Immunological Synapse PDF Free Download
The proper physiological functioning of most eukaryotic cells requires their assembly into multi-cellular tissues that form organized organ systems. Cells of the immune system develop in bone marrow and lymphoid organs, but as the cells mature they leave these organs and circulate as single cells. Antigen receptors (TCRs) of T cells search for membrane MHC proteins that are bound to peptides derived from infectious pathogens or cellular transformations. The detection of such specific peptide–MHC antigens initiates T cell activation, adhesion, and immune-effectors functions. Studies of normal and transformed T cell lines and of T cells from transgenic mice led to comprehensive understanding of the molecular basis of antigen-receptor recognition and signaling. In spite of these remarkable genetic and biochemical advances, other key physiological mechanisms that participate in sensing and decoding the immune context to induce the appropriate cellular immune responses remain unresolved.
TCR recognition is tightly regulated to trigger sensitive but balanced T cell responses that result in the effective elimination of the pathogens while minimizing collateral damage to the host. The sensitivity of TCR recognition has to be properly tempered to prevent unintended activation by self-peptide–MHC complexes that cause autoimmune diseases. It is likely that once the TCR is engaged by a peptide– MHC and TCR signaling begins, additional regulatory mechanisms, involving other receptors, would increase the fidelity of the response. Such mechanisms that interpret TCR recognition within physiological settings may provide excellent targets for selective manipulation of immune responses, either enhancing or suppressing the immunity. However, the study of T cell activation under physiological conditions faces many technical challenges.
Cloned T cell lines and TCR transgenic mice can address the extremely low frequency of antigen-specific T cells within the circulating mature lymphocytes. Anti-receptor antibodies and soluble purified receptor–ligands are commonly used to selectively engage a particular receptor, even within a polyclonal lymphocyte population, without engaging any of the many other receptors on the immune cells. Such approaches were instrumental for identifying the molecular and functional role of adhesion receptors (LFA-1), co-stimulatory receptors (CD4, CD8, CD28)…
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