A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Glycoproteins found on the membrane or surface of cells.
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.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Group of disorders which feature accumulations of active HISTIOCYTES and LYMPHOCYTES, but where the histiocytes are not LANGERHANS CELLS. The group includes HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SINUS HISTIOCYTOSIS; xanthogranuloma; reticulohistiocytoma; JUVENILE XANTHOGRANULOMA; xanthoma disseminatum; as well as the lipid storage diseases (SEA-BLUE HISTIOCYTE SYNDROME; and NIEMANN-PICK DISEASES).
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.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
A group of related disorders characterized by LYMPHOCYTOSIS; HISTIOCYTOSIS; and hemophagocytosis. The two major forms are familial and reactive.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
Condensed areas of cellular material that may be bounded by a membrane.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Collection of granular epithelial cells in the uterine muscle beneath the placenta that develop during pregnancy in certain species of animals.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
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.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. In PLATELETS and T-LYMPHOCYTES it may play a role in the cellular degranulation process.
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.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
An order of insects comprising three suborders: Anisoptera, Zygoptera, and Anisozygoptera. They consist of dragonflies and damselflies.
A discipline or occupation concerned with the study of INSECTS, including the biology and the control of insects.
Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.
Activities performed to identify concepts and aspects of published information and research reports.
A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of CELL MEMBRANES, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
Tumors or cancer of the SKIN.
Injections introduced directly into localized lesions.
The transference of either one or both of the lungs from one human or animal to another.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Inflammation of the BRONCHIOLES leading to an obstructive lung disease. Bronchioles are characterized by fibrous granulation tissue with bronchial exudates in the lumens. Clinical features include a nonproductive cough and DYSPNEA.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Benign epidermal proliferations or tumors; some are viral in origin.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
... and the demonstration of their playing a role in the perforin-granzyme-based mechanism of T-cell-mediated cytotoxicity, and to ... "Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity". Science. 265 (5171): 528-30. doi:10.1126/ ... Rouvier, E; Luciani, MF; Golstein, P (1993). "Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity". Journal of ...
2004). "Granzyme M mediates a novel form of perforin-dependent cell death". J. Biol. Chem. 279 (21): 22236-42. doi:10.1074/jbc. ...
Most tumors elicit an immune response in the host that is mediated by tumor antigens, thus distinguishing the tumor from other ... perforin-independent mechanism". Journal of Immunology. 174 (4): 1783-6. doi:10.4049/jimmunol.174.4.1783. PMID 15699103. ... Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ (February 2005). "Cutting edge: contact-mediated suppression by CD4+CD25+ ... but this simultaneously disrupts the clearance of virus by the cell-mediated immune response and enhances the reservoir by ...
Blood, 2004 PMID 15205258 Fratricide of CD8+ cytotoxic T lymphocytes is dependent on cellular activation and perforin-mediated ... 2008 PMID 18586679 Lysine 144, a ubiquitin attachment site in HIV-1 Nef, is required for Nef-mediated CD4 down-regulation. Jin ... Journal of Immunology, 2006 PMID 17056525 HIV Nef-mediated CD4 down-regulation is adaptor protein complex 2 dependent. Jin YJ, ...
"Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma ... This encoded protein was found to be associated with the macromolecular complex of granzymes and perforin, which may serve as a ... implications for granule-mediated apoptosis in vivo". Journal of Immunology. 162 (9): 5345-50. PMID 10228010. Schick BP, ... mediator of granule-mediated apoptosis. GRCh38: Ensembl release 89: ENSG00000122862 - Ensembl, May 2017 "Human PubMed Reference ...
It is secreted by these cells along with the pore forming protein perforin to mediate apoptosis in target cells. Granzyme B has ... Perforin has a radius of 5.5 nm and granzyme B has a stokes radius of 2.5 nm and can therefore pass through the perforin pore ... It is produced by many types of cell to protect themselves from accidental granzyme B mediated cell death. PI-9 is metastable ... The destruction of insulin producing β cells in pancreatic islets is mediated by T cells and granzyme B contributing to Type 1 ...
Voskoboinik I, Smyth MJ, Trapani JA (2006). "Perforin-mediated target-cell death and immune homeostasis". Nat. Rev. Immunol. 6 ... Perforin is released by cytotoxic T cells and lyses virally infected and transformed cells. In addition, perforin permits ... Perforin functions via two distinct mechanisms. Firstly, like C9, high concentrations of perforin can form pores that lyse ... 2007). "Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and ...
CD8+ T cells then mediate keratinocyte cell death through release of a number of molecules, including perforin, granzyme B, and ... Initial interest in Intravenous immunoglobulin (IVIG) came from research showing that IVIG could inhibit Fas-FasL mediated ...
Perforin, unlike GNLY, binds preferably to cholesterol rich membranes and permeabilizes the infected cell which allows the ... Ma LL, Spurrell JC, Wang JF, Neely GG, Epelman S, Krensky AM, Mody CH (November 2002). "CD8 T cell-mediated killing of ... When a cytotoxic cell discovers any infected cell the content of the cytotoxic granules is released by receptor-mediated ... This molecule is found in cytotoxic granules, along with other cytotoxic molecules, such as granzymes and perforin. The ...
NK-92 cells can be engineered to include both CD16 and CARs to allow them to perform both ADCC mediated killing via IgG1 ... Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell, ... NK cells secrete a high level of cytokines which help mediate their function. NK cells interact with HLA-C to produce cytokines ... O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH (May 2006). "T cell- and B cell-independent adaptive immunity mediated by ...
2002). "Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role ... 2000). "Proteinase inhibitor 9, an inhibitor of granzyme B-mediated apoptosis, is a primary estrogen-inducible gene in human ... for granzyme B-mediated proteolysis in reproduction". Mol. Hum. Reprod. 7 (12): 1133-42. doi:10.1093/molehr/7.12.1133. PMID ...
The granules are released into an immune synapse formed with a target cell, where perforin mediates the delivery of the ... which then inhibits T cell-mediated tumor clearance. Perforin's role in protecting the body against lymphoma was emphasized ... Perforin and granzymes have been found to have a directly related ability to protect the body against the formation of ... In NK cells and T cells, granzymes are packaged in cytotoxic granules along with perforin. Granzymes can also be detected in ...
... or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as ... and cytotoxic mediators like perforin and granzyme that enter the target cell and promote cell death by triggering apoptosis. ... CD16a mediated costimulation provides a positive signal in the activated CD4+ T cells and not in the quiescent cells which lack ... CD16a signaling is mediated by phosphorylation of Syk (pSyk). A study now suggests induced expression of CD32a upon activation ...
... of perforin and granzyme from the redirected T cell that induces the targeted disease cell to die through an apoptosis mediated ...
... by inducing perforin- and granzyme-mediated cell death and reducing Wnt signaling in tumor cells. Glypican GRCh38: Ensembl ... October 2019). "A Frizzled-Like Cysteine-Rich Domain in Glypican-3 Mediates Wnt Binding and Regulates Hepatocellular Carcinoma ...
... target cell by CD8 on the veto cell and killing can then be mediated via either the Fas/FASL pathway or the Perforin mediated ... These are the same T-cells that mediate graft rejection. This means that the addition of donor-veto cells to the donor graft ... The large number of veto cells helped overcome the graft rejection that was mediated by the host CD8 T-cell precursors. An ... Hence veto activity is selective but is not T-cell receptor mediated. Both clonal anergy and clonal deletion have been shown to ...
Goebel WS, Schloemer RH, Brahmi Z (1996). "Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple ... Perforin-1 is a protein that in humans is encoded by the PRF1 gene and the Prf1 gene in mice. Perforin is a pore forming ... perforin at the US National Library of Medicine Medical Subject Headings (MeSH) Perforin at NLM Genetics Home Reference. ... and natural killer-cell-mediated cytolysis. Perforin is thought to act by creating holes in the plasma membrane which triggers ...
"Perforin-independent extracellular granzyme B activity contributes to abdominal aortic aneurysm". Am. J. Pathol. 176 (2): 1038- ... "Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm". Cell Death Dis. 2 ... "Perforin-Independent Extracellular Granzyme B Activity Contributes to Abdominal Aortic Aneurysm". The American Journal of ...
