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Central Tolerance

T-cell central tolerance in the thymus

QuestionAnswer
Describe neonatal HSC development into effector cells. The foetal liver produces B1 B-cells and gamma-delta T-cells. Both of which are involved in the immediate immune response
Describe (generally) cells from the BM. The bone marrow produces B-cells and T-cells. BM B-cells are produced as immature cells that develop fully in the periphery. Bone marrow thymocytes travel to the thymus (CCL25/CCR9) for positive and negative selection.
Which cytokine is responsible for HSC to choose the CLP lineage? IL-7 and the cell is now either pro-B or pro-T.
Which cytokines trigger the differentiation of pro-B cells to the b-cell lineage? IL-4 and IL-6.
Which cytokines trigger the differentiation of pro-B cells to the t-cell lineage? IL-2
Which cell type will a pro-T cell select for if it is exposed to IL-15? Natural Killer Cell
If a CLP is exposed to IL-3, which type of dendritic cell will it select for? Plasmacytoid
What does "development is not always linear" refer to in the context of BM cell development? Cells can switch lineage paths during development and become a completely different cell type than anticipated.
Explain the maturation stages of lymphoctytes from HSC to full development and differentiation. Stem Cell, Pro-Lymphoctye, pre-lymphocyte (first sign of ag receptor), immature lymphocyte (first sign of full Ag receptor-dependent on self Ag), mature lymphocyte, differentiated effector lymphocyte
Describe thymic development Initial thymus cells are laid down by the foetal liver and then colonised by BM progenitor-lymphocytes. The thymus is largest at birth and then shrinks with age.
Describe the architecture of the thymus The thymus is divided into layers-the cortex and medulla. The cortex contains cortical epithelial cells and BM dervived thymocytes. The medulla contains medullary epithelial cells, BM derived medullary macrophages and BM derived medullary dendritic cells.
Where does a thymocyte enter the thymus? At the cortico-medullary junction.
Where does a mature T-cell exit the thymus following positive and negative selection? At the medullary blood vessel
At which double negative stage do gamma-delta T-cells develop in the Thymus and describe their surface phenotype at that stage. Gamma-delta T-cells develop at the DN2 stage and are c-kit+CD44+CD25+
How does Notch1 contribute to T-cell development Constitutive expression of Notch1 in the BM selects towards T-cell lineage and against B-cell development. Conversely, expression of Lunatic Fringe, a Notch1 inhibitor, directs towards a B-cell lineage.
Describe receptor rearrangement in T-cell development On entering the Thymus, T-cells rearrange their alpha and beta TcR. Once double positive, they then rearrange further via VDJ recombination.
Explain Positive Selection Process in the Cortex of the Thymus in which T-cells are tested for their ability to recognise self-MHC. Testing is via cortical epithelial cells.
Explain Negative Selection Cells are tested for their ability to NOT be self reactive. This occurs in the medulla and is via DCs, macrophages and EC's. NOTE EC express AIRE (autoimmune regulator) here.
Created by: A Bundy
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