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

Abstract

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.

Introduction to the immunology of pregnancy

“…As discussed by Dr. Petroff and Dr. Ding, 6,7 none of these previous postulations have proven correct. Therefore, it is critical to carefully review them.…”

“…and Dr. Petroff,7,11 as well as by Drs. Morelli and Sadovsky12 who present a new mechanism of communication between the placenta and the maternal immune system.An intriguing aspect of the immunology of pregnancy has been the role of immune cells at the implantation site, which represent a high percentage of the cell types of the endometrium and increase during early pregnancy.…”

“…Dr. Petroff and her colleagues provide a historical overview of medicine and its impact on our understanding of immunology and pregnancy and how some concepts have taken years if not centuries to evolve. 7 Dr. Ding and colleagues provide a new view of the mechanism associated with the adaptation of the maternalfetal immune system. 6 Dr. Liao's group describes new mechanisms of immune regulation that involve the expression of new immune check points.…”

“…The role of NK cells, macrophages, and T cells is extensively reviewed in this issue. 7,8,13,21 From an immunological point of view, pregnancy was considered a monolithic process where the function of immune cells and the immunological environment are the same in the first, second and third trimester. However, we observed that dendritic cells are essential for the preparation of the endometrium for implantation by creating an inflammatory environment 22,23 leading us to change the concept that pregnancy is only an anti-inflammatory environment.…”

“…There is no scientific evidence that can demonstrate immune suppression; instead, the maternal immune system is strong and capable of protecting the mother and the fetus. However, as discussed by Sun and Petroff, 7,11 there are specific mechanisms of tolerance to paternal antigens that are not associated with systemic immune suppression and have a long term impact on the maternal immune response. 37 All these studies suggest that the process of tolerance during pregnancy resembles tumor-induced tolerance rather graft-induced tolerance.…”