Figure 1.

How tolerance is established and may fail. Generation of immune repertoires in central lymphoid organs, thymus, and bone marrow is accompanied by deletion of self reactive lymphocytes by apoptosis. The “leakiness” of this process requires back up by peripheral tolerance. Tolerance fails because of the interaction of a wrong environment with the wrong genes, resulting in autoimmune disease. Options for treatment will increasingly include new selective immunotherapies in place of present global immunosuppression