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Immunology week 8 > NK cells > Flashcards

NK cells Flashcards

1
Q

Are NK cells granular? Leukocytes or lymphocytes?

A

Yes, they are large granular innate lymphocytes?

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2
Q

What poulation in the perihperal blood islarger? NK or B cells?

A

NK cells outnumber B cells in the blood.

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3
Q

Where do NK cells go to mature? and where else are they found?

A

They mature in the lymph nodes, interactions with DCs, and also maybe involves neutrophils and monocytes (CD11b+ CD27+ to CD11b+ CD27-).

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4
Q

What two ways are NK cells activated?

A

via germ line encoded receptors, or by cytokines such as IL-12, IL-15 and IL-18.

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5
Q

Functions of NK cells?

A

mainly to kill virally infected and transformed cells have granules which help in this (includes tumours) (no prior sensitisation required).
Influence other immune responses via cytokines and chemokines production, particularly IFN-y and TNFa.

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6
Q

How are NK cells connected to the adaptive immune response?

A

By influencing DCs, macrphages and by binding antibodies for ADCC.

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7
Q

how can NK cell chemokine production help in HIV?

A

NK cells produc chemokines that compete for the HIV co receptor CCR5.

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8
Q

what is CD16?

A

The low affinity Fc receptor, helps to mediate ADCC.

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9
Q

What two markers are commonly used to identify NK cells?

Broadly what populations can these separate?

A

CD16 and CD56.
CD56 bright and CD16 low are immature NK cells. they produce more cytokines and are less cytotoxic.

CD56low CD16+ are mature cytokines, more granular and cytotoxic (more CD16 and ADCC). Also do produce cytokines though.

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10
Q

What changes in receptors are seen generally with maturation?

A

Generally as NK cells mature, they change receptors from NKG2A to KIRs (perhaps this new combination helps to mediate cytoxicity.

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11
Q

what two viruses are NK cells very important in?

A

NK cells especially important for influenza and herpes infections- individuals without NK cells have severe herpes and EBV.

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12
Q

Evidence for nK cells and cancer in humans?

A

Humans which lower incidence of cancer had higher NK cell cytolytic activity.

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13
Q

What NK receptor important in NK memory responses?

A

NK cells with Ly49H receptor are expanded following (CMV?) infection.

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14
Q

How are NK cells important in pregnancy? Regulation of adaptive immune system and DC maturation?

A

Important for perhaps the invasion of the extravillous trophoblasts and pre-ecalmpsia risk.
Can influence innate immune cells DCs to influence adaptive immunity, and maybe produce IL-2. Could potentially regulate T cell responses by direct cytotoxicity?
May produce G-MCSF for DC maturation, but may also kill them to control numbers?

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15
Q

Recognistion of what is important for NK cell inhibition? What about in a mismatch?

A

MHC 1 helps to inhibit NK cell activation. MHC mismatch can still cause an a’lloreactive’ NK cell response as NK inhibition via MHC I incomplete.

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16
Q

What progenitor are NK cells derived from in the bone marrow?

A

Bone marrow CD34+ progenitor.

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17
Q

Where do NK cells mature?

A

In SLOs like lymhp nodes and tonsils.

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18
Q

What other markers of mature NK cells used apart from CD56 and CD16?

A

CD94/NKG2A, Nkp46+.

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19
Q

Do NK cells have the IL-7R CD122?

A

no.

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20
Q

what common progenitor do NK cells share with ILCs? what TFs important in this progenitor?

A

CILP, expresses Id2 and Tox.

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21
Q

what cells come from CILP and CHILP?

A

CILP gives rise to ILCregs (sox2 Id3), LTis, and NK cells.

CHILP gives rise to the ILCs 1 2 and 3.

22
Q

What Tfs for CHILP?

A

GATA3 and Tcf7

23
Q

What TF is important for NK cells, but not ILCs?

A

T-bet and Eomes inparticular. ILCs can do without Eomes.

24
Q

What is CD122?

A

The IL-15 recptor, similarly to CD8+ Tregs, expressed on NK cells.

25
Q

What NK receptor is inhibitory and binds HLA-E? (relevant in pregnancy)

A

CD94/NKG2A binds the leading sequence of classical MHC 1.

26
Q

What NK activatory receptor binds HLA-G dimer and has tolerogenic effects?

A

LILRB1

27
Q

What kind of receptors bind HLA-C and are inhibitory for group 1 and 2?

