eliminating human cancer cells, as part of the revolution in cancer immunotherapy. (
  • When the two are used simultaneously, natural killer cells increase down the specific MYD88 pathway, creating an antitumor immunotherapy advantage. (
  • This is a landmark accomplishment for the field of stem cell-based medicine and cancer immunotherapy. (
  • There are several other clinical trials using NK cells as an immunotherapy for cancer, but those trials use NK cells directly from a donor or from the patient. (
  • The main disadvantage of taking cells from a patient and developing them into a cellular immunotherapy product is that the process can take weeks. (
  • In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. (
  • CD19 is an ideal target antigen for immunotherapy because it is expressed on nearly all leukemia cells in most patients with B-cell acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL) [13] , [14] . (
  • Are Natural Killer Cells the Next Big Thing in Immunotherapy? (
  • NK cells were first explored as immunotherapy candidates in the 1980s, but human understanding of biology and biomanufacturing kept a tight lid on the potential. (
  • Indeed, homeostatic proliferation of T cells can markedly enhance their reactivity to foreign antigens and recent work has shown this may be a therapeutic benefit in cancer immunotherapy ( 23 - 25 ). (
  • The NANT Cancer Vaccine is the first combination immunotherapy protocol to orchestrate the delivery of metronomic low dose radiation and chemotherapy with molecularly informed tumor associated antigen vaccines and natural killer cells , to activate the innate and adaptive immune system and to induce immunogenic cell death. (
  • The result paves the way for developing an "off the shelf" immunotherapy that doesn't need to be personalized for each patient, the authors report in a study published last week (June 18) in Cell Stem Cell . (
  • The off-the-shelf, iPSC-derived natural killer (NK) cell cancer immunotherapy received U.S. Food and Drug Administration approval to move into clinical trials in November 2018. (
  • NantKwest (Nasdaq:NK) is a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases. (
  • NantKwest, a member of the NantWorks ecosystem of companies, is an innovative clinical-stage immunotherapy company focused on harnessing the power of the innate immune system by using the natural killer cell to treat cancer and virally induced infectious diseases. (
  • Challenges lie in the microenvironment which is suppressive for NK cells.SummaryNK cell immunotherapy in childhood cancers is promising and recent works aim to overcome challenges. (
  • They usually express surface marker CD16, CD56, and CD8 (only 80% of NK cell) in human. (
  • De Maria A, Bozzano F, Cantoni C, Moretta L (2011) Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. (
  • Initially, human NK cells have been divided into two functionally distinct subpopulations based on the expression level of CD56. (
  • These cells were stained with FITC anti-CD56 and Per-CP anti-CD3 monoclonal antibodies, and the NCRs were stained with PE-conjugated anti-NKG2D, NKp46, NKp30, and NKp44 monoclonal antibodies. (
  • Marlin R reported on NCR manifestations, such as NKp46, NKp30, NKp44, and NKG2D of CD56+CD3- NK cells in the decidua during the first trimester of pregnancy [ 9 ]. (
  • There are two kinds of NK cells: mature NK cells (CD56dim+CD16+, CD56+CD16+CD3-) and immature NK cells (CD56bright+CD16-, CD56+CD16-CD3-) [ 16 ]. (
  • The cytokine production of CD56+CD3-CD16- NK cells is higher than that of CD56+CD3-CD16+ NK cells, which possibly gives the former a role in maintaining pregnancy [ 18 , 20 ]. (
  • On their cell surfaces, NK cells express the specific cell surface antigens, CD16 and CD56 (NKH-1), with the CD56 marker being found on all activated NK cells (2). (
  • CD56 is normally expressed at low density on cells in peripheral blood but increases in expression are seen following in vitro growth and stimulation (3). (
  • Tim-3 protein is expressed on essentially all mature CD56 dim CD16 + NK cells and is expressed heterogeneously in the immature CD56 bright CD16 - NK-cell subset in blood from healthy adults and in cord blood. (
  • Tim-3 expression was induced on CD56 bright CD16 − NK cells after stimulation with IL-15 or IL-12 and IL-18 in vitro, suggesting that Tim-3 is a maturation marker on NK cells. (
  • 4 CD56 dim CD16 + NK cells are considered mature NK cells and are differentiated from the immature CD56 bright CD16 - NK-cell subset. (
  • For example, the monokine IL-15 appears to be required for type 2 cytokine production by CD56 bright NK cells. (
  • The majority (approximately 90%) of human NK cells are CD56 dim and express high levels of FcγRIII (CD16), whereas a minority (approximately 10%) are CD56 bright and CD16 dim/neg . (
  • 6 7 Resting CD56 dim NK cells are more cytotoxic against NK-sensitive targets than CD56 bright NK cells. (
  • 11 However, after activation with IL-2 or IL-12, CD56 bright cells exhibit similar or enhanced cytotoxicity against NK targets compared to CD56 dim cells. (
  • CD56 bright NK cells also express the adhesion molecule L-selectin (CD62L), which mediates initial interactions with vascular endothelium. (
  • Therefore, CD56 bright and CD56 dim NK cells differ in their proliferative response to IL-2, intrinsic cytotoxic capacity, NKR repertoire, and adhesion molecule expression. (
  • We show that CD56 bright NK cells are the primary population responsible for NK cell cytokine production in response to monokines. (
  • Engraftment can be improved by allowing some degree of mismatch between the tissue antigens of the donor and recipient and, in diseases such as leukemia, also provides a powerful means for helping destroy host-derived leukemic cells. (
  • observed that for NK cells, a greater level of NK cell reactivity against host antigens correlated with a higher incidence of successful transplantation. (
  • MHC class I molecules consist of the main mechanism by which cells display viral or tumor antigens to cytotoxic T-cells. (
  • Natural killer T (NKT) cells recognize glycolipid antigens presented by the MHC class I-related glycoprotein CD1d. (
  • The NK cells can evade immune rejection even if they are derived from donor iPSCs because they do not produce the human leukocyte antigens on their cell surfaces that activate the body's immune cells. (
  • The TCR on NKT cells is unique in that it recognizes glycolipid antigens presented by the MHC I-like molecule CD1d. (
  • I went on to investigate the impact of this advanced differentiation phenotype on NK cell responses in two vaccination studies: Gambian subjects of all ages made negligible NK cell CD107a, CD25, and IFN-γ responses to influenza or DTPiP vaccine antigens. (
  • NK cells are recognized primarily by the expression of two surface markers - CD16 and CD56NK cells. (
  • Importantly, NK cells also link the innate and adaptive immune responses, contributing to the initiation of adaptive immune responses and executing adaptive responses using the CD16 FcgRIIIA immunoglobulin Fc receptor. (
  • We then demonstrated that FcγRIIIa-158V displays higher affinity for rituximab than FcγRIIIa-158F by comparing rituximab concentrations inhibiting the binding of 3G8 mAb (anti-CD16) with VV NK cells and NK cells homozygous for FcγRIIIa-158F (FF). (
  • F) Histograms show CD16 expression for mock, bystander and VZV + NK cells from one representative donor. (
  • Graph shows frequency of CD16 + NK cells when untreated or with IL-2 (shaded) for six donors. (
  • The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. (
  • However, the allogeneic NK cells cause more adverse events and can be rejected by the host immune system after repeated injections. (
  • For instance, NK cells and CAR-NK therapeutics can be produced from inherently allogeneic ("off-the-shelf") cell lines, which means a single cell line or donor could produce an infinite number of therapeutic doses. (
  • Generation of donor natural killer cells from CD34 progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study," Bone Marrow Transplantation, vol. (
  • Recent reports outline the role of allogeneic antileukemic NK effectors in the graft-versus-leukemia effect but the regulation of NK cell activation in the setting of graft-versus-leukemia effect remains unknown. (
  • The efficacy of graft-versus-leukemia effect following allogeneic stem cell bone marrow transplantation in CML prompted the search for immune effectors. (
  • CYNK-001 (Celularity) is an investigational, cryopreserved, allogeneic natural killer cell therapy derived from placental hematopoietic stem cells. (
  • SAN DIEGO and WARREN, N.J., Jan. 29, 2020 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") announced it has initated a clinical and manufacturing collaboration with Celularity, Inc., a Warren, New Jersey, based clinical-stage cell therapeutics company delivering transformative allogeneic cellular therapies derived from the postpartum human placenta. (
  • The objective of the collaboration is to expand the therapeutic use of Celularity's CYNK-001, an allogeneic, off-the-shelf, placental-derived Natural Killer (NK) cell therapy, to the treatment and prevention of coronavirus infections. (
