Killer Cells, Natural: 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.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.Killer Cells, Lymphokine-Activated: Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.Cytotoxicity, Immunologic: 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.Calbindin 2: A calbindin protein that is differentially expressed in distinct populations of NEURONS throughout the vertebrate and invertebrate NERVOUS SYSTEM, and modulates intrinsic neuronal excitability and influences LONG-TERM POTENTIATION. It is also found in LUNG, TESTIS, OVARY, KIDNEY, and BREAST, and is expressed in many tumor types found in these tissues. It is often used as an immunohistochemical marker for MESOTHELIOMA.Receptors, Natural Killer Cell: 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.6-Cyano-7-nitroquinoxaline-2,3-dione: A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.Inhibitory Postsynaptic Potentials: Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Parvalbumins: Low molecular weight, calcium binding muscle proteins. Their physiological function is possibly related to the contractile process.2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.T-Lymphocytes: 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.Pyramidal Cells: Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Receptors, KIR: A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells.Receptors, Antigen, T-Cell, alpha-beta: T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.Killer Factors, Yeast: Protein factors released from one species of YEAST that are selectively toxic to another species of yeast.Lymphocyte Activation: 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.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Pre-B Cell Receptors: Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.Cytokine-Induced Killer Cells: Mononuclear leukocytes that have been expanded in CELL CULTURE and activated with CYTOKINES such as INTERLEUKIN-2 to produce large numbers of highly cytotoxic cells.Nerve Net: A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction.Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.Whale, Killer: The species Orcinus orca, in the family Delphinidae, characterized by its black and white coloration, and huge triangular dorsal fin. It is the largest member of the DOLPHINS and derives its name from the fact that it is a fearsome predator.Natural Killer T-Cells: A specialized subset of T-LYMPHOCYTES that exhibit features of INNATE IMMUNITY similar to that of NATURAL KILLER CELLS. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D ANTIGEN.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Flow Cytometry: 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.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.NK Cell Lectin-Like Receptor Subfamily C: A subclass of NK cell lectin-like receptors that associates with members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY D to form heterodimeric receptors for HLA-E antigen.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.NK Cell Lectin-Like Receptor Subfamily D: A subclass of NK cell lectin-like receptors that associates with a variety of members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY C to form heterodimeric receptors for HLA-E antigen.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Mice, Inbred C57BLAntigens, Differentiation, T-Lymphocyte: Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Models, Neurological: Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Interferon-gamma: 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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Receptors, Antigen, T-Cell, gamma-delta: T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).Receptors, KIR2DL3: A KIR receptor that has specificity for HLA-C ANTIGEN. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL2 RECEPTORS and the KIR2DL3 RECEPTORS.Receptors, KIR3DL1: A KIR receptor that has specificity for HLA-B ANTIGENS. It is an inhibitory receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.Spleen: An encapsulated lymphatic organ through which venous blood filters.HLA-C Antigens: Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.NK Cell Lectin-Like Receptor Subfamily K: An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Receptors, KIR2DL1: A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL2 RECEPTOR and the KIR2DL3 RECEPTORS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.Interleukin-15: Cytokine that stimulates the proliferation of T-LYMPHOCYTES and shares biological activities with IL-2. IL-15 also can induce proliferation and differentiation of B-LYMPHOCYTES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Receptors, NK Cell Lectin-Like: Structurally-related receptors that are typically found on NATURAL KILLER CELLS. They are considered lectin-like proteins in that they share sequence homology with the carbohydrate binding domains of C-TYPE LECTINS. They differ from classical C-type lectins, however, in that they appear to lack CALCIUM-binding domains.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Antigens, CD8: Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.Perforin: 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.Receptors, KIR2DL4: A KIR receptor that has specificity for HLA-G antigen. It contains D0 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.Cytotoxicity Tests, Immunologic: The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.Mice, Inbred BALB CNK Cell Lectin-Like Receptor Subfamily A: An inhibitory subclass of NK cell lectin-like receptors that interacts with CLASS I MAJOR HISTOCOMPATIBILITY ANTIGENS and prevents the activation of NK CELLS.Antibody-Dependent Cell Cytotoxicity: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Granzymes: 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.CD4-Positive T-Lymphocytes: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells.Receptors, KIR2DL2: A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL1 RECEPTORS and the KIR2DL3 RECEPTORS.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.CD8-Positive T-Lymphocytes: 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.NK Cell Lectin-Like Receptor Subfamily B: A subclass of NK cell lectin-like receptors that includes both inhibitory and stimulatory members.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.T-Lymphocytes, Cytotoxic: 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.Antigens, CD56: 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.Genes, T-Cell Receptor beta: DNA sequences encoding the beta chain of the T-cell receptor. The genomic organization of the TcR beta genes is essentially the same in all species and is similar to the organization of Ig genes.Immunity, Innate: 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.Receptor-CD3 Complex, Antigen, T-Cell: Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.Lymphocytes: 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.Immunity, Cellular: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Antigens, Ly: A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.Models, Immunological: Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Pore Forming Cytotoxic Proteins: 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.Natural Cytotoxicity Triggering Receptor 3: A 30 kDa stimulatory receptor found on resting and activated NATURAL KILLER CELLS.Complementarity Determining Regions: Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).Antigens, CD1d: A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.K562 Cells: An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.Genes, T-Cell Receptor alpha: DNA sequences encoding the alpha chain of the T-cell receptor. The genomic organization of the TcR alpha genes is essentially the same in all species and is similar to the organization of Ig genes.