This causes T cells to exert cytotoxic activity on tumor cells by producing proteins like perforin and granzymes, independently ... Helwick C (June 2008). "Novel BiTE antibody mediates contact between T cells and cancer cells". Oncology NEWS International. 17 ...
In this pathway perforins and granzymes are taken up by the target cell. In this pathway, the perforins facilitate the entry of ... The CTL-mediated immune system can be divided into two phases. In the first phase, functional effector CTLs are generated from ...
This IL-6R mediated Tfh accumulation and support for antibody generation enables viral control in chronic infections. In 2020, ... TGF-β was found to suppress granzyme and perforin expression as well as the transcription factor eomesodermin, which limits ... Zúñiga's lab studies the strategies used by viruses to persist inside the host and mediate chronic infection, with a focus on T ... Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses. Nat Commun. 2017 ...
Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent ... IL-35-mediated induction of a potent regulatory T cell population. „Nat Immunol". 11 (12), s. 1093-1101, grudzień 2010. DOI: ... T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. „J Exp Med ... All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co- ...
In cell-mediated therapies like CAR-T cell therapy, immune cells are extracted from the patient, genetically engineered to ... When NK cells encounter antibody-coated cells, the latter's Fc regions interact with their Fc receptors, releasing perforin and ... Antibody-dependent cell-mediated cytotoxicity (ADCC) requires antibodies to bind to target cell surfaces. Antibodies are formed ... It appears that (cancer-mediated) upregulation of PD-L1 on the cell surface may inhibit T cells that might otherwise attack. PD ...
Cytolytic granule mediated cell apoptosis[edit]. NK cells are cytotoxic; small granules in their cytoplasm contain proteins ... Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell, ... Antibody-dependent cell-mediated cytotoxicity[edit]. Infected cells are routinely opsonized with antibodies for detection by ... CD16 (FcγIIIA) plays a role in antibody-dependent cell-mediated cytotoxicity; in particular, they bind IgG. ...
2008). "Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by ... 2008). "Identification of defective Fas function and variation of the perforin gene in an epidermodysplasia verruciformis ...
The injection of Treg cells specific for a tumor antigen also can reverse experimentally-mediated tumor rejection based on that ... Granzyme or perforin secretion upon contact Upregulation of cAMP after contact, inducing anergy (reduced proliferation and IL-2 ... Vadasz, Z; Haj T; Kessel A; Toubi E. (Jun 2013). "B-regulatory cells in autoimmunity and immune mediated inflammation". FEBS ... Treg cells are not the only cells that mediate peripheral tolerance. Other regulatory immune cells include T cell subsets ...
Salient elements mediating tissue injury for each type of disorder include: SJS, SJS/TEN, and TEN: These three SCARs are ... and perforin); and two cytokines that stimulate the proliferation and activation of natural killer and T cells (viz., ... studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury. Rare ... and Type III hypersensitivity reactions of the adaptive immune system mediated by IgE, IgG, and/or IgM antibodies; and c) SCARs ...
Cytotoxic T cells and NK cells release molecules like perforin and granzymes by a process of directed exocytosis to kill ... David J, Butterworth A, Vadas M (1980). "Mechanism of the interaction mediating killing of Schistosoma mansoni by human ...
Furthermore, maturation of CD8+ T cells is mediated by CD40 signalling. Once the naïve CD8+ T cell is bound to the infected ... Through the action of perforin, granzymes enter the cytoplasm of the target cell and their serine protease function triggers ... When exposed to infected/dysfunctional somatic cells, TC cells release the cytotoxins perforin, granzymes, and granulysin. ... TC cells are resistant to the effects of their perforin and granzyme cytotoxins. A second way to induce apoptosis is via cell- ...
MAIT cells can be activated in ways that involve, and do not involve, MR1-mediated antigen presentation. However, MR1- ... After activation, MAIT cells also produce cytolytic molecules perforin and granzyme B, which form pores in the bacterially- ... These strains avoid MAIT cell-mediated elimination because they have unusual riboflavin metabolic pathways that do not produce ... Hinks, Timothy S. C. (2016). "Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways, ...
positive regulation of Arp2/3 complex-mediated actin nucleation. • actin filament-based movement. • endosomal transport. • ... Particularly in NK cells it participates in the synapse formation and polarization of perforin to the immune synapse for NK ... Wu Y, Spencer SD, Lasky LA (March 1998). "Tyrosine phosphorylation regulates the SH3-mediated binding of the Wiskott-Aldrich ... Tian L, Nelson DL, Stewart DM (March 2000). "Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome ...
antimicrobial humoral immune response mediated by antimicrobial peptide. • cytolysis by host of symbiont cells. ... "Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response". Science. 311 (5768): 1770-3. doi:10.1126/ ...
... (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a ... inducing the NK cell to release proteins such as perforin and proteases known as granzymes, which causes the lysis of the ... 1987). "Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated ... Hashimoto, G.; Wright, P. F.; Karzon, D. T. (1983-11-01). "Antibody-dependent cell-mediated cytotoxicity against influenza ...
Aberrant B cell receptor-mediated feedback - A feature of human autoimmune disease is that it is largely restricted to a small ... Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible. ... Many common human autoimmune diseases can be seen to have a substantial innate immune mediated immunopathology using this new ...
B cells play a large role in the humoral immune response, whereas T cells are intimately involved in cell-mediated immune ... When exposed to these infected or dysfunctional somatic cells, effector CTL release perforin and granulysin: cytotoxins that ... B cells and T cells, two different types of lymphocytes, carry out the main activities: antibody responses, and cell-mediated ... Humoral and cell-mediated immune responses limit malaria parasite multiplication, and many cytokines contribute to the ...
Grewal I, Flavell R. "CD40 and CD154 in cell-mediated immunity". Annu Rev Immunol. 16: 111-35. PMID 9597126.. ... seperti perforin) yang dapat membentuk pori pada membran plasma target, membuat ion, air, dan toksin masuk ke dalamnya. Hal ini ... Baldridge JR, Buchmeier MJ (1992). "Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus ... "T Cell-Mediated Immunity". Immunobiology: The Immune System in Health and Disease. 5th edition (dalam bahasa Inggris). ...
A Common Fold Mediates Vertebrate Defense and Bacterial Attack. . In: Science. . 317, Nr. 5844, 2007, S. 1548-51. doi:10.1126/ ... Eukaryotische MACPF-ähnliche Proteine kommen beim Perforin und dem C9 des Komplementsystems als Teil der Immunabwehr vor.[3] ... Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis. . In: ...
"A Common Fold Mediates Vertebrate Defense and Bacterial Attack". Science. 317 (5844): 1548-51. doi:10.1126/science.1144706. ... Perforin. *Pore-forming toxin. References[edit]. *^ Peitsch MC, Tschopp J (1991). "Assembly of macromolecular pores by immune ... and cytotoxic T-lymphocyte-mediated cytolysis". Nature. 322 (6082): 831-4. doi:10.1038/322831a0. PMID 2427956.. ...
... or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as ... and cytotoxic mediators like perforin and granzyme that enter the target cell and promote cell death by triggering apoptosis. ... CD16a mediated costimulation provides a positive signal in the activated CD4+ T cells and not in the quiescent cells which lack ... This process is known as antibody-dependent cell-mediated cytotoxicity (ADCC). FcγRIII on NK cells can also associate with ...
... mediated apoptosis of T cells". Arthritis Rheum. 62 (10): 2919-29. PMID 20533543. doi:10.1002/art.27602.. ... "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". ...
Granzyme or perforin secretion upon contact. *Upregulation of cAMP after contact, inducing anergy (reduced proliferation and IL ... It is induced by prior exposure to that specific antigen[1][2] and contrasts with conventional immune-mediated elimination of ... Vadasz, Z; Haj T; Kessel A; Toubi E. (Jun 2013). "B-regulatory cells in autoimmunity and immune mediated inflammation". FEBS ... Treg cells are not the only cells that mediate peripheral tolerance. Other regulatory immune cells include T cell subsets ...
The crystal structure of dermicidin has been solved in solution to reveal a hexameric helix-bundle, mediated by Zn ion binding. ... antimicrobial humoral immune response mediated by antimicrobial peptide. • killing of cells of other organism. • defense ...
