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Flashcards in L11 Deck (28)
1

Which receptors are responsible for T cell adhesion?

LFA on T cell - ICAM on APC
- Integrins
CD4 a little

2

What receptors are responsible for T cell signal transduction?

CD3 & weird squiggly receptors with ITAM
Some CD4

3

What is the concept of inside-out signaling for T cells?

Chemokine or TCR binding
- Create conformation change - ↑integrin receptor affinity
- Cluster integrin receptors around TCRs
NET: stronger adhesion of APC & T cell --> stronger TCR signaling

4

What cytokine is important for T cell costimulation?

IL2 - T cell differentiation and proliferation
Signal 1 + 2 = T cell activation
IL2 production AND
+ alpha subunit to IL2-R -> high affinity receptor --> respond stronger to IL2 produced

5

Which receptors are inhibitory of T cells?

T cell - APC
PD 1 - PD
CTLA4 - B7

6

Where do you usually find CTLA4 receptors in a resting T cell? What happens when T cell activated?

Inside cell in vesicles
T cell activation:
- Move to surface
- Interact with B7 with higher affinity
- Recruits ITIMs

7

What are T cell microclusters?

The idea that TCRs can't signal transduce
Instead, they recruit all needed molecules into a cluster underneath

8

Explain TCR signal transduction.

TCR binds
Lck +P to ITAMs on CD3 & weird squiggly
Recruits ZAP70

9

What are the 3 goal TFs of the TCR signaling cascade? What is their communal function?

NA-FT
NFkB
AP1
All ↑ IL 2 for T cell differentiation and proliferation

10

How do T cells make NA-FT?

Lck
ZAP 70
IP3
↑[Ca2+]
Calcineurin

11

How do T cells make NFkB?

Lck
ZAP 70
PKC
NFkB

12

How do T cells make AP1?

Lck
ZAP70
RAS signaling
MAP kinase
AP1

13

What is methotrexate?

Drug that blocks T cell replication

14

What is belatacept?

Drug blocks signal 2: B7-CD28
No T cell development

15

What is cyclosporin? What is the genetic variant for metabolism?

Inactivates calcineurin
CYP3A5

16

What is basiliximab?

Ab against IL2-R
No clonal expansion of T cells

17

What is sirolimus?

Blocks IL2-R signaling

18

What chemokine receptor directs cells into the B zone of lymph nodes? T zone?

B zone: CXCR5
T zone: CCR7

19

What chemokine directs T cells out of the lymph node into the blood?

S1P

20

What chemokine directs T cells out of the blood and into specific tissues?

CXCR3

21

What is the fxn of drug FTY720?

Blocks S1P receptor
T cells stay in lymph node

22

In general, tyrosine phosphatases work to decrease tyrosine kinase activity in T cell inactivation. What happens if you have mutations in your phosphatases?

Inability to regulate immune responses:
Cancer - too much T cell dampening
Autoimmunity - too little

23

What is activation induced cell death?

Negative regulation of T cells
FasL expressed on T cells after activation
FasL + Fas (receptor on neighboring T cells)
- Fas = TNF death receptor, works via caspases
Fas trimerizes
DNA fragmentation

24

What is human autoimmune lymphoproliferative syndrome (ALPS)?

Mutation in Fas
No activation induced cell death of T cells

25

What is CD95?

Fas receptor on T cells

26

What is necessary for BCR activation?

Cross linking!!!

27

Explain BCR signaling. What are the downstream products?

Cross link BCRs & bind TAAPA
Blk, Fyn, or Lyn +P to ITAMs on CD19 & Ig alpha/beta
SYK
Downstream products: NF-AT, NFkB, AP1

28

What is the negative regulation for B cells?

Ab Fc region binds BCR instead of antigen
Enacts ITIM