Fetal‐placental antigens and the maternal immune system: Reproductive immunology comes of age

Reproductive physiology and immunology as scientific disciplines each have rich, largely independent histories. The physicians and philosophers of ancient Greece made remarkable observations and inferences to explain regeneration as well as illness and immunity. The scientific enlightenment of the renaissance and the technological advances of the past century have led to the explosion of knowledge that we are experiencing today. Breakthroughs in transplantation, immunology, and reproduction eventually culminated with Medawar’s discovery of acquired immunological tolerance, which helped to explain the transplantation success and failure. Medawar’s musings also keenly pointed out that the fetus apparently breaks these newly discovered rules, and with this, the field of reproductive immunology was launched. As a result of having stemmed from transplantation immunology, scientist still analogizes the fetus to a successful allograft. Although we now know of the fundamental differences between the two, this analogy remains a useful tool to understand how the fetus thrives despite its immunological disparity with the mother. Here, we review the history of reproductive immunology, and how major and minor histocompatibility antigens, blood group antigens, and tissue‐specific “self” antigens from the fetus and transplanted organs parallel and differ.