Block 1 Lecture 8 -- T Cells Flashcards

1
Q

Where is Class I MHC/HLA presented?

A

to CD8

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2
Q

Describe structure of MHC/HLA Class I.

A

2 units; 3 disulfides

    • alpha + beta2 microglobulin
    • peptide-binding cleft (peptide needed for alpha stability)
    • transmembrane region
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3
Q

Describe structure of MHC/HLA Class II

A

2 units; 3 disulfides

    • alpha + beta
    • peptide binding cleft
    • transmembrane region
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4
Q

How is Class I p-MHC associated?

A

infected cell’s Ag is transported into ER by TAP

    • Transporter of Ag Peptides
    • MHC I is intra-ER, binds Ag and vesicle goes to PM
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5
Q

How is Class II MHC associated?

A

ER vesicle containing MHC Class II fuses with phagocytosed vesicle

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6
Q

Where are Class I MHC’s located?

A

all nucleated cells

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7
Q

Where are Class II MHC’s located?

A

traditional APCs

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8
Q

What happens when cell presents Ag to CD8?

A

effector T cell kills Ag-expressing target

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9
Q

What happens when APC present Ag in MHC II to CD4?

A

effector T cell activates macrophages

effector T cell looks for B partner to stimulate Abs

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10
Q

Describe T cell development

A

stem – pro – pre – double positive – single positive/immature – mature

from cortex to medulla, to periphery (when naive!)

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11
Q

When do T cells begin expressing CD3?

A

double positive

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12
Q

Characteristics of Pre-T?

A

VDJ recombination has occurred

pre-T receptor (single chain)

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13
Q

Characteristics of Double Positive T?

A

alpha-beta TCR is finished;

undergoing +/- selection

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14
Q

Where are T cells activated?

A

in medulla of lymph nodes … they circulate through periphery to find Ag in lymph nodes

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15
Q

Describe T-cell requirements for activation?

A
    • TCR-MHC
    • CD28–APC costimulatory molecule (B7)
    • adhesion interaction with LFA-1
    • cytokines (usually IL-12)
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16
Q

How do T cells proliferate?

A

autocrine IL-2

17
Q

What proteins are involved in signal transduction for the T-cell when activated?

A

CD4

CTLA4 and PD1 inhibit!

18
Q

Waht proteins are involved in Ag recognition for the T-cell during activation?

A

TCR, CD3 (+ITAM), CD28

19
Q

What proteins are involved in adhesion during the T cell activation?

A

LFA-1 (T cell) with ICAM-1 of APC

20
Q

With what ligand does CTLA 4 interact?

21
Q

With what ligand does PD-1 interact?

22
Q

Describe signal transduction during T-cell activation?

A

TCR lipid raft complex

    • Lck phosphorylation pathways
    • activation of PLCy1, Ras/MAPK
23
Q

What are the signature cytokines of Th1 cells?

A

IFN-y

IgG, macrophage activation

24
Q

What are the signature cytokines of Th2 cells?

A

IL-4, IL13, IL5

Th2 amplification, IgE (mast degranulation), gut motility, eosinophils

25
What are the signature cytokines of Th17 cells?
IL-22 IL-17 (stimulate WBC to release chemokines) -- inflammation, tissue response, anti-microbial peptides
26
How are Th1's activated?
**microbes NK (IFN-y); DCs and macrophages (IL12)
27
How are Th2's activated?
**Helminths, allergy DCs (MHC2) mast and eosinophils (IL-4)
28
How are Th17's activated?
**bacteria | APCs (MHC2, IL6,1, TGF-beta)
29
What are the 2 mechanisms of CD8 killing?
1) perforin/granzyme | 2) Fas/FasL-mediated
30
Describe perforin-granzyme killing
perforin induces uptake of granzymes into endosome | caspases are released into cytosol to activate apoptosis
31
Describe Fas-FasL killing
FasL on CTL binds Fas on target | apoptosis
32
Describe T-cell exhaustion
chronic infection pathogens induce B7, PD1L -- no cytokines, reduced proliferation, no target killing
33
What is the function of Tregs?
prevent self-activation and over-activation - - important in gut flora - - inhibit T, B, NK
34
What are the anti-cancer immunotherapies acting with T-cells?
Anti-CTLA4 mAb (targets T-cell inhibitory protein) Anti-PD1/PDL1 -- PD1 on T cell