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MIIM30003 > Immune Regulation > Flashcards

Immune Regulation Flashcards

1
Q

what is the central mode of regulation?

A

repertoire selection

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2
Q

What is the peripheral mode of regulation?

A

peripheral deletion
anergy
regulatory receptors
regulatory T cells

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3
Q

When does central tolerance take place?

A

during formation of T and B cells to remove auto reactive T and B cells

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4
Q

How does deletion of T cells in periphery occur?

A

apoptosis of T cells
targets mitochondrial pathway of killing
extrinsic or intrinsic

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5
Q

How does intrinsic deletion through apoptosis occur?

A

lack of IL-2 and IL-7 leads to upregulation of p53 - proapoptotic factors

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6
Q

How does extrinsic deletion through apoptosis occur?

A

through Fas/FasL pathway

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7
Q

What causes suppression of T cell responses/inhibition

A

response to chronic stress
tumours, viral infection

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8
Q

How does inhibition via CTLA-4 occur?

A

cytotoxic T lymphocyte associated protein 4 (CD152) binds CD80 and CD86 on APCs. inhibits via decoy or intracellular activity

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9
Q

How does inhibition via PD-1 occur?

A

programmed cell death 1
binding to PD-L1 and PD-L2
important in modulating immune responses

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10
Q

What is exhaustion?

A

persistent stimulation of T cells

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11
Q

What is stalemate?

A

virus/tumour-immune equilibrium

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12
Q

What are 4 medications used to manipulate checkpoint blockades?

A
  1. ipilimumab
  2. involumab
  3. pembrolizumab
  4. atezolizumab
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13
Q

What is the proposed role of PD1

A

suggested it can establish and reverse HIV latency

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14
Q

Where does generation of Treg cells occur?

A

can occur in thymus or periphery

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15
Q

What is the dual role of TGFb

A

TGFb is typically anti-inflammatory but can also stimulate naive T cells

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16
Q

What are 2 effector functions of Treg cells

A

can act on other T cells or APCs
important balance in immune responses

17
Q

What are the suppressive cytokines of Treg cells

A

TGFb and IL-10
leads to alteration of transcription program

18
Q

How do Treg cells promote cell death?

A

express granzymes and perforin usually in CD8 T cells
requires Tregs to have long stimulation

19
Q

How do Treg cells disrupt function?

A

reduce metabolic capacity, which means less energy for effector functions
high affinity IL-2 receptor
displaced T cell interactions w DC

20
Q

Describe the role of granzyme B in inflammation and apoptosis

A

granzyme B triggers apoptosis but can also have other inflam effects

21
Q

What is tolerance?

A

process by which immune cells are made non-responsive to self-antigens

22
Q

What is AIRE?

A

an important regulator for -ve selection in thymus
eg. in presence of AIRE protein, thymic medullary cells express tissue-specific proteins leading to deletion of tissue-reactive T cells
eg. in absence of AIRE, T cells reactive to tissue-specific antigens mature and leave the thymus

23
Q

What is APS Type 1

A

lack of AIRE resulting in autoimmune reactions against endocrine glands

24
Q

What is peripheral tolerance for B cells?

A

second checkpoint, similar to central tolerance
receptor editing doesn’t happen bc these cells are mature and can’t rearrange light-chain loci

25
Q

Link between somatic hypermutation and auto reactive B cells?

A

auto reactive B cells can form during somatic hypermutation
will be at a competitive disadvantage in GC reactions

26
Q

How does antigen sequestration/ignorance occur?

A

happens in situations where escaped cells don’t ever see antigen
can happen in sympathetic ophthalmia

27
Q

How does suppressing immune response lead to anergy?

A

inhibition of TCR signalling through Cbl-b which attaches to ZAP-70
ubiquitinatino of complex leads to degradation

28
Q

When does molecular mimicry occur?

A

when antigen is structurally similar to self-proteins

29
Q

How do auto reactive cells become anergic?

A

when stimulated with antigen under non-inflam conditions and made active again with sufficient stimulation

30
Q

What 2 situations break down tolerance mechanisms?

A
  1. molecular mimicry
  2. alloreactivity
31
Q

What are tolerogenic DCs?

A

DCs which still present Ag but down regulates co-stimulatory molecules and up regulates inhibitory molecules

32
Q

Use an examples to describe how gut microbiota can affect DCs

A

polysaccharide A of B.fragilis interacts with TLR2 of DCs to alter signalling and protects against experimental colitis
cause disease and metabolic conditions

33
Q

What does central tolerance involve for T cells?

A

removing auto reactive T lymphocytes during development

34
Q

How does peripheral tolerance work in T cells?

A

occurs via self antigen presentation or antigen sequestration

35
Q

What are 3 ways that Tregs can become activated against auto antigen?

A
  1. produce cytokines to dampen immune response
  2. direct killing of auto reactive cells
  3. disrupting function of auto reactive cells so its harder to exert effector functions

MIIM30003 (5 decks)

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