Immune recognition and immune tolerance

Question 1

Where do Pre-T cells mature?

Answer 1

In the Thymus

Question 2

Describe the process of Thymic Education.

Answer 2

1. Expression of a functional TCR and double positive expression of CD4+ and CD8+ -TCR genes rearranged and paired. Thymocytes with a non-functional TCR die.
2. Positive Selection in the medulla for self MHC - Thymocytes that recognise MHC II will lose their CD8+ and Thymocytes that recognise MHC I will lose their CD4+. Cells that do not recognise either will die by neglect.
3. Negative Selection in the cortex to eliminate high affinity self-reative T cells - Cells that bind to Thymic Medullary Epithelial Cells (TMECs) with low/moderate affinity survive. Those which bind with high affinity are actively destroyed.

Question 3

What are the cells that are crucial in testing the strength of affinity of thymocytes during Negative Selection?

Answer 3

Thymic Medullary Epithelial Cells (TMECs)

These cells possess transcription factors that allow them to express Tissue Restricted Antigens (TRAs) - self tissue antigens

Examples of some TRAs:

Question 4

Failure of TMECs leads to what kind of diseases?

Give an example

Answer 4

Autoimmune diseases such as APS type 1

(Autoimmune Polyendocrine Syndrome)

Question 5

Some T cells that pass thymic education and escape into the periphery might still have a high affinity for self antigens. How are these T cells dealt with?

Answer 5

Peripheral Tolerance Mechanisms:

1. Anergy - Signal 2 is not provided as APCs do not upregulate expression of CD86 when infection/inflammation is not present. T cell becomes unresponsive to future stimulation.
2. Treg Cells - Suppression through cell-cell contact and via the release of anti-inflammatory cytokines.

Question 6

For which 3 situations is peripheral tolerance with anergy useful?

Answer 6

1. Tolerance to antigens not expressed in the thymus
2. Tolerance to food antigens
3. Tolerance to commensal bacteria

Question 7

What are the 2 main types of Regulatory T cells?

Answer 7

1. nTreg - Produced in the thymus and respond to self antigens.
2. aTreg - Developed in the periphery in response to constant low level exposure to antigen.

Question 8

Deficiency in nTreg results in the development of what multiple autoimmune disease condition?

What causes this?

Answer 8

IPEX

Dysfunction in the FOXP3 transcription factor that is necessary in Treg development.

Question 9

Where does activation of naive lymphocytes take place?

Answer 9

In secondary lymphoid organs.

Question 10

Which cytokines are produced by Th1 cells?

Answer 10

Question 11

Which cytokines are produced by Th2 cells?

Answer 11

Question 12

Which cytokines are produced by Th17 cells?

Answer 12

Question 13

Which cytokines are produced by Treg cells?

Answer 13

Question 14

True or False: Most effector T and B cells die by neglect/cytokine starvation following the removal of an infection.

Answer 14

True

Macrophages then remove the apoptosed cells.

Question 15

Where do T memory cells reside following the clearance of infection?

Answer 15

Bone marrow

Question 16

Where do Plasma cells reside following the clearance of infection?

Answer 16

Lymph nodes

Question 17

Where do B memory cells reside following the clearance of infection?

Answer 17

Spleen