Tolerance and Autoimmunity - Morell

Question 1

What is meant by immune tolerance?

Answer 1

Unresponsiveness to self antigens, while maintaining responsiveness to foreign antigens.

Question 2

Central mechanisms of tolerance occur when?

Answer 2

During lymphocyte development.

Question 3

Peripheral mechanisms of tolerance occur when?

Answer 3

After lymphocyte maturation

Question 4

Where does central tolerance occur?

Answer 4

Bone marrow (B-cells) and Thymus (T-cells)

Question 5

The process by which self-reactive TCR/BCRs undergo apoptosis during development is called?

Answer 5

Negative selection

Question 6

Which protein turns on expression of self protein in the thymus during T-cell development?

Answer 6

AIRE

Question 7

3 ways B-cells deal with self-reactivity

Answer 7

1. Receptor editing (VDJ recomb. light chain).
2. Clonal deletion
3. Anergy

Question 8

Some self-reactive T-cells that do not undergo deletion become?

Answer 8

Regulatory T-cells (Tregs)

Question 9

3 Mechanisms of peripheral tolerance

Answer 9

1. Immune privilege
2. Anergy/Deletion
3. Tregs/Bregs

Question 10

Immune privileged sites include

Answer 10

Brain, eye, testes, uterus (fetus)

Question 11

Expression markers for Tregs

Answer 11

CD25, CD4, and Foxp3 (txn factor).

Question 12

Peripheral anergy

Answer 12

Anergic T-cells as a function of only receiving one activation signal (MHC-peptide) without signal 2 (B7/CD28).

Question 13

Examples of organ-specific autoimmune diseases

Answer 13

T1D, Myasthenia gravis, autoimmune

Question 14

Examples of systemic autoimmune diseases

Answer 14

Rheumatoid arthritis

Question 15

Antibody-mediated disease which causes destruction of erythrocytes through recognition of Rh.

Answer 15

Hemolytic anemia

Question 16

Graves Disease

Answer 16

Antibodies against thyroid stimulating hormone receptor cause release of thyroxine and hyperthyroidism

Question 17

Myasthenia Gravis

Answer 17

Antibodies against acetylcholine receptors – No muscle contraction

Question 18

Goodpasture’s Syndrome

Answer 18

Antibodies against basement membrane in the kidney. Recruitment of neutrophils and macrophages –> Inflammation

Question 19

Type 1 Diabetes

Answer 19

T-cell mediated killing of insulin-producing Beta cells in the pancreas.

Question 20

Which T-cell subsets are thought to contribute most to autoimmune disorders?

Answer 20

Th1 and Th17

Question 21

Post-translational modification that is associated with rheumatoid arthritis.

Answer 21

Citrullinated proteins