  • Both companies have expressed their interest in starting clinical development efforts for anti-coronavirus allogeneic NK cell therapy immediately. (
  • Typically, immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis . (
  • However, the rituximab concentration resulting in 50% lysis (EC 50 ) observed with NK cells from VV donors was 4.2 times lower than that observed with NK cells from FF donors (on average 0.00096 and 0.00402 μg/ml, respectively, P = 0.0043). (
  • This study supports the conclusion that FCGR3A genotype is associated with response to rituximab because it affects the relationship between rituximab concentration and NK cell-mediated lysis of CD20+ cells. (
  • It is believed that NK cells, in turn, evolved as an evolutionary response to this adaption, as the loss of the MHC would deprive these cells of the inhibitory effect of MHC and render these cells vulnerable to NK-cell mediated lysis. (
  • Moreover, ABL/ABL confers to target cell susceptibility to NK cell lysis ( 6 ). (
  • These NK cells release proteins called perforins and granzyme, a cytoplasmic granule, which destroys the target cell by apoptosis. (
  • When these proteins and Proteases are released close to a cell intended for killing, perforin create pores in the cell membrane of the target cell through which granzymes and associated molecules can enter, inducing apoptosis. (
  • Perforin, hinting at the functional basis of its name, perforates the cell membrane of the cell targeted for elimination, allowing the proteins and other chemicals to enter, thereby inducing apoptosis (programmed cell death) that destroys the virus along with the infected cell. (
  • The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis . (
  • Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis . (
  • lysing a virus-infected cell would only release the virions, whereas apoptosis leads to destruction of the virus inside. (
  • [20] Granules in NK cells (and also stimulated killer T cells) contain proteins responsible for signaling and facilitating cell apoptosis, the most well understood of which are perforin, granzyme, calreticulin, and glycosaminoglycan. (
  • Natural killer cells do not require prior exposure of the immune system to the antigen and kill their victims by programmed cell death (apoptosis). (
  • Evaluation of cytotoxic function and apoptosis in IL-12/IL-15-treated umbilical cord or adult peripheral blood natural killer cells by a propidium-iodide based flow cytometry. (
  • 11 Tim-3 is a type I transmembrane protein that contains no defined signaling motifs in its cytoplasmic domain, but it has been implicated both in activation and inhibition of immune responses 12 , 13 and in the induction of apoptosis of Tim-3-bearing cells through interactions with galectin-9. (
  • As well as having potent cytotoxic activity, natural killer (NK) cells have a regulatory role and interactions between NK cells and dendritic cells (DCs) aid DC maturation and adaptive immunity. (
  • Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. (
  • NK cells share many features with leukocytes of the innate immune system, such as: granular cytoplasm, spontaneous activity, and susceptibility to positive regulation by immune stimuli (dendritic cells' cytokinin). (
  • Identification of a human homologue of the dendritic cell-associated C-type lectin-1, dectin-1. (
  • Molecular communications with in vitro bone-marrow-derived dendritic cells showed further natural killer cell activation properties that were derived from the oral spirulina treatments. (
  • Altered functions of plasmacytoid dendritic cells and reduced cytolytic activity of natural killer cells in patients with chronic HBV infection," Gastroenterology, vol. (
  • Here we show that dendritic cells derived from monocytes of CML patients are selectively endowed with NK cell stimulatory capacity in vitro . (
  • We further show, using a gene transfer approach in mouse bone marrow progenitors, that ABL/ABL is necessary to promote dendritic cell-mediated NK cell activation. (
  • The dendritic cell/NK cell cross-talk in ABL/ABL-induced CML seems unique because JunB or IFN consensus sequence binding protein loss of functions, associated with other myeloproliferative disorders, do not promote dendritic cell-mediated NK cell activation. (
  • Altogether, the clonal ABL/ABL dendritic cells display the unique and selective ability to activate NK cells and may participate in the NK cell control of CML. (
  • This study also highlights the deleterious role of imatinib mesylate at the dendritic cell level for NK cell activation. (
  • Human studies have clearly shown that mostly mature dendritic cells [i.e., cells activated by lipopolysaccharide (LPS) or type I IFN or mycobacteria] are endowed with NK cell stimulatory capacities in vitro ( 14 - 18 ). (
  • In CML patients, between 73% and 100% of monocyte-derived dendritic cells (CML dendritic cells) are positive for the chimeric ABL/ABL gene ( 19 , 20 ). (
  • Many reports showed that dendritic cells derived from both normal volunteers (normal dendritic cells) and CML patients differentiated and matured in culture ( 19 , 21 - 24 ) but there are conflicting data regarding the ability of CML dendritic cells compared with normal dendritic cells to stimulate T cells ( 19 , 20 , 25 - 31 ). (
  • However, the effects of BCR/ABL translocation on the capacity of dendritic cells to activate NK cells have never been studied. (
  • 14 Tim-3 is expressed on CD4 + T cells, dendritic cells, monocytes, 15 ⇓ - 17 CD8 + T cells, 18 , 19 and NK cells. (
  • Uterine NK cells protect the embryo against serious infections, whereas peripheral NK cells are important in protecting the body against viral infections and cancer cells. (
  • In concert with other members of the innate response, NK cells are important for the initial control of many viral and bacterial pathogens ( 5 ⇓ - 7 ). (
  • Natural killer (NK) cells are part of the innate immune defense against infection and cancer and are especially useful in combating certain viral pathogens. (
  • When you contract a viral disease, the pathogen enters your body and infects your cells. (
  • NK cells are involved in both viral disease and diseases such as cancer and autoimmune conditions. (
  • Put another way, the NK cells keep viral replication in check while the adaptive arm of your immune system "learns" the properties of the virus and creates antibodies to match. (
  • Research confirms that when you are deficient in NK cells, you're far more susceptible to viral infections, and likely tumor formation as well. (
  • As these are stress-molecules, released by cells upon viral infection, they serve to signal to the NK-cell the presence of viral pathogens. (
  • They serve to contain viral infections while the adaptive immune response is generating antigen -specific cytotoxic T cells that can clear the infection. (
  • Kuang, E. Viral Evasion of Natural Killer Cell Activation. (
  • However, use of viral transduction methods raises the safety concern of viral integration into the NK cell genome. (
  • Ludmila Cardoso-Alves at the Institute of Pathology studied the role of TRAIL in the response against a virus that is a natural pathogen in rodents and often serves as a model of viral infection in immunology. (
  • Reference: "Non-apoptotic TRAIL function modulates NK cell activity during viral infection" by Ludmila Cardoso Alves, Michael D. Berger, Thodoris Koutsandreas, Nick Kirschke, Christoph Lauer, Roman Spörri, Aristotelis Chatziioannou, Nadia Corazza and Philippe Krebs, 19 November 2019, EMBO Reports . (
  • Compromised function of natural killer cells in acute and chronic viral hepatitis. (
  • Altfeld, "Control of human viral infections by natural killer cells ," Annual Review of Immunology, vol. (
  • Studies have established that there is robust activation of [natural killer] cells during viral infection regardless of the virus class," Xiaokui Zhang, PhD, chief scientific officer of Celularity, said in the statement. (
  • any potential market for NK cells for the treatment and prevention of coronavirus and Sorrento's potential position in the anti-viral immunity industry. (
  • Natural killer (NK) cells comprise 5% to 20% of human peripheral blood lymphoid cells and are a critical component of the immune system, providing protection against viral infections and contributing to tumor immune surveillance. (
  • Natural Killer (NK) cells are a safeguard in the human body designed to recognize and detect cells under stress due to cancer or viral infection. (
  • NK cells are unique, however, as they have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. (
  • However, when Tim-3 was cross-linked with antibodies it suppressed NK cell-mediated cytotoxicity. (
  • In preclinical studies, the addition of haNK to a variety of therapeutic antibodies has led to increased tumor cell killing when compared to the antibody alone. (
  • ProMab's strategic focus is on the development of monoclonal antibodies and their application in cell therapy through the integration of next generation sequencing, bioinformatics, high-throughput screening technologies, and novel in vitro in vivo validation tools. (
