Natural Killer Cells Flashcards
Size, disitribution, function.
Large cells. Make of 5-10% of lymphocytes, can lyse cells
Marker for human NK cells
CD16
NK cells doesn’t have…
TCR
Two NK cell functions
Indirect: secretion of IFNγ, Direct: secretion of cytolytic granules.
Primary cytokine capable of activating NK cells
IL-12
Stages in cytotoxic killing:
1: formation of immune synapse, 2: cytoskeletal rearrangement, 3: lytic granules deployed, 3: target cell killed
Mode of killing by NK cells
Apoptosis
Perforin
Makes holes in cell membrane
Granzymes
Activates caspases
Triggers of NK cell killing:
Antibody mediated, recognition of stressed ligands, recognition of lack of MHC class I.
Antibody-mediated
Recognition of antibody by CD16 (FcγIIIA)
NK inhibitory receptors
Bind to MHC I
Stress induced ligands
MHC-like molecules, binding activating receptors on NK cells
NKG2A
Lectin-like. Inhibitory. Binds eg. MHCI, HLA-E
NKG2D
Lectin-like. Binds eg. MHC I - like molecules. Stress proteins. MIC-A, B
Variegated expression
Any one NK cells expresses a different subset of receptors.
HLA-E
Present peptide cleaved from other MHC molecules. Is a marker for amount of MHCI expressed at any point.
Inhibitory signal
Receptor binding causes ITIM phosphorylation. Recruits SHP-1. SHP-1 dephosphorylates VAV1.
VAV1
Key intermediate in NK cell activation.
Activating signal
ITAM phosphorylation recruits DAP10. DAP10 feeds into activation of PI3K. Activation of VAV1
KIRs
Bind to allele specific HLA-A, B, C. Kan be activating or inhibitory.
Allele specificity
Lower for A, B and C HLA. Most receptors are specific for C. But some are for A and B as well
NK cell education
Immature NK cells bind with inhibitory KIR to self-HLA-C. Activating receptors activate them self as to cancel out inhibitory signal. Any signal disturbing this balance will be regarded as aberrant.
Need for NK cells
Good for virus resistance
MCMV-cells
Express m157, which binds activating receptor Ly49H. Mice without are more susceptible.
Memory?
Some indication of a kind of memory.