T Cells 6 Flashcards

(46 cards)

1
Q

what happens after T cell activity?

A

contraction and negative regulation of T cells

and restoration of epithelial activity

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2
Q

when does the immune response contract?

A

within 10-14 days of infection –> at the end of the primary immune response, once Ag is cleared

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3
Q

how do Treg cells help with contraction?

A

by releasing inhibitory cytokines

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4
Q

how are lymphocytes lost for clonal contraction?

A

via apoptosis

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5
Q

which types of lymphocytes remain after clonal contraction? what type of response will they be needed for?

A

memory cells –> for secondary response when antigen is encountered again

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6
Q

what are the 2 unknown aspects of clonal contraction?

A
  1. is clonal contraction triggered by a lack of Ag or an active switch?
  2. how are memory cells selected for survival instead of death induction
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7
Q

what are the 2 apoptosis pathways?

A
  1. intrinsic pathway
  2. extrinsic pathway
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8
Q

what is another name for the intrinsic apoptosis pathway? how does the intrinsic pathway work?

A

“death by neglect”

lack of IL2Ralpha expression = absence of IL-2 survival signal = apoptosis

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9
Q

what property of IL-2Ralpha allows the intrinsic pathway to occur? what type of molecules have this common property?

A

IL-2Ralpha has transient expression, so it is impermanent and can therefore be reduced when needed

common for all cytokine receptor expression

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10
Q

what are the 2 types of inhibitory/regulatory receptors?

A
  1. CTLA-4
  2. PD-1
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11
Q

what is the function of CTLA-4?

A

downregulates T cell activation

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12
Q

how does CTLA-4 downregulate T cell activation?

A

binds B7 molecules with higher affinity than CD28, so it sequesters B7 and prevents CD28 binding

ultimately shuts down signaling pathways

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13
Q

when is CTLA-4 induced?

A

after signal 1,2,3 about 24h after T cell activation

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14
Q

when does CTLA-4 activity peak?

A

2-3 days post-stimulation

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15
Q

how does CTLA-4 get expressed on cell membrane?

A

CTLA-4 is fully translated intracellularly but undergoes PHOSPHORYLATION (post-translational regulation)

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16
Q

how many B7 molecules does CD28 bind vs how many B7 molecules does CTLA-4 bind?

A

1 CD28 binds 1 B7

1 CTLA-4 binds 2 B7

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17
Q

describe what happens when effector T cell binds APC (describe without vs with CTLA-4)

A

WITHOUT:
- Effector T cell binds APC
- CD28 can bind B7 and allow proliferation

WITH CTLA-4:
- Effector T cell binds APC
- CTLA-4 binds B7, blocking CD28 and blocking proliferation

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18
Q

ultimately, how does CTLA-4 affect sensitivity of T cells to APCs and how does affect proliferation?

A

CTLA-4 makes activated T cells less sensitive than naive T cells to stimulation by APCs

reduces IL-2 production which reduces proliferation and prevents lymphocyte overgrowth

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19
Q

what happens in mice that don’t have CTLA-4?

A

too many lymphocytes –> disease

20
Q

what cells express PD-1?

A

activated T cells express PD-1

21
Q

What does PD-1 bind? (2)

22
Q

what type of cells express PDL-1?

A

constitutively express on many cells

23
Q

what type of cells express PDL-2?

A

on APCs during inflammation

24
Q

what is the function of PD-1?

A

downregulates T cell activation/function

25
what is PD-1 a marker of? when is this common?
marker of T cell exhaustion, common in chronic diseases
26
why is PD-1 a marker of exhaustion?
if cell gets tired of proliferating, etc. it will "wave a white flag" aka allow PD-1 activity
27
what are the 2 subsets of Treg cells?
1. Natural Treg (nTreg) 2. Induced/adaptive Treg (iTreg)
28
where do nTregs come from?
produced directly in thymus and can exert its function as is
29
when are nTregs selected?
have high affinity for self peptides to dampen immune response to them helps prevent autoimmunity
30
what 5 molecules do nTregs express?
1. TCR 2. CD4 3. IL2Ralpha 4. CTLA-4 5. FoxP3 (master transcriptional regulator)
31
do nTregs express IL-2?
no, so they rely on other cells
32
where do iTregs come from?
arise in periphery from CD4+ T cells
33
what 5 molecules do iTregs express?
1. TCR 2. CD4 3. IL2Ralpha 4. CTLA-4 5. usually FoxP3 (master transcriptional regulator)
34
what are the 4 steps of iTreg signaling?
1. signal 3: IL-2, TGF-beta 2. TF: STAT5 3. master transcriptional regulator: FoxP3 4. secretes IL-10, TGF-beta
35
what effector cytokines do both Treg cell types secrete? what type of cytokines are they?
IL-10 and TGF-beta anti-inflammatory cytokines
36
how do IL-10 and TGF-beta affect immune cells? what specific type of immune cell do they mainly affect?
IL-10 and TGF-beta repress immune cells, mainly T cells
37
what are the 4 main functions of Tregs?
1. deplete local area of stimulating cytokines 2. produce immunosuppressive/anti-inflammatory cytokines 3. directly kill T cells 4. inhibit APC activity
38
how do Tregs deplete the local area of stimulating cytokines?
express IL-2Ralpha (CD25) to sequester IL-2 and prevent proliferation signal
39
do Tregs make their own IL-2?
no, they steal it from other cells and only express IL-2Ralpha
40
what anti-inflammatory cytokines do Tregs produce? what do they do?
IL-10 and TGF-beta stop pro-inflammatory cytokines
41
how do Tregs directly kill T cells? (2)
1. granzymes 2. metabolic disruption
42
how do Tregs inhibit APC activity? (2)
1. B7 sequestration by CTLA4 2. endocytose B7 from APCs
43
what are 3 roles of IL-10?
1. inhibits MHC expression from APCs 2. inhibits B7 expression from APCs 3. inhibit production of TH1 and TH17 cytokines
44
what are 2 roles of TGF-beta?
1. inhibits T cell proliferation 2. inhibits development and function of TH1 and TH2
45
where does nTreg arise? why?
nTreg arises in thymus --> mainly recognizes self-peptide:MHC
46
where does iTreg arise? why?
iTreg arises in periphery --> recognizes self-peptide/Ag peptide:MHC