Lecture 26 Flashcards

1
Q

What does negative regulation involve?

A

Receptors, mechanisms, and cell types (Tregs)

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2
Q

How do Tregs dampen effect T cell responses (post infection)

A

Tregs release inhibitory cytokines

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3
Q

Pathways of Apoptosis

A

Intrinsic and Extrinsic pathways

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4
Q

What is the Intrinsic pathway of apoptosis

A

Death by neglect
T cell gets activated (signal 1 and 2)–>produce cytokines with transient receptors (IL2Ralpha) (impermanent)–>eventually signaling stops through these receptors–>lack of signaling = absence of survival signal–>apoptosis

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5
Q

What is the Extrinsic pathway of apoptosis

A

Rely on external source to initiate apoptosis
Triggered by Fas-FasL
involves CTLs

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6
Q

What causes activation on APC and T cells

A

B7.1 and B7.2 binding on antigen presenting cells = activation
CD28 binding on T cells = activation

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7
Q

What interaction causes negative regulation

A

CTLA4 interacting with B7.1 and B7.2 to block T cell activation

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8
Q

Examples of an inhibitory/regulatory receptors

A

CTLA4 and PD1

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9
Q

What receptor is expressed on Naive T cells

A

CD28

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10
Q

What receptors do T cells express 24 hours activation

A

CD28 AND CTLA-4 receptors (regulatory function to prevent overexpression of T cells)

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11
Q

Where is CTLA-4 found before post translational modification

A

Intracellularly

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12
Q

Where is CTLA-4 found after post translational modification

A

Phosphorylation allows CTLA-4 to be expressed on cell surface

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13
Q

Consequence of negative regulation by CTLA-4

A

Inhibit proliferation of T cells

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14
Q

Where is PD-1 expressed

A

On activated T cells

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15
Q

What does PD-1 bind to

A

PDL-1 (expressed on many cells) and PDL-2 (on APC during inflammation)

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16
Q

Consequence of PD-1 signaling

A

Downregulation of T cell activation

17
Q

What is PD-1 a marker of

A

T cell exhaustion (apparent in chronic disease)

18
Q

What cytokines are associated with iTreg’s Signal 3

A

IL-2 and TGFbeta

19
Q

What effector cytokines are associated with iTreg

A

IL-10 and TGFbeta (anti-inflammatory cytokines)

20
Q

What master transcriptional regulator is associated with iTregs

A

FoxP3

21
Q

Main action of iTreg

A

iTregs suppress immune responses to maintain immune tolerance to self antigens (prevent autoimmunity)

22
Q

What are the Treg subsets

A

Natural Tregs and Induced (adaptive) Tregs

23
Q

Where are natural Tregs derived

A

Thymus-derived

24
Q

How are natural Tregs selected

A

Selected for high affinity for self peptides to dampen immune response to them

25
Q

Which receptors do natural Tregs express

A

TCR, CD4, IL2Ralpha, CTLA-4
Also express FoxP3 (master transcriptional regulator)

26
Q

Where do induced Tregs/iTregs arise

A

In periphery from CD4+ T cells

27
Q

What receptors do iTregs express

A

TCR, CD4, IL2Ralpha, and CTLA-4
Also express FoxP3 but some exceptions

28
Q

iTreg signaling pathway

A

Naive CD4+ T cell–>IL-2 and TGFbeta (signal 3)–>STAT 5 (transcription factor)–>FoxP3 (master transcriptional regulator)–>IL-10 and TGFbeta secretion

29
Q

Action of Tregs (both natural and induced)

A

1) Secrete IL-10 and TGF-beta
2) Represses other immune cells, mainly T cells

30
Q

How do Tregs cells negatively regulate immune responses

A

1) Deplete local area of stimulating cytokines (express IL2Ralpha (CD25) chain–>sequester IL-2)
2) B7 sequestration by CTLA-4
3) Produce immunosuppressive cytokines (IL-10 and TGFbeta)
4) Directly kill T cells through granzymes and metabolic disruption

31
Q

Consequences of B7 sequestration by CTLA-4

A

1) Inhibits APC activity by reducing co-stimulatory molecule expression and pro-inflammatory cytokine secretion
2) Reduce T cell differentiation and activation

32
Q

Action of IL-10 (Treg anti-inflammatory cytokine)

A

Inhibits production of TH1 and TH17 cytokines

33
Q

Action of TGFbeta (Treg anti-inflammatory cytokine)

A

Inhibits T cell proliferation and inhibit the development and function of TH1 and TH2