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Immune system cells, such as T cells and B cells, have proteins on their surface that allow them to recognize foreign invaders and attack them. Areas on these proteins can vary from cell to cell, allowing them to react to a variety of threats. Occasionally, T cells and B cells are produced that react to proteins that are expressed by the body's own cells, called autoantigens. Clonal deletion is a process that allows these cells to be neutralized before they are released into the body, where they could potentially begin attacking healthy tissue.
T cells are produced in bone marrow, but they mature in the thymus, a gland near the heart, and B cells are produced in the bone marrow. Despite their different places of origin, both of these cell types use a similar method of clonal deletion to ensure that mature immune cells that react to autoantigens are not released into the blood stream. During the process of maturing, these cells come into contact with a limited range of cells, such as macrophages, and thymic dendritic cells. These cells have a variety of surface proteins, called antigens, that they present to the immune cells, so that those cells that produce a reaction can be weeded out.
To use the thymus as an example, thymic dendritic cells use a process of presentation, allowing T cells to attempt to bind surface proteins, to screen them for clonal deletion. Immature T cells that react to these autoantigens form a protein complex with the thymic cell. In the event that this protein complex forms, it triggers a self-destruct sequence, called apoptosis, in the T cell, so that it does not mature and enter the body, where it could potentially launch a harmful response if it encountered another cell with that protein.
The body contains many other types of cells other than those seen in the thymus and bone marrow, so clonal deletion must account for autoantigens not normally found in these tissues. The thymus does this by having thymic dendritic cells that contain surface proteins usually found elsewhere, such as in pancreatic tissue. Clonal deletion can then occur with immune cells that would normally react to these pancreatic proteins, and a similar process regulates the B cells maturing in the marrow. Some disease states, such as diabetes, could be partially caused by a failure of the body to present the full range of the body's antigens to maturing immune cells, allowing these cells to mature and attack healthy tissue.
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