Immunological Tolerance

Question 1

What is tolerance?

Answer 1

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

Question 2

What is central tolerance?

Answer 2

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

Question 3

What is peripheral tolerance?

Answer 3

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

Question 4

What are the two options for a T cell that has a high affinity for self-antigen in the thymus?

Answer 4

1. Deletion by apoptosis.

2. Become regulatory T cells.

Question 5

The transcription factor responsible for the regulation of expression of peripheral proteins in the thymus is encoded by what gene?

Answer 5

Autoimmune Regulatory Gene (AIRE)

Question 6

What syndrome occurs when AIRE is defective?

Answer 6

Autoimmune Polyendocrine Syndrome (APS).

Question 7

How can autoimmune polyendocrine syndrome (APS) present?

Answer 7

1. Mucocutaneous candidiasis.
2. Hypoparathyroidism.
3. Adrenal insufficiency.

Question 8

What do regulatory T cells express?

Answer 8

CD25 and transcription factor Foxp3.

Question 9

What arises from a mutation in Foxp3?

Answer 9

IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome).

Question 10

What cytokines do regulatory T cells produce?

Answer 10

IL-10 (inhibits activation of lymphocytes)

TGF-Beta

Question 11

What three things can occur when a self reactive T cell i the periphery encounters its self antigen?

Answer 11

1. Anergy
2. Apoptosis
3. Suppression by T reg cells.

Question 12

What are 2 ways a T cell can be put in a state of anergy?

Answer 12

1. Lack of costimulation.

2. Inhibitory receptors.

Question 13

What two signals to CD4 helper T cells need to be activated?

Answer 13

1. MHC/antigen

2. B7 binding CD28

Question 14

What inhibitory receptor do T cells use when the recognize self antigens?

Answer 14

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

Question 15

When is CTLA-4 expressed?

Answer 15

Always on reg T cells, on cytotoxic T cells AFTER activation, serving as an “off switch”.

Question 16

What has a higher affinity for B7, CD28 or CTLA-4?

Answer 16

CTLA-4

Question 17

What two pathways of apoptosis can be triggered by peripheral engagement of a T cell with a self antigen?

Answer 17

1. Poor costimulation causing the leak of mitochondrial proteins which will activate caspases (enzymes that induce apoptosis).
2. Poor costimulation leading to stimulation of Fas-FasL apoptosis pathway.

Question 18

What do reg T cells express that blocks B7 on APCs?

Answer 18

CTLA-4

Question 19

What two processes can occur when B cells encounter self antigen in the bone marrow?

Answer 19

1. Edit their receptors

2. Deletion through apoptosis

Question 20

What genes are reactivated during B cell receptor editing?

Answer 20

RAG genes

Question 21

Which Ig chain is edited during B cell receptor editing?

Answer 21

Light chain.

Question 22

What type of dendritic cells promote reg T cells?

Answer 22

CD103+ dendritic cells.