NATURAL AND INDUCED TOLERANCE IN AN IMMUNE NETWORK MODEL

It has been proposed that the immune system can be partitioned into ce ntral and peripheral immune systems. Recently, Carneiro et al. (1996a, b) proposed a network model incorporating B and T lymphocytes that exp licitly accounts for that partition. This model, however, had some lim itations that are tackled here. Two main changes were introduced: the average idiotypic connectivity is now an explicit function of time bas ed on empirical evidence; and the activation of T lymphocytes by antig en is described by a log-bell shaped dose response curve. The new mode l, which also accounts for the CIS and PIS distinction, shows more rea sonable results since the frequencies of tolerant, immune or autoimmun e responses to an antigen are now correct. The model provides a new in terpretation for tolerance induction during the neonatal period, and f or the adult tolerance induction by low or high doses of antigen. It p redicts that natural tolerance for antigens available during the neona tal period can be kept indefinitely upon their removal, while toleranc e induced in the adult stages is rapidly lost upon transient removal o f the antigen. A semiquantitative analysis of the model provides a sim ple explanation for the different results in terms of the frequency at which a limited set of canonical connectivity structures emerge durin g ontogenesis. (C) 1998 Academic Press.