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Immunology > Lecture 31 - NK Cells > Flashcards

Lecture 31 - NK Cells Flashcards

1
Q

How were NK cells first observed?

A

Lymphocytes in mice were observed to kill tumour cells

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2
Q

Adherent cells in the spleen

A

Macrophages

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3
Q

Surface markers identifying T cells

A

CD3, TCR

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4
Q 
NK cell identifying surface markers 
1)
2)
3)
4)
5)
A

1) CD3/TCR -
2) Surface IG -
3) CD161 (NK1.1) +
4) CD56 +
5) CD16 can be present, but not always

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5
Q

NKT cell identifying surface markers
1)
2)
3)

A

1) CD3/TCR +
2) Surface IG -
3) CD161 (NK1.1)

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6
Q 
Features of NK cells
1)
2)
3)
4)
A

1) Innate lymphocytes
2) Lack antigen-specific Ig receptors
3) Express a number of receptors that control activation
4) Thought not to undergo clonal expansion, but this is being challenged

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7
Q

Time after viral infection that NK response peaks

A

~3 days

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8
Q

Cytokine that induces NK response

A

IFNg

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9
Q

NK cell functions
1)
2)
3)

A

1) Lysis of target cells (perforin, granzymes, Fas/FasL)
2) Secrete cytokines (IFNg, TNFa)
3) Secrete chemokines

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10
Q

Things that can activate NK cells
1)
2)
3)

A

1) Cytokines (IL-12, IL-15, IL-18, IFNg)
2) Cellular interactions (antibody-dependent cellular cytotoxicity)
3) Natural cytotoxicity

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11
Q 
Antibody-dependent cellular cytotoxicity
1) 
2) 
3) 
4)
A

1) IgG binds to target cell
2) IgG detected by CD16 (FcgRIII) on NK cell
3) CD16 is associated with a CD3-like adaptor that has ITAMS
4) Lysis of cell

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12
Q

Natural cytotoxicity
1)
2)
3)

A

1) An innate ability of NK cells, doesn’t require antibodies
2) Kills virus-infected cells
3) MHCI inhibits NK cell activation. NK cell inspects target cell, if target cell lacks MHCI, killed

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13
Q

Cells susceptible to NK lysis
1)
2)

A

1) Some viruses downregulate MHCI expression to avoid CD8+ detection. NK cells kill these
2) Tumour cells often have defective MHCI

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14
Q

Viruses that interfere with MHCI expression
1)
2)
3)

A

1) Cytomegalovirus
2) Herpes simplex virus
3) HIV

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15
Q

3 types of inhibitory receptors in NK cells

A

1) Ly49
2) Killer-cell immunoglobulin-like receptors (KIR, CD158)
3) CD94/NKG2A

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16
Q

Ly49
1)
2)
3)

A

1) Inhibitory receptor expressed by rodent NK cells
2) Members of C-type lectin superfamily
3) Recognise H-2D, H-2K class I molecules

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17
Q 
Killer cell immunoglobulin-lie receptors (KIR)
1) 
2) 
3) 
4)
A

1) Expressed by primate NK cells
2) Family of receptors (CD158a-f)
3) Members of Ig-like superfamily
4) Recognise HLA-B (Bw4) and HLA-C MHCI molecules (and some HLA-A)

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18
Q

MHCI molecules recognised by KIR

A

HLA-B (Bw4), HLA-C, some HLA-A

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19
Q

CD94/NKG2A
1)
2)
3)

A

1) Highly conserved through evolution
2) Members of C-type lectin superfamily
3) Recognises non-classical MHCI (HLA-E in humans)
4) Ubiquitous expression, non-polymorphic (only 2 alleles in human population)

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20
Q

What do NK inhibitory receptors signal thorough?