Entrez Gene: PRF1 perforin 1 (pore forming protein)". *↑ Thiery J, Keefe D, Boulant S, Boucrot E, Walch M, Martinvalet D, ... and cytotoxic T-lymphocyte-mediated cytolysis". Nature 322 (6082): 831-4. PMID 2427956. doi:10.1038/322831a0.. ... Fink TM, Zimmer M, Weitz S, Tschopp J, Jenne DE, Lichter P (Sep 1992). "Human perforin (PRF1) maps to 10q22, a region that is ... xullo de 1998). "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell ...
Rosado, C.J. s sod. (2007). "A common fold mediates vertebrate defense and bacterial attack". Science. 317 (5844): 1548-51. doi ... and cytotoxic T-lymphocyte-mediated cytolysis". Nature. 322 (6082): 831-4. doi:10.1038/322831a0. PMID 2427956.. .mw-parser- ... Vzpostavljeno iz »https://sl.wikipedia.org/w/index.php?title=Perforin&oldid=4016839« ...
More recently, FasL-mediated apoptosis of T cells has also been suggested as an immune-evasive mechanism by which tumors can ... Cytotoxic T-cell activity: Fas-induced apoptosis and the perforin pathway are the two main mechanisms by which cytotoxic T ... Defective Fas-mediated apoptosis may lead to oncogenesis as well as drug resistance in existing tumors. Germline mutation of ... Increases in Fas-mediated signaling have been implicated in the pathology of low-risk myelodysplastic syndromes (MDS) and ...
2001) Perforin is a protein produced by CD8+ T cells, which plays a central role in the cytotoxic killing mechanisms by ... Th2 mediated anti-tumor activity primarily involves recruitment of eosinophils to the tumor environment via IL-4 and IL-13. ... CD4+ T cell-mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFNγ receptor expression on ... Perforin and interferon-γ activities independently control tumor initiation, growth, and metastasis. Blood 97, pp. 192-197. ...
The overall complex belongs to MAC/perforin-like (MACPF)/CDC superfamily. Pore formation involves binding the C9 molecules to ... July 2016). "Target deletion of complement component 9 attenuates antibody-mediated hemolysis and lipopolysaccharide (LPS)- ...
... they secrete perforin, which punches holes in target cells, followed by granzymes, which induce apoptosis in the target cells. ... as effector cells for antibody-mediated killing via CD16 modified cells and as effector cells for chimeric antigen receptor ( ...
Perforin and granzymes work in synergy to mediate cholangiocyte injury in experimental biliary atresia.. Shivakumar P1, Mourya ... Perforin and granzymes have complementary roles mediating epithelial injury by NK and CD8 T cells. The prevention of ... Perforin and granzymes work in synergy to mediate cholangiocyte injury in experimental biliary atresia ... Perforin and granzymes work in synergy to mediate cholangiocyte injury in experimental biliary atresia ...
A potential role of CD8+ T cells by direct lysis of infected cells was investigated in perforin-deficient mice generated by ... CD8+ T cell-mediated protection against an intracellular bacterium by perforin-dependent cytotoxicity Eur J Immunol. 1994 Dec; ... The absence of perforin-mediated cytotoxicity resulted in delayed clearance of Listeria from the spleen but not the liver after ... A potential role of CD8+ T cells by direct lysis of infected cells was investigated in perforin-deficient mice generated by ...
Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis.. Hodgson PD1, Grant MD, ... Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis ... Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis ... Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis ...
Antigen dependently activated cluster of differentiation 8-positive T cells cause perforin-mediated neurotoxicity in ... cells-that share the direct perforin-mediated cytotoxic pathway on outcome after cerebral ischemia in mice. Although CTLs and ... from perforin knock-out or interferon-γ knock-out mice into Rag1 knock-out mice revealed that CTL neurotoxicity was mediated by ... Accordingly, CTLs isolated from wild-type or interferon-γ knock-out but not from perforin knock-out mice induced neuronal cell ...
Adoptive transfer of human papillomavirus E7-specific CTL enhances tumor chemoresponse through the Perforin/Granzyme-mediated ... of IL-12 cDNA eradicates established melanomas by Trp2180-188-specific CD8+ CTLs in a perforin/granzyme-mediated and IFN-γ- ... The therapeutic effect of IT-EP/IL12 was absent in perforin-deficient mice, indicating that tumor elimination occurred through ... Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model. Cancer Res 61(3):1005-1012 ...
Fas (CD95/Apo-1)-Mediated Damage to Ventricular Myocytes Induced by Cytotoxic T Lymphocytes From Perforin-Deficient Mice: A ... suggesting that CTL-induced Fas-based myocyte dysfunction is mediated by IP (3). We conclude that a Fas-based perforin- ... derived from perforin gene-knockout (P-/-) mice, and murine ventricular myocytes. Fas expression on isolated ventricular ... prevented Fas-mediated myocyte dysfunction. Additionally, intracellular application (through the patch pipette) of the active ...
7 C). As expected, IL-12-mediated suppression of DA3-H60 metastases was perforin dependent, and IL-18-mediated suppression of ... Herein we have clearly shown in models of NK cell-mediated suppression that the perforin-mediated therapeutic activity of ... NKG2D Recognition and Perforin Effector Function Mediate Effective Cytokine Immunotherapy of Cancer Mark J. Smyth , Mark J. ... Critical Contribution of NKG2D to Perforin-mediated Tumor Suppression by IL-2 or IL-12. Having established which experimental ...
... ... Perforin (PRF1) is essential for immune surveillance and studies report decreased perforin in chronic fatigue syndrome (CFS), ...
Perforin proteostasis is regulated through its C2 domain: supra-physiological cell death mediated by T431D-perforin. Cell Death ... Perforin proteostasis is regulated through its C2 domain : supra-physiological cell death mediated by T431D-perforin. In: Cell ... Perforin proteostasis is regulated through its C2 domain : supra-physiological cell death mediated by T431D-perforin. / Brennan ... title = "Perforin proteostasis is regulated through its C2 domain: supra-physiological cell death mediated by T431D-perforin", ...
... but not perforin-mediated cytotoxicity. This is explained by the lesser intensity of Thy-1-mediated signaling in T cells. The ... but not perforin-mediated cytotoxicity. This is explained by the lesser intensity of Thy-1-mediated... ... While the TCR-triggered signaling initiates both perforin- and Fas ligand (FasL)-Fas-mediated mechanisms of cytotoxicity, it ... While the TCR-triggered signaling initiates both perforin- and Fas ligand (FasL)-Fas-mediated mechanisms of cytotoxicity, it ...
On the basis of these results, we propose a new model for granzyme-perforin-induced target cell lysis in which granzyme B is ... Induction of the lytic pathway, however, required a second signal that was provided by perforin or adenovirus (Ad2). The ... it trafficks to an intracellular compartment and accumulates until release is stimulated by the addition of perforin. We found ... perforin. Using indirect immunofluorescence and also direct visualization of fluorescein isothiocyanate (FITC)-conjugated ...
SNARE-mediated perforin and cytokine release in NK cells (2011-2013). Abstract:. Cytotoxic cells release both perforin for cell ... While perforin is released from granules fusing at immune synapses, cytokines are trafficked separately and released ...
... granzyme/perforin-mediated cytolysis; and direct modulation of APC function [1, 2, 30]. TGF-β, a multifunctional cytokine, may ... Treg-mediated antioxidative effects may be vitally important neuroprotective mechanisms. FoxP3+CD25+CD4+ Tregs suppressed ... E. M. Shevach, "Mechanisms of Foxp3+ T regulatory cell-mediated suppression," Immunity, vol. 30, no. 5, pp. 636-645, 2009. View ... Importantly, FoxP3+CD25+CD4+ Treg-mediated immunosuppression could be protective or harmful at different stages of stroke [12, ...
Vol 5: Large T Antigen-Specific Cytotoxic T Cells Protect Against Dendritic Cell Tumors through Perforin-Mediated Mechanisms ... Here, we document that the MuTuDC line was rejected in C57BL-6 mice by a CD4 T cell help-independent, perforin-mediated CD8 T ... Vol 5: Large T Antigen-Specific Cytotoxic T Cells Protect Against Dendritic Cell Tumors through Perforin-Mediated Mechanisms ... Vol 5: Large T Antigen-Specific Cytotoxic T Cells Protect Against Dendritic Cell Tumors through Perforin-Mediated Mechanisms ...