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mice, Knockout: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Galactosylceramides: Cerebrosides which contain as their polar head group a galactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in beta-galactosidase, is the cause of galactosylceramide lipidosis or globoid cell leukodystrophy.Immunological Synapses: The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.H-2 Antigens: The major group of transplantation antigens in the mouse.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Lymphocyte Count: The number of LYMPHOCYTES per unit volume of BLOOD.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Antigens, CD4: 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.Antigens, CD1: Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.Immunotherapy, Adoptive: Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)Receptors, Interleukin-2: Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.Cell SeparationAntigens, CD2: Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.Natural Cytotoxicity Triggering Receptor 1: A 46-kD stimulatory receptor found on resting and activated NATURAL KILLER CELLS. It has specificity for VIRAL HEMAGGLUTININS that are expressed on infected cells.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Receptors, Fc: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.Receptors, KIR3DS1: An activating KIR receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a short cytoplasmic tail.Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Genes, T-Cell Receptor: DNA sequences, in cells of the T-lymphocyte lineage, that code for T-cell receptors. The TcR genes are formed by somatic rearrangement (see GENE REARRANGEMENT, T-LYMPHOCYTE and its children) of germline gene segments, and resemble Ig genes in their mechanisms of diversity generation and expression.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.Immunologic Surveillance: The theory that T-cells monitor cell surfaces and detect structural changes in the plasma membrane and/or surface antigens of virally or neoplastically transformed cells.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Lysosomal-Associated Membrane Protein 1: 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.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Receptors, KIR3DL2: A KIR receptor that has specificity for HLA-A3 ANTIGEN. It is an inhibitory receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.Monocytes, Activated Killer: Monocytes made cytotoxic by IN VITRO incubation with CYTOKINES, especially INTERFERON-GAMMA. The cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.Mycotoxins: Toxic compounds produced by FUNGI.Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.Lymphoma, T-Cell: A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.Antigens, CD57: Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.G(M1) Ganglioside: A specific monosialoganglioside that accumulates abnormally within the nervous system due to a deficiency of GM1-b-galactosidase, resulting in GM1 gangliosidosis.Self Tolerance: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.HLA-B Antigens: Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Gene Rearrangement, delta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Histocompatibility Antigens Class II: Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Immunoglobulin Light Chains, Surrogate: An immunolglobulin light chain-like protein composed of an IMMUNOGLOBULIN VARIABLE REGION-like peptide (such as light chain like lambda5 peptide) and an IMMUNOGLOBULIN CONSTANT REGION-like peptide (such as Vpreb1 peptide). Surrogate light chains associate with MU IMMUNOGLOBULIN HEAVY CHAINS in place of a conventional immunoglobulin light chains to form pre-B cell receptors.Epitopes: Sites on an antigen that interact with specific antibodies.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Antigens, CD45: High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.Biological Products: Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesRNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Cell Line, Tumor: A cell line derived from cultured tumor cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Muromegalovirus: A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, causing infection involving several organs in mice and rats. Murid herpesvirus is the type species.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.B-Lymphocyte Subsets: A classification of B-lymphocytes based on structurally or functionally different populations of cells.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Mice, Inbred CBAAdoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Degranulation: 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.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Interleukin-18: A cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK CELLS and CYTOTOXIC T-LYMPHOCYTES, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Leukocyte Count: The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... and phosphotyrosine-independent inhibitory signaling by a killer cell Ig-like receptor cytoplasmic domain in human NK cells". J ... Selvakumar A, Steffens U, Dupont B (1997). "Polymorphism and domain variability of human killer cell inhibitory receptors". ... "Human diversity in killer cell inhibitory receptor genes". Immunity. 7 (6): 753-63. doi:10.1016/S1074-7613(00)80394-5. PMID ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... Fan QR, Long EO, Wiley DC (2000). "Cobalt-mediated dimerization of the human natural killer cell inhibitory receptor". J. Biol ... 1997). "Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors". J. Immunol. 159 (8): 3875-82. ... 2001). "Recognition of HLA-Cw4 but not HLA-Cw6 by the NK cell receptor killer cell Ig-like receptor two-domain short tail ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... "The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors ... 2000). "Diversity of the p70 killer cell inhibitory receptor (KIR3DL) family members in a single individual". Mol. Cells. 10 (1 ... of the activation-induced cell death inhibition mediated by a p70 inhibitory killer cell Ig-like receptor in Jurkat T cells". J ...
Killer-cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... "Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors". Nature. 389 (6646): 96 ... Fan QR, Long EO, Wiley DC (May 2001). "Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 ... Fan QR, Long EO, Wiley DC (2001). "Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 ...
