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?

A

B7

21
Q

With what ligand does PD-1 interact?

A

PD-L1

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
Q

What are the signature cytokines of Th17 cells?

A

IL-22
IL-17
(stimulate WBC to release chemokines)
– inflammation, tissue response, anti-microbial peptides

26
Q

How are Th1’s activated?

A

**microbes
NK (IFN-y);
DCs and macrophages (IL12)

27
Q

How are Th2’s activated?

A

**Helminths, allergy
DCs (MHC2)
mast and eosinophils (IL-4)

28
Q

How are Th17’s activated?

A

**bacteria

APCs (MHC2, IL6,1, TGF-beta)

29
Q

What are the 2 mechanisms of CD8 killing?

A

1) perforin/granzyme

2) Fas/FasL-mediated

30
Q

Describe perforin-granzyme killing

A

perforin induces uptake of granzymes into endosome

caspases are released into cytosol to activate apoptosis

31
Q

Describe Fas-FasL killing

A

FasL on CTL binds Fas on target

apoptosis

32
Q

Describe T-cell exhaustion

A

chronic infection
pathogens induce B7, PD1L
– no cytokines, reduced proliferation, no target killing

33
Q

What is the function of Tregs?

A

prevent self-activation and over-activation

    • important in gut flora
    • inhibit T, B, NK
34
Q

What are the anti-cancer immunotherapies acting with T-cells?

A

Anti-CTLA4 mAb (targets T-cell inhibitory protein)
Anti-PD1/PDL1
– PD1 on T cell