The immunologic basis of the fetal-maternal relationship

Preferential histoincompatible pregnancies and efficient fetal development by an active selective immune response of the female have to occur concomitantly in order to ensure the propagation of mammalian species. A compromise solution between phylogeny and ontogeny, with respect to transplantation antigens, would be the deviation of the maternal anti-fetal immune response towards an active protective reaction. To accomplish this the fetus will have to express during its development MHC-encoded molecules which, either because of their unique intrinsic molecular structure or because of their association with specific fetal membrane-associated products, will lead to different and mainly enhancing immunogenic interactions with the immune system of the mammalian female. Such interactions may be facilitated by a variety of regulatory products induced during pregnancy. A better understanding of the possibly unique way of immune response of females against 'modified self' antigens, as suggested above, may contribute to our understanding of a longstanding fact, namely, the increased frequency of autoimmune diseases in females.