Fan QR, Long EO, Wiley DC (May 2001). "Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 ... MHC Class I molecules, like HLA-C, are expressed in nearly all cells, and present small peptides to the immune system which ... "N-linked carbohydrate on human leukocyte antigen-C and recognition by natural killer cell inhibitory receptors". Hum. Immunol. ... "Kinetics of interaction of HLA-C ligands with natural killer cell inhibitory receptors". Immunity. 9 (3): 337-44. doi:10.1016/ ...
"NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor". The Journal of Experimental Medicine. 185 ( ... on the surface of natural killer cells interacts with Human Leukocyte Antigen (HLA)-E on target cells. Natural killer (NK) ... "Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for ... of differentiation and a receptor that is involved in cell signaling and is expressed on the surface of natural killer cells in ...
... is a receptor for natural killer cells. There are 7 NKG2 types: A, B, C, D, E, F and H. NKG2D is an activating receptor on the ... NK cell surface. NKG2A dimerizes with CD94 to make an inhibitory receptor (CD94/NKG2). IPH2201 is a monoclonal antibody ...
2004). "Structure of the saccharide-binding domain of the human natural killer cell inhibitory receptor p75/AIRM1". Acta ... a novel member of the sialoadhesin family that functions as an inhibitory receptor in human natural killer cells". J. Exp. Med ... "Characterization of inhibitory signaling motifs of the natural killer cell receptor Siglec-7: attenuated recruitment of ... expressed by human natural killer cells and monocytes". J Biol Chem. 274 (48): 34089-95. doi:10.1074/jbc.274.48.34089. PMID ...
"Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors". Proceedings of the National Academy ... Natural killer (NK) cells are lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. Several ... "Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors". Nature Immunology. 4 ( ... Killer cell lectin-like receptor subfamily B, member 1, also known as NK1.1,KLRB1, NKR-P1A or CD161 (cluster of differentiation ...
2004). "Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors". Proc. Natl. Acad. Sci. U.S. ... 2004). "The LLT1 receptor induces IFN-gamma production by human natural killer cells". Mol. Immunol. 40 (16): 1157-63. doi: ... This gene encodes a member of the natural killer cell receptor C-type lectin family. The encoded protein inhibits osteoclast ... 2003). "Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors". Nat. Immunol. ...
... is also known as Natural Killer Cell Receptor 2B4 This gene encodes a cell surface receptor expressed on natural killer cells ( ... Watzl C, Stebbins CC, Long EO (2000). "NK cell inhibitory receptors prevent tyrosine phosphorylation of the activation receptor ... natural killer cell receptor 2B4". Online Mendelian Inheritance in Man (OMIM) 605554 "CD244 molecule, natural killer cell ... Kumaresan PR, Mathew PA (2000). "Structure of the human natural killer cell receptor 2B4 gene and identification of a novel ...
... are a class of natural killer cell receptor. Ly-49 proteins are a diverse set of C-type lectins that are expressed on NK cells ... Upon binding ligands, most Ly-49 receptors will deliver an inhibitory signal, preventing killing of the target cell. In the ... Ly-49 receptors or killer cell lectin-like receptor subfamily A (KLRA), ... Hao L, Klein J, Nei M (February 2006). "Heterogeneous but conserved natural killer receptor gene complexes in four major orders ...
NK cells possess two types of surface receptors: activating receptors and inhibitory receptors, including killer-cell ... Natural killer cell activation is determined by the balance of inhibitory and activating receptor stimulation. For example, if ... Natural Body Guards: How Your Killer Cells Get Motivated. Livescience.com. Retrieved on 2007-10-20. Natural Killer Cells at the ... which is a ligand for NK cell inhibitory receptor NKG2A) and HLA-G (which is a ligand for NK cell inhibitory receptor KIR2DL4) ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... "Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor ... "Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158)". Immunol Rev. 181: ... 2002). "Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations". Genes ...
... natural killer cells, T and B cells) and the signalling properties of each receptor. All of the Fcγ receptors (FcγR) belong to ... Coggeshall KM (Jun 1998). "Inhibitory signaling by B cell Fc gamma RIIb". Current Opinion in Immunology. 10 (3): 306-12. doi: ... Trinchieri G, Valiante N (1993). "Receptors for the Fc fragment of IgG on natural killer cells". Natural Immunity. 12 (4-5): ... FcγRIII receptors on the surface of natural killer (NK) cells stimulate the NK cells to release cytotoxic molecules from their ...
Vivier, E; Anfossi N (2004). "Inhibitory NK-cell receptors on T cells. Witness of the past, actors of the future". Nat Rev ... Natural killer T cells should not be confused with natural killer cells. The term "NK T cells" was first used in mice to define ... Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer ... semi-invariant T-cell receptor and NK cell markers. NKT cells are a subset of T cells that coexpress an αβ T-cell receptor, but ...
... are receptors expressed on the plasmatic membrane of Natural Killer cells (NK cells). KARs work with inhibitory Killer-cell ... and Killer Inhibition Receptors (KIRs). Both type of receptors act together to activate or not activate the Natural Killer cell ... natural killer cells can discharge their function properly through two types of receptors: Killer Activation Receptor (KAR) ... Killer Activation Receptors) and the NK KIRs (meaning: Killer Inhibitory Receptors). Such receptors have a broad binding ...
