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POM Flashcards (Y1) > Immune Tolerance > Flashcards

Immune Tolerance Flashcards

1
Q

Why is immune regulation necessary?

A

Avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
Prevent inappropriate reactions against self antigens

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2
Q

Give the definition of autoimmunity

A

Immune response against self antigen

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3
Q

Is autoimmunity physiological or pathological?

A

Pathological

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4
Q

What are the features of autoimmune disease?

A
  • Imbalance between immune activation and control
  • Underlying cause: failure of control mechanisms
  • Underlying causative factors: susceptibility genes + environmental influences (more prevalent in women)
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5
Q

What is Crohn’s Disease caused by?

A

Immune responses against microbial agents

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6
Q

What is the definition of an allergy?

A

Harmful immune responses to non-infectious agents that cause tissue damage and disease.

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7
Q

What are allergic reactions mediated by?

A
  • IgE antibody and mast cells (acute anaphylactic shock)

- T cells - delayed hypersensitivity

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8
Q

In Hypercytokinemia and Sepsis, what is wrong with the immune response?

A

Too much immune response
Often a positive feedback loop
Triggered by pathogens entering wrong compartment (sepsis) of failure to correctly regulate immune response

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9
Q

Give the steps of cell-mediated immunity

A

Induction - Cell infected DC collects material
MHC:peptide TCR interaction
Effector - Naive T cell becomes effector
Effector cell sees MHC:peptide on infected cell; performs function (e.g, apoptosis - CD8)
Memory - Effector pool contracts to memory

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10
Q

What is the cardinal feature of all immune responses?

A

Self-limitation
Immune response eliminates antigen that initiated the response and then immune response declines as activation signals decrease

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11
Q

What are the 3 signals that are required to activate the T or B cells?

A

Antigen Recognition
Co-Stimulation - protein interactions on cell surface of APC, T cells and B cells
Cytokine Release

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12
Q

Describe the 3 possible end outcomes of infection

A

Resolution - No tissue damage, returns to normal. Phagocytosis of debris by macrophages.
Repair - Healing with scar tissue and regeneration. Fibroblasts and collagen synthesis.
Chronic Inflammation - Active inflammation and attempts to repair damage ongoing.

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13
Q

What is meant by immunological tolerance?

A

Tolerance is specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen.

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14
Q

What condition occurs when there is a lack of immunological tolerance?

A

Autoimmunity

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15
Q

What is the therapeutic potential of immunological tolerance?

A
  • Can be exploited to prevent graft rejection, treat autoimmune and allergic diseases
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16
Q

What are the 2 types of tolerance?

A

Central - destroy self-reactive T or B cells before they enter circulation
Peripheral - destroy self-reactive T or B cells once they are in circulation

17
Q

How does B cell selection occur in the bone marrow?

A

If immature B cells encounter antigen in a form which can crosslink their IgM, apoptosis is triggered.

18
Q

Which 3 ways does T cell selection occur in the thymus?

A

Useless - Doesn’t bind to any self-MHC at all; death by neglect (apoptosis)
Dangerous - Binds to self-MHC too strongly; apoptosis triggered (negative selection)
Useful - Binds self-MHC weakly; signal to survive (positive selection)

19
Q

How can a T-cell developing in the thymus encounter MHC bearing peptides expressed in other parts of the body?

A

Specialised transcription factor - Autoimmune Regulator (AIRE) - allows thymic expression of genes that are expressed in peripheral tissue

20
Q

What happens if there is a mutation in AIRE?

A

Multi-organ immunity (APECED)

21
Q

What are the fates of self-reactive lymphocytes in central tolerance?

A

Apoptosis
Change in receptors (receptor editing - B cells)
Development of regulatory T cells (CD4 + T cells only)

22
Q

What are the fates of self-reactive lymphocytes in peripheral tolerance?

A

Anergy
Apoptosis
Suppression

23
Q

What are the 3 pathways that a B cell can go into after maturation?