A 
KIR 2DL1 (binds group C2)
KIR 2DL2/3 (binds group C1)
28
Q

what kind of KIR receptors bind HLA-C 1/2 and are activatory?

A

KIR 2DS1/2 bind C1 and C2 and are stimulatory.

29
Q

What does the inhibitory NK2GA/CD94 actually recognise presented by HLA-E?
What does the activating NKG2C recognise on HLA-E?

A

NKG2A recognises The leading sequence of HLA-E.

NKG2C recognises the CMV virally loaded leading peptide on HLA-E.

30
Q

what is HLA-E equivalent in mice?

A

It is Qa1.

31
Q

What kind of domains do KIRs, and the mice equivalent Ly49 have?

A

Ig domains in humans, in mice htey are C-type lectins.

32
Q

What is naming for inhibitory and activating KIRs?

What shows how many Ig domains?

A

Inhibotrs have DL, activating has DS. number, e.g. KIR 2DL1 has 2 Ig domains.

33
Q

What do KIRs recognise?

A

MHC 1 expression. May have some specificity for kind of HLA (e.g HLA-C1/C2) where the alpha chain is particularly important.
Also may recognise bit of peptide, but binds on side of MHC, so sensitivity and its relevance is less.

34
Q

What signalling motifs do KIR receptors use?

A

Use ITIM motifs for signalling.

35
Q

Do activating or inhibtiory KIRs have higher affinity?

A

Activating have a lower affintiy thatn inhibitory counterparts.

36
Q

3 ways diversity within KIRs is seen although they are germ line encoded?

A
  1. KIRs are highly polymorphic (need to recognise different HLAs).
  2. They are inherited as haplotypes (two from mother and father)
  3. Expession of KIRs is variable in different cells, due to epigenetic divseristy which is stable once determined.
37
Q

What bit of peptide do KIRs recognise?

A

C-terminal anchor residues of peptide.

38
Q

What are some examples of the natural cytotoxicity receptors? And what do they reognise?

A

NKp30/44/46 which recognise slef/foreign antigens like viral haemagglutins.

39
Q

what does the NKG2D receptor co stimulatory receptors recognise?

A

They recognise self ligands expreesed during stress e.g. MICA/ MICB.

40
Q

What do the activatory NK receptors have to do for signalling?

A

They have to recruit additionally adaptor moelcules for signalling.

41
Q

What are the 3 adaptor molecules that activator NK receptors have to recruit for singlalig?

A

either DAP10/12, FcEIIy or CDzeta.

42
Q

whihc activating recpotrs use homodimer of DAP 12 for signalling?

A

NKp44 and activating KIRs use DAP12 homodimer.

43
Q

What signalling molecules do CD16 receptors recruit?

A

Either homodimer of fcEIy or CDzeta. Or a heterodimer of both.

44
Q

What signalling molecule do NKp30 and Nkp46 recruit?

A

heterodimer of FcEIy and CD zeta.

45
Q

What adaptor molecules does NKG2D recptors use?

A

DAP 10, which uses non-ITAM motifs.

46
Q

What ligands can NKp30, Nkp44 and Nkp46 recognise?

A

NKp44/46viral haemagluttinins.

Nkp30 recognises B7-H6 self ligand expressed on some tumour cells.

47
Q

Can these activating recepotrs (except CD16) activate alone?

A

NOrmally requires help from another stimulatory recptor e.g. SLAM receptor 2B4, DNAM-1 or NKG2D.

48
Q

What do initial ITAM signalling steps look like for NK receptors?

A

SYK activation of ITAMs and ZAP70 activation.

49
Q

What signallig pathways do activating recepotrs trget?

A

Activate PI3K, SLP76 and Grb2 which activates VAV1 importantly. This helps in immune synapse formation and granular trafficking.

50
Q

Why might 2B4 and DNAM1 be required in conjunction with other activator signals for signalling?

A

they can inhibit SHIP-1 activation, and provide second phosphorylation of SLP76.

51
Q

How do inhibitory receptors inhibit activation?

A

By activating phosphatases SHP-1 and 2 and SHIP-1 that act to dephosphyrate molecules involved i activatory signalling, e.g. IP3, PIP3, SLP7-76. Thus VAV1 is inactive and cannot activate the GTPase Rho activity.

Immunology week 8 (4 decks)

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