NK Cells

Question 1

NK cells originate from

Answer 1

Bone marrow

Question 2

NK cell main locations

Answer 2

blood, spleen, liver

Question 3

NK cell trafficking receptors

Answer 3

Chemotactic Rs, Cytokine Rs, Adhestion Rs

Question 4

NK cell roles

Answer 4

1. kill stressed, infected or tumour cells (activated by IL-2 and IFN gamma)
2. cytokine and chemokine production (IFN gamma, TNF-alpha, IL-17, IL-22, MIP-1a and b) –> activates macrophages

Question 5

How do NK cells recognize targets?

Answer 5

Low expression of MHC 1, increased expression of MICA and MICB

Question 6

NK cell receptor that binds MHC is?

Answer 6

KIR/KLR (or CD158) depending on species

Question 7

KIRs

Answer 7

type 1 TM protein, highly polymorphic. Include the LILR family. Both KIR and LILR families have activating and inhibitory receptors. Expression of KIRs and KLRs is mutually exclusive (with the exception of Ly49)

Question 8

KLRs

Answer 8

aka NKG2D, activating receptor. Recognizes stress proteins like MICA and MICB. High expression of stress proteins will bind NKG2D to override inhibitory signal and allow for NK cell killing

Question 9

Perforin-dependent mechanism of NK cell killing

Answer 9

Perforin released from NK cells creates a pore in the target cell membrane. This allows for granulysin (toxic granule) to enter the target cell via these pores and induce apoptosis

Question 10

Fas/FasL (CD95/CD95L) mechanism of NK cell killing

Answer 10

NK cells express FasL and abnormal cells may express Fas. Binding of these two induces apoptosis of the target cell

Question 11

CD16 killing pathway of NK cells (ADCC)

Answer 11

NK cells may recognize target cells through antibody dependent pathway using CD16. CD16 is an Fc receptor expressed on NK cells. Antibodies bind antigen and NK cell, NK cell can then kill target cell

Question 12

Cytokines that regulate NK cell activity

Answer 12

IL-1, IL-2, IL-12, IL-15, IL-18, IL-21, type I and type II IFNs
Treatment of NK cells with these turns them into LAKs (cells with increased cytotoxic capacities).

Question 13

NKT cells

Answer 13

cross between NK and T cells. They are of thymic origin, have specificity against a few pathogens. Express invariant alpha/beta TCR, but also express KLRs. Mainly CD4+ or double negative. Mainly recognize glycolipid antigens on bacteria. Activated by IL-15. No memory cells. Play a role in allergy, antitumour immunity, autoimmunity, antimicrobial immunity

Question 14

NK DCs

Answer 14

Dendritic cells with some NK cell properties. Present in spleen, liver, LNs, thymus. Spontaneously lyse tumour cells and can present antigen to T cells. Produce lots of IFN gamma