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MIIM30002 > Lecture 27: Immunoregulation > Flashcards

Lecture 27: Immunoregulation Flashcards

1
Q

What is immune regulation important for?

A

the maintenance of immune responses to avoid excessive damage

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2
Q

What are the basic modes of regulation?

A

central e.g. repertoire selection

peripheral e.g. peripheral deletion, anergy, regulatory receptors, regulatory T cells

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3
Q

What is AIRE?

A

an important regulator involved in the expression of antigen from different sites of the body
not possible to express every single type

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4
Q

What is Autoimmune Polyglandular Syndrome (APS) Type 1 caused by?

A

lack of AIRE resulting in autoimmune reactions against endocrine glands

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5
Q

Why is central tolerance not perfect?

A

some clones may be able to escape selection and leave the thymus

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6
Q

Why is peripheral tolerance important?

A

potential formation of autoreactive B cells during somatic hypermutation

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7
Q

What do activation thresholds of B cells prevent?

A

stimulation by autoantigens e.g. B cells specific for the constant region of IgG -> rheumatoid arthritis

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8
Q

When does antigen sequestration occur?

A

in situations where escaped cells never see the antigens (antigen is never presented to T cells)
relevant for immune privileged sites

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9
Q

What can antigen sequestration result in?

A

instances such as sympathetic ophthalmia

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10
Q

What is the role of central tolerance during the formation of T and B cells?

A

help with removing autoreactive T cells

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11
Q

When does self presentation usually occur?

A

in the absence of inflammation

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12
Q

How does peripheral T cell tolerance occur?

A

removal of autoreactive T cells through apoptosis

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13
Q

How are T cells triggered to undergo apoptosis (deleted) during peripheral T cell tolerance (intrinsic)?

A

targeting the mitochondrial pathway of killing - intrinsic

lack of IL-2 and IL-7 signaling leads to upregulation of Bim which executes apoptosis

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14
Q

How are T cells triggered to undergo apoptosis (deleted) during peripheral T cell tolerance (extrinsic)?

A

through Fas/FasL pathway

also important in regular immune responses

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15
Q

How does anergy contribute to peripheral T cell tolerance?

A

renders cells unresponsive
involves biochemical signals to modulate TCR signalling
can be overridden with strong stimuli

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16
Q

How does anergy occur?

A

inhibition of TCR signalling through CbI-b

involved in the normal cessation of immune responses

17
Q

What is the role of inhibition in regards to peripheral T cell tolerance?

A

response to chronic stress e.g. tumours and persistent viral infections

18
Q

How does inhibition occur?

A

cytotoxic T lymphocyte associated protein 4 binds CD80 and CD86 (B7.1 B7.2) on APCs
inhibits activated T cells via decoy or intracellular activity

19
Q

What is the role of PD-L1 and PD-L2?

A

important in modulating immune responses

PD-1 = programmed cell death 1

20
Q

What does persistent stimulation of T cells lead to?

A

exhaustion which produces a stalemate situation where there is a virus/tumour-immune equilibrium

21
Q

What is a proposed role of PD-1?

A

role in the establishment and reversal of HIV latency

22
Q

What can peripheral tolerance manage?

A

detection of self-antigen in the periphery in multiple ways

23
Q

How can deletion of self-reactive T cells occur?

A

via the Fas-FasL pathway

24
Q

How can autoreactive cells be rendered anergic?

A

when stimulated with antigen under

non-inflammatory conditions

25
Q

How can autoreactive or overactive T cells be inhibited?

A

via engagement with inhibitory checkpoint markers (CTLA4 and PD1 as molecules of interest)

26
Q

What can manipulation of checkpoint blockades open up?

A

strategies for managing chronic infections and anti-tumour responses

27
Q

Where can Treg cells be generated? Which cells are committed to the Treg lineage?

A

in the thymus or in the periphery

thymocytes at the cusp of negative selection can be committed to the Treg lineage

28
Q

What is an indicator of Treg cells?

A

transcription factor Foxp3

29
Q

What are IL-2 and TGF-beta important for?

A

the induction of Foxp3

30
Q

What is the dual role of TGF-beta?

A

an anti-inflammatory cytokines which is also involved in the stimulation of naive T cells which dictates the inflammatory nature of the cell depending on the presence of absence of IL-6

31
Q

What happens if there is no IL-6 present during stimulation of naive T cells?

A

presentation of microbiota derived antigens by retinoic acid producing DCs promote Treg formation since there is no IL-6 present to suppress retinoic acid

32
Q

What happens if there is IL-6 present during stimulation of naive T cells?

A

suppresses retinoic acid and favours development of Th17

33
Q

What are the effector functions of Treg cells?

A

can act on other T cells or APCs

suppressive cytokines and secreted molecules, cytolysis, metabolic disruption, targeting DCs by other mechanisms

MIIM30002 (25 decks)

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