ABSTRACT
This chapter suggests that anti-idiotypic immune responses to nonself-major histocompatibility complex (MHC) are involved in maternal tolerance to the fetus and in allograft acceptance. It argues that suppression of the response is a necessity for the survival of the species and that such mechanisms have evolved from anti-idiotypic reactions directed primarily against clones reactive to self-MHC. A possible explanation for the development of natural auto- and/or alloantibodies to HLA antigens is that allosensitization of immunosuppressed individuals through transplantation leads to the aberrant proliferation of B-cell clones producing antibodies against self-MHC antigens. Responsiveness or nonresponsiveness to HLA merely reflects the prevalence of Ab, or Ab2. It is apparent that if Ab2 plays a biological role, securing maternal tolerance to the fetus, it should prevail early during pregnancy. The chapter considers the network regulation of alloimmune responses and that their existence is a necessity for the survival of the species.
