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 semiallogeneic (composed of 50% paternal antigens) and therefore as foreign to the maternal immune system, but it evades rejection by the maternal immune system through unknown mechanisms. Subsequent studies demonstrating the presence of active maternal immune system components at the implantation site supported Medawar’s original thesis. As a result, investigators began to pursue 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. Since Medawar’s original observation, numerous studies have been performed to explain this phenomenon, many centering on how the fetus and placenta counter an active 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.