... and the demonstration of their playing a role in the perforin-granzyme-based mechanism of T-cell-mediated cytotoxicity, and to ... "Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity". Science. 265 (5171): 528-30. doi:10.1126/ ... Rouvier, E; Luciani, MF; Golstein, P (1993). "Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity". Journal of ...
2004). "Granzyme M mediates a novel form of perforin-dependent cell death". J. Biol. Chem. 279 (21): 22236-42. doi:10.1074/jbc. ...
Although the in vivo studies using gld mice suggest a minor involvement of perforin-mediated killing in IL-18 antitumor effects ... The perforin pathway, however, appears to be the predominant cytolytic pathway mediating IL-12 antitumor effects. ... Cytotoxicity of NK cells against tumor appears to be mediated by apoptosis induced by delivery of perforin/granzyme or Fas ... 3⇑). These results indicate that IL-12 antitumor effects are mainly mediated through perforin pathways, consistent with other ...
The studies reported here first address the role of perforin in mediating immunity to HC. Remarkably, perforin-deficient ... T cells mediate their effect is through perforin. Moreover, in the absence of perforin, we show here that CD8+ T cells do have ... these surprising data highlight a critical role for perforin in mediating primary immunity to HC. Finally, the role of perforin ... Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 369: 31. ...
Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol. 2006;6:940-52.PubMedCrossRefGoogle Scholar ... LAT region factors mediating differential neuronal tropism of HSV-1 and HSV-2 do not act in trans. PLoS One. 2012;7:e53281. ... Tissari J, Sirén J, Meri S, Julkunen I, Matikainen S. IFN-α enhances TLR3-mediated antiviral cytokine expression in human ...
... perforin, granzyme B) was performed as previously described (5). For determination of serum alloantibody titers, 200 μl ... T cells induce acceptance of pulmonary allografts through IFN-γ-mediated production of nitric oxide (5). CCR7-mediated synapses ... Antibody-mediated rejection in lung transplantation. Curr Transplant Rep. 2015;2(4):316-323.. View this article via: PubMed ... Antibody-mediated rejection (AMR) has emerged as an important cause of lung graft failure. In the current issue of the JCI, a ...
2005 Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 123: 335-346. ... Development of the Cellular Immune System of Drosophila Requires the Membrane Attack Complex/Perforin-Like Protein Torso-Like. ... MEMBRANE attack complex/perforin-like (MACPF) proteins comprise a large, functionally diverse superfamily of molecules that ... 2010 The structural basis for membrane binding and pore formation by lymphocyte perforin. Nature 468: 447-451. ...
2006) Perforin-mediated target-cell death and immune homeostasis. Nature Rev 6:940-952.. ... Scale bar: 5 μm.) The graph (Right) displays the percentage of FLAG-WIP colocalizing with perforin (black bars) and perforin ... In resting cells 71 ± 11% of FLAG-WIP colocalized with perforin and 74 ± 17% of perforin colocalized with FLAG-WIP. Although ... of WIP with perforin and 78 ± 9% of perforin with WIP) (Fig. 1 A). ...
"Target cell-induced perforin mRNA turnover in NK3.3 cells is mediated by multiple elements within the mRNA coding region.". ... "Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2).". ... "Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand-mediated pathways for target cell lysis.". Vergelli M., ... "Human perforin employs different avenues to damage membranes.". Praper T., Sonnen A., Viero G., Kladnik A., Froelich C.J., ...
Impaired T-bet-pSTAT1α and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma *Katerina Andreev ... Impaired T-bet-pSTAT1α and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma *Katerina Andreev ... Rights & permissionsfor article Impaired T-bet-pSTAT1,i,α,/i, and perforin-mediated immune responses in the tumoral region of ... Rights & permissionsfor article Impaired T-bet-pSTAT1α and perforin-mediated immune responses in the tumoral region of lung ...
Nef-Mediated Inhibition of Perforin Expression. David McDonald, National Institute of Allergy and Infectious Disease, USA ...
Lastly, trophoblast clearance occurred largely through a direct cytolytic perforin-dependent mechanism, because perforin- ... Immune-Mediated Rejection of Ectopic Trophoblasts in Vivo.. Because trophoblasts are not rejected by the maternal immune system ... C and D) NK cell- and perforin-dependent clearance of TSGFP. (C) A compilation of all of our experiments with trypsinized TSGFP ... Intrinsic susceptibility of mouse trophoblasts to natural killer cell-mediated attack in vivo. Adrian Erlebacher, Amanda K. ...
Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol 2006;6(12):940-952. ... By breeding perforin- (Prf1−/−), Ashen- (Rab27a−/−), and syntaxin-11-deficient (Stx11−/−) mice, we generated Rab27a+/− Stx11+/− ... Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8+ T cells and dendritic cells. Blood 2013;121( ... Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis. Haematologica 2007;92(7):978-981. ...
Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol 2006;6:940-952. ... At birth, perforin expression is readily detected in cord blood NK cells, but not T cells (Figure 5A,B). The lack of perforin- ... Histograms depict perforin expression in CD3−CD56+ NK cells. (B) Quantification of perforin staining by flow cytometry. Values ... Profiles show (A) CD56 versus perforin mAb staining of CD3+ T cells and (B) CD56 versus perforin mAb staining of CD3− cells. ...
Perforin is a 70 kD cytolytic protein that is expressed in the cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and ... Perforin is one of the major effector molecules used by cytotoxic T cells and NK cells to mediate targeted cell lysis. ... Mediates targeted cell lysis Cell Type T cells, NK cells Biology Area Cell Biology, Immunology, Innate Immunity, Neuroscience ... Perforin is a 70 kD cytolytic protein that is expressed in the cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and ...
Perforin is a 70 kD cytolytic protein that is expressed in the cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and ... Perforin is one of the major effector molecules used by cytotoxic T cells and NK cells to mediate targeted cell lysis. ... 1 reviews Alexa Fluor® 647 anti-human Perforin Antibody Rated 5 / 5 based on 1 reviews. , Review Me Product Citations ... Mediates targeted cell lysis Biology Area Cell Biology, Immunology, Innate Immunity, Neuroscience Molecular Family Cytokines/ ...
