NATURAL TOLERANCE IN A SIMPLE IMMUNE NETWORK

The following basic question is studied here: In the relatively stable molecular environment of a vertebrate body, can a dynamic idiotypic i mmune network develop a natural tolerance to endogenous components? Th e approach is based on stability analyses and computer simulation usin g a model that takes into account the dynamics of two agents of the im mune system, namely B-lymphocytes and antibodies. The study investigat es the behavior of simple immune networks in interaction with an antig en whose concentration is held constant as a function of the symmetry properties of the connectivity matrix of the network. Current idiotypi c network models typically become unstable in the presence of this typ e of antigen. It is shown that idiotypic networks of a particular conn ectivity show tolerance towards auto-antigen without the need for ad h oc mechanisms that prevent an immune response. These tolerant network structures are characterized by aperiodic behavior in the absence of a uto-antigen. When coupled to an auto-antigen, the chaotic attractor de generates into one of several periodic ones, and at least one of them is stable. The connectivity structure needed for this behavior allows the system to adopt particular dynamic concentration patterns which do not lead to an unbounded immune response. Possible implications for t he understanding of autoimmune disease and its treatment are discussed . (C) 1995 Academic Press Limited