Tolerance and Autoimmunity

Question 1

Describe the two mechanisms that deal with immature T cells that bind self with high affinity

Answer 1

1. Destruction of cell

2. Development of regulatory T cells

Question 2

What stage does Treg cells skip?

Answer 2

They skip the mature naive stage. They go from immature T cells to effector T cells.

Question 3

How are Tregs recognized?

Answer 3

Surface expression of CD4 and CD25( always expressed); Also expresses transcription factor with Foxp3 in the nucleus.

Question 4

Discuss the transcription factor AIRE.

Answer 4

Located in the nucleus of Thymic epithelial cells, it promotes the transcription of genes encoding proteins from major organs. Allows it to present peptides from all organ systems to developing T cells.

Question 5

What is the consequence of an AIRE deficiency?

Answer 5

Autoimmune immature T cells survive in the thymus; Cause massive autoimmunity.

Question 6

How is peripheral tolerance maintained?

Answer 6

1. Suppress the autoreactive T cells by Tregs
2. Conversion of autoreactive T cells into Tregs
3. Apoptosis of autoreactive T cell.
4. Anergized autoreactive T cell

Question 7

Describe an Anergic cell.

Answer 7

A cell that is no longer responsive to antigen stimulation.

Question 8

How does a T cell become anergic?

Answer 8

1. If the TCR binds to MHC/peptide in the ABSENCE of co-stimulation.
2. Co-stimulator molecule is CTLA-4 and PD-1; inhibitory molecules

Question 9

Describe CTLA-4 expression in autoreactive Tcells.

Answer 9

High expression

Question 10

How are mature naive T cells turned into Tregs?

Answer 10

Exposed to high levels of TGF-B in secondary lymphoid tissue; Called an induced Treg.

Question 11

What are the 3 ways a Treg can suppress an autoreactive T cell?

Answer 11

1. Express high levels of CTLA-4 (Binds to B7); Prevents co-stimulation.
2. Express high levels of high affinity IL-2 receptor and starve the autoreactive t cell.
3. Secrete IL-10 and TGF-B; Inhibits Th1 responses.

Question 12

What happens to an autoreactive T cell that is over exposed to self antigens?

Answer 12

A release of cytochrome c from mitochondria in the T cell; Stimulates caspases and apoptoses the cell. Can also express Fas receptor and ligand.

Question 13

What does autoimmunity rely on?

Answer 13

Genetics and Environment

Question 14

What if there is a deficiency in FoxP3?

Answer 14

Patient would not be able to produce Tregs.

Question 15

Discuss the Bystander Effect.

Answer 15

When an APC expresses co-stimulatory molecules after phagocytosing an organism and activates an autoreactive T cell that was close by.

Question 16

Discuss Molecular mimicry.

Answer 16

When a pathogen produces a peptide that mimics a self peptide. This peptide can be presented to and activate autoreactive cells.

Question 17

What are the 3 mechanisms to deal with autoreactive B cells? (central tolerance)

Answer 17

1. Receptor editing; RAG enzymes are activated again to rearrange VL. Heavy chain not rearranged.
2. Destruction
3. Anergy

Question 18

What are the 3 mechanisms to deal with autoreactive B cells?(peripheral tolerance)

Answer 18

1. Anergy
2. Destruction
3. High expression of inhibitory receptors.