Where do Pre-T cells mature?
In the Thymus
Describe the process of Thymic Education.
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.
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.
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.
What are the cells that are crucial in testing the strength of affinity of thymocytes during Negative Selection?
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:
Failure of TMECs leads to what kind of diseases?
Give an example
Autoimmune diseases such as APS type 1
(Autoimmune Polyendocrine Syndrome)
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?
Peripheral Tolerance Mechanisms:
- 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.
- Treg Cells - Suppression through cell-cell contact and via the release of anti-inflammatory cytokines.
For which 3 situations is peripheral tolerance with anergy useful?
- Tolerance to antigens not expressed in the thymus
- Tolerance to food antigens
- Tolerance to commensal bacteria
What are the 2 main types of Regulatory T cells?
- nTreg - Produced in the thymus and respond to self antigens.
- aTreg - Developed in the periphery in response to constant low level exposure to antigen.
Deficiency in nTreg results in the development of what multiple autoimmune disease condition?
What causes this?
Dysfunction in the FOXP3 transcription factor that is necessary in Treg development.
Where does activation of naive lymphocytes take place?
In secondary lymphoid organs.
Which cytokines are produced by Th1 cells?
Which cytokines are produced by Th2 cells?
Which cytokines are produced by Th17 cells?
Which cytokines are produced by Treg cells?
True or False: Most effector T and B cells die by neglect/cytokine starvation following the removal of an infection.
Macrophages then remove the apoptosed cells.
Where do T memory cells reside following the clearance of infection?
Where do Plasma cells reside following the clearance of infection?
Where do B memory cells reside following the clearance of infection?