Immunological Tolerance

Question 1

Tolerance:

Answer 1

Lack of an immune response when immune cells are exposed to antigen.

Question 2

Central tolerance:

Answer 2

Elimination of self reactive T and B cells during development in the thymus or bone marrow.

Question 3

Peripheral tolerance:

Answer 3

Mechanisms after the lymphocyte has left bone marrow or thymus and encounters self antigen.

Question 4

When T cells show a high affinity for self-antigen in the thymus (2):

Answer 4

1. Deleted by apoptosis.

2. Survive and become regulatory T cells.

Question 5

Transcription factor that regulates the expression of peripheral proteins in thymic tissue:

Answer 5

AIRE

- Autoimmune regulatory gene.

Question 6

AIRE (3):

Answer 6

• Encodes a transcription factor that is expressed in the thymic medulla.
• Controls the expression of the thymic tissue restriction antigens.
• When defective –> autoimmunity.

Question 7

Regulatory T cells (4):

Answer 7

• Most are CD4 T cells.
• Inhibit the activation of conventional CD4 and CD8 T cells and thus can prevent autoimmune and allergic disease.
• Produce IL-10 and CTLA-4.
• Express CD25 and transcription factor Foxp3.

Question 8

When a self reactive T cell in the periphery encounters its self antigen it (3):

Answer 8

1. Anergy.
2. Deletion through apoptosis.
3. Suppression by T regulatory cells.

Question 9

Anergy:

Answer 9

A state of immune unresponsiveness after antigen encounter.

• Absent co-stimulation.
• CTLA-4 binds and blocks B7 on the APC and delivers inhibitory signals to the T cell.

Question 10

CTLA-4:

Answer 10

Always expressed on Treg cells and is expressed on cytotoxic T cells after their activation, serving as an “off switch”.
- Has higher affinity for B7 than CD28.

Question 11

Suppression by Tregs (4):

Answer 11

• Grow in response to IL-2.
• Produce cytokines IL-10 and TGF-beta.
• Express CTLA-4.
• Consume IL-2 so that is unavailable for effector T cells.

Question 12

When developing B cells encounter self antigen in the bone marrow (2):

Answer 12

1. Edit receptors.

2. Deletion through apoptosis.

Question 13

B cell receptor editing (3):

Answer 13

• Reactivate RAG genes.
• Resume Ig light chain recombination and make new light chain.
• Same heavy chain is expressed.