  • The absence of perforin-mediated cytotoxicity resulted in delayed clearance of Listeria from the spleen but not the liver after primary infection, overall susceptibility to Listeria however was not increased. (nih.gov)
  • These results indicate that the protective effect of CD8+ T cells against an intracellular bacterium mainly evident in secondary infection is mediated by a perforin-dependent pathway, presumably cytotoxicity, and less by other direct or indirect effector mechanisms. (nih.gov)
  • Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis. (nih.gov)
  • In particular, interleukin (IL)-2 or IL-12 suppressed tumor metastases largely via NKG2D ligand recognition and perforin-mediated cytotoxicity. (rupress.org)
  • T cell-mediated cytotoxicity can be triggered by cross-linking of TCR or Thy-1 surface proteins. (oup.com)
  • While the TCR-triggered signaling initiates both perforin- and Fas ligand (FasL)-Fas-mediated mechanisms of cytotoxicity, it was not clear which mechanism was utilized by Thy-1-triggered signals and which pathway of cytotoxicity was triggered at low levels of antigen expression. (oup.com)
  • It is shown that glycophosphatidylinositol-linked surface glycoprotein Thy-1 preferentially activates FasL-Fas- but not perforin-mediated cytotoxicity. (oup.com)
  • The data suggest that Thy-1-triggered Fas-mediated cytotoxicity is completely dependent on cross-talk between Thy-1 and TCR signals since mutations in TCR-CD3 complex molecules or inhibition of tyrosine kinases or calcineurin abolished or strongly inhibited Thy-1-triggered FasL-Fas-mediated cytotoxicity. (oup.com)
  • Lower concentrations of antigenic peptide or levels of cross-linking with anti-TCR-CD3 mAb are required to trigger Fas-mediated than perforin-mediated cytotoxicity by different cytotoxic T lymphocyte (CTL) lines and clones, and it is shown that cross-linking of Thy-1 is much less efficient in triggering accumulation of second messengers (intracellular Ca 2+ ) than cross-linking of TCR on CTL. (oup.com)
  • Taken together, these data reflect the possibility of differential activation of FasL and/or perforin pathways of cytotoxicity depending on the nature of activating stimuli and surface receptor. (oup.com)
  • The functions of these T cells were also investigated, leading in particular to the identification of Granzyme A and GZMB (then called CTLA-1 and CTLA-3) and the demonstration of their playing a role in the perforin-granzyme-based mechanism of T-cell-mediated cytotoxicity, and to the discovery of the second, Fas ligand/Fas receptor based pathway of cytotoxicity. (wikipedia.org)
  • Furthermore, rIL-18 administration augmented the cytotoxicity of liver lymphocytes harvested from perforin-deficient mice, whereas rIL-12 administration did not. (jimmunol.org)
  • Cytotoxicity of NK cells against tumor appears to be mediated by apoptosis induced by delivery of perforin/granzyme or Fas cross-inking by FasL ( 14 ). (jimmunol.org)
  • Inherited forms of HLH are caused by biallelic mutations in several effectors of granule-dependent lymphocyte-mediated cytotoxicity. (bloodjournal.org)
  • In order to determine whether the accumulation of partial genetic defects in lymphocyte-mediated cytotoxicity can contribute to the development of HLH, we generated mice that were doubly or triply heterozygous for mutations in HLH-associated genes, those coding for perforin, Rab27a, and syntaxin-11. (bloodjournal.org)
  • Cell‐mediated cytotoxicity is a critical response in maintaining and regulating good immune health by the highly selective removal of either virally infected or cancerous cells. (els.net)
  • T and NK cells mediated cytotoxicity is required for immune regulation and clearance of pathogen‐infected cells. (els.net)
  • Perforin, granzymes and death receptors are essential for cell‐mediated cytotoxicity. (els.net)
  • Schematic of perforin‐/granzyme‐mediated cytotoxicity. (els.net)
  • 2002) Sustained antibody‐dependent cell‐mediated cytotoxicity (ADCC) in SIV‐infected macaques correlates with delayed progression to AIDS. (els.net)
  • Golstein P and Griffiths GM (2018) An early history of T cell‐mediated cytotoxicity. (els.net)
  • 2006a) A simplified method for the rapid fluorometric assessment of antibody‐dependent cell‐mediated cytotoxicity. (els.net)
  • 2006b) An adenovirus‐based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody‐dependent cellular cytotoxicity against non‐subtype B HIV strains. (els.net)
  • Fas-based lymphocyte-mediated cytotoxicity against syngeneic activated lymphocytes : a regulatory pathway? (nii.ac.jp)
  • Perforin-1 contains a single copy of a C2 domain in its C terminus and plays a role in lymphocyte-mediated cytotoxicity [ PMID: 9058810 ]. (ebi.ac.uk)
  • We investigated the contribution of CD95 and PFN/GrB-mediated cytotoxicity to apoptotic and necrotic mechanisms of cell death in human renal cell carcinoma. (aacrjournals.org)
  • In addition, antibodies to Fas ligand blocked cytotoxic activity, suggesting that some of the antitumor cytotoxicity was Fas ligand mediated. (aacrjournals.org)
  • 8 ] described that virus-induced IFN-α and IFN-β are potent inducers of NK cell-mediated cytotoxicity and that NK cells are important contributors to innate defense against viral infections. (medsci.org)
  • We conclude that type I IFN can protect cancer cells from T cell-mediated cytotoxicity through regulation of Serpinb9 . (jci.org)
  • The major defense of the body against virus-infected and tumorigenic cells is cytotoxic T lymphocyte (CTL)-mediated cytotoxicity, which also plays a role in autoimmune diseases and transplant rejection. (scbt.com)
  • During CTL-mediated cytotoxicity, CTL granules containing perforin are exocytosed. (scbt.com)
  • It has been shown that abrogation of perforin function by Ca2+-complexing agents leads to decreased levels of necrosis, demonstrating that both necrosis and apoptosis contribute to CTL-mediated cytotoxicity. (scbt.com)
  • CD4 effectors generated in vitro can promote survival against a highly pathogenic influenza virus via an antibody-independent mechanism involving class II-restricted, perforin-mediated cytotoxicity. (unl.edu)
  • Granule -mediated exocytosis via perforin and granzyme B resulting in cytotoxicity (cell death). (dermnetnz.org)
  • These cells do possess Fc receptors for IgG and can kill target cells using antibody-dependent cell-mediated cytotoxicity. (thefreedictionary.com)
  • NCR (natural cytotoxicity receptors), a type of type 1 transmembrane proteins of the immunoglobulin superfamily, upon stimulation, mediate NK killing and release of IFNγ. (wikipedia.org)
  • Granule-exocytosis and Fas-mediated pathways of NK cell-mediated cytotoxicity. (kenyon.edu)
  • Entry and trafficking of granzyme B in target cells during granzyme B-perforin-mediated apoptosis. (semanticscholar.org)
  • Granzyme B binds to target cells mostly by charge and must be added at the same time as perforin to trigger apoptosis. (semanticscholar.org)
  • Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. (semanticscholar.org)
  • Since IL-18 enhances Fas ligand (FasL) expression on NK cell lines, the IL-18 antitumor effects could be mediated by FasL-induced cross-linking of Fas and subsequent tumor apoptosis. (jimmunol.org)
  • We hypothesized that IL-18 antitumor effects were mediated by Fas-FasL-induced apoptosis of tumor cells since IL-18 has been reported to enhance FasL expression on NK cell lines ( 8 ). (jimmunol.org)
  • Granzymes belong to the serine protease family and induce the death of target cells through caspase-dependent activation of apoptosis or in a caspase-independent manner by SET complex-mediated induction of single-strand DNA nicks ( 8 ). (pnas.org)
  • Although freshly isolated and cultured tumors expressed CD95 on their surface, they were resistant to CD95-mediated apoptosis. (aacrjournals.org)
  • The results indicated that CD8 + CTL-mediated apoptosis of target cells does not lead to the death of intracellular T. gondii tachyzoites. (asm.org)
  • [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. (kenyon.edu)
  • Administration of FUT-175 to perforin-deficient mice after RRV infection decreased the development of jaundice, minimized epithelial injury, and improved long-term survival. (nih.gov)
  • A potential role of CD8+ T cells by direct lysis of infected cells was investigated in perforin-deficient mice generated by homologous recombination. (nih.gov)
  • Protection against a secondary infection was drastically impaired in perforin-deficient mice. (nih.gov)
  • Adoptive transfer of immune spleen cells to recipients revealed that anti-Listeria protection by CD8+ T cells from perforin-deficient versus normal mice was about 10-fold reduced in livers and about 100-fold reduced in the spleen of recipients. (nih.gov)
  • CD4+ T cells from immune control and perforin-deficient mice conferred comparable protection. (nih.gov)
  • Here we examined the effects of adaptive and innate immune cells-cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells-that share the direct perforin-mediated cytotoxic pathway on outcome after cerebral ischemia in mice. (sigmaaldrich.com)
