Lecture 17

Question 1

How does the adaptive immune system kill a virus infected cell?

Answer 1

• antibody response (neutralize before infection)
• CTL response to kill the virus infected cell

Question 2

How does the innate immune system kill a virus infected cell?

Answer 2

• interferon induction of anti-viral response
• NK cell
• gamma/delta T cells

Question 3

How do viruses block the MHC I pathway?

Answer 3

• blocking TAP, or PLC
• retain MHC I in the ER
• redirecting MHC I into a lysosome
• down regulation of MHC I gene

Question 4

What happens when infected cells express stress-induced molecules?

Answer 4

they can be recognized by NK cells and gamma/delta T cells

Question 5

What are NK cells?

Answer 5

• lymphocytes that lack CD3 and express CD56
• 2 kinds: cytotoxic and IFN-y secreting

Question 6

What do the two kinds of NK cells do?

Answer 6

Cytotoxic: kill virus infected cells by using cell to cell contact
IFN-y: activate macrophages after receiving cytokines from them

Question 7

What do NK cell’s inhibitory and activating receptors do?

Answer 7

inhibitory: binds to MHC class I on target cell’s surface
activating: bind to stress-induced proteins

Question 8

What is an example of an inhibitory receptor process on an NK cell?

Answer 8

SHP-1: a phosphatase that gets activated when a NK cell binds to an inhibitory receptor to MHC I

Question 9

What is an example of an activating receptor process on an NK cell?

Answer 9

activating receptor binds to ligand, results in phosphorylation of Vav-1– leads to activation of NK’s cytotoxic machinery

Question 10

How does SHP-1 control NK activity?

Answer 10

developing: activation of SHP-1 inactivates Vav-1 by removing phosphate
post-grad: makes sure NK is only engaged when needed (default is to override activating receptors)

Question 11

What is an MIC protein?

Answer 11

look like MHC I (but no peptide or b2 microglobulin), only expressed on stressed cells

Question 12

How does an NK cell determine if the cell is healthy or not

Answer 12

Healthy: NK binds to HLA-E– inhibitory signalling>activating signalling
Unhealthy: less MHC signalling and more MIC signalling– activating signalling>inhibitory signalling

Question 13

How does NK cell actually do the killing part?

Answer 13

• NK’s integrin binds to ICAM-1 on target cell (integrins are activated because of chemokines binding and leading NK cell to the site of infection)
• adhesion molecules stick the NK to the target cell (so it doesn’t spread), and lytic granules are released for apoptosis

Question 14

What is antibody dependent cell mediated cytoxicity? (ADCC)

Answer 14

target is coated with IgG, Fc binds to FcyRIII receptor on NK cell
- NK cells lytic granules are released onto the surface of the target cell

Question 15

How do NK cells interact with resident macrophages?

Answer 15

macrophage releases IL-12 and IL-15 and NK cell proliferates into IFN-y secreting cell
- IFN-y binds to a receptor on the macrophage and stimulates it to increase phagocytosis and cytokines

Question 16

What do yd T cells release?

Answer 16

perforin and granzyme
- secrete IFN-y to stimulate macrophages

Question 17

What is the difference between NK cells and yd T cells?

Answer 17

NK cells would target infected cells lacking MHC class I (nothing to bind to the
inhibitory receptor), γδT cells could kill infected cells still expressing MHC class I
(even though it does not recognize antigen presented by MHC class I)

Question 17

What is the difference between NK cells and yd T cells?

Answer 17

NK cells would target infected cells lacking MHC class I (nothing to bind to the
inhibitory receptor), γδT cells could kill infected cells still expressing MHC class I
(even though it does not recognize antigen presented by MHC class I)