L12

Question 1

How many signals do naive T cells need for activation? Effector T cells? What happens in each step?

Answer 1

Naive = 2 signals
- MHC & costim
- MAKE granules 
Effector = 1, MHC
- Granule exocytosis

Question 2

What changes occur to a draining lymph node?

Answer 2

↑inflammation
↑cytokines
Recruit lymphocytes - REGARDLESS of antigen specificity
Via selectins and integrins upregulated on HEVs

Question 3

What are 3 important T cell receptors for lymph node honing? Explain their significance in context the steps towards diapedesis.

Answer 3

CD26L (selectin receptor)
- Binds L selectin on HEV
*Rolling/tethering*
CCR7 (chemokine receptor)
- Binds CCL12/21 on HEV
*Stimulation/signal*
LFA1 (integrin receptor)
- Binds ICAM  on HEV
*Adhesion*

Question 4

What is the significance of chemokine activation of vascular walls?

Answer 4

Inside out signaling
Integrin receptor changes from low –> high affinity
Get FIRM adhesion

Question 5

What changes are made to recruit cells to specific tissues?

Answer 5

Modify chemokine receptor for tissue specific chemokines

Question 6

What cytokine do CD8 T cells secrete? What is the fxn of this cytokine?

Answer 6

IFN gamma

Improves macrophage phagocytosis & inflammation

Question 7

How do CD8 create MEMORY?

Answer 7

ADD CD4 to normal CD8 activation by DC

1. CD4 & CD8 recognize antigen on same DC
2. DC licensing

Question 8

What is DC licensing?

Answer 8

CD40L from CD4 T cells or inflam signals (like TLRs on DCs) modify a DC to make it provide optimal help for CD8s

Question 9

What are the 2 ways CD8 cells can actually kill cells?

Answer 9

1. Perforins + granzymes
2. Fas/FasL –> (suicide mechanism) DNA breakdown via caspases
   Or some combo of both

Question 10

What is the disease resulting from perforin deficiency?

Answer 10

Hemophagocytic lymphohistiocytosis (HLH)
- Genetic or acquired
- CD8s get revved up but can’t do anything about it –> secrete INF gamma and get inflam, stimulate macrophages
Symptoms:
- Splenomegaly, fever, etc
- High levels of inflam cytokines in blood

Question 11

How could you treat HLH?

Answer 11

Immuno-suppressants

+Ab against INF gamma - block macrophage recruitment and toxicity

Question 12

Are CD8 cells one and done killers?

Answer 12

No - can kill multiple targets

As long as have enough granules

Question 13

What cytokines make Th1 cells?

Answer 13

IL12

IFN gamma

Question 14

What is the function of Th1 cells?

Answer 14

Fight intracellular pathogens

Autoimmunity

Question 15

What cytokines do Th1 cells secrete? What cells are helped by this?

Answer 15

IFN gamma

Macrophages

Question 16

What cytokines make Th2 cells?

Answer 16

IL4

Question 17

What is the function of Th2 cells?

Answer 17

Extracellular parasites

Allergy

Question 18

What cytokines do Th2 cells make? What cells are helped?

Answer 18

IL4 & 13

Mast cells, eosinophils, basophils

Question 19

What cytokines make Th17 cells?

Answer 19

TGFbeta
IL 6
IL23

Question 20

What is the function of Th17 cells?

Answer 20

Extracellular bacteria
Fungi
Autoimmunity

Question 21

What cytokines do Th17 cells make? What cells are helped?

Answer 21

IL 12
IL 22
Neutrophils indirectly

Question 22

What cytokines make Tregs? What is the molecular mechanism?

Answer 22

IL1-
TGF beta
Via FoxP3/Stat5

Question 23

What cytokines do Treg make?

Answer 23

TGF beta

IL10

Question 24

What Abs do Th1s influence the creation of? Th2?

Answer 24

Th1 = IgG 1 & 3 (opsonize)
Th2 = IgE & neutralizing Abs

Question 25

What is the name for macrophages activates by Th1 cells?

Answer 25

Delayed type 4 hypersensitivity (DTH)

Question 26

What is Job’s syndrome?

Answer 26

Lose STAT3 fxn
No Th17
= primary immnodeficiency
Hyper IgE - unclear why

Question 27

Explain the mechanism for getting Shingles (herpes virus 3).

Answer 27

As you age, T cell memory effectiveness decreases

Can’t keep the intracell virus in check –> comes back