2004). "KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity". Blood. 104 (9): 2858-66. ... 2007). "The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells". Blood ... 2004). "Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is ... Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, ...
Because natural killer cells target virally infected host cells and tumor cells, inhibitory KIR receptors are important in ... Natural killer cell cytolysis of target cells and cytokine production is controlled by a balance of inhibitory and activating ... KIR3DS1 NK cell receptors bind directly to the MHC class I molecules on the surface of target cells. Human killer cell ... Natural killer (NK) cells are a type of lymphocyte cell involved in the innate immune system's response to viral infection and ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... "The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors ... 2000). "Diversity of the p70 killer cell inhibitory receptor (KIR3DL) family members in a single individual". Mol. Cells. 10 (1 ... 1996). "Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer ...
Han Y., Zhang M., Li N., et al. KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity. ( ... The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. (англ.) // ... Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is ... Chen C. H., Floyd H., Olson N. E., et al. Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation ...
... including NK cells, T cells, and B cells. Inhibitory receptors regulate the immune response to prevent lysis of cells ... on natural killer cells". J. Clin. Immunol. 23 (2): 141-5. doi:10.1023/A:1022580929226. PMID 12757266. Verbrugge A, de Ruiter T ... is differentially expressed during human B cell differentiation and inhibits B cell receptor-mediated signaling". Eur. J. ... "Leukocyte-associated Ig-like receptor-1 functions as an inhibitory receptor on cytotoxic T cells". J. Immunol. 162 (10): 5800-4 ...
2005). "Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells ... 2003). "The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes ... 2003). "Selective cross-talk among natural cytotoxicity receptors in human natural killer cells". Eur. J. Immunol. 33 (5): 1235 ... a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the ...
"Probing the cis interactions of the inhibitory receptor Siglec-7 with alpha2,8-disialylated ligands on natural killer cells and ... Sialic acid is a key determinate of oligosaccharide structures involved in cell-cell communication, cell-substrate interaction ...
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based ... Killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1 is a protein that in humans is encoded by the ... Levinson RD, Okada AA, Ashouri E, Keino H, Rajalingam R (February 2010). "Killer cell immunoglobulin-like receptor gene-cluster ...
Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis. Immunology Letters. March 2017 ... Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer ... Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2. JCI insight. 2017-08-17, ... Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine ...
Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I ... Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.. Fan QR1, Long EO, Wiley DC. ... We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to ... Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously ...
This result demonstrated that the increased NKG2D expression and imbalance between inhibitory receptors of dNK cells and HLA-G ... Levels of inhibitory receptors KIR2DL4 and ILT-2, their ligand HLA-G, and activating receptor NKG2D in human decidua, and NKG2A ... In this study, we used human dNK cells co-cultured with human extravillous cytotrophoblast (EVT) cells following YFP-Toxoplasma ... However, if Toxoplasma gondii (T. gondii) infection induced abnormal pregnancy was related to dNK cells changes is not clear. ...
NK cells directly identify and lyse cancer cells. Nascent transformed cells elicit NK cell activation and are eliminated. ... NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors ... NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors ... NK cells directly identify and lyse cancer cells. Nascent transformed cells elicit NK cell activation and are eliminated. ...
... biological response modifiers and the family of cell adhesion-promoting molecules. ... Antiviral Treatment Alters the Frequency of Activating and Inhibitory Receptor-Expressing Natural Killer Cells in Chronic ... "Antiviral Treatment Alters the Frequency of Activating and Inhibitory Receptor-Expressing Natural Killer Cells in Chronic ...
Receptor dynamics shape NK cell function. Natural killer (NK) cells are a subset of innate lymphoid cells that target virally ... Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor ... Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor ... Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor ...
Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible ... Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I ... T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen- ... Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. Nature. 402:623-631. ...
Killer Cells, Natural, Lectins, Lectins, C-Type, Leukocytes, Mononuclear, Membrane Glycoproteins, NK Cell Lectin-Like Receptor ... of HLA epitopes and killer inhibitory receptor expression to the functional alloreactive specificity of natural killer cells. ... of HLA epitopes and killer inhibitory receptor expression to the functional alloreactive specificity of natural killer cells, ... of HLA epitopes and killer inhibitory receptor expression to the functional alloreactive specificity of natural killer cells. ...
keywords = "Co-inhibitory signal, Glucocorticoid-induced TNF receptor, Invariant NKT cell",. author = "Shuming Chen and Ndhlovu ... Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells. In: European Journal of ... Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells. European Journal of ... Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells. / Chen, Shuming; Ndhlovu ...
Leveraging the power of high-parameter cell sorting and single-cell multi-omics to profile intra-tumoral immune cells in a ... Evaluating expression patterns of multiple inhibitory and stimulatory receptors on natural killer cells using flow cytometry ... Evaluating expression patterns of multiple inhibitory and stimulatory receptors on natural killer cells using flow cytometry 9 ... Evaluating expression patterns of multiple inhibitory and stimulatory receptors on natural killer cells using flow cytometry. 9 ...