  • They were named "natural killers" because of the initial notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. (
  • similarly, if the activating signal is dominant, then NK cell activation will result. (
  • Innate immune cells are a first-line defense against pathogens and are thought to respond consistently to infection, regardless of previous exposure, i.e., they do not exhibit memory of prior activation. (
  • Thus, these experiments identify an ability of innate immune cells to retain an intrinsic memory of prior activation, a function until now attributed only to antigen-specific adaptive immune cells. (
  • Rajagopalan, "Controlling natural killer cell responses: integration of signals for activation and inhibition," Annual Review of Immunology, vol. (
  • They were named "natural killers" because of the initial notion that they do not require activation in order to kill cells that are "missing self" markers of major histocompatibility complex (MHC) class I . However, it is now known that the cells are activated. (
  • NKRs are variously associated with activation or inhibition of natural killer (NK) cells. (
  • The in vivo dynamics of the NKT cell population in response to glycolipid activation remain poorly understood. (
  • Consequently, we found that activation of anergic NKT cells with α-GalCer exacerbated, rather than prevented, B16 metastasis formation, but that these cells retained their capacity to protect mice against experimental autoimmune encephalomyelitis. (
  • They're called natural killers, because they don't require activation by prior exposure. (
  • At first, a sub cell line showed slight expressions of NT response, but as the study furthered, they noticed natural killer cell activation signals going off through expressions of Rae-1, a ligand for NK activation. (
  • Activation mechanisms of natural killer cells during influenza virus infection. (
  • Conclusions LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. (
  • There is no effect of HLA matching on NK cell activation. (
  • Activation of natural killer cells during microbial infections. (
  • However, to-date, studies of human NK cell have been performed in vitro and as a result their function in vivo is less well-understood. (
  • Therefore, in vivo models showing that NK cells survive and maintain function long-term are eagerly desired. (
  • This time, a research group of immunology Laboratory of the Central Institute for Experimental Animals, Kawasaki City, and Keio University, School of Medicine has successfully developed a humanized mouse model using NOG-IL-2 Tg mice that support to develop and maintain human NK cells suitable for in vivo cell function studies. (
  • The research team confirmed that these NK cells strongly inhibited tumor growth in both in vivo and in vitro experiments. (
  • Miller JS, Soignier Y, Panoskaltsis-Mortari A et al (2005) Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. (
  • The difference in immunophenotype of the ex vivo expanded NK cells resulted from different culture methods may affect the final efficacy. (
  • In vivo developmental stages in murine natural killer cell maturation. (
  • These less differentiated cells may retain some capacity to control HCMV infection, and at the same time represent a possible target for generation of 'memory-like' NK cells in vivo in vaccine induced NK cell responses. (
  • [17] This enables NK cells to recognize tumor and infected, especially virally infected, cells without previous stimulation, which resulted in rapid and "natural" cytotoxicity. (
  • A further significant difference between NK cells and T and B cells is that NK cells are capable of responding to antibody-coated target cells, neoplastic cells and virally infected cells without prior sensitization (1). (
  • These cutting-edge techniques include methods for cloning and culturing, measuring cytoxicity against tumours and virally infected cells, analysis of development in vitro, migration assays, signal transduction testing, detecting cytokine production, and protein expression approaches. (
  • NK cells are the body's first line of defense due to the innate ability of NK cells to rapidly identify and destroy cells under stress, such as cancer or virally-infected cells. (
  • NantKwest's "off-the-shelf" activated NK cell platform is designed to destroy cancer and virally infected cells from the body. (
  • NK Cells are not a subset of the T lymphocyte family. (
  • Here, we investigated 6 related patients with autosomal recessive growth retardation, adrenal insufficiency, and a selective NK cell deficiency characterized by a lack of the CD56dim NK subset. (
  • In addition, the specific loss of the NK CD56dim subset in patients was associated with a lower rate of NK CD56bright cell proliferation, and the maturation of NK CD56bright cells toward an NK CD56dim phenotype was tightly dependent on MCM4-dependent cell division. (
  • As members of the T cell family, iNKT cells represent a subset that exhibits both innate and adaptive characteristics and directs ensuing immune responses. (
  • Recent reports suggest that B cells also undergo homeostatic proliferation in B cell-deficient hosts ( 29 ), although this may be a property of a subset of B cells ( 30 ). (
  • NK cells provide rapid responses to virus-infected cells, acting at around 3 days after infection , and respond to tumor formation. (
  • Natural killer cells are important immune cells that provide the first line of defense against malaria infection but show significant differences in their responses in the human population. (
  • The molecular mechanisms through which natural killer cells are activated by parasites are largely unknown, and so is the molecular basis underlying the variation in natural killer cell responses to malaria infection in the human population. (
  • To address this gap in knowledge, Preiser, Chen and colleagues analyzed transcriptional differences between human natural killer cells that respond and don't respond to malaria infection. (
  • The findings suggest that MDA5 could contribute to variation in natural killer cell responses to malaria infection in the human population. (
  • Moreover, the study provides new insights into a mechanism by which natural killer cells are activated by parasites and reveals a possible molecular target to control malaria infection in humans. (
  • The study reveals how natural killer cells recognize parasite-infected red blood cells and possible approaches to treat malaria infection by boosting host immunity," says corresponding author Jianzhu Chen. (
  • Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection," Hepatology (Baltimore, Md), vol. (
  • The subsequent disease process involves your cell-mediated immune response, which activates your NK cells, along with chemicals that attract them to the site of infection, where the white blood cells basically chew up and spit out the infected cells. (
  • Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection. (
  • NK cell markers associated with maturity influence VZV infection of NK cells and are modulated by VZV. (
  • Altered monocyte and NK cell phenotypes correlate with posttrauma infection. (
  • During a virus infection, NK cells also keep the body's own immune cells such as the T cells at bay in order to avoid excessive killing of intact body cells. (
  • Cardoso-Alves investigated the infection in mice whose NK cells did not have TRAIL and found that these mice were able to fight the virus better than the control animals. (
  • We found Elizabeth had an overactive immune system with lots of NK cells, or natural killer cells , that kill infection. (
  • NK cell tolerance is partially reversed in HCV infection. (
  • People become ill so suddenly from inhalational anthrax that there isn't time for a T cell response, the more traditional cellular immune response," said UTMB assistant professor Janice Endsley, lead author of a paper now online in the journal Infection and Immunity. (
  • In further experiments, the group compared the anthrax infection responses of normal mice and mice that were given a treatment to remove NK cells from the body. (
  • The NKp46 cell surface marker constitutes, at the moment, another NK cell marker of preference being expressed in both humans, several strains of mice (including BALB/c mice ) and in three common monkey species. (
  • uNK cells have an important role during pregnancy in both, humans and in mice. (
  • Interestingly, histological studies with Mcm4-depleted mice showed grossly abnormal adrenal morphology that was characterized by non-steroidogenic GATA4- and Gli1-positive cells within the steroidogenic cortex, which reduced the number of steroidogenic cells in the zona fasciculata of the adrenal cortex. (
  • Humanized mice were generated by transplanting 2.5 x 104 human cord blood-derived CD34+ HSC cells into irradiated NOG-IL-2 mice. (
  • Unexpectedly, they found that human NK cells predominantly developed in the mice after transplantation of human hematopoietic stem cells. (
  • In addition, the NK cells could maintain the function and survived for the long term in the mice. (
