SELF-NONSELF DISCRIMINATION AND TOLERANCE IN T-LYMPHOCYTE AND B-LYMPHOCYTE

The immune system must not only fight off infections, but also ensure that it does not react against its own body tissues. Since clones of l ymphocytes have predetermined reactivities, some will be self-reactive and have the potential to cause damage. They should therefore be neut ralized in some way. In a system as complex and important as that gove rning self-tolerance, many mechanisms must exist to neutralize autoagg ressive lymphocytes. They may be classified under two main groups. In one the tolerant state arises from the physical or functional silencin g of potentially autoaggressive lymphocytes after antigen encounter. T his may involve clonal deletion, clonal abortion or clonal anergy. In the second, regulatory mechanisms of the immune system itself may hold autoreactive lymphocytes in check, for example through the operation of idiotypic network interactions and the action of specialized suppre ssor cells. Much evidence has accumulated for the physical deletion of autoreactive T cells as they mature in the thymus. The fate of any th at escape thymus censorship has been the subject of recent research an d is discussed here. Under certain conditions, self-tolerance must als o be imposed at the B-cell level to prevent the production of potentia lly damaging autoantibodies. Although the mechanisms which silence sel f-reactive lymphocytes are very efficient, self-tolerance can break do wn, and autoimmunity will thus ensue. The main factors responsible for this are briefly described here.