ABSTRACT
Increased understanding of immune cell activation and regulation makes plausible the development of clinical strategies to control unwanted immune responses in a specific manner. The normal safeguards collectively termed immune tolerance refer to the immune system’s ability to control and prevent undesirable immune responses that lead to autoimmune diseases, asthma, or allergies, while still permitting protective immune responses to infection, vaccination, or tumor growth. The adaptive immune system, which consists of a vast repertoire of thymus-dependent T-lymphocytes and bone marrow-derived B-lymphocytes, achieves self tolerance both by eliminating dangerous cells that strongly recognize self tissues and by controlling those potentially self-reactive lymphocytes that escape deletion and are found throughout the body. Cell surface receptor molecules found on B- and T-lymphocytes determine the specificity of each cell by their ability to attach with lock-and-key accuracy to specific target molecules, termed antigens. T cell receptor molecules (TCR) bind to antigens comprised of short protein segments (peptides), derived from foreign or self proteins, that are held precisely in a pocket-like groove of self antigen presenting molecules, termed major histocompatibility complex (MHC) class I or MHC class II molecules. In this way, T cells recognize a complex of peptide-MHC molecules displayed on the surface of antigen presenting cells (APC). The B lymphocyte antigen receptor (BCR) is a membrane-bound immunoglobulin that recognizes antigen directly. Antigen binding by the TCR or BCR leads to aggregation of receptors on the cell surface, which brings together additional molecules within the cell to initiate a cascade of enzymatic reactions eventually leading to activation of genes in the nucleus. Gene activation determines how the cells respond to antigens; for example, by cell growth, secretion of factors, and activation of direct effector functions, such as the ability to destroy infected cells or secrete specific antibodies. Once activated, B cells release their immunoglobulin as antibodies that bind their antigens in blood or other tissues. Activated T cells may directly kill their target cells or help B cells to produce antibodies by direct cell-cell contact. They also produce soluble cytokines that mediate a variety of functions. 1
