Mechanism and computer simulation of immune complex formation, opsonization, and clearance.

A computer simulation of immune complex formation, opsonization, and clearance has been developed (ICMODEL) that uses equations describing the kinetics of known immunologic processes and an additional pathologic process of immune complex-mediated tissue damage and antigen production. ICMODEL was used to (1) compare simulated with reported immune response kinetics, (2) evaluate the relative stability of the immune system described by the simulation, and (3) determine the conditions required to produce high immune complex levels as found in patients with immune complex-mediated disease. ICMODEL simulated primary and secondary immune responses as well as short- and long-term immunity. ICMODEL also depicted a relatively stable immune response system. Under certain conditions, however, the system could be perturbed, resulting in an unstable response. For example, when the rate constant regulating Fc gamma-mediated phagocytosis was decreased and the rate constant regulating immune complex-mediated tissue damage/antigen production was increased, immune complex concentrations oscillated with time and increased exponentially. These data suggest that ICMODEL can be used to define the specific parameters that, when perturbed, will give rise to increased immune complex concentrations. As such, this model has direct implications for studies of immune complex-mediated disease in human patients.