... inhibitory NKRs block cytolysis upon recognition of markers of healthy self cells. Most Lys49 receptors are inhibitory; some ... human myeloid inhibitory C-type lectin-like receptor (MICL), mast cell-associated functional antigen (MAFA), killer cell lectin ... Natural killer cell receptor-like, C-type lectin-like domain (IPR033992). Short name: NKR-like_CTLD ... This entry represents a C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs), including ...
Burshtyn DN, Shin J, Stebbins C, Long EO (2000) Adhesion to target cells is. disrupted by the killer cell inhibitory receptor. ... Fan QR, Long EO, Wiley DC (2001) Crystal structure of the human natural. killer cell inhibitory receptor KIR2DL1-HLA-Cw4 ... Natural killer cell signaling pathways. Science. 306: 1517-1519.. 2. Lanier LL (2008) Up on the tightrope: natural killer cell ... role of natural killer cell receptors. Nat Rev Immunol 9: 568-580.. 6. Gleimer M, Parham P (2003) Stress management: MHC class ...
... class I ligands and play a key role in the regulation and activation of NK cells. The functional importance o... ... Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) ... Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. *Townsley E ... Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory ...
... inhibit the cytotoxic activity of natural killer (NK) cells by recruitment of the tyrosine phosphatase SHP-1 to immunoreceptor ... Killer cell immunoglobulin-like receptors (KIR) inhibit the cytotoxic activity of natural killer (NK) cells by recruitment of ... Killer Cells, Natural / cytology, drug effects, physiology*. Lymphocyte Function-Associated Antigen-1 / immunology, physiology ... Cell Adhesion / drug effects, physiology*. Cell Line. Dose-Response Relationship, Drug. Flow Cytometry. Gene Expression. HLA-C ...
Zinc bound to the killer cell-inhibitory receptor modulates the negative signal in human NK cells. J. Immunol. 1998. 161: 1299- ... Natural killer cell receptors in cattle: a bovine killer cell immunoglobulin-like receptor multigene family contains members ... Natural killer cell receptors in cattle: a bovine killer cell immunoglobulin-like receptor multigene family contains members ... Fan, Q. R., Long, E. O. and Wiley, D. C., Cobalt-mediated dimerization of the human natural killer cell inhibitory receptor. J ...
Natural killer cells might adapt their inhibitory receptors for memory Megan A. Cooper ... Critical role for the Ly49 family of class I MHC receptors in adaptive natural killer cell responses *From the Cover ... Isolation and characterization of NY-ESO-1-specific T cell receptors restricted on various MHC molecules Michael T. Bethune, ... Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells, and promote their ...
Indeed, NK cells express at the cell surface HLA-specific inhibitory receptors (including killer immunoglobulinlike receptors [ ... Murine NKG2d and CD94 are clustered within the natural killer complex and are expressed independently in natural killer cells. ... a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med. 1999;190:1505- ... Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses. J Virol. 1995;69:1328- ...
KIRs are human natural killer (NK) cell receptors for MHC class I molecules. Most inhibit the activity of NK cells thus ... Killer cell immunoglobulin like receptor 2DL3 antibody. *KKA3 antibody. *Natural killer cell inhibitory receptor antibody ... Two main families of receptors for HLA class I have been discovered on human NK cells: Killer cell Immunoglobulin-like ... The KIR receptors are an extremely diverse family of receptors. In addition to receptors for HLA, NK cells also express pattern ...
Evaluating Expression Patterns of Multiple Inhibitory and Stimulatory Receptors on Natural Killer Cells. Speaker:. Mirko ... Cell Biology. Title. PDF/AV. Speaker(s). Date. Enabling a Deeper Understanding of What is on, in, and Made by the Cell. Robert ... Stem Cells. Title. PDF/AV. Speaker(s). Date. Simplifying Stem Cell Characterization and Analysis with A Personal Flow Cytometer ... Deciphering the Cell Surface Proteome of Stem Cells Using Antibody Libraries. Christian Carson. 04/2012. ...
NK cells possess two types of surface receptors: activating receptors and inhibitory receptors, including killer-cell ... 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 ... Natural killer cell activation is determined by the balance of inhibitory and activating receptor stimulation. For example, if ...
NK cells use two groups of receptors, inhibitory and activating (6). Inhibitory NK receptors prevent NK activation upon ... Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu. Rev. Immunol. 19:197-223. ... Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK ... Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK ...
Natural cytotoxicity receptors (NCR); Natural killer cell group (NKG) Natural Killer (NK) cells are a major... ... Killer immunoglobulin-like receptors (KIR); Killer lectin-like receptors (KLR); ... Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex. Nat Immunol. 2001;2:452-60. ... Killer immunoglobulin-like receptors (KIR); Killer lectin-like receptors (KLR); Natural cytotoxicity receptors (NCR); Natural ...
Killer Cell Immunoglobulin Like Receptor, Two Ig Domains And Long Cytoplasmic Tail 3, including: function, proteins, disorders ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... natural killer cell immunoglobulin-like inhibitory receptor for HLA-C antigens,2DL3,58kDa *KIR2DL3 ... Natural Killer Cell Receptors: Human Target Cell - NK Cell Ligand-Receptor Interactions. Natural Killer Cell Receptors: Human ...