  • In mice, preconditioning with purified host-reactive NK cells removed the need for the usual preablation of recipient bone marrow by irradiation, and these animals did not develop T cell-mediated GVHD seen in control mice. (
  • Incidence of GVHD was also absent in these mice, suggesting a possible role for host-derived NK cells in GVHD. (
  • Research has found that removing NKT cells from genetically engineered mice quells their asthma, Mashal says, and mice or monkeys do have asthmatic responses when NKT cells are activated in their lungs. (
  • Dietary consumption of Echinacea by mice afflicted with autoimmune (type I) diabetes results in long-lasting immunostimulation of NK cells only and no indication of increased autoimmunity. (
  • Here, we show that a single administration of the synthetic glycolipid α-galactosylceramide (α-GalCer) induces long-term NKT cell unresponsiveness in mice. (
  • After orally administering hot water extracts of spirulina to the mice, they watched for molecular signals in the major histocompatibility complex of the mice cells. (
  • Surprisingly, NK survival is also compromised after transfer of cells into IL-15Rα −/− mice, implying that IL-15 responsiveness by bystander cells is critical for NK maintenance. (
  • The presence of a proper bone marrow microenvironment is thought to be necessary for proper NK function, since mice treated with agents that affect the bone marrow, such as 89 Sr (( 13 )) or estradiol (( 14 )), are unable to fully support the maturation of NK cells. (
  • Mice without TRAIL had more protective T cells and were therefore better able to remove virus-infected cells. (
  • This is not limited to mice, but also affects human NK cells. (
  • Kaufman's team created the mouse models by transplanting human ovarian cancer cells into mice whose immune systems had been suppressed to prevent them from rejecting the human cells. (
  • The mice that got the CAR-T cells actually wound up getting sick, losing weight, and getting these toxicities, whereas the CAR-NK-cell-treated mice didn't," Kaufman says. (
  • Within this group, distinguishable subpopulations have been identified, including CD4 + CD8 - cells and CD4 - CD8 - cells that are present in mice and humans, and CD4 - CD8 + cells that are found only in humans. (
  • Hybridoma produced by the fusion of splenocytes from BALB/c mice immunized (BALB/c X C57BL/6)F1 (CbyB6F1) lymphokine-activated killer (LAK) cells and mouse myeloma cellline. (
  • All the mice died with equal rapidity when given a large dose of anthrax spores, but the non-treated (NK cell-intact) mice had much lower levels of bacteria in their blood. (
  • The next step, according to Endsley, is to apply an existing NK cell-augmentation technique (many have already been developed for cancer research) to mice, in an attempt to see if the more numerous and active NK cells can protect them from anthrax. (
  • An example that highlights this potential problem is found in a recent report demonstrating a pathogenic role for natural killer T (NKT) and natural killer (NK) cells in acetaminophen-induced liver injury (AILI) in C57Bl/6 mice in which DMSO was used to facilitate acetaminophen (APAP) dissolution. (
  • We report that NKT and NK cells do not play a pathologic role in AILI in C57Bl/6 mice in the absence of DMSO. (
  • Although AILI was significantly attenuated in mice depleted of NKT and NK cells prior to APAP treatment in the presence of DMSO, no such effect was observed when APAP was dissolved in saline. (
  • STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease. (
  • Like natural killer cells, NKT cells can also induce perforin-, Fas-, and TNF-related cytotoxicity, but this is generally not thought to be their primary function. (
  • We conclude that β-1,3-glucan may induce NK cell memory- like immunity. (
  • The number of uNK cells increases post-ovulatory by the migration of circulating NK cells, as well as differentiation of haematopoietic stem cells. (
  • Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation [ PMID: 15123656 ]. (
  • She says that researchers must visually inspect them daily and physically remove cells that are showing signs of differentiation. (
  • Other studies have focused on the role of soluble factors in regulating NK differentiation and function, and this has lead to identification of IL-15 as a key factor in NK cell ontogeny. (
  • Indeed, the NK cell differentiation process is itself poorly understood. (
  • Since human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body, these cells can be used as starting material to mass produce NK cells at significant scale in a cost-effective manner. (
  • The ABL/ABL transgene in CD34 + DR + cells causes abnormal NK cell differentiation ( 8 , 9 ). (
  • Origin and differentiation of natural killer cells. (
  • Kärre K (2002) NK cells, MHC class I molecules and the missing self. (
  • Amir Horowitz, PhD, an assistant professor of oncological sciences at the Icahn School of Medicine at Mount Sinai, studies NK cells through the lens of the human leukocyte antigen (HLA) molecules that "educate" them. (
  • A common evolutionary adaption to this seen in both intracellular microbes and tumours is a chronic down-regulation of these MHC I molecules, rendering the cell impervious to T-cell mediated immunity. (
  • Therefore, target cell surface molecules can be found on the surface of NK cells. (
  • The results provide a framework for evaluating models of NK cell repertoire formation, and how the repertoire is molded by host class I MHC molecules. (
  • NK cell lytic activity is often inhibited by MHC class I molecules expressed by target cells. (
  • The MHC-dependent alterations in the Ly49 repertoire are likely to reflect mechanisms that ensure that NK cells are useful and self-tolerant in the context of the limited set of MHC molecules the host happens to inherit. (
  • In addition, NK cells release messenger molecules that support the immune defense. (
  • The lack of TRAIL made the NK cells "tamer": they had reduced killer function and instead produced more messenger molecules that activate other immune cells. (
  • MicroRNAs (miRNAs) are small RNA (≈ 22 nt) molecules expressed endogenously in cells. (
  • Licensing of natural killer cells by host major histocompatibility complex class I molecules. (
  • It is likely that this mutant will be invaluable for further investigations in tumour immunology just as the nude mouse has been indispensable in evaluating the role of thethymus in the development of the T-lymphoid system and the role of T cells in the rejection of tumours. (
  • In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. (
  • Natural killer (NK) cells are innate lymphoid cells (ILC) that can kill virus-infected or transformed cells. (
  • Natural killer (NK) cells are innate lymphoid cells that have been increasingly recognised as important in lung allograft tolerance and immune defence. (
  • MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells. (
  • There is also significant variation in lymphoid and myeloid cell populations with increasing age. (
  • Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse. (
  • Additionally, tissue-resident NK cells with distinct phenotypical and functional characteristics have been identified. (
  • Here, we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. (
  • In recent years, more subpopulations of NK cells have been identified, and we now know that in addition to conventional circulating NK cells, there are also tissue-resident NK cells with distinct phenotypical and functional characteristics ( 4 ). (
  • NK cells thus exert sophisticated biological functions that are attributes of both innate and adaptive immunity, blurring the functional borders between these two arms of the immune response. (
  • Finally, the functional difference between VV and FF NK cells was restricted to rituximab concentrations weakly sensitizing CD20. (
  • Recent work by others suggests that the numbers of NK cells and their functional ability to lyse stimulating target cells is influenced by factors such as stress and illness. (
  • Using flow cytometry to quantitate cells and a standard cytotoxicity assay to measure cell function, we are currently assessing the numbers and functional ability of NK cells. (
  • Design Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. (
  • Many clinical studies have indicated that NKT cell deficiencies and functional defects might also contribute to similar human diseases, although there is no real consensus about the nature of the NKT cell defects or whether NKT cells could be important for the diagnosis and/or treatment of these conditions. (
  • Functional and morphologic studies of purified NK‐1.1+ cells. (
  • Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. (
  • The discovery that a unique type of lymphocyte was responsible for "natural" or spontaneous cytotoxicity was made in the early 1970s by doctoral student Rolf Kiessling and postdoctoral fellow Hugh Pross, in the mouse, and by Hugh Pross and doctoral student Mikael Jondal in the human. (
  • Natural killer cells (also known as NK cells, K cells, and killer cells) are a type of lymphocyte (a white blood cell) and a component of autoimmune system. (