A

Antibody Production
Memory
Affinity maturation (self-reactive B cells can develop at this point)

24
Q

Describe what affinity maturation is

A

B cells can change specificity after leaving bone marrow
This improves antibody quality
Exposure to environmental antigens self-antigens in the context of infections can make them less tolerogenic

E.g Anti-Streptococcus pyrogens antibodies can cross react with heart muscle

25
Q

What is Anergy?

A

Anergy is one of three processes that induce tolerance, modifying the immune system to prevent self-destruction.

26
Q

How does Ignorance lead to peripheral tolerance of T cells?

A

T cells contract as a population, become anergic or no longer reactive

27
Q

At which sites specifically, would ignorance occur in this context?

A

Immunologically privileged sites (or compartmentalisation of cells) where T cells don’t come into contact with antigen
Immune reactions may cause more harm than good and so antigens in these sites do not elicit an immune response, e.g. eyes or brain

28
Q

Describe Antigen Induced Cell Death in context of peripheral tolerance of T cells

A

Activation of T cell receptors influenced by nature of initial T cell activation events can result in apoptosis instead of development into memory cell
In peripheral T cells it is often caused by induction of expression of death ligand, Fas ligand CD95

29
Q

What do T regulatory cells do?

A

Block T cell activation
Inhibit effect of matured T cells
Inactive DCs and other lymphocytes
Through production of immune-suppressive cytokines (TGF-beta, IL-10, IL-35)

30
Q

What transcription factor do Treg cells express and what condition is caused by a mutation in this TF?

A

FoxP3
Severe and fatal autoimmune disorder - IPEX syndrome
Scurfy in mice

31
Q

Describe the function of IL-10

A 
Key anti-inflammatory cytokine
Pleiotropic - multi-functional 
Blocks pro-inflammatory cytokine synthesis including TNF, IL-6, IL-8, IFN-gamma
Acts on a range of cells
Down-regulates macrophage function 
Has viral mimics (EBV virus)
32
Q

What might be the reason for T-regulatory cells being present in only mammals?

A

Critical in pregnancies
Foetus gets half MHC from mum and other half from dad
These may be seen as foreign antigens
Immunological tolerance is necessary

33
Q

Describe the 2 different types of T-regulatory cells

A

Natural T-regulatory cells (nTreg)
- Development in thymus and requires recognition of self antigen during T cell maturation
- Reside in peripheral tissues to prevent harmful reactions against self
Inducible regulatory T cells (iTreg)
- Develop from mature CD4 T cells that are exposed to antigen in periphery
- May be generated during immune responses to prevent collateral damage

Tregs reflect the Th subsets seen in T effectors

34
Q

What is the function of chemokines?

A

Chemokines drive movement around the body
Act like address labels sending stuff to the right place
Chemokine receptor profiles change with activation state of cells
Cells move up chemokine gradient

35
Q

What are the functions of cytokines?

A

Program the immune response
Focus it for the right kind of response
Can be inflammatory or anti-inflammatory
Examples: IFN-gamma, IL-2, IL-10

36
Q

What defines T helper cell type?

A

Transcription factors

Cytokines shake transcription factor pathways

37
Q

What is it called when CD4 cells neutralise one another?

A

Cross regulation

38
Q

Explain how T cells boost antibody responses (in terms of licensing model)

A
  1. Antigen
    T cell - MHC:peptide on DC or B cell
    B cell - soluble antigen
  2. Co-stimulation
    T cell - expresses CD40L to activate B; expresses CD28 to be activated
    B cell - expresses CD40 to be activated by T cell; expresses B7 to activated T cell
  3. Cytokine: IL-21
39
Q

Explain the process in which T cells shape the antibody response

A 
CD4 T cells release a certain type of cytokine
Cytokine detected by B cell
The antibody that the B cell will produce will now have it constant region altered (gene cassettes can be swapped in and out), determining its class (A, D, E, G or M)
This way, the class of antibody produced is dependent on the cytokine triggered
The cytokine released depends on T helper cell type

POM Flashcards (Y1) (28 decks)

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