... This article or section may require restructuring to meet Wikipedias .Please discuss this issue on the ... Activating and inhibitory receptors Aside from the Fc receptor, Natural Killer cells express a variety of receptors that serve ... 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 ...
Cell Movement. *IV. Natural Killer Cells Express Seven Transmembrane Chemokine Receptors. *V. Natural Killer Cells Express ... These receptors are either inhibitory or activating. Inhibitory receptors contain the immune receptor tyrosine-based inhibitory ... Single Transmembrane-Spanning Domain Receptors in Natural Killer Cells. *VII. Sojourn of Human Natural Killer Cells into ... Human natural killer (NK) cells are important cells of the innate immune system. These cells perform two prominent functions: ...
Expression of killer cell inhibitory receptors on human uterine natural killer cells. Eur J Immunol. 1997;27: 979-983. ... Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med. 1989;320: 1731-1735. ... 2 It was suggested that such diversity of NK receptors enables the killing of infected cells by at least a subset of NK cells.3 ... The killer immunoglobulin-like receptor (KIR) family recognizes class I major histocompatibility complex (MHC) molecules and ...
  • However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
  • Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. (frontiersin.org)
  • First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
  • In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition. (bloodjournal.org)
  • 6 Importantly, NCRs play a crucial role in NK-mediated recognition and killing of most target cells because monoclonal antibody (mAb)-mediated disruption of the NCR/ligand(s) interactions may abrogate the NK-mediated killing of tumor-transformed cells of autologous, allogeneic, or (in the case of NKp46) xenogeneic origin. (bloodjournal.org)
  • NK cells provide rapid responses to virus-infected cells, acting at around 3 days after infection , and respond to tumor formation. (wikipedia.org)
  • NK cells were first discovered by their cytotoxic potency against tumor cells (Kiessling et al. (springer.com)
  • The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in human. (springer.com)
  • Especially, in natural killer (NK) cells, which lack a gene arrangement system to recognize foreign antigens, the inhibitory receptors for MHCIs recognize and eliminate cells that fail to express MHCIs, due to viral infections or tumor formation. (frontiersin.org)
  • Unlicensed NK cells are basically hyporesponsive, but seem to have important roles in tumor elimination and viral clearance. (frontiersin.org)
  • Natural killer cells are able to kill tumor and virus-infected cells ( 1 ). (jimmunol.org)
  • In the present study, we examined T cells expressing CD161 in the peripheral blood, the tumor tissue and in malignant effusions of patients with several types of malignancies. (aacrjournals.org)
  • Expression of CD161 in CD4 + or CD8 + (lacking CD56) T cells isolated from peripheral blood ( n = 61), tumor specimens ( n = 8), and malignant effusions ( n = 37) of cancer patients was examined using four-color flow cytometry. (aacrjournals.org)
  • Both types of NK receptors, namely killer cell immunoglobulin-like receptors and C-type lectin receptors, have been detected on peripheral T lymphocytes ( 1 - 6 ), as well as on tumor infiltrating lymphocytes in melanoma ( 7 - 9 ), renal cell carcinoma ( 10 , 11 ), and cervical carcinoma patients ( 12 ). (aacrjournals.org)
  • In contrast, CD161 + T cells (mostly CD8 + ), not skewed to Va24 TCR, were found to accumulate in human liver and were able to exhibit strong cytotoxicity against various tumor cell lines ( 16 ). (aacrjournals.org)
  • Over one half of T cells (either CD4 or CD8), isolated from epithelial and lamina propria layers of duodenum and colon, express CD161 and are capable of producing IFN-γ and tumor necrosis factor-α, but not IL-4, upon activation with phorbol 12-myristate 13-acetate and ionomycin ( 17 ). (aacrjournals.org)
  • stimulates natural killer cell cytolysis and release of tumor necrosis factor. (thefreedictionary.com)
  • Natural killer (NK) cells have the ability to recognize and eliminate tumor cells, making them ideal candidates for tumor immunotherapy , . (plos.org)
  • Gamma delta T-cell response to cellular stress signals expressed by tumor cells makes them promising candidates for cancer immunotherapy. (aacrjournals.org)
  • Because of their ability to recognize different stress signals provided by tumor cells, γδ T cells also hold an alternative promise in cancer therapy. (aacrjournals.org)
  • Phosphoantigens are produced at high levels by tumor cells and have been successfully used to generate clinical scale quantities of Vγ9Vδ2 T cells in vitro and to expand them in vivo in active vaccination-type trials. (aacrjournals.org)
  • Despite increasing evidence of their role in tumor surveillance, Vδ2 neg γδ T cells have been largely neglected in cancer cell therapy because of the limited knowledge about the antigens they recognize, which have restricted their specific and large-scale expansion for clinical purposes. (aacrjournals.org)
  • These aAPCs are based on K562 tumor cells genetically modified to express CD64, CD86, CD137L, and a membrane-bound form of IL15. (aacrjournals.org)
  • Activation of γδ T cells purified from PBMCs or cord blood with aAPCs induces clinical-grade expansion of polyclonal γδ T-cell lines with broad specificity toward cancer cells, and capacity to reduce tumor biomass and increase survival in an ovarian cancer xenograft model. (aacrjournals.org)