  • [7] The role of NK cells in both the innate and adaptive immune responses is becoming increasingly important in research using NK cell activity as a potential cancer therapy. (
  • Natural Killer (NK) cell identifies cancer cell. (
  • NK cells make up around 5-20% of the white blood cells circulating in the bloodstream and are also critical cells for 'immunosurveillance' in the process of cancer development. (
  • Indeed, cancer treatments using this capacity of NK cells have already been developed. (
  • For several years already, it is well known that tumor growth can be reduced by suppressing autophagy in cancer cells. (
  • Here, we discuss these checkpoints and the recent body of work that focuses on adenosinergic signaling as a target for natural killer cell of cancer. (
  • Childs RW, Carlsten M (2015) Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens. (
  • Natural Killer T cells & cancer progression? (
  • Cancer is a disease of the cells, which are the body's basic building blocks. (
  • Since NK cells have the ability to differentiate between normal, healthy cells and abnormal cells, such as those infected by a virus or that have turned cancerous, scientists are looking for ways to enhance NK cell function as a way to improve the effectiveness of cancer treatments. (
  • 2 Present address: Tumour Vascular Biology Group, Cancer Biology and Stem Cells, School of Medicine, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. (
  • Natural Killer Cell Protocols: Cellular and Molecular Methods offers immunologists, cancer researchers, virologists, and cell biologists today's most comprehensive collection of both established and cutting-edge techniques, methods that will contribute significantly to advancing our understanding of this fascinating and critically important class of cells. (
  • Natural killer cells, about 20 µm wide, attack a cancer cell. (
  • NKT Therapeutics, which revealed its $8 million first-round financing in March , has rallied venture capitalists to back its efforts to develop drugs that target lesser-known immune cells that potentially play key roles in asthma, cancer, and a bevy of other major illnesses. (
  • Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer. (
  • Natural killer (NK) cells are white blood cells that have a limited ability to kill cancer cells. (
  • Unlike antigen specific T cells, NK cells do not require the presence of a specific tumor antigen for the recognition and killing of cancer cells. (
  • Blinatumomab is the first clinically successful member of this class, targeting cancer cells via CD19 and engaging T-cells by CD3. (
  • Blueberry consumption may double the population of our cancer-fighting immune cells, and the spices cardamom and black pepper may boost their activity. (
  • If, however, you add some natural killers, then about 5% of the cancer cells are wiped out. (
  • And, if you add more and more, and all of a sudden, same number of natural killer cells, but they're now able to kill off ten times more cancer cells. (
  • up around 30 or 40% cancer cell clearance. (
  • The first patients received the cells in February at the University of California, San Diego (UCSD) Moores Cancer Center and MD Anderson Cancer Center. (
  • This clinical trial represents the first use of cells produced from human induced pluripotent stem cells to better treat and fight cancer," says Dan Kaufman of UCSD in a press release . (
  • NK cells are immune cells in the same family as T and B cells, and are very good at targeting cancer cells for destruction. (
  • Laboratory experiments have shown they do so by attacking cells that have lost their major histocompatibility complexes-self-recognition signals that tell the immune system not to attack-a phenomenon that can happen among cancer cells but not to healthy cells. (
  • Experts are not sure what proportion of cancer cells lose that signal, says Sandip Patel , who is the lead physician running the clinical trial at the Moores Cancer Center, but they are hopeful that the clinical trial can help determine which cancer patients could benefit the most from NK cell treatment. (
  • Cancer patients may not be able to produce enough NK cells to fight their cancer, so the idea, says Patel, is to reinforce their supplies. (
  • For instance, a clinical trial of NK cells in France is using NK cells on nine patients with gastrointestinal cancer, according to . (
  • Recent findings highlighted that NK cells can even target cancer stem cells. (
  • This finding warrants future investigations to find the implication of NK cell specific genetic defects in cancer development and treatment, and NK cell deficiency syndrome should be revisited to enhance our understanding. (
  • Qi L, Zhang Q, Miao Y, Kang W, Tian Z, Xu D, Xiao W, Fang F. Interleukin-33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development. (
  • Researchers have shown that NK cells can still wreak havoc on cancer when other immune cells are disabled, they're the tumor-busting force behind the health benefits of exercise, and long-term survival rates for some of the deadliest cancers appear to be influenced by the activity of NK cells and the genes that control them. (
  • Perhaps most important, NK cells can identify and target cancer cells with or without CARs. (
  • It could also create the opportunity to combine immunotherapies to create a one-two punch that sends cancer cells to their death. (
  • Killer cells of the immune system detect and kill infected cells or cancer cells. (
  • The so-called natural killer (NK) cells are cells of the innate immune system that recognize and eliminate infected cells or cancer cells. (
  • NK cells are therefore particularly important for immunity - if they are defective, recurrent infections with several viruses and cancer can develop. (
  • Accordingly, this pathway is considered a promising approach to trigger the self-destruction of cancer cells. (
  • NK cells may kill cancer cells that remain in your body after your last chemotherapy treatment. (
  • Stem-cell-derived natural killer cells engineered in a similar way to CAR-T cells may pave the way to "off the shelf" cancer therapies that aren't patient-specific. (
  • C AR-T therapies-genetically engineered T cells that destroy cancer cells-have proven to be promising options when other treatments fail. (
  • Now, researchers report that natural killer cells, grown from human induced pluripotent stem (IPS) cells and modified in a similar way to CAR-T cells, are effective against ovarian cancer in a mouse model. (
  • For Lewis Lanier , leader of the University of California, San Francisco's cancer immunology program who was not involved in the study, the findings serve as a proof of concept, "that you can take the IPS cell and actually get a product out of it," he says. (
  • Unmodified NK cells isolated from peripheral blood or umbilical cord blood have also been shown to be effective against acute myelogenous leukemia in several clinical trials , and a few trials testing NK cells equipped with CARs in other forms of blood cancer have begun. (
  • After testing the CARs' efficacy in destroying cancer cells in vitro, they selected the most effective constructs, expressed them in iPS cells, and differentiated these into NK cells. (
  • In February 2019, as part of a phase I clinical trial at Moores Cancer Center at UC San Diego Health, Ruff became the first patient in the world to be treated for cancer with a human-induced pluripotent stem cell (iPSC)-derived cell therapy called FT500. (
  • Sandip Patel, MD, and Dan Kaufman, MD, PhD, of UC San Diego School of Medicine enjoy a light-hearted moment before Derek Ruff receives the first treatment for cancer of a human-induced pluripotent stem cell (iPSC)-derived cell therapy called FT500. (
  • Together with Fate Therapeutics, we've been able to show in preclinical research that this new strategy to produce pluripotent stem cell-derived natural killer cells can effectively kill cancer cells in cell culture and in mouse models. (
  • Kaufman has been collaborating with Fate Therapeutics over the past four years to bring iPSC-derived NK cells to patients with cancer. (
  • NK cells are specialized immune cells that are very potent at killing cancer cells. (
  • Work in Kaufman's lab, in collaboration with Fate and investigators at the Masonic Cancer Center, University of Minnesota, defined conditions to efficiently produce NK cells at a scale suitable for clinical use. (
  • Anti-gp340 Monoclonal Antibody Description: 100 g Research Focus: cancer & cell proliferation Storage: -20C Shipping Temperature: 4C. (
  • Developed by researchers at RIKEN, Japan's flagship research institution, the technique opens the door to effective new cell-targeted treatments for cancer. (
  • Yet while clinical trials have shown that injection of the glycolipid α-GalCer can effectively activate an NKT cell antitumor response, most cancer patients have very few NKT cells, which has prevented the wider application of this therapy. (
  • When tested using a mouse model, the cells successfully reproduced the effects of natural NKT cells and suppressed tumor growth, validating the approach and setting the stage for powerful clinical applications in cancer therapy. (
