8 - Immunology of Pregnancy

Abstract

More than 60 years ago Medawar proposed a theory as to why the fetus, a semiallograft, is not rejected by the maternal immune system. He recognized for the first time the unique immunology of the maternal-fetal interface and its potential relevance for transplantation. In his original work, he described the “fetal allograft analogy,” where the fetus is viewed as a semiallogeneic conceptus (made of paternal antigens and therefore foreign to the maternal immune system) that, by unknown mechanisms, has evaded rejection by the maternal immune system. Subsequent studies demonstrated the presence of an active maternal immune system at the implantation site, and this provided evidence to support Medawar's original notion. As a result, investigators began to pursue the mechanisms by which the fetus might escape such maternal immune surveillance. Furthermore, alterations in these pathways in pregnancy complications, such as recurrent abortion and preeclampsia, where the immune system is thought to play a central role, have been used as further evidence for Medawar's hypothesis of the semiallogeneic fetus. As a consequence, since Medawar's original observation, numerous studies have been performed to explain this paradigm, many of which have been centered on how the fetus and placenta fight against an active and aggressive maternal immune system. The objectives of this chapter are to review some of the significant events involved in human implantation related to the interaction between the maternal immune system and the fetus, to challenge some traditional concepts, and to propose a new perspective for the role of the immune system and immunologic processes in pregnancy.