  • In this study, using the immunohistochemistry technique it was verified the expression of HLA-E in 122 biopsies of thyroid neoplams and 21 biopsies of goiter representing the nonneoplastic lesions Furthermore, the expression of HLA-E was correlated with the percentage of NK cells in the tumor microenvironment. (usp.br)
  • Expression of Ocil/Clr-b on mouse tumor cell lines inhibits NK cell-mediated killing. (jove.com)
  • The natural killer (NK) cell is a critical part of anti-tumor immunity. (medsci.org)
  • Surgical resection is one of the primary treatments for solid tumors, but the dissemination of tumor cells into the blood and lymphatic systems inevitably occurs during surgery. (medsci.org)
  • Whether the residual tumor cells lead to clinical deterioration depends on the balance between perioperative factors promoting cancer survival and growth and the host's anti-tumor defenses [ 1 ]. (medsci.org)
  • This is primarily due to difficulties in purifying tumor cells from surrounding normal tissues. (aacrjournals.org)
  • Also, in the case of neuroblastoma, most available data were obtained by the assessment of NK-mediated killing of various tumor cell lines. (aacrjournals.org)
  • The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. (aacrjournals.org)
  • To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment, using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8). (aacrjournals.org)
  • Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). (aacrjournals.org)
  • When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor or FLT3 ligand) and costimulation by agonistic α-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. (aacrjournals.org)
  • Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
  • However, CD56 dim NK cells can produce cytokines, specifically IFN-γ, after cell triggering via NKp46 of NKp30 activating receptors or after stimulation with combinations of IL-2, IL-12, and IL-15 ( 7 ). (frontiersin.org)
  • The cytokines Interferon play a crucial role in NK-cell activation. (bionity.com)
  • NK cells are activated in response to interferons or macrophage -derived cytokines. (bionity.com)
  • Natural Killers cell's are activated in response interferons or macrophages derived cytokines. (sooperarticles.com)
  • A small subset of T cells coexpressing CD161 and an invariant Va24JaQ T-cell receptor (TCR) α chain, paired predominantly with Vβ11, is defined as analogous to murine NK1.1 + T cells and possesses immunoregulatory features through production of both Th1 and Th2 cytokines. (aacrjournals.org)
  • 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. (slideshare.net)
  • Compared to HC, AS patients had a significantly increased CD160 expression on peripheral NK cells and concomitantly decreased peripheral NK cell number, and increased CD160 expression was positively related to the levels of serum lipids and IFN-γ, TNF-α and IL-6 inflammation cytokines, which all are risk factors for atherogenesis, and inversely correlated with peripheral NK cell number. (biomedcentral.com)
  • Furthermore, engagement of CD160 receptor on NK cells from AS patients triggers a significantly increased production of inflammation cytokines and subsequent NK cell apoptosis, and blockade of TNF-α prevented the increased apoptosis of NK cells from AS patients after CD160 engagement, indicating a critical role of TNF-α in mediating NK cell loss by CD160 engagement. (biomedcentral.com)
  • During the acute stage of KD, activation of vascular endothelial cells and increased serum levels of proinflammatory cytokines are involved in the occurrence of inflamed and injured vessels (15,16). (docme.ru)
  • To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. (stanford.edu)
  • Here we performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells.We used cytometry by time-of-flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)-2, IL-15 or a combination of IL- 12/IL-15/IL-18. (stanford.edu)
  • CyTOF provides insights into the effects of cytokines on the phenotype and function of NK cells, which could inform future research efforts and approaches to NK cell immunotherapy. (stanford.edu)
  • In addition, CMV alters the function of cytokines and their receptors, and interacts with complement factors. (prolekare.cz)
  • Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. (warwick.ac.uk)
  • A small fraction of KIR3DL1*004 folds correctly and leaves the endoplasmic reticulum to be expressed on the surface of primary NK and transfected NKL cells, in a form that can be triggered to inhibit NK cell activation and secretion of IFN-γ. (jimmunol.org)
  • This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit MHC class I exprssion or alter its conformation. (genome.jp)
  • Natural killer (NK) cells are a subset of innate lymphoid cells that target virally infected and malignant cells. (sciencemag.org)
  • NK cells constitute the third major subset of lymphocytes and kill tumors and virus-infected cells without prior sensitization ( 1 ). (rupress.org)
  • NK Cells are not a subset of the T lymphocyte family. (wikipedia.org)
  • 2 It was suggested that such diversity of NK receptors enables the killing of infected cells by at least a subset of NK cells. (bloodjournal.org)
  • Moreover, uterine natural killer (uNK) cells are a distinct, specialised NK subset, endowed with immunoregulatory and angiogenic properties, necessary for local (spiral) arteries development. (els.net)
