Exam 3: Natural Killer Cells (NK) Flashcards
T/F NK cells are part of innate immunity and the first response to a viral infection (2-3 days after infection)
T
What induces anti-viral response
IFN alpha and IFN beta
Signal transduction through TLRs- Type 1 IFN
TLR3 (intracellular TLR) can bind viral nucleic acids. TLR3 associated with adaptor molecule TRIF to induce Type 1 IFN response by activating the transcription factor IRF-3 and IRF-7 to drive anti-viral immune responses (IFN-beta)
Signaling through cytosolic recptors
viral RNAs can be recognized by RIG-1 or MDA-5 or STING (CYTOSOLIC RECEPTORS)to also induce expression of IFN thru IRF3 and IRF7
what are some cytosolic responses used in anti-viral response?
RIG-1
MDA-5
STING
What 2 genes do IFN activate to inhibit protein synthesis?
2-5(A) synthase –> break down poly A +mRNA (degrades Poly (A) tail
PKR –> phosphorylates eIF-2 to be non-functional (affects all protein synthesis)
What unique receptor do NK cells have?
Inhibitory receptors
How do inhibitory receptors on NK cells work?
binding of inhibitory receptor to MHC Class 1 leads to no killing in NORMAL CELLS
BUT IN VIRUS-INFECTED CELLS
binding of only ligang and NK activating receptor leads to killing since there is no self binding thru MHC Class 1
How do NK cells recognize self cells?
Presence of MHC Class I –> SELF
Which receptors are involved in NK recognition of self
CD94:NKG2 heterodimer
KIR
T/F Virus-infection leads to underexpression of MHC I
T
What motif is associated with KIR?
ITIM
What is the sequence of an ITIM?
I/VXYXXL
What do ITIMS recruit?
Phosphatases (SHP1)
What ITAM receptor is associated with NK cells
DAP12
T/F ITIMS antagonize ITAMS
T
What are some ITIM receptors?
Ly49a
NKG2A:CD94 (heterodimer)
T/F NK cells have receptors that lead to killing, inhibition, and cytokine production
T
What NK receptors lead to killing?
DAP12 (ITAM) coupled to NKG2D
What NK receptors lead to inhibition (ITIMS)?
Ly49a
CD94:NKG2a heterodimer
What NK receptors lead to cytokine production?
DAP10 coupled with NKG2D
What does NKG2D do?
ITAM that binds MIC-A, MIC-B, or RAET1 that are induced by stress
What does Ly49a bind?
Carbohydrates
What are some common forms of cellular stress?
- Viral hijack of cell protein synthesis machinery
- Hypoxia (tumor cells that reach their max growth and lose ability to get oxygen from blood vessels –> signal for MICa, MIC-b)
T/F Viral infection and tumor cells induces NK killing by decreased MHC Class I expression
T; viral proteins overuse protein synthesis to the point where less MHC I is expressed; remember tumor cells induce more stress via hypoxia
What is ADCC?
Antibody dependent cellular cytotoxicity?
What receptors allow NK cells to recognize antibodies bound to target cells?
FcgammaRIII (ITAM)
How do NK cells kill and lyse target cells?
SAME WAY AS CTL 1. Ca2+ influx 2. Granule migration to CTL membrane 3. Exocytosis of perforin monomers 4. Polymerization of perforin on Target cell membrane 5. Generation of complete pores 6. endocytosis of Granzymes 7. Activation of Caspase-8 Activation of Caspase-3 8. Active apoptosis effectors
T/F Other cells like neutrophils, eosinophils and macrophages are also cytotoxic
T
T/F NK cells are the same as NK T cells
F: NK T cells have CD4 and CD8 and facilitate IL-4 production in TH2 responses
What two methods increase NK cell killing?
- increase cellular stress
2. decrease protein synthesis to decrease MHC I expression
What is PD1?
Immune checkpoint inhibitor that kills Ag-specific T cells
What cytokine is associated with cell mediated immunity?
IFN gamma
