Some aspects of complementarity in the immune system - A bird's eye view

The burden of this paper is the suggestion that the defence capacity of the immune system is rather limited. It cannot stand in readiness to deal with a practically endless diversity and abundance of microbes. In contrast to conventional thinking the current model proposes: (1) The core idea that ce lls of the immune system are basically and constantly interconnected with h ost cells (e.g., through TCR-MHC interactions) and that foreign antigens (p eptides) may tend to obstruct such interactions. Peptides presented during a viral infection typically decrease complementarity between the structures that are the products of the major histocompatibility complex (MHC) genes (or other genes related to it) and T cells. The altered MHC profile exposes infected cells to a polyclonal immune attack from other T cells such that tissue destruction occurs in an allograft rejection-like fashion. This may explain why a substantial portion of T cell numbers is activated when only a small number of specific T cells is 'obstructed' from functioning by the presence of non-self peptides. (2) Phagocytes 'see' targets even in a nonim mune host because complement distribution associated with polyreactive natu ral antibodies magnifies sensitization differences between pathogens and ho st cells. (3) There is only a probability that hypermutation will successfu lly change the genome in some B cell clones to produce high affinity antibo dies that prevent the re-infection of the host by the same pathogen, but ca nnot conquer primary infections. (4) The history of the development of the immune responses suggests that during prolonged interaction between host an d microbes in our natural habitat, carried on over many generations, the ad aptive antibody population may facilitate the evolution of the natural anti body repertoire. The model predicts that microbes, which are not a part of the local environment, may invade the organism without significant resistan ce. The model is discussed in various interactions for survival in the cont ext of infection and tumorigenicity. Copyright (C) 2001 S. Karger AG, Basel .