CENTRAL IMMUNE-SYSTEM, THE SELF AND AUTOIMMUNITY

We model how auto-reactive B cells are kept under control by an idioty pic network. Autoimmunity occurs when the control is broken by an infe ction or not achieved through an abnormal ontogenetic evolution. We de scribe the idiotypic network, viz., the central immune system, by idio type-anti-idiotype pairs which are coupled to a set of highly connecte d clones, which interact with each clone of the network. Some clones o f the central immune system recognize self-antigen. We find a huge var iety 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 membe r of an idiotype-anti-idiotype pair. In a healthy individual, an autoi mmune disease is induced by an antigen infection which triggers a tran sition 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 possibl e therapy which simply reverses the processes that have lead to the au toimmune disease. In the early development of the central immune syste m its highly connected, core part serves to draw the more specific clo nes of idiotype-anti-idiotype pairs into the network. In order to avoi d autoimmunity in ontogenetic evolution the anti-idiotype of an auto-r eactive 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.