C1 NK cells

Question 1

describe NK cells

1. where do they develop
2. restrictions?
3. dependencies

Answer 1

1. Bone marrow (2y lymphoid organs)
2. MHC-I/II restricted
3. independent of RAG1/2 (no rearrangement)

Question 2

Name Nk cell markers

Answer 2

CD3- forms signaling complex of TCR
CD56+ isoform neural adhesion factor ((specific to CD8))
NKp46+ natural cytotoxicity factor

Question 3

Role of Il-21

Answer 3

induces maturation of human CD3+ stem cells –> NK cells

Question 4

what markers are required to make stem cells NK cells

Answer 4

IL-15 from APC cells (e.g. DC)

marker for CD56

Question 5

Name actions of NK cell

Answer 5

1. secrete cytokines & chemokines (e.g. IFNy & TNF a)
2. Kill infected & transformed cells

Question 6

explain difference between NK cytotoxic Tc

Answer 6

1. cytokines have constitutively expressed granules whereas Tc need to be stimulate before granule expression
2. both Tc & NK interact w/ infected & malignant cells w/ decreased expression of MHC-1 —> NK also kill DC which express normal amounts of HLA molecules.

Question 7

what type of cells do NK cells kill

Answer 7

own cells only! reduced inflammation

Question 8

what results in activation of NK cells

Answer 8

= opposing signal. (tug of war)

+ve & -ve regulators & balance of stimulation of activation receptors & inhibitors

Question 9

how are NK cells activated in tumor cells

Answer 9

1. loss of MHC expression - promotes killing of tumor cells

2. Upreg of stress-induced ligands promotes killing of tumor cells

Question 10

give examples of activation signaling & inhibitory signaling - what class do they recognize

Answer 10

activation: natural cytotoxicity receptors, & KIR: Killer cell immunoglobin like receptor
inhibition: KIR - inhibitory immunoglobin killer receptors.
Inhibitory recognize class la (HLA-A, B, C) or non classical Ib (HLA-E)

Question 11

Name the cytokines involved in activation & inhibitory signaling

Answer 11

IL-1, IL-12, IL-15, IL-18, IL-21, IFNa/B

can induce cell proliferation, NK induced cytotoxicity &/or production of IFNy

Question 12

Which chemokines are important for recruiting NK to tissues during inflammatory response

Answer 12

CXCL8, CCl3 & CXCL1 from endothelial cells, macrophages, neutrophils, fibroblasts, mast cells, eosinophils

Question 13

what is required for NK cell to exert cytotoxic effect on target cell

Answer 13

Immunological synapse

Question 14

what molecules provide close contact

Answer 14

adhesion molecules: a4B2 integrin & leukocyte function-associated antigen-1 (LFA-1)
LFA-1 transduces signals which result in an NK-cell target conjugate and can be sufficient to trigger NK cytotoxicity

Question 15

what are nectins
where are they expressed
which cells have high expression
what does stong binding of nectins result in

Answer 15

adhesion molecules
expressed on epithelial cells & help to form junctions between between cells
tumor cells have high expression
cell cytotoxicity

Question 16

name ligands for nectins

Answer 16

recognise nectins & nectin like molecules on target cells
CD226: nectin & nectin like 5
CD96: nectin like 5
CRTAM: nectin-like 2

Question 17

1. what does interaction of LFA-1 & ICAM-1 result in?

2. CD16 interaction with Fc of IgG?

Answer 17

1. granule polarization

2. degranulation –> stimulates ADCC: antibody dependent cell mediated cytotoxicity

Question 18

what is the process of granule release

Answer 18

needs co-engagemnet of both receptors before granules released
interaction of other receptors w/ ligands may also result in cell killing
activation similar to CTL cells - involves perforin & caspase 3 activation: induces apoptosis of cells target