Exam 3: Natural Killer Cells (NK)

Question 1

T/F NK cells are part of innate immunity and the first response to a viral infection (2-3 days after infection)

Answer 1

T

Question 2

What induces anti-viral response

Answer 2

IFN alpha and IFN beta

Question 3

Signal transduction through TLRs- Type 1 IFN

Answer 3

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)

Question 4

Signaling through cytosolic recptors

Answer 4

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

Question 5

what are some cytosolic responses used in anti-viral response?

Answer 5

RIG-1
MDA-5
STING

Question 6

What 2 genes do IFN activate to inhibit protein synthesis?

Answer 6

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)

Question 7

What unique receptor do NK cells have?

Answer 7

Inhibitory receptors

Question 8

How do inhibitory receptors on NK cells work?

Answer 8

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

Question 9

How do NK cells recognize self cells?

Answer 9

Presence of MHC Class I –> SELF

Question 10

Which receptors are involved in NK recognition of self

Answer 10

CD94:NKG2 heterodimer

KIR

Question 11

T/F Virus-infection leads to underexpression of MHC I

Answer 11

T

Question 12

What motif is associated with KIR?

Answer 12

ITIM

Question 13

What is the sequence of an ITIM?

Answer 13

I/VXYXXL

Question 14

What do ITIMS recruit?

Answer 14

Phosphatases (SHP1)

Question 15

What ITAM receptor is associated with NK cells

Answer 15

DAP12

Question 16

T/F ITIMS antagonize ITAMS

Answer 16

T

Question 17

What are some ITIM receptors?

Answer 17

Ly49a

NKG2A:CD94 (heterodimer)

Question 18

T/F NK cells have receptors that lead to killing, inhibition, and cytokine production

Answer 18

T

Question 19

What NK receptors lead to killing?

Answer 19

DAP12 (ITAM) coupled to NKG2D

Question 20

What NK receptors lead to inhibition (ITIMS)?

Answer 20

Ly49a

CD94:NKG2a heterodimer

Question 21

What NK receptors lead to cytokine production?

Answer 21

DAP10 coupled with NKG2D

Question 22

What does NKG2D do?

Answer 22

ITAM that binds MIC-A, MIC-B, or RAET1 that are induced by stress

Question 23

What does Ly49a bind?

Answer 23

Carbohydrates

Question 24

What are some common forms of cellular stress?

Answer 24

1. Viral hijack of cell protein synthesis machinery
2. Hypoxia (tumor cells that reach their max growth and lose ability to get oxygen from blood vessels –> signal for MICa, MIC-b)

Question 25

T/F Viral infection and tumor cells induces NK killing by decreased MHC Class I expression

Answer 25

T; viral proteins overuse protein synthesis to the point where less MHC I is expressed; remember tumor cells induce more stress via hypoxia

Question 26

What is ADCC?

Answer 26

Antibody dependent cellular cytotoxicity?

Question 27

What receptors allow NK cells to recognize antibodies bound to target cells?

Answer 27

FcgammaRIII (ITAM)

Question 28

How do NK cells kill and lyse target cells?

Answer 28

``` 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 ```

Question 29

T/F Other cells like neutrophils, eosinophils and macrophages are also cytotoxic

Answer 29

T

Question 30

T/F NK cells are the same as NK T cells

Answer 30

F: NK T cells have CD4 and CD8 and facilitate IL-4 production in TH2 responses

Question 31

What two methods increase NK cell killing?

Answer 31

1. increase cellular stress | 2. decrease protein synthesis to decrease MHC I expression

Question 32

What is PD1?

Answer 32

Immune checkpoint inhibitor that kills Ag-specific T cells

Question 33

What cytokine is associated with cell mediated immunity?

Answer 33

IFN gamma