  • The company plans to promptly initiate this trial, which is believed to be the first ever clinical evaluation of a genetically engineered, allogenic, off-the-shelf, natural killer cell for the treatment of patients with cancer. (
  • The FDA's authorization to initiate this clinical trial achieves a significant milestone for NantKwest as we begin clinical investigation of the use of haNK cell therapy for the treatment of cancer in a wide range of cancer types. (
  • In Phase 1 clinical trials in patients with late stage cancer, NantKwest's NK cells have been successfully administered as an outpatient infusion therapy without any reported severe side effects, even at doses of 10 billion cells. (
  • Over a few short years, the cell therapy industry has made significant progress with remarkable patient responses to therapy being seen in a few select cancer indications. (
  • While encouraging, a significant need still exists for the majority of cancer types where existing cell therapies have not been shown to be effective," said Dr. Soon-Shiong. (
  • Natural killer cells have potent cancer cell killing capabilities, yet are often overlooked as the immune system's first line of defense against cancer and other foreign invaders. (
  • Without question, cancer patients deserve better treatment options and I welcome the opportunity to present my vision for next generation NK cell therapies at the Summit. (
  • Multiple myeloma is a cancer that forms from white blood cells that are found in the bone marrow and are normally vital to a healthy immune system. (
  • Natural killer (NK) cells are white blood cells that roam through the blood stream, attacking infections and potentially cancer-causing cells. (
  • The technology to grow NK cells from umbilical cord blood was developed by Nina Shah, M.D., assistant professor and Elizabeth J. Shpall, M.D., professor in the department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. (
  • Herein, we show that cytokine-activated NK cells transferred into naïve hosts can be specifically detected 7-22 days later when they are phenotypically similar to naïve cells and are not constitutively producing IFN-γ. (
  • While creating various mouse strains for generating humanized mouse models, the research team developed a new NOG mouse sub-strain, NOG-hIL-2 expressing the human cytokine IL-2, which supports the proliferation of T-cells. (
  • Importantly, both tumor- and cytokine-activated NK cells induced DC maturation in a TNFSF14-dependent manner. (
  • The relationships between NCRs and the intracellular cytokine expression of CD56+ NK cells in peripheral blood NK cells and the uterine endometrium have been analyzed [ 14 , 15 ]. (
  • Allogeneicity also means engineered NK cells don't trigger negative immune responses in patients, such as cytokine release syndrome, which has led to multiple clinical holds and patient deaths for trials involving CAR-T therapies. (
  • Whereas Tim-3 has been used to identify dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully responsive with respect to cytokine production and cytotoxicity. (
  • As reported in the July issue of the Journal of Clinical Investigation , these iPS cells enabled them to generate large numbers of NKT cells that secrete abundant IFN-γ, a TH1 cytokine that activates antitumor functions. (
  • Our aNK, haNK and taNK platform addresses certain limitations of T cell therapies including the reduction of risk of serious "cytokine storms" reported after T cell therapy. (
  • Our haNK®, and t-haNK™ platforms have been designed to address certain limitations of CAR T-cell therapy including the capability to infuse cell therapy in an outpatient setting which allows for potential reduction of risk for serious cytokine storms and protracted serious adverse events. (
  • Granules differ between species, with rat uNK cells displaying an increased number of small granules than murine cells. (
  • Natural Killer Cells are cytotoxic and contain small granules in their cytoplasm, which in turns contain special proteins such as perforin and proteases known as granzymes. (
  • To do this, the team immobilized a white blood cell using a pair of optical laser tweezers and watched with a super-res microscope as the so-called Natural Killer cell's actin filaments parted, creating a tiny portal through which enzyme-filled granules passed to kill targeted diseased tissue. (
  • The place where an NK cell and its target touch is about a hundredth of a millimeter wide, and the tiny actin proteins and granules are doing something of a dance, constantly changing position over the few minutes from initial contact to the death of the target. (
  • Unlike T and B cells, NK cells have few azurophillic granules and a high cytoplasm-nuclear ratio. (
  • A type of leukemia in which large natural killer (NK) cells (a type of white blood cell) that contain granules (small particles) are found in the blood. (
  • Zhang said CYNK-001 has demonstrated "a range of biological activities" that would allow its cellular therapy to potentially recognize and kill infected cells. (
  • The TCRs present on type I NKT cells recognize the antigen alpha-galactosylceramide (alpha-GalCer). (
  • Less is known about a smaller population of NKT cells, known as type II NKT cells (or noninvariant NKT cells), which express a wider range of TCR alpha chains and do not recognize the alpha-GalCer antigen. (
  • NK cells react to cells that lack self-MHC class I. Yet, since many NK cells cannot recognize self-MHC, mechanisms such as NK cell licensing protect against autoreactivity. (
  • Somehow these NK cells were able to recognize that there was something hostile there, and they actually caused the death of these bacteria," Endsley said. (
  • These NKG2D.ζ cells targeted and killed immunosuppressive myeloid-derived suppressor cells in xenografted tumor microenvironments and in tissue culture studies with human neuroblastoma cells. (
  • Unlike previous strategies used in attempts to downmodulate myeloid-derived suppressor cells in the tumor microenvironment, these NKG2D.ζ cells have no off-target toxicities and continue to relieve immunosuppression long after they are first administered-about two weeks in the lab. (
  • The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response . (
  • NK cells also play a role in the adaptive immune response: numerous experiments have demonstrated their ability to readily adjust to the immediate environment and formulate antigen-specific immunological memory, fundamental for responding to secondary infections with the same antigen. (
  • By contrast, adaptive immune cells display immunologic memory that has 2 basic characteristics, antigen specificity and an amplified response upon subsequent exposure. (
  • The first is to understand how to keep NK cells instead of loosing them, and second is to keep them around, as they have an important regulatory function to limit adaptive immune response. (
  • Absence of NK cells leads to unregulated adaptive immune system and in some cases it may leads to death. (
  • Your immune system consists of two different branches - cell-mediated immunity (innate) and humoral immunity (adaptive). (
  • Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. (
  • Perhaps, Horowitz says, this is because "NK cells are part of innate immunity, not adaptive immunity. (
  • [10] , [11] Thus, NK cells are now considered to be a conjunction point of both the innate and adaptive immune systems. (
  • Natural killer (NK) cells are important effectors of both innate and adaptive immune responses. (
  • Indeed, defects in innate immunity, including natural killer (NK) cells, often lead to uncontrolled, fatal infections ( 1 ⇓ - 3 ). (
  • NK cells are a component of the innate immune system identified in animals as serving an essential role in antiviral immunity. (
  • Natural killer (NK) cells which belong in innate immunity, play an important role for defense against invading pathogens and microbes. (
  • As long as your cell-mediated immune system is activated first and the humoral immune system is activated second, you will have long-lasting immunity against that pathogen. (
  • On a side note, naturally acquired herd immunity in a population comes into play when a very high percentage of individuals have gone through this sequence of cell-mediated and humoral immune response. (
  • Echinacea purpurea and Panax ginseng enhance cellular immune function of peripheral blood mononuclear cells both from normal individuals and patients with depressed cellular immunity. (
  • Since humans and animals are exposed to β-1,3-glucan through inhalation of components of the cell wall of microbes or consumption of dietary grains, we asked whether isolated β-1,3-glucan plays a role in shaping NK cell immunity. (
  • Natural killer (NK) cell activity is a conventional parameter used to determine the performance lytic activity against tumor as well as virus-infected cells in innate immunity. (
  • Homeostatic proliferation does not actually replace the naive pool: naive T cells stably acquire a memory-like phenotype during homeostatic expansion and thymic output is required to replenish the naive T cell pool ( 21 , 22 ). (