  • Adoptive CTL transfer from perforin knock-out or interferon-γ knock-out mice into Rag1 knock-out mice revealed that CTL neurotoxicity was mediated by perforin. (sigmaaldrich.com)
  • Accordingly, CTLs isolated from wild-type or interferon-γ knock-out but not from perforin knock-out mice induced neuronal cell death in vitro. (sigmaaldrich.com)
  • The therapeutic effect of IT-EP/IL12 was absent in perforin-deficient mice, indicating that tumor elimination occurred through conventional perforin/granzyme lysis by CTLs. (springer.com)
  • To investigate the mechanism(s) underlying CTL damage to the myocardium through activation of the Fas receptor (Fas/CD95/Apo-1) by the Fas ligand, we explored the interaction between peritoneal exudate CTLs (PELs), derived from perforin gene-knockout (P-/-) mice, and murine ventricular myocytes. (ovid.com)
  • Here, we document that the MuTuDC line was rejected in C57BL-6 mice by a CD4 T cell help-independent, perforin-mediated CD8 T cell response to the SV40LgT without pre-activation or co-injection of adjuvants. (duhnnae.com)
  • Remarkably, perforin-deficient knockout (PfKO) mice were shown to have accelerated mortality and increased fungal burden following a lethal or sublethal primary challenge. (jimmunol.org)
  • Interestingly, depletion of CD8 + T cells in PfKO mice caused a further increase in fungal burden and accelerated mortality, suggesting a perforin-independent role for CD8 + T cells. (jimmunol.org)
  • Here, we directly evaluated the role of perforin in controlling infection of a lineage I New York isolate of WNV in mice. (asm.org)
  • In the few perforin-deficient mice that survived initial challenge, viral persistence was observed in the CNS for several weeks. (asm.org)
  • CD8 + T cells required perforin to control WNV infection as adoptive transfer of WNV-primed wild-type but not perforin-deficient CD8 + T cells greatly reduced infection in the brain and spinal cord and enhanced survival of CD8-deficient mice. (asm.org)
  • Recent experiments with mice have provided insight into cell-mediated immune protection against WNV ( 9 , 60 ). (asm.org)
  • To elucidate the mechanisms of CD8 + T-cell-mediated control of WNV infection, prior studies were performed with genetically deficient mice and the lineage II Sarafend strain of WNV ( 64 ). (asm.org)
  • No change in mortality after infection was observed in mice that were genetically deficient in perforin, Fas, or Fas ligand. (asm.org)
  • Compared to wild-type mice, equivalent virus titers were observed on days 10 and 13 after infection in the brains of perforin-, Fas-, or Fas ligand-deficient mice. (asm.org)
  • concluded that perforin did not play a crucial role in the recovery from WNV infection, although higher viral burden and mortality were observed in perforin- × Fas ligand-deficient mice. (asm.org)
  • Angiostasis and tumor rejection were observed in perforin but not in IFN-γ-deficient mice. (aacrjournals.org)
  • Please note that the Kagi perforin knock-out mice may synthesize a truncated form of the protein which may be recognized by eBioOMAK-D. In IL-2 stimulated mouse splenocytes, NK cells (as determined by CD49b staining) contain perforin while CD8 cells contain little to none and can vary with culture conditions. (fishersci.com)
  • Decreased tumor surveillance in perforin-deficient mice. (uzh.ch)
  • Lethally infected mice given influenza virus-specific CD4 cells deficient in perforin showed greater weight loss and a slower time to recovery than mice given WT influenza virus-specific CD4 cells. (unl.edu)
  • The Fas ligand (FasL)/Fas and the perforin-granzyme cytotoxic pathways presumably play a central role in the development of hepatocellular injury in viral hepatitis. (nih.gov)
  • We have found that woodchuck lymphoid cells kill cell targets via both the FasL/Fas and the perforin death pathways. (nih.gov)
  • CD8 + T cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or Fas ligand-dependent pathways. (asm.org)
  • While Th1 CD4 T cells specific for the Mtb antigen ESAT-6 restrict in vivo Mtb growth, this inhibition is independent of IFNγ or TNF and does not require the perforin or FAS effector pathways. (prolekare.cz)
  • Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand-mediated pathways for target cell lysis. (ebi.ac.uk)
  • The antitumor effect of T cells is executed either through CD95 or Perforin (PFN)/Granzyme B (GrB) pathways. (aacrjournals.org)
  • Perforin dependence of natural killer cell-mediated tumor control in vivo. (uzh.ch)
  • To define the mechanisms used by cytotoxic cells, we investigated the role of perforin and granzymes in a neonatal mouse model of rotavirus (RRV)-induced biliary atresia. (nih.gov)
  • The studies reported here first address the role of perforin in mediating immunity to HC. (jimmunol.org)
  • Finding a Balance between Protection and Pathology: The Dual Role of Perforin in Human Disease. (mayo.edu)
  • Thomas H, Trapani J, Kay T. The role of perforin and granzymes in diabetes. (labome.org)
  • The pore forming, Ca 2+ -dependent protein, perforin, is essential for the function of cytotoxic lymphocytes, which are at the frontline of immune defence against pathogens and cancer. (monash.edu)
  • In the widely accepted model of granule-mediated killing by cytotoxic lymphocytes, granzyme B entry into the target cell is facilitated by the pore forming molecule, perforin. (semanticscholar.org)
  • Perforin is a 70 kD cytolytic protein that is expressed in the cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. (biolegend.com)
  • This invention concerns novel compositions and methods for for the protection of organs and cells from damage caused by activated lymphocytes, NK-cells and NK-like cells, more particularly compositions and methods for the protection of vascular endothelial cells from immune system-mediated damage. (freepatentsonline.com)
  • Perforin is one of the cytolytic mediators present in the cytoplasmic granules of cytotoxic T lymphocytes (CTL) and natural killer cells (NK). (fishersci.com)
  • Moreover, perforin is involved in immune defense against tumors and virus infections as mediated by cytotoxic lymphocytes. (fishersci.com)
  • Our laboratory studies the molecular mechanisms that control the migration of lymphocytes into sites of autoimmune-mediated tissue damage, such as pancreatic islets in type 1 diabetes and salivary glands in Sjogren s syndrome. (stanford.edu)
  • Perforin is primarily expressed in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, but has also been observed in an astrocyte population of the human brain. (scbt.com)
  • GvHD is mediated by alloreactive donor lymphocytes that reside in the graft and target nonmalignant host tissues. (wiley.com)
  • Perforin-dependent control of virally infected target cells by activated CD8 + T and natural killer (NK) cells occurs through the granzyme-dependent granule exocytosis pathway, which results in programmed cell death ( 15 , 50 , 54 ). (asm.org)
  • When a cytotoxic cell discovers any infected cell the content of the cytotoxic granules is released by receptor-mediated exocytosis. (wikipedia.org)
  • Therefore, perforin-mediated exocytosis is evidently necessary for NK-cell-mediated immune surveillance of senescent cells both in vitro and in vivo. (weizmann.ac.il)
  • 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. (kenyon.edu)
  • Cytotoxic cells release both perforin for cell-cell killing and cytokines in immunity and defence. (edu.au)
  • These data established an essential role for perforin in primary immunity systemic HC infection. (jimmunol.org)
  • Together, these data suggest that CD8 + T cells can mediate immunity to HC through both perforin-dependent and -independent mechanisms. (jimmunol.org)
  • MEMBRANE attack complex/perforin-like (MACPF) proteins comprise a large, functionally diverse superfamily of molecules that include the mammalian immunity proteins complement component 9 (C9) and perforin. (genetics.org)
  • A vaccine approach based on cell-mediated immunity that avoids some of these drawbacks is discussed here. (cdc.gov)
  • We review the literature on the role of CD4+ and CD8+ T cell-mediated immunity in influenza infection and the available data on the role of these responses in protection from highly pathogenic influenza infection. (cdc.gov)
  • Mouse models of influenza A virus pneumonia provide a well-developed experimental system to analyze T cell-mediated immunity. (cdc.gov)
  • In support of this finding is our discovery that key mediators of IFNγ- dependant immunity, inducible nitric oxide synthase and phagocyte oxidase, were not required for the early protective events mediated by adoptively transferred Th-1 skewed CD4 T cells. (prolekare.cz)
  • Our results are contrary to a dominant role for IFNγ production by effector CD4 in Mtb protection, but strongly support a requirement for Th1 mediated immunity to Mtb. (prolekare.cz)
