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MCD – Immunology 6 - T-lymphocytes and antigen recognition Anil Chopra 1. Outline the origins and functions of T lymphocyte subsets. T-lymphocytes are originally synthesised in the bone marrow, but they travel to the thymus gland to mature. They start off in the cortex of the thymus and complete maturation in the medulla. In their process of maturation, they undergo many different “check points. First they have to synthesis the T-cell receptor by gene rearrangement: Then the chain is checked to see if it is functional, if its not, then the cell is ordered to die by apoptosis. The TCR (T-cell receptor) is checked to see if it is working and is not autoreactive. If it is useless or dangerous, cell is ordered to die by apoptosis. By the end only 5% of thymocytes survive. There are 2 main types of T-cell: T-Helper Cell – expresses CD4 and they can only bind to MHC (Major Histocompatibilty complex) class II. They are split into Th1 and Th2 depending on the cytokines they produce. They help activate macrophages and secrete cytokines. Cytotoxic/ Killer – T cell – expresses CD8 and can only bind to MHC class I. These kill infected cells and also microbes themselves. 2. Briefly describe the structure and distribution of major histocompatibility complex (MHC) class 1 and class II molecules. In order to become activated, the T-cells need to bind to the MHC – Major Histocompatibility Complex. These present antigens to T-cells and come in 2 classes: MHC Class I – these are presented on nearly all cells. MHC Class II – these are only presented on special APCs (antigen presenting cells such as B-lymphocytes, macrophages and dendritic cells. 3. Outline the mechanisms by which antigen presenting cells (APCs) process and present endogenous antigens. • • • • Human MHC genes are highly polymorphic: large number of alternative different versions of the same gene within the population Each version is termed an allele A group of MHC alleles linked on one chromosome is termed MHC haplotype Different people have different immune responsiveness. The inheritance is however, co-dominant. 4. Compare and contrast antigen recognition by B and T lymphocytes and by CD4+ and CD8+ T lymphocytes B-cells recognise intact extracellular antigens T-cells recognise processed antigens presented by MHC molecules. CD4 T-lymphocytes recognise antigens presented by MHC type II (only on APCs). CD8 T-lymphocytes recognise antigens presented by MHC type I (on most cells)