Tolerance and Auto-Immunity Flashcards

1
Q

Self tolerance

A

Failure to react against own cells and their components/products

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2
Q

Antigen receptor rearrangement in adaptive immune cells (B and T cells) can result in what?

A

Some cells recognize self-epitopes, creating potential for auto-reactivity
These self-reactive cells need to be dealt with so they don’t cause autoimmune disease

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3
Q

Immune system balance

A

Key to functional immune system
Too much reactivity: autoimmune disease, chronic inflammation
Too much tolerance: immunodeficiency, persistent/overwhelming infection

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4
Q

Negative selection

A

Thymic destruction of self-reactive T cells: strong TCR signaling in response to self-antigen results in apoptosis

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5
Q

Immunologically privileged sites

A

Tissues that have barriers that normally prevent immune cells from entering
Brain, eye, testes, uterus

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6
Q

AIRE

A

Autoimmune regulator
Enables central tolerance to tissue-restricted antigens
Under control of AIRE protein, thymic medullary cells express tissue-specific proteins, deleting tissue-reactive T cells

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7
Q

Transcription factor expressed by T regulatory cells

A

FoxP3

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8
Q

CD4 T cells with strong reactivity to self can become what type of T cells?

A

T regulatory cells

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9
Q

Function of T regulatory cells

A

Suppression of peripheral immune responses

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10
Q

Mechanisms of T regulatory suppression

A

Production of immunosuppressive cytokines
Outcompete effector T cells for IL2, inhibiting their expansion
Interfere with ability of antigen presenting cells to provide activating signals

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11
Q

Peripheral (outside of bone marrow and thymus) mechanisms to control self-reactive T cells

A

Apoptosis, anergy, regulation

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12
Q

Anergy of T cells

A

Functional unresponsiveness: diminished ability to divide, produce cytokines, kill target cells
Induced by APCs presenting self-antigen to T cells in absence of inflammation through T cell receptor only, causing anergic tolerance of self-reactive T cells

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13
Q

Tolerance failure of B cells

A

Auto-antibodies, those directed against self, can result in autoimmune disease

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14
Q

Central tolerance mechanisms of B cells

A

Death of self-reactive cells
Induction of anergy
Receptor editing: B cell continues light chain rearrangement, producing new BCR

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15
Q

Peripheral tolerance mechanisms of B cells

A

Induced to die
Become anergic in spleen
B cells that have undergone somatic hypermutation can be tested for auto-reactivity again: those that remain self-reactive undergo apoptosis

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16
Q

Tolerance is more easily induced under what conditions?

A

Induced during neonatal stage

Oral intake of substance

17
Q

Examples of tolerance

A

Tolerance to fetus in pregnancy
Oral tolerance
Tolerance to innocuous foreign substances (dyes, detergents, etc.)

18
Q

Autoimmune disease is caused by failure of what?

A

Self-tolerance

19
Q

Examples of autoimmune diseases

A
Psoriasis
Rheumatoid arthritis
Grave's disease
Lupus
Crohn's disease
Multiple sclerosis
Type 1 diabetes
20
Q

Autoimmune disease: incidence

A

Common, and increasing

21
Q

What types of cells mediate autoimmune diseases?

A

B and T cells

22
Q

Are autoimmune diseases systemic, or organ specific?

A

Some are systemic (lupus, rheumatoid arthritis)

Some are organ-specific (Crohn’s disease, multiple sclerosis, type 1 diabetes)

23
Q

Many autoimmune diseases are linked to what gene?

A

HLA (human leukocyte antigen, encodes MHC)

24
Q

What gender are autoimmune diseases more common in?

A

Women

25
Q

Can environmental factors play a role in autoimmune disease?

A

Yes- food (gluten, etc.), stress, toxins (smoking, etc.), infection

26
Q

Do immune alterations and symptoms of autoimmune disease happen at the same time?

A

No- early environmental exposure can trigger events that later lead to autoimmune disease

27
Q

How can tissues that are normally protected become targets of autoimmune disease?

A

Damage to tissues that are normally protected can cause the release of self-antigens

28
Q

Molecular mimicry and autoimmune disease

A

Epitopes found in a pathogen can be same as or very similar to self-epitopes
Results in production of cross-reactive antibodies or activation of auto-reactive T cells

29
Q

Perpetuation and amplification of autoimmune disease

A

Breach of tolerance leads to more inflammation and self-antigen exposure

30
Q

Treatment of autoimmune disease

A

Immunosuppression

Newer treatment: monoclonal antibody therapy (deplete immune cells or block pathologic cytokines)