A

ITIMs (Immunoreceptor tyrosine–based inhibitory motifs)

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21
Q

Ly49 ITIM configuration

A

Ly49 is a dimer, one ITIM per cytosolic part of Ly49 monomer

22
Q

CD158 ITIM configuration

A

2 ITIMs per cytosolic region of CD158

23
Q

CD158

A

Killer cell immunoglobulin-like receptor (KIR)

24
Q

Another name for killer cell immunoglobulin-like receptor

A

CD158

25
Q

How do NK inhibitory receptors signal?
1)
2)
3)

A

1) Receptor is bound
2) ITIM Is phosphorylated
3) SHIP is activated, which prevents NK cell activation

26
Q 
Different forms of killer cell immunoglobulin-like receptor
1) 
2) 
3) 
4)
A

1) Have either 2 or 3 extracellular domains
2) Are either S or L form (short cytoplasmic tail or long cytoplasmic tail form)
3) S forms lack ITIMs. L forms have ITIMs.
4) S lack ITIMs, so aren’t actually inhibitory receptors

27
Q

What do different domain-types of killer cell immunoglobulin-like receptors do?

A

Detect different HLA types

28
Q

CD158a

A

2DL1

29
Q

CD158b

A

2DL2/3

30
Q

What do killer cell immunoglobulin-like receptors 2DL1 and 2DL2/3 detect?

A

HLA-C group 1 and 2

31
Q

What does CD158a detect?

A

HLA-C group 2

32
Q

What does CD158b detect?

A

HLA-C group 1

33
Q

Which NK cell receptor detects Bw4?

A

KIR 3DL1

34
Q

What does KIR 3DL1 detect?

A

Bw4

35
Q

What does KIR 3DL2 detect?

A

A3/A11

36
Q

Which NK cell receptor detects HLA A3/A11?

A

KIR 3DL2

37
Q

Number of MHCI epitopes recognised by KIR

A

4

These are mutually exclusive. A MHCI can only be one of these types

38
Q 
MHCI epitopes recognisable by KIR
1)
2)
3)
4)
A

1) Group 1 HLA-C (or C-1)
2) Group 2 HLA-C (or C-2)
3) Bw4
4) A3/A11

39
Q

Do all HLA alleles possess either C1, C2, Bw4 or A3/A11 determinants?

A

No.

This is thought to minimise competition between CD8+ and NK cells

40
Q

HLA types that often don’t possess NK-recognised epitopes

A

HLA-A and HLA-B

41
Q

HLA alleles that KIR mostly recognises

A

HLA-C

42
Q

What defines Bw4/Bw6 HLA-B alleles?
1)
2)

A

1) Specific amino acid sequence between amino acids 77 and 83.
2) This sequence lies within the alpha-helix which makes up part of the binding groove of HLA-B

43
Q

What defines C1 and C2 HLA-C alleles?

A

Amino acid 80 asparagine or lysine

44
Q

KIR HLA binding site

A

On the join between the two Ig-like domains of the protein

45
Q

Where on an MHCI molecule do KIR normally bind?

A

The edges

46
Q

Is there variation in which inhibitory receptors NK cell express?

A

Yes.

47
Q 
Why might it be beneficial for NK cells to express different inhibitory molecules?
1) 
2) 
3) 
4)
A

1) Some viruses (EG: HIV with nef) inhibit the expression of some MHCI alleles (HIV inhibits HLA-A, HLA-B, doesn’t affect HLA-C)
2) Some NK cells will be inhibited by HLA-C expression, but some NK cells lack inhibitory receptors for HLA-C
3) These NK cells will be able to kill HIV-infected cell
4) Normal cells express HLA-A, HLA-B and HLA-C, so aren’t killed by NK cells

48
Q

Allele of NK surface receptor that results in delayed progression to AIDS
1)
2)

A

1) Bw4

2) Nef-mediated downregulation of Bw4 leads to killing of infected cells

49
Q

Effect of allotype on acute myeloid leukaemia patients

A

If there is a KIR-ligand mismatch between patient and bone-marrow donor, then NK cells are produced that kill tumour cells

50
Q

KIR that recognises HLA-Bw4

A

CD158e

Immunology (30 decks)

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