  • The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. (
  • Influence of NK cell magnetic bead isolation methods on phenotype and function of murine NK cells. (
  • V. Correlate NK cell persistence, phenotype, and function with overall response. (
  • Our project, focussed on tumour immunology, aims to understand the mechanisms by which tumour cells are eliminated by the immune system. (
  • In a study from the Department of Microbiology and Immunology at Hokkaido University in Japan, spirulina extract was found to excite antitumor natural killer cell response. (
  • According to the American Society of Gene and Cell Therapy, cell therapy is defined as "the administration of living whole cells for the patient for the treatment of a disease. (
  • Interleukin-2 drug therapy to maintain NK cell activity. (
  • Subjects who respond well after one treatment cycle may be eligible to continue NK cell therapy. (
  • Kaufman collaborates with Fate Therapeutics, a biotech firm that developed the therapy, and researchers at the University of Minnesota to develop natural killer (NK) cell products including the one used in the study. (
  • In this regard, the autologous NK cell therapy is safer. (
  • This article reviews the published results of clinical trials and discusses strategies to enhance the efficacy of the NK cell therapy. (
  • Furthermore, currently available standard anticancer therapy, molecularly targeted agents, and checkpoint inhibitors may directly or indirectly enhance the efficacy of NK cell therapy. (
  • This FDA clearance will allow Celularity to begin a phase 1/phase 2 clinical trial of its natural killer cell therapy in up to 86 patients with COVID-19 . (
  • In addition, Sorrento would utilize current existing capacity in its "state-of-the-art" cGMP cell therapy manufacturing facilities in San Diego, California, to supplement Celularity's new cGMP facility in Florham Park, New Jersey. (
  • The combined capacity would support the rapid scale-up and sustained production of the novel cell therapy. (
  • Sorrento is already in contact with leading scientists and local Chinese experts to discuss the clinical validation and logistics requirements to fast-track CYNK-001 cell therapy available in China for this particularly urgent indication. (
  • Our study not only provides definite proof that terminally differentiated NKT cells can be directly reprogrammed to pluripotency but also increases the availability of mature NKT cells with desired functions to establish optimal NKT cell therapy. (
  • We are thrilled to have received notification from the FDA that our first haNK cell therapy program has been authorized to proceed into Phase I clinical trials and are focused on moving swiftly to begin this study," said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest. (
  • As an "off-the-shelf" therapy, NantKwest's NK cells do not rely on a patient's own often compromised immune system. (
  • In addition to being a universal cell-based therapy that does not require individualized patient sourcing or matching, our NK cell products have been largely administered in the outpatient setting as an "off-the-shelf" living drug. (
  • We believe, NantKwest's CAR-based NK cell therapy may represent a much needed new treatment option for these patients. (
  • Even with treatment, which typically involves the use of chemotherapy, steroids, targeted therapy, and in some cases, stem cell transplant, survival often can only be extended to 4 to 5 years. (
  • Long-term remissions in some patients after stem cell transplants from donors have been observed, but treatment-related toxicity limits the widespread use of this therapy. (
  • The cell therapy infusion resulted in no toxicity and no occurrences of graft-versus-host disease. (
  • Determine the overall response of medulloblastoma to NK-cell therapy. (
  • Curcumin may improve outcome in chemotherapy-refractory Natural killer/T-cell lymphoma (NKTL). (
  • Natural killer (NK) cell neoplasms, which include extranodal NK/T-cell lymphoma (nasal and extranasal) and aggressive NK cell leukemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent. (
  • Extranodal NK/T-cell lymphoma most commonly affects the nasal cavity and other mucosal sites of the upper aerodigestive tract. (
  • Based on currently available data, treatment of nasal NK/T-cell lymphoma should consist of radiotherapy, with or without multiagent chemotherapy. (
  • You take some lymphoma cells in a petri dish, and you add cardamom, and nothing happens. (
  • The goal of this clinical research study is to learn if giving cells called natural killer (NK) cells after receiving 1 of 3 pre-treatment plans and a UCB transplant can improve response in patients with MDS, leukemia, lymphoma, or MM. The safety of this treatment and whether NK cells can lessen the risk of graft versus host disease (GVHD) will also be studied. (
  • Kwong, "Consistent Patterns of Allelic Loss in Natural Killer Cell Lymphoma," The American Journal of Pathology, vol. (
  • Natural killer cells, or NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system . (
  • [1] This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells. (
  • It is a type cytotoxic lymphocyte that represents major part of innate immune system and is specialized to kill certain types of target cells, especially those that became infected with virus or have become cancerous. (
  • Natural killer cells (or NK cells ) are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system . (
  • Aggressive NK cell leukemia must be distinguished from T-cell large granular lymphocyte leukemia and indolent NK cell lymphoproliferative disorder, both of which are indolent. (
  • Natural killer cells are derived from Pluripotent Hematopoietic stem cells and are considered as important cells of the immune system. (
  • Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants," Science, vol. (
  • Chronic myelogenous leukemia (CML) is a clonal malignancy of the hematopoietic stem cell harboring a 9;22 translocation which fuses the ABL proto-oncogene to the ABL gene leading to constitutive tyrosine kinase activity necessary and sufficient for massive overproduction of granulocytic cells ( 1 ). (
  • The role of NK cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation has been recently unraveled ( 3 , 4 ). (
  • NK cells can thus limit or exacerbate immune responses. (
  • Regulation of immune responses by NK cells. (
  • Tuning of natural killer cell reactivity by NKp46 and Helios calibrates T cell responses. (
  • There, perforin creates pores to form transport channels on the target cells' membrane and other accessory proteins chaperon granzyme into the target cells, where it signals different processes of cytolysis. (
  • The stably established lines exhibited ES cell-like morphology and expressed the same proteins (SSEA, Oct 3/4 and Nanog) as iPS cells derived from fibroblasts. (
  • NKp46 and NKp30 are expressed either in resting or in activating NK cells, while NKp44 is expressed only in activated NK cells. (
  • Most studies of uNKs use murine cells to model the human equivalent: unless stated otherwise, this section focuses on murine uNKs only. (
  • In summary, we have identified what we believe to be the first human mutation in MCM4 and have shown that it is associated with adrenal insufficiency, short stature, and NK cell deficiency. (
  • Establishing their role in human health has been challenging, with the most direct insight coming from the study of NK cell-deficient individuals. (
  • Understanding the mechanisms of NK cell functions may lead to fresh therapeutic strategies for the treatment of human disease, in general, and particularly in the fight against malaria. (
  • The utility of NK cells in human health has been underscored by a growing number of persons who are deficient in NK cells and/or their functions. (
  • Various Nucleofector™ Kits and corresponding Amaxa™ Optimized Protocols are available for the transfection of human NK cells using the different Nucleofection™ Platforms. (
  • Optimal kits for transfection of human monocytes in the 4D-Nucleofector™ and 96-well Shuttle™ System are the P3 Primary Cell Kits used in combination with cell-type specific protocols. (
  • Primary human natural killer cells were transfected by Nucleofection™ with a plasmid encoding the enhanced green fluorescent protein eGFP. (
  • The factors that drive human NK cell development are poorly understood, especially compared to T and B cells, because their development is much less tissue restricted," points out Emily M. Mace, PhD, an assistant professor of pediatrics at Columbia University. (
  • The new study Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium which is published in eLife shows two functions of the cells not previously known. (
  • Also the researchers data suggest that acutely stressed cells in the lining of the womb are responsible for generating the elusive 'implantation signal' in the human uterus. (
  • This lecture focuses on natural killer cells (or NK cells) which are, in my heavily biased opinion, the most interesting cells of the human immune system. (
  • NK cells (brown) patrolling between cells of a healthy human lymph node. (
