Placental immunology and maternal alloimmune responses

During pregnancy, women are tolerant of their semi-allogeneic fetus whilst not being immunosuppressed and indeed readily form alloantibodies. This ‘Immunolog-ical Paradox of Pregnancy ’ may be explained by an understanding of placental anatomy and immunology. Trophoblast cells form the interface between the fetus and maternal tissues and blood and escape allorecognition because they lack classi-cal human leucocyte antigen (HLA) class I and II molecules. Local immunoregula-tion, or tolerance, in the decidua is mediated partly by HLA-G+ extravillous trophoblasts (EVT) that invade the tissue and prevent killing by maternal natural killer cells, cytotoxic T cells and macrophages. Placental hormones orchestrate the composition and regulatory function of maternal immune cells. In contrast, syncy-tiotrophoblast cells at the surface of chorionic villi, in contact with maternal blood, maintain a state of mild maternal systemic immunity via activation of innate immunity and skewing towards humoral immunity. This enables maintenance of a healthy immune system in pregnant women and robust protective antibody responses to pathogens whilst enabling survival of the fetus. However, this has th