  • The NKp44 induction involved mainly a particular NK cell subset expressing the CD56 marker at high density, CD56 bright . (asm.org)
  • Conclusions -These results show that KIR expression is restricted to CD56 + /CD3 − true NK cell lymphomas originating from the nose, gut, and skin, as well as in a subset of extranodal T cell lymphomas originating from the small intestine, which possessed a cytotoxic phenotype. (bmj.com)
  • So far, much attention has been given to the predominant subset of circulating γδ T cells, the Vγ9Vδ2 T cells, which are strongly activated by nonpeptide phosphorylated metabolites of isoprenoid biosynthesis pathway (called phosphoantigens). (aacrjournals.org)
  • Besides Vγ9Vδ2 T cells, all the other γδ T cells (collectively called Vδ2 neg γδ T cells) populate many epithelial tissues where they represent an important component of intraepithelial lymphocytes, so likely the main subset of human γδ T cells in the whole body, and an important first-line defense against diverse host assaults. (aacrjournals.org)
  • 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. (jci.org)
  • 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. (jci.org)
  • In the active phase of DSS-induced colitis mouse, the frequency of NKG2A+ T cells was significantly decreased in the peripheral blood and increased in the intestine, suggesting the mobilisation of this T cell subset to the sites of inflammation. (ovid.com)
  • Our study demonstrates the frequency of NKG2A+ T cells is decreased in both PBMCs and LPMCs in UC patients, implicating this T cell subset as a potential therapeutic target for UC. (ovid.com)
  • found that the activating receptor NKp46 and the inhibitory receptor Ly49A exhibited dynamic movements in the plasma membrane that differed between educated and hyporesponsive NK cells. (sciencemag.org)
  • Interfering with receptor dynamics reduced signaling by NKp46, indicating that the dynamic movements of these receptors are likely important determinants of NK cell responsiveness. (sciencemag.org)
  • We developed a refined version of the image mean square displacement (iMSD) method (called iMSD carpet analysis) and used it in combination with single-particle tracking to characterize the dynamics of the activating receptor NKp46 and the inhibitory receptor Ly49A on resting educated versus hyporesponsive murine NK cells. (sciencemag.org)
  • The faster and more dynamic movement of NKp46 in educated NK cells may facilitate a swifter response to interactions with target cells. (sciencemag.org)
  • 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. (wikipedia.org)
  • NKp46 is the only NCR involved in human NK-mediated killing of murine target cells. (nih.gov)
  • Analysis in this study of KIR3DL1*004 membrane traffic in NK cells shows this allotype is largely misfolded but stably retained in the endoplasmic reticulum, where it binds to the chaperone calreticulin and does not induce the unfolded protein response. (jimmunol.org)
  • Several positions of polymorphism modulate KIR3DL1 abundance at the cell surface, differences that do not necessarily correlate with the potency of allotype function. (jimmunol.org)
  • Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. (gopubmed.org)
  • High short-term mortality of ALCF was associated with NK cell, especially related to KIR3DL1 and FASL ( P NK = 0.036, P KIR3DL1 = 0.0265, P FasL = 0.0008). (scirp.org)
  • Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation [ PMID: 15123656 ]. (ebi.ac.uk)
  • In the murine thymus, FcγRII and FcγRIII are expressed on early thymocyte precursors, which can differentiate in both T and NK cells. (begellhouse.com)
  • The binding of NKp44-Fc to the BCG surface was confirmed with immunogold labeling using transmission electron microscopy, suggesting the presence of a putative ligand(s) for human NKp44 on the BCG cell wall. (asm.org)
  • NKp44 detects cell-free mycobacteria and HIVgp41 [ 8 ]. (hindawi.com)
  • To our knowledge, this is the first report that describes the increased cytotoxicity of NK cells following the acquisition of CARs via trogocytosis. (plos.org)
  • In the early stage of acute HBV infection, the cytotoxicity of NK cells increases, IL-2 levels rise, both play the clearance of the virus. (scirp.org)
  • In a first part of this study, we compared functions of NK cells in subjects carrying HLA-B -21Mor 21T using interleukin-2 (IL-2)-activated NK cells and leukemic cells from patients with acute myeloid leukemia (AML). (gu.se)
  • PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with acute myeloid leukemia in remission. (clinicaltrials.gov)
  • The encoded protein has been identified as an anchor for tyrosine phosphatase SHP-1, and may induce cell death in myeloid leukemias. (origene.com)
  • Phase II Study of Haploidentical Natural Killer Cell Infusion for Treatment of Relapsed or Persistent Myeloid Malignancies Following Allogeneic Hematopoietic Cell Transplantation. (gopubmed.org)
  • Either disrupting the actin cytoskeleton or adding cholesterol to the cells prohibited activating signaling, suggesting that the dynamics of receptor movements within the cell membrane are critical for the proper activation of NK cells. (sciencemag.org)
  • Coligation of mAb B23.1 bound to gp49B1 and IgE fixed to the high-affinity Fc receptor for IgE on the surface of mouse bone marrow-derived mast cells inhibited exocytosis in a dose-related manner, as defined by the release of the secretory granule constituent beta-hexosaminidase, as well as the generation of the membrane-derived lipid mediator, leukotriene C4. (pnas.org)