  • She suggests that the toxicities could have been due to the human T cells attacking the mouse immune system, because of species-specific differences. (
  • My lab was the first to produce natural killer cells from human pluripotent stem cells. (
  • While NK cells can be isolated from the blood of donors or patients, this trial uses NK cells entirely produced in the lab from human iPSCs. (
  • Presumed guilty: natural killer T cell defects and human disease. (
  • In this Review, we describe the approaches that have been used to analyse the NKT cell populations of various patient groups, suggest new strategies to determine how (or indeed, if) NKT cell defects contribute to human disease, and discuss the prospects for using NKT cells for therapeutic benefit. (
  • We statistically examined the parameters related to the NK cell activity of human peripheral blood mononuclear cells (PBMCs) by multiple regression analysis, and obtained a formula with NK cell % and RNA levels of two genes in isolated NK cells. (
  • Surprisingly, they found that NK cells were also able to detect and kill anthrax bacteria outside of human cells. (
  • This new partnership allows NantKwest to leverage the breadth of our monoclonal antibody generation and validation platform, our human antibody library screening capabilities, together with NantKwest's strong NK cell engineering, manufacturing, and clinical expertise," said John Wu, President and CEO of ProMab Biotechnologies. (
  • A first-in-human Phase I study of multiple myeloma patients combined expanded cord blood-derived natural killer cells with transplantation of a patient's own stem cells and high-dose chemotherapy with little or none of the side effects seen with current treatments. (
  • At the Innate Killer Summit, held last month in San Diego, scientists in industry and academia described the approaches they are using to improve cell therapies. (
  • The idea is to turn cold tumor microenvironments into hot ones, that is, to relieve endogenous immunosuppression so that CAR T-cell therapies can do their work. (
  • Lakshmipathy is the director of research and development where she uses her expertise in stem cell research to guide the development of analytical assays and other workflow advancements, especially for CAR T therapies. (
  • The immune cells live up to their name in natural settings, but engineered therapies have delivered mixed results in clinical trials. (
  • Since FT500 does not need to be matched to a patient like other T-cell therapies, researchers say FT500 can be administered in the outpatient setting as an "off-the-shelf" cell product, reducing the time and resources needed to treat patients. (
  • Dr. Soon-Shiong's keynote address will provide a vision of next generation NK cell therapies and feature a review of translational R&D activities, state-of-the-art manufacturing requirements, along with clinical progress. (
  • We eagerly anticipate growing our relationship with ProMab and accelerate the development of these new and innovative, next-generation off-the shelf, CAR-based NK cell therapies. (
  • However, the greater the mismatch, the more vigorously residual T cells in the donor BM will react against the recipient tissues, leading to graft-versus-host disease (GVHD). (
  • NK cells can promote tolerance, such as through the depletion of donor antigen-presenting cells. (
  • D & E) Plots show CD57 expression between mock and VZV cultured NK cells (D) and between bystander and VZV + NK cells (E), from one representative donor. (
  • A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK cells via trogocytosis. (
  • Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw-treated donor cells expressing anti-CD19 CARs. (
  • Graft-versus-host disease is a condition in which the patient's immune system is attacked by the donor stem cells. (
  • The disease can occur in patients who have received donor stem cells or immune. (
  • Natural Killer (NK) cells are the leading maternal immune cells which act as a natural defense system and help in fighting infections. (
  • With natural killer cells now arriving onto the scene of the tumor-ridden cells, the implanted melanoma slowly regressed, until the natural killer cell defense effectively eliminated the entire tumor. (
  • Biology of natural killer cells. (
  • Her work reveals two important aspects of NK cell biology. (
  • Recent advances have added clarity to this diagnosis and identified defects in 3 genes that can cause NK cell deficiency, as well as some of the underlying biology. (
  • eGFP expression in natural killer cells is shown after Nucleofection™ without (A) and with plasmid DNA (B). (Courtesy of J. Sundbäck and K. Kärre, Karolinska Institutet, Microbiology and Tumor Biology Center, Stockholm, Sweden). (
  • Researchers at the Imperial College London and the University of Oxford are reporting in the journal PLoS Biology that they can see the inner workings of white blood cells at the highest resolution ever documented. (
  • While the effects of immunosuppression agents on NK cells may currently be largely unintentional, further understanding of NK cell biology in lung allograft recipients may allow these cells to serve as biomarkers of graft injury and as therapeutic targets. (
  • Despite the hurdles ahead, the startup has a deep understanding of NKT cell biology that comes from its founding researchers-Steve Balk, of Beth Israel Deaconess Medical Center, Mark Exley, of Harvard Medical School, and Brian Wilson, at Massachusetts General Hospital-who are experts in the field (they've also been research collaborators for years prior to founding the startup in early 2008. (
  • But before we talk about any of these fascinating aspects of NK cell biology, let's start back in 1975 when natural killer cells were first discovered. (
  • Synopsis This text presents a comprehensive collection of detailed experimental protocols for studying the cell biology, biochemistry, and molecular biology of natural killer (NK) cells. (
  • The biology of NKT cells. (
  • These processes, and how they integrate with NK cell maturation, are currently poorly understood. (
  • In order for NK cells to defend the body against viruses and other pathogens, they require mechanisms that enable the determination of whether a cell is infected or not. (
  • The state of the field in 1975 was that the immune system had two broad strategies for destroying pathogens or diseased cells within the body. (
  • Secondly, cellular cytotoxicity relied on immune cells to kill pathogens. (
  • NK cells share a similar cytolytic mechanism of granule-exocytosis [12] with killer T cells where they utilize the two crucial cytolytic enzyme: perforin and granzyme. (
  • NK cells can also use perforin to kill cells in the absence of antibody. (
  • There are two types of NK cells - uterine NK cells and NK cells that are circulating in the peripheral blood stream. (
  • Uterine NK cells are normally present in the endometrium (inner epithelial layer of the uterus) and thrive in the presence of high progesterone levels. (
  • Presence of uterine NK cells in close proximity to extravillous trophoblast (EVT) cells has shown a vital role during the trophoblast incursion process. (
  • Uterine NK cells have cytotoxic effects, particularly against K562 cells. (
  • Uterine NK cells result in the production of angiogenic growth factors such as angiogenin, angiopoietin (Ang)-1, Ang-2, vascular endothelial growth factor (VEGF)-A, VEGF-C, placental growth factor, keratinocyte growth factor, fibroblast growth factor, and platelet-derived growth factor-BB (PDGF-BB) during early phases of pregnancy. (
  • Uterine NK cells are closely aggregated in close proximity to the spiral arteries during an early phase of the pregnancy, which aid in mediating the vascular changes at the time of pregnancy. (
  • When peripheral NK cells enter the site of inflammation uterine NK cells become incapable of protecting the embryo against the peripheral NK cells action. (
  • Steroids are the treatment choice for controlling high uterine NK cells levels before and after conception. (
  • The population of NK cells in the uterine tissue will only persist if pregnancy occurs. (
  • The origin of uNK cells has been suggested to occur in two phases dependent on the stage of uterine tissue remodelling. (
  • Although it has long been known that the lining of the womb harbors dynamic uterine natural killer cells, no functions have so far been given to these cells outside of pregnancy. (
  • First the researchers discovered that the uterine natural killer cells remodel and refresh the lining of the womb at the time of embryo implantation. (
  • This is the first time a role for uterine natural killer cells in the lining of the womb has been identified outside of pregnancy. (
  • Excessive inflammation or insufficient clearance by uterine natural killer cells makes miscarriage more likely. (
  • Uterine decidual cells have depressed NK cytotoxicity [ 3 - 5 ]. (
  • Mature NK cells, which are present in peripheral blood, make up almost all NK cells, and, in the decidua, there is a large amount of immature NK cells that are known as uterine NK cells [ 17 - 19 ]. (
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