Natural killer cell mediated cytotoxicity
Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. 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. The mechanism of NK cell killing is the same as that used by the cytotoxic T cells generated in an adaptive immune response; cytotoxic granules are released onto the surface of the bound target cell, and the effector proteins they contain penetrate the cell membrane and induce programmed cell death.
Organismal Systems; Immune system
Natural killer cell mediated cytotoxicity
killer cell immunoglobulin-like receptor 3DL
killer cell immunoglobulin-like receptor 2DL1/2/3
killer cell immunoglobulin-like receptor 2DL5
killer cell lectin-like receptor subfamily C1
killer cell lectin-like receptor subfamily D member 1
tyrosine-protein phosphatase non-receptor type 6 [EC:
tyrosine-protein phosphatase non-receptor type 11 [EC:
intercellular adhesion molecule 1
intercellular adhesion molecule 2
integrin alpha L
integrin beta 2
focal adhesion kinase 2 [EC:
guanine nucleotide exchange factor VAV
Ras-related C3 botulinum toxin substrate 1
Ras-related C3 botulinum toxin substrate 2
Ras-related C3 botulinum toxin substrate 3
p21-activated kinase 1 [EC:
mitogen-activated protein kinase kinase 1 [EC:
mitogen-activated protein kinase kinase 2 [EC:
mitogen-activated protein kinase 1/3 [EC:
tumor necrosis factor superfamily, member 2
granulocyte-macrophage colony-stimulating factor
killer cell immunoglobulin-like receptor 2DS
killer cell lectin-like receptor subfamily C2/3
natural cytotoxicity triggering receptor 2
TYRO protein tyrosine kinase binding protein
lymphocyte cell-specific protein tyrosine kinase [EC:
Influenza A virus hemagglutinin
immunoglobulin heavy chain
low affinity immunoglobulin gamma Fc receptor III
natural cytotoxicity triggering receptor 1
natural cytotoxicity triggering receptor 3
high affinity immunoglobulin epsilon receptor subunit gamma
CD3Z antigen, zeta polypeptide
tyrosine-protein kinase ZAP-70 [EC:
spleen tyrosine kinase [EC:
lymphocyte cytosolic protein 2
linker for activation of T cells
phosphatidylinositol phospholipase C, gamma-1 [EC:
phosphatidylinositol phospholipase C, gamma-2 [EC:
SH3-domain binding protein 2
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:
phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
tyrosine-protein kinase Fyn [EC:
SHC-transforming protein 1
SHC-transforming protein 2
SHC-transforming protein 3
SHC-transforming protein 4
growth factor receptor-bound protein 2
son of sevenless
A-Raf proto-oncogene serine/threonine-protein kinase [EC:
B-Raf proto-oncogene serine/threonine-protein kinase [EC:
RAF proto-oncogene serine/threonine-protein kinase [EC:
MHC class I-related protein
UL16 binding protein
killer cell lectin-like receptor subfamily K member 1
hematopoietic cell signal transducer
natural killer cell receptor 2B4
serine/threonine-protein phosphatase 2B catalytic subunit [EC:
serine/threonine-protein phosphatase 2B regulatory subunit
nuclear factor of activated T-cells, cytoplasmic 1
nuclear factor of activated T-cells, cytoplasmic 2
classical protein kinase C alpha type [EC:
classical protein kinase C beta type [EC:
classical protein kinase C gamma type [EC:
SH2 domain-containing protein 1B
SH2 domain-containing protein 1A
interferon gamma receptor 1
interferon gamma receptor 2
interferon receptor 1
interferon receptor 2
tumor necrosis factor ligand superfamily member 10
tumor necrosis factor receptor superfamily member 10A/B
tumor necrosis factor ligand superfamily member 6
tumor necrosis factor receptor superfamily member 6
granzyme B [EC:
caspase 3 [EC:
BH3 interacting domain death agonist
killer cell lectin-like receptor subfamily A member 1
killer cell lectin-like receptor subfamily A member 3
killer cell lectin-like receptor subfamily A member 7
killer cell lectin-like receptor subfamily A member 9
killer cell lectin-like receptor subfamily A member 4
killer cell lectin-like receptor subfamily A member 8
retinoic acid early transcript 1
Chiesa S, Tomasello E, Vivier E, Vely F.
Coordination of activating and inhibitory signals in natural killer cells.
Mol Immunol 42:477-84 (2005)
Insights into seven and single transmembrane-spanning domain receptors and their signaling pathways in human natural killer cells.
Pharmacol Rev 57:339-57 (2005)
Vivier E, Nunes JA, Vely F.
Natural killer cell signaling pathways.
Science 306:1517-9 (2004)
Colucci F, Di Santo JP, Leibson PJ.
Natural killer cell activation in mice and men: different triggers for similar weapons?
Nat Immunol 3:807-13 (2002)
Signaling for cytotoxicity.
Nat Immunol 1:372-4 (2000)
Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, Takeda K, van Dommelen SL, Degli-Esposti MA, Hayakawa Y.
Activation of NK cell cytotoxicity.
Mol Immunol 42:501-10 (2005)
Djeu JY, Jiang K, Wei S.
A view to a kill: signals triggering cytotoxicity.
Clin Cancer Res 8:636-40 (2002)
Smyth MJ, Takeda K, Hayakawa Y, Peschon JJ, van den Brink MR, Yagita H.
Nature's TRAIL--on a path to cancer immunotherapy.
Immunity 18:1-6 (2003)
Fine-tuning NK cell responses: it's a family affair.
Nat Immunol 6:961-2 (2005)
Bonnema JD, Leibson PJ.
Signal transduction during NK cell activation.
Chem Immunol 64:28-43 (1996)
Tassi I, Presti R, Kim S, Yokoyama WM, Gilfillan S, Colonna M.
Phospholipase C-gamma 2 is a critical signaling mediator for murine NK cell activating receptors.
J Immunol 175:749-54 (2005)
Rao A, Luo C, Hogan PG.
Transcription factors of the NFAT family: regulation and function.
Annu Rev Immunol 15:707-47 (1997)
Wu J, Lanier LL.
Natural killer cells and cancer.
Adv Cancer Res 90:127-56 (2003)
Cerwenka A, Lanier LL.
Natural killer cells, viruses and cancer.
Nat Rev Immunol 1:41-9 (2001)
Blott EJ, Griffiths GM.
Nat Rev Mol Cell Biol 3:122-31 (2002)
The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal.
Nat Rev Immunol 3:361-70 (2003)
Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.
Granzyme B: a natural born killer.
Immunol Rev 193:31-8 (2003)
Liu D, Xu L, Yang F, Li D, Gong F, Xu T.
Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition.
Proc Natl Acad Sci U S A 102:123-7 (2005)
Trotta R, Puorro KA, Paroli M, Azzoni L, Abebe B, Eisenlohr LC, Perussia B.
Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases.
J Immunol 161:6648-56 (1998)
Jevremovic D, Billadeau DD, Schoon RA, Dick CJ, Leibson PJ.
Regulation of NK cell-mediated cytotoxicity by the adaptor protein 3BP2.
J Immunol 166:7219-28 (2001)
MAPK signaling pathway
Calcium signaling pathway
Cytokine-cytokine receptor interaction
JAK-STAT signaling pathway
KEGG ORTHOLOGY (93)
All databases (93)
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