NK cells Flashcards
where are NK cells found
the bloodstream
what sort of response do NK cells inflict
anti viral/anti-tumourgenic cytotoxic response
are NK cells antigen specific
no, they recognise generic features of abnormal cells such as loss of MHCI
give 4 examples of NK activating receptors
NKG2D, Cd16, 2B4 and NKp46
on which cells are nk activating receptors upregulated
virally infected or cancerous cells
what is the result of ligand binding to NK activating receptors
cell killing by granule release
what are some of the ligands for NKG2D activating receptor
UL16 binding proteins, ULBP1-4 and MHCI related molecules MCA and MICB
under what circumstances is NKG2D upregulated
cellular stress eg oxidative stress, heat shock and genotoxic stress
which virus target UL16 ligand of NKG2D receptor
human cytomegalovirus and karposi’s sarcoma associated herpes virus K5 protein
what type of ligand does the CD16 NK activating receptor bind
fc region of IgG antibodies- acts as an intermediate between adaptive and innate
what type of response does IgG binding to CD16 activating receptor elicit
antibody-dependent cellular cytotoxicity
which cells do NKp46 and 2B4 recognise
cells infected with common viral pathogens
what is the ligand for NKp46 activating receptor
influenza virus aglycoprotein haemaglutnin
which ligand does activating receptor 2B4 bind
CD48 expressed by B-lymphocytes. expression of this ligand in B cells is activated by EBV infection
which ligand do many NK inhibitory receptors bind
MHCI
describe the missing/altered self hypothesis
MHCI is down regulated by viruses and cancer cells. when it is not expressed on the cell surface the inhibitory receptor cannot bind thus leading to no inhibition signal and thus activation
how do CD94/NKG2A act as inhibitory receptors
normally bind HLA-E but loss of MHCI molecules results in the loss of signal peptides which results in the loss of HLA-E expression and so inhibitory signals are stopped
describe the signalling cascade of CD16 and NKp46
ITAM domains in the cytoplasmic region of the receptors propagate signals via syk kinases
describe the signalling cascade of inhibitory receptors in the presence of ligand
binding iduces phosphorylation of the tyrosine in the ITIM domain and recruitment of phosphates which dephosphorylate intracellular targets, inhibiting NK activation
what do granules released by NK cells contain
perforin and granzymes
how do granules only kill abnormal cells
secretion is polarised towards the contact point in the lytic immunological synapse
describe the 3 stages of granule exocytosis
- immunological snaps is formed. around it you het receptor signalling and cytoskeletal actin thinning so granules can dock and fuse with the membrane. adhesion molecules form a ring around the synapse and signalling molecules cluster at the centre of the synapses.
- the microtubule organising centre (MTOC) shifts towards the synapse so granules re polarised towards the synapse
- granules fuse with the PM and release cytotoxic molecules
how is granule release disrupted in griselli’s syndrome
a mutation in Rab27a prevents granule docking
how is granule release disrupted in FHL4
mutations in syntaxin 11 (a snare protein) prevents fusion of granules with the membrane
