T-cell differentiation
11 important questions on T-cell differentiation
What are DN cells?
Double negative cells, the most immature ones in the thymus. They differentiate into double positive thymocytes. They are then checked for possible useful TCR specificities and positively selected to become an intermediate and finally single positive CD8+ or CD4+ cells
How are T-cells selected in the thymus?
Cells with too weak or too high MHC binding are negatively selected. CD25+ cells are selected in the same manner, but they are chosen with higher MHC affinity.
What do different forms of DC-T-cell contact assure?
quality and heterogenicity of the immune response
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Which co-stimulators are needed for T-cell activation and why?
Activated APCs upregulate their expression of e.g. B7, which interacts with CD28 on the T-cell. Also, IL-12 is needed. If those costimulators are not present, this will result in T-cell anergy
What is the effect of IL2 and cyclins?
Cell proliferation
Which are the 3 steps in CD4+ cell development?
induction, commitment and amplification
Which cytokines play a role in Th1 differentiation?
DCs secrete IL12, NKs secrete IFN gamma, leading to IFN gamma amplification in the T-cell, which causes it to give a Th1 response with even more IFN gamma via activation of T-bet, leading to antibody production.
Which cytokines play a role in Th2 differentiation?
Mast cells and T-cells secrete IL-4, amplifying IL-4 production in T-cells. Via Stat-6 and Gata3, this induces Th2 differentation, leading to secretion of IL4, IL5 and IL13 and IgE production & mucosal activity.
Which cytokines play a role in Th17 differentiation?
DCs secrete IL6 and IL1, leading to activation of Stat3 and IL21 production, giving positive feedback to the cell. This together with IL23 production of DCs leads to Th17 differentiation via the RORyt pathway and IL17 and IL 22 production, causing inflammation
What is the use of T follicular helper cells?
They can direct antibody class switching. IL-4 induces switching to IgG1 and IFN induces switching to IgG2a. This is induced by IL21 and the Bcl6 pathway
Which cytokines play a role in Treg differentiation?
TGF beta via the FoxP pathway in the cell. The cell then secretes TGF beta, IL 10 and IL 35
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