Introduction to the immunology of pregnancy
The concept that the immune system in pregnancy is a “unique complexity” since on one hand it has to tolerate the paternal antigens present in the fetus, while maintaining an active protective mechanism against microbial infections is introduced.
Abstract
Cases of recurrent abortion, implantation failure, and babies with hemolytic disease of the newborn still puzzle us with the question “why did your mother reject you?” Immunological rejection was introduced more than 70 years ago by Sir Peter Medawar, a Nobel laureate that recognized pregnancy as a semiallograft that escapes rejection. Medawar, in the early 1950s, acknowledged for the first time the unique immunological complexity of the maternalfetal interaction and its potential relevance for transplantation. He described the “fetal allograft analogy” in which the fetus is viewed as a semiallogeneic conceptus that evades rejection. Over the next 50– 60 years, research has focused on elucidating mechanisms of immune tolerance that could explain the fetal allograft paradigm. The inadequate understanding of the immunology of pregnancy has major repercussions on how we approach the treatment and prevention of multiple pregnancy complications. The challenging questions that we confront as reproductive immunologists include: (i) are pregnant women more susceptible to infectious disease threats, (ii) how does a viral infection affect the fetus and the pregnancy outcome, and (iii) are prophylaxis and treatment appropriate and beneficial for pregnant women? More than a decade ago, we introduced the concept that the immune system in pregnancy is a “unique complexity”1 since on one hand it has to tolerate the paternal antigens present in the fetus, while maintaining an active protective mechanism against microbial infections.2 In the last 10 years, we have witnessed major growth in our understanding of the immunology of pregnancy that has shaped the clinical relevance and approach to reproduction. To discuss some of the questions and new perspectives, we invited experts on the field to examine basic concepts and clinical challenges. The foundation of reproductive immunology consists of the question: how can the mother tolerate the fetus for a full 9 months? Medawar proposed three possibilities that have been extensively explored: (1) Isolation of the fetus from the maternal immune system (mechanical barrier); (2) immunological suppression of the maternal immune system; or (3) the fetus could be antigenically immature— invisible to the mother.3– 5