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At times, it may be necessary for certain cells in the body to undergo programmed self-destruction, in a process termed apoptosis. Cells may undertake apoptosis in response to infection or damage, or simply as part of the overall course of tissue growth. This programmed death is activated by a pathway of signal transduction, triggered by a special protein called the Fas ligand. Another protein, called the Fas receptor, exists on the surface of many cells, and is the site where this ligand can dock and induce the self-destruct response. Changes to this pathway, involving the relationship between receptor and ligand, may be involved in some disease states.
Binding the Fas receptor allows for activation of programmed cell death activities. Fas ligands contain three areas that must all attach to corresponding areas on the cell surface to set this process into motion. After this occurs, the Fas receptor passes signals to the interior of the affected cell, and other protein regions which are called death domains, join with the ligand and receptor to form a complex. This complex then activates and releases compounds called caspases, killing the cell.
Proper immune system function relies, at least in part, on the presence of the Fas receptor on cells. Infected cells and certain immune cells, called lymphocytes, that are no longer needed by the body, can be destroyed in a controlled manner through the process of apoptosis. Afterward, their constituent molecules can be re-used by the body, or disposed of, as needed. Upon recognition by the immune system, white blood cells called T-cells use the Fas ligand to change the Fas receptor on cells targeted for death into an active form, with three regions the ligand can recognize. Binding then occurs, so that these unneeded or potentially harmful cells can be eliminated in a way that generally does not damage nearby cells.
Certain disease states can involve the disruption of the normal relationship between the Fas receptor and its ligand. Tumor cells may generate abnormally large amounts of the ligand protein, which can then damage nearby cells, producing more nutrients for the tumor, as well as preventing the immune system from harming it. Autoimmune deficiency syndrome (AIDS), may cause its effects of killing white blood cells through improper activation of the Fas receptor on these cells. During the progression of AIDS, the apoptosis pathway seems to be more easily triggered, which may result from a sensitivity to this activation.
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