Exam 3: Natural Killer Cells (NK) Flashcards

1
Q

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

A

T

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2
Q

What induces anti-viral response

A

IFN alpha and IFN beta

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3
Q

Signal transduction through TLRs- Type 1 IFN

A

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)

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4
Q

Signaling through cytosolic recptors

A

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

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5
Q

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

A

RIG-1
MDA-5
STING

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6
Q

What 2 genes do IFN activate to inhibit protein synthesis?

A

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)

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7
Q

What unique receptor do NK cells have?

A

Inhibitory receptors

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8
Q

How do inhibitory receptors on NK cells work?

A

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

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9
Q

How do NK cells recognize self cells?

A

Presence of MHC Class I –> SELF

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10
Q

Which receptors are involved in NK recognition of self

A

CD94:NKG2 heterodimer

KIR

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11
Q

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

A

T

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12
Q

What motif is associated with KIR?

A

ITIM

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13
Q

What is the sequence of an ITIM?

A

I/VXYXXL

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14
Q

What do ITIMS recruit?

A

Phosphatases (SHP1)

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15
Q

What ITAM receptor is associated with NK cells

A

DAP12

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16
Q

T/F ITIMS antagonize ITAMS

A

T

17
Q

What are some ITIM receptors?

A

Ly49a

NKG2A:CD94 (heterodimer)

18
Q

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

A

T

19
Q

What NK receptors lead to killing?

A

DAP12 (ITAM) coupled to NKG2D

20
Q

What NK receptors lead to inhibition (ITIMS)?

A

Ly49a

CD94:NKG2a heterodimer

21
Q

What NK receptors lead to cytokine production?

A

DAP10 coupled with NKG2D

22
Q

What does NKG2D do?

A

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

23
Q

What does Ly49a bind?

A

Carbohydrates

24
Q

What are some common forms of cellular stress?

A
  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)
25
Q

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

A

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

26
Q

What is ADCC?

A

Antibody dependent cellular cytotoxicity?

27
Q

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

A

FcgammaRIII (ITAM)

28
Q

How do NK cells kill and lyse target cells?

A
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
29
Q

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

A

T

30
Q

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

A

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

31
Q

What two methods increase NK cell killing?

A
  1. increase cellular stress

2. decrease protein synthesis to decrease MHC I expression

32
Q

What is PD1?

A

Immune checkpoint inhibitor that kills Ag-specific T cells

33
Q

What cytokine is associated with cell mediated immunity?

A

IFN gamma