Tolerance and Auto-Immunity

Question 1

Self tolerance

Answer 1

Failure to react against own cells and their components/products

Question 2

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

Answer 2

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

Question 3

Immune system balance

Answer 3

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

Question 4

Negative selection

Answer 4

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

Question 5

Immunologically privileged sites

Answer 5

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

Question 6

AIRE

Answer 6

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

Question 7

Transcription factor expressed by T regulatory cells

Answer 7

FoxP3

Question 8

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

Answer 8

T regulatory cells

Question 9

Function of T regulatory cells

Answer 9

Suppression of peripheral immune responses

Question 10

Mechanisms of T regulatory suppression

Answer 10

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

Question 11

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

Answer 11

Apoptosis, anergy, regulation

Question 12

Anergy of T cells

Answer 12

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

Question 13

Tolerance failure of B cells

Answer 13

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

Question 14

Central tolerance mechanisms of B cells

Answer 14

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

Question 15

Peripheral tolerance mechanisms of B cells

Answer 15

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

Question 16

Tolerance is more easily induced under what conditions?

Answer 16

Induced during neonatal stage

Oral intake of substance

Question 17

Examples of tolerance

Answer 17

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

Question 18

Autoimmune disease is caused by failure of what?

Answer 18

Self-tolerance

Question 19

Examples of autoimmune diseases

Answer 19

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

Question 20

Autoimmune disease: incidence

Answer 20

Common, and increasing

Question 21

What types of cells mediate autoimmune diseases?

Answer 21

B and T cells

Question 22

Are autoimmune diseases systemic, or organ specific?

Answer 22

Some are systemic (lupus, rheumatoid arthritis)

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

Question 23

Many autoimmune diseases are linked to what gene?

Answer 23

HLA (human leukocyte antigen, encodes MHC)

Question 24

What gender are autoimmune diseases more common in?

Answer 24

Women

Question 25

Can environmental factors play a role in autoimmune disease?

Answer 25

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

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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

Question 28

Molecular mimicry and autoimmune disease

Answer 28

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

Question 29

Perpetuation and amplification of autoimmune disease

Answer 29

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

Question 30

Treatment of autoimmune disease

Answer 30

Immunosuppression

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