  • Rotavirus infection of primary human pDCs provides a powerful experimental system for the study of mechanisms underlying pDC-mediated innate immunity to viral infection and reveals a potentially novel dsRNA-dependent pathway of IFNalpha induction. (stanford.edu)
  • Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma. (mayo.edu)
  • In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediates protective antiviral and anti-tumour immunity. (uzh.ch)
  • CD8 + T-cell-mediated immunity is one of the major protective mechanisms. (asm.org)
  • However, the underlying mechanisms of CD8 + cell-mediated protective immunity are not completely understood. (asm.org)
  • Alexa Fluor® 647 anti-human Perforin Antibody Rated 5 / 5 based on 1 reviews. (biolegend.com)
  • Antibody-mediated protection is therefore effective against homologous viral strains but inadequate against heterologous strains with serologically distinct coat proteins. (cdc.gov)
  • Description: The eBioOMAK-D antibody reacts with mouse perforin (pore-forming protein, pfp, Prf). (fishersci.com)
  • I am using Perforin 1 (F-1): sc-136994 monoclonal antibody to stain paraffin embedded tissue. (scbt.com)
  • NK cells can also use perforin to kill cells in the absence of antibody. (thefreedictionary.com)
  • Based on the increased expression of granzymes by perforin-deficient cytotoxic cells in long-term cytolytic assays, we found that the inhibition of granzymes by nafamostat mesilate (FUT-175) blocked cholangiocyte lysis. (nih.gov)
  • Perforin is one of the major effector molecules used by cytotoxic T cells and NK cells to mediate targeted cell lysis. (biolegend.com)
  • Calcium-dependent plasma membrane binding and cell lysis by perforin are mediated through its C2 domain: A critical role for aspartate residues 429, 435, 483, and 485 but not 491. (ebi.ac.uk)
  • 0.05), supporting a perforin/granzyme-mediated target of cell lysis. (aacrjournals.org)
  • The effect of CD8 + cytotoxic T-lymphocyte (CTL)-mediated lysis of host cells on the viability of intracellular T. gondii was investigated. (asm.org)
  • The present study was therefore designed to determine whether CD8 + CTL-mediated lysis of host cells is associated with the killing of intracellular T. gondii tachyzoites. (asm.org)
  • Perforin (PRF1) is essential for immune surveillance and studies report decreased perforin in chronic fatigue syndrome (CFS), an illness potentially associated with stress and/or infection. (cdc.gov)
  • Disease-causing mutations have been identified in genes encoding perforin ( PRF1 /FHL2), Munc13-4 ( UNC13D /FHL3), and syntaxin-11 ( STX11 /FHL4). (bloodjournal.org)
  • However, the loss of perforin in vivo delayed but did not prevent the obstruction of bile ducts. (nih.gov)
  • Perforin is a pore-forming protein that facilitates the entry of cytotoxic serine proteases, such as granzymes, into target cells by forming transmembrane channels in target cell membranes. (scbt.com)
  • RRV-infected hepatic NK and CD8 T cells increased the expression of perforin and injured cholangiocytes in short-term culture in a perforin-dependent fashion. (nih.gov)
  • Perforin and granzymes have complementary roles mediating epithelial injury by NK and CD8 T cells. (nih.gov)
  • B ) Median Fluorescence Intensity (MFI) histograms showing perforin expression by NK and CD8 T cells after saline or RRV challenge. (nih.gov)
  • To recognize the potential contribution of FasL and perforin-based cell killing in hepadnaviral infection, we adopted a cytotoxic assay using murine Fas+ P815 and human Fas- K562 cells as targets. (nih.gov)
  • The involvement of the perforin pathway was confirmed by treatment of K562 cells with colchicine to inhibit the microtubule-dependent perforin release. (nih.gov)
  • Comparative analysis showed that peripheral lymphoid cells from acute WHV hepatitis, but not those from chronic WHV infection, are more cytotoxic and that this increase seems to be entirely due to activation of perforin-mediated killing. (nih.gov)
  • The data indicate that acute infection in woodchucks is associated with the augmented capacity of lymphoid cells to elicit perforin-dependent killing, but in chronic infection, independent of the severity of liver disease and duration of chronicity, these cells have the same or lower cytotoxic potential as PBMC from healthy controls. (nih.gov)
  • Non-Fas-mediated killing of P815 and K562 target cells by peripheral blood mononuclear cells (PBMC) from woodchucks with newly acquired and chronic woodchuck hepatitis virus (WHV) infections and from healthy controls. (nih.gov)
  • b) The Fas-negative K562 cells were used intact (untreated) or tested in the presence of the perforin release inhibitor colchicine. (nih.gov)
  • Antigen dependently activated cluster of differentiation 8-positive T cells cause perforin-mediated neurotoxicity in experimental stroke. (sigmaaldrich.com)
  • This is explained by the lesser intensity of Thy-1-mediated signaling in T cells. (oup.com)
  • While perforin is released from granules fusing at immune synapses, cytokines are trafficked separately and released circumferentially in NK cells. (edu.au)
  • Vol 5: Large T Antigen-Specific Cytotoxic T Cells Protect Against Dendritic Cell Tumors through Perforin-Mediated Mechanisms Independent of CD4 T Cell Help. (duhnnae.com)
  • The antitumor effect of IL-18 appears to be primarily mediated by asialo GM1 + cells. (jimmunol.org)
  • IL-18 mediates other important functions, including enhancement of NK cell activity and stimulation of proliferation of activated T cells ( 1 , 2 , 3 , 4 , 5 ). (jimmunol.org)
  • These results suggested that rIL-18 antitumor effects were mediated primarily by asialo GM1 + cells in an IFN-γ-independent fashion. (jimmunol.org)
  • IL-12 enhances the cytolytic activity of NK-like cells primarily by inducing expression of perforin ( 15 , 16 ). (jimmunol.org)
  • Thus, it was of interest to determine how NK cells mediate IL-18-induced antitumor effects. (jimmunol.org)
  • Effector mechanisms that could mediate intracellular killing of HC include cytokines such as IFN-γ and TNF-α and/or direct cytolytic activity by T and NK cells. (jimmunol.org)
  • For example, complement component 9 and perforin function to directly form pores in the membrane of Gram-negative pathogens or virally infected/transformed cells, respectively. (genetics.org)
  • Conversely, activation of NK cells, mediated by recognition of their ligands by activation receptors, triggers a complex and highly regulated response leading to death of a target cell ( 3 - 5 ). (pnas.org)
  • This idea has gained support from the discovery of HLA-G, a nonclassical MHC class I molecule expressed by human trophoblasts that is thought to potentially protect these cells from NK cell-mediated attack ( 13 ). (pnas.org)
  • In infants, NK cells are the predominant perforin-containing cell type. (bloodjournal.org)
  • Granules are exocytosed from the effector cell(s) and internalised into the target cells via perforin‐mediated pores. (els.net)
  • Analogous results were obtained when wild-type or perforin-deficient CD8 + T cells were added to congenic primary cortical neuron cultures. (asm.org)
  • Taken together, our data suggest that despite the risk of immunopathogenesis, CD8 + T cells use a perforin-dependent mechanism to clear WNV from infected neurons. (asm.org)
  • CD8 + T cells could control neuronal infection through several independent mechanisms, including a class I major histocompatibility complex (MHC)-restricted and perforin-dependent cell death pathway or a Fas ligand-dependent cell death pathway, or through the production of antiviral cytokines such as gamma interferon (IFN-γ) or tumor necrosis factor alpha. (asm.org)
  • In contrast, T cells, which mediate cellular immune responses, can target internal proteins common to heterologous viral strains. (cdc.gov)
  • There may be at least two paths to protect beta cells from T cell-mediated death. (frontiersin.org)
  • Mutations in perforin-1 lead to familial hemophagocytic lymphohistiocytosis type 2, a rare, rapidly fatal, autosomal recessive immune disorder characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines [ PMID: 10583959 ]. (ebi.ac.uk)
  • In contrast, we demonstrated that tumor cell death mediated by PFN/GrB can be achieved in the absence of functional caspase activity and is accompanied by a dramatic accumulation of nonapoptotic necrotic cells. (aacrjournals.org)
  • Herein, we demonstrate that depsipeptide promotes tumor-specific T-cell-mediated killing of B16/F10 murine melanoma cells. (nih.gov)
  • Furthermore, we found that depsipeptide increased levels of perforin in T cells. (nih.gov)
  • 16. A method for reducing immune-mediated damage to cells, tissue or organs comprising: contacting a cell, tissue or organ with an immunoprotecting amount of a composition comprising brefeldin. (freepatentsonline.com)
  • 19. A method for reducing immune-mediated damage to cells, tissue or organs comprising: contacting a cell, tissue or organ with an expressible nucleic acid encoding an Hsp47-related immunoprotective polypeptide. (freepatentsonline.com)
  • In contrast stimulation of splenocytes with anti-CD3/CD28 antibodies does result in an increase of perforin on both NK cells and CD8 cells. (fishersci.com)
  • eBioOMAK-D is also crossreactive to human perforin and co-stains CD56 positive cells in PBMC. (fishersci.com)
  • This enhanced response depended on CD8 + T cells and was mediated by enhanced susceptibility to T cell-mediated killing. (jci.org)
  • The regulatory T-cells secrete perforin and granzymes, and suppression is associated with the specific killing of APCs presenting antigen to effector T-cells. (diabetesjournals.org)
  • A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3. (uzh.ch)
  • Multifunctional CD4 Cells Expressing Gamma Interferon and Perforin Med" by Deborah M. Brown, Sarah Lee et al. (unl.edu)
  • These cells expressed granzyme B (GrB) and required perforin to lyse peptide-pulsed targets. (unl.edu)
  • 2012). Moreover, in the mouse model of liver fibrosis, perforin knockout leads to more severe fibrosis and accumulation of senescent activated stellate cells in the liver. (weizmann.ac.il)
  • 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. (thefreedictionary.com)
  • 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. (kenyon.edu)
  • Perforin is involved in the killing function by CTLs and NKs and has an important role in the immune response against tumors and virus infections. (fishersci.com)
  • Killing of the target cell is achieved by formation of an immune synapse and localized secretion of lytic granules containing perforin and granzymes. (pnas.org)
  • Injury to neurons after West Nile virus (WNV) infection is believed to occur because of viral and host immune-mediated effects. (asm.org)
  • A genetic deficiency of perforin molecules resulted in higher viral burden in the CNS and increased mortality after WNV infection. (asm.org)
  • Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. (medsci.org)
  • The first approach is to control or regulate effector T cell responses, and the second is to enhance beta cell survival or resistance to T cell-mediated death. (frontiersin.org)
  • In contrast to mutations leading to loss of perforin and Munc13-4 function, it is unclear how syntaxin-11 loss-of-function mutations contribute to disease. (bloodjournal.org)
  • Expression of perforin and Granzyme B do not always correlate (as discussed above in the CD8 population of IL-2 stimulated splenocytes). (fishersci.com)
  • Killing is achieved by localized secretion of lytic granules containing granzymes and perforin at the cell-cell contact site, known as the immune synapse ( 6 , 7 ). (pnas.org)
  • This molecule is found in cytotoxic granules, along with other cytotoxic molecules, such as granzymes and perforin. (wikipedia.org)
  • We conclude that a Fas-based perforin-independent mechanism of CTL action can account for the immunopathology seen in the allotransplanted heart, myocarditis, and dilated cardiomyopathy. (ovid.com)
  • At least 50% of pathological missense mutations in perforin result in protein misfolding and retention in the endoplasmic reticulum. (monash.edu)
  • Using a variety of biochemical assays that assess protein stability and acquisition of complex glycosylation, we demonstrated that the binding of Ca 2+ to the C2 domain stabilises perforin and regulates its export from the endoplasmic reticulum to the secretory granules. (monash.edu)
  • As perforin is a thermo-labile protein, we hypothesised that by altering its C2 domain it may be possible to improve protein stability. (monash.edu)
  • Furthermore, by introducing the T431D mutation into A90V perforin, a pathogenic mutation, which results in protein misfolding, we corrected the A90V folding defect and completely restored perforin's cytotoxic function. (monash.edu)
  • Pore-forming members of the membrane attack complex/perforin-like (MACPF) protein superfamily perform well-characterized roles as mammalian immune effectors. (genetics.org)
  • Actin polymerization at the leading edge of the cell is facilitated by Wiskott-Aldrich syndrome protein (WASp)-mediated activation of the Arp2/3 complex ( 12 ). (pnas.org)
  • Originally identified as WASp binding protein ( 15 ), WIP was later demonstrated to actively participate in actin rearrangements through retardation of WASp-mediated ( 16 ) and enhancement of cortactin-mediated actin polymerization ( 17 ). (pnas.org)
  • Furthermore, stimulated Perforin Knock-out (developed by Walsh) splenocytes do not stain with eBioOMAK-D nor is any protein detectable by western blotting with eBioOMAK-D as well as other anti-mouse perforin antibodies. (fishersci.com)
  • Expression of Granzyme B is dramatically increased (more than 10,00 fold based on mRNA estimates and significantly at the protein level based on western blotting and flow analysis) compared to a minimal increase (10-100 fold) in perforin mRNA and protein with IL-2 stimulation. (fishersci.com)
  • It is thought that tumor rejection by CD8 + T-cell effectors is primarily mediated by direct killing. (aacrjournals.org)
  • Specifically, cell-mediated responses typically focus on peptides from internal influenza proteins, which are far less susceptible to antigenic variation. (cdc.gov)
  • Perforin is one of the major cytolytic proteins of cytolytic granules. (fishersci.com)
  • The T cell death knell: immune-mediated tumor death in renal cell carcinoma. (semanticscholar.org)
  • Perforin forms pores in the cell membrane, allowing granzymes to enter the target cell. (pnas.org)
  • We discuss the advantages of developing a vaccine based on cell-mediated immune responses toward highly pathogenic influenza virus and potential problems arising from immune pressure. (cdc.gov)
  • Perforin, unlike GNLY, binds preferably to cholesterol rich membranes and permeabilizes the infected cell which allows the entry of GNLY and granzymes. (wikipedia.org)
  • These findings reveal that STAT5-directed therapies may have negative effects: In addition to impairing NK-cell-mediated tumor surveillance, they may even promote tumor growth by enhancing angiogenesis. (aacrjournals.org)
  • We show that the new signal interceptors targeting the JAK-STAT5 pathway may have dangerous side effects that must be taken into account in clinical trials: inhibiting JAK-STAT5 has the potential to promote tumor growth by enhancing NK-cell-mediated angiogenesis. (aacrjournals.org)
  • The function of perforin-1 is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes [ PMID: 15576364 ]. (ebi.ac.uk)
  • These data demonstrate that CTL may overcome tumor resistance to apoptotic modes of cell death via GrB-mediated cellular necrosis, supporting the development of immunotherapeutic strategies for the treatment of RCC. (aacrjournals.org)
  • C, TDB-mediated T-cell activation was measured using flow cytometry. (aacrjournals.org)
  • E, TDB mediated killing of ovarian cancer cell lines measured by flow cytometry, EC 50 are indicated. (aacrjournals.org)
  • The mechanisms underlying the CD8 + T-cell-mediated clearance of the intracellular pathogen Toxoplasma gondii are, however, not completely understood. (asm.org)
  • Interleukin-6 attenuates insulin-mediated increases in endothelial cell signaling but augments skeletal muscle insulin action via differential effects on tumor necrosis factor-alpha expression. (labome.org)
  • Human perforin gene variation is geographically distributed. (mayo.edu)
  • In infants with biliary atresia, hepatic Granzymes A and B mRNA, but not Perforin, increased at the time of portoenterostomy. (nih.gov)
  • All NK receptors are germ-line encoded and independent of RAG-mediated recombination ( 8 ). (frontiersin.org)
  • Perforin is a cytolytic mediator and is stored in and released by cytoplasmic granules. (fishersci.com)
  • The two BSAPs contain a membrane attack complex/perforin (MACPF) domain but share very little sequence similarity. (asm.org)
  • Mutant perforin displayed markedly enhanced thermal stability and lytic function, despite its trafficking from the endoplasmic reticulum remaining unchanged. (monash.edu)
  • Induction of the lytic pathway, however, required a second signal that was provided by perforin or adenovirus (Ad2). (semanticscholar.org)
  • Cytokines implicated include perforin/granzyme, granulysin, Fas-L and tumour necrosis factor alpha ( TNF α). (dermnetnz.org)
  • The perforin pathway, however, appears to be the predominant cytolytic pathway mediating IL-12 antitumor effects. (jimmunol.org)
  • Our results suggest that a significant decrease in immune function within aged tumor-bearing hosts can result in diminished tumor rejection mediated by an immunotherapy. (springermedizin.de)
  • Using indirect immunofluorescence and also direct visualization of fluorescein isothiocyanate (FITC)-conjugated granzyme B, we demonstrate internalization in the absence of perforin. (semanticscholar.org)
  • The C2 domain mediates calcium-dependent binding to lipid membranes. (abcam.com)
  • Therefore, there is a direct relationship between the replication efficiencies of different rotavirus strains in MEFs and strain-related variations in NSP1-mediated antagonism of the type I IFN response. (stanford.edu)