T Cell Development and Selection in the Thymus 10)Explain the events that take p
ID: 260264 • Letter: T
Question
T Cell Development and Selection in the Thymus 10)Explain the events that take place in the different developmental stages during the journey of thymocytes through the cortical area of a thymus capsule. 11)Which events (and what order) take place during Double Negative stages of thymocyte development? 12)What are cortical and medullary epithelial cells and what are their function? 13)Explain what is positive and negative selection in relation to T cell development? And where do these two process take place? 14)Explain the differences of central and peripheral tolerance in relation to T cells 15)What is the relevance of CD44 and CD25 markers in the understanding of T cell development? 16)Explain the chronological events regarding DNA rearrangement happening in thymocytes during the journey of development of these cells in the thymus. 17)Why lymphocyte development/selection is important within the context of human immunity?Explanation / Answer
13) The double positive T cells undergo thymic selection where it gains the ability to differentiate between self and non-self cells. This self-tolerance occurs mainly during T cell maturation in the thymus. About 95% of the T cells formed die befiore they are ready to mature and emigrate into peripheral lymphatic organs. Double positive T cells undergo two selection processes in thymus - Positive and negative selection.
Positive selection - The double positive pre-T cell interacts with self MHC molecules expressed on epithelial cells in the thymic cortex. This interaction results in the survival and differentiation of the double positive T cells, whereas the dpouble positive cells that do not make such interaction are not selected and dies by apoptosis.
This means that T-cell even as mature cell when leaves thymus, it will respond to antigen only when Ag is bound to the MHC molecule that the developing T-cell encountered in the thymus. This process is MHC restriction. Hence T cells recognize antigens bound with self-MHC proteins but not in association with foreign MHC.
Negative selection - T cells expressing TCRs specific for both foreign and self antigens can develop in thymus and survive positive selection. If T cells reacts with self antigens in tissues, it could result in autoimmune response. Therefore it is important to select T cells capable of responding to self MHC complexed with foreign or non-self peptide antigens. This is done by negative selection. negative selection is the procein which T cells whose TCRs biond strongly to self peptide antigens in association with self MHC molecules are deleted. This removes T-cells expressing TCRs that are strongly reactive against self antigens and develops self tolerance.
Positive selec tion works by promoting the selective survival and expansion of T cells with self-MHC restricted TCRs. whereas negative selection promotes apoptosis of T cells whose receptors recognize self-peptide antigen-MHC complexes in the thymus with high affinity.
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