That pregnancy in eutherian mammals can endure is a miracle of transplantation biology. Intuitively the conceptus should be rejected as a result of maternal recognition of paternally-derived fetal antigens encoded by the major histocompatibility complex (MHC). The immune system of the mother mounts an initial response toward the embryo (sensitized lymphocytes and cytotoxic antibodies have been detected in several mammals). The threat of allograft rejection (Table 5-12) is greatest in those animals that implant intrusively and go on to establish a hemochorial placenta.
Several proposals have been set forth to explain maternal tolerance of a fetal graft. A simplistic view of tolerance is that the placenta acts as a nonimmunogenic mechanical barrier. Some studies indicate that the placenta neutralizes maternal antibodies. Decidual tissue impedes uterine lymphatic drainage (diminishing fetal antigen exchange) in intrusive implanters. Alternatively, immunosuppressