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POM Week 2 > Immune Tolerance > Flashcards

Immune Tolerance Flashcards

1
Q

Define Immune regualtion

A

Control of the immune response to prevent inappropriate immune reactions

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2
Q

Why is immune regulation important?

A

Prevents:
Responses against self
Tissue damage
Excessive lymphocyte activation

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3
Q

What does failure in control result in?

A

Autoimmunity
Allergy
Hypercytokinemia and Sepsis

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4
Q

Define autoimmunity

A

Immune response against self-antigen

Often classified under ‘immune-mediated inflammatory diseases’

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5
Q

What are the two principles of autoimmunity?

A

Susceptibility genes and environmental trigger

Systemic or organ-specific

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6
Q

What are the main features of autoimmune disease?

A

Imbalance between immune activation and control
Immune response is inappropriately directed/ controlled
Many are chronic and self-perpetuating

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7
Q

What are the main features of immune-mediate inflammatory disease?

A 
Chronic with prominent inflammation 
Can be autoimmune or response against microbial antigen 
(Crohn's)
May be caused by T-cells and antibodies
May be systemic or organ specific
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8
Q

What are examples of immune-mediate inflammatory disease?

A

Rheumatoid arthritis
IBS
MS
Psoriasis

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9
Q

What is Allergy?

A

Harmful response to non-infectious antigens that cause tissue damage and disease
Can be mediated by IgE and mast cells (acute anaphylactic shock)
Or mediated by T-cells- delayed type hypersensitivity

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10
Q

What is Hypercytokinemia and Sepsis?

A

Too much immune response
Often in a positive feedback loop
Triggered by pathogen entering the wrong compartment (sepsis) or failure to regulate response to the correct level

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11
Q

How is a response licensed?

A

3 required signal model

  1. Antigen recognition
  2. Co-stimulation: cell-cell contact
  3. Cytokine release
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12
Q

What is self-limiting response?

A

Cardinal feature of all immune responses: SELF LIMITATION
Manifested by decline of immune response
Principle mechanism: immune responses eliminated antigen that initiated responses
First signal for lymphocyte removed

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13
Q

What are the three phases of cell mediated immunity?

A

Induction
Effector
Memory

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14
Q

What are the three options for the end of response?

A

Resolution
Repair
Chronic Inflammation

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15
Q

What is resolution?

A

No tissue damage, returns to normal.

Phagocytosis of debris by macrophages

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16
Q

What is repair?

A

Healing with scar tissue and regeneration

Fibroblast and collagen synthesis

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17
Q

What is chronic inflammation?

A

Active inflammation and attempts to repair damage ongoing

18
Q

What is tolerance?

A

Specific unresponsiveness to an antigen that is induces by exposure to that antigen

19
Q

Why is tolerance important?

A

Therapeutic potential- inducing tolerance may be exploited to prevent graft rejection, treat allergy and auto-immune diseases

20
Q

What is Central tolerance?

A

Destroys self-reactive T or B cells before they enter the circulation

21
Q

What is Peripheral tolerance?

A

Destroy or control any self-reactive T or B cells which do enter the circulation

22
Q

How does central tolerance happen with B-cells?

A

If immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM
Apoptosis is triggers

23
Q

How does central tolerance happen with T-cells?

A

Need to select for T cell receptors which are capable of binding self MHC
Removed if useless or too dangerous

24
Q

What is AIRE?

A

AutoImmune REgulator
Transcription factor that allows expression of all human proteins
Enables self deselection

25
Q

What do mutations in AIRE result in?

A

Multi-organ autoimmunity

26
Q

How does peripheral tolerance work?

A

Removal of self-reactive cells already in circulation

27
Q

What is anergy?

A

Mechanism of peripheral tolerance
Naive T-cells need co-stimulatory signals in order to become activated
Most cells lack these proteins and MHC class II
If naive T-cell sees MHC without appropriate co-stimulatory protein it becomes anergic

28
Q

What does anergic mean?

A

Less likely to be stimulate in future

Even is co-stimulation is then present

29
Q

What is ignorance?

A

Mechanism of peripheral tolerance
Antigen may be present in too low a concentration to reach the threshold for T-cell receptor triggering
Immunologically privileged sites e.g. eye
Compartmentalisation of the cells and antigen control interactions

30
Q

What us antigen induced cell death?

A

Mechanism of peripheral tolerance

Activation through the T-cell receptor can result in apoptosis

31
Q

What are the three mechanism of peripheral tolerance?

A

Anergy
Ignorance
Antigen induces cell death

32
Q

What are the 5 types of T-helper cells?

A 
T-helper 1 cells 
T-helper 2 cells 
Follicular helper T cells
Th17 cells
T-reg
33
Q

What do T helper 1 cells do?

A

Produce interferon gamma

Boost intracellular immune response

34
Q

What do T-helper 2 cells do?

A

Produce IL-4,5,13

Boost anti-multicellular organism réponse

35
Q

What do follicular helper T cells do?

A

Produce IL-21

Essential for generation of isotope-switched antibodies

36
Q

What do Th17 cells do?

A

Secrete IL-17 in autoimmune diseases such as arthritis

Important for the control of bacteria

37
Q

What do T-reg cells do?

A

Regulate the activation of effector functions of other T-cells
Inhibit other T-cells
Necessary to maintain tolerance to self-antigen
Make FoxP3 transcription factor

38
Q

How are T-helpers defined?

A

Cytokines they release

Transcription factors they use

39
Q

Why is regulation key in pregnancy?

A

Pregnancy can be seen as a parasitic infection

Exposure to new antigen

40
Q

How can tolerance be lost?

A

Exposure to environmental antigens or self-antigens in the context of infection can alter the outcome

41
Q

What is IL-10?

A

Key anti-inflammatory cytokine
Multi functional
Acts on a range of cells
Blocks pro-inflammatory cytokine synthesis

POM Week 2 (12 decks)

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