Central immune system, the self and autoimmunity.

We model how auto-reactive B cells are kept under control by an idiotypic network. Autoimmunity occurs when the control is broken by an infection or not achieved through an abnormal ontogenetic evolution. We describe the idiotypic network, viz., the central immune system, by idiotype-anti-idiotype pairs which are coupled to a set of highly connected clones, which interact with each clone of the network. Some clones of the central immune system recognize self-antigen. We find a huge variety of fixed points which can be classified as tolerant, autoimmune, and neutral states according to the concentration of the auto-reactive antibody. Most significant are auto-reactive clones which are a member of an idiotype-anti-idiotype pair. In a healthy individual, an autoimmune disease is induced by an antigen infection which triggers a transition from a tolerant to an autoimmune state. Autoimmunity is induced more readily by an antigen coupling to the anti-idiotype than by one interacting with the auto-reactive clone itself. We indicate a possible therapy which simply reverses the processes that have lead to the autoimmune disease. In the early development of the central immune system its highly connected, core part serves to draw the more specific clones of idiotype-anti-idiotype pairs into the network. In order to avoid autoimmunity in ontogenetic evolution the anti-idiotype of an auto-reactive clone must be formed in advance by a sufficiently long period of time. Thus, a well ordered succession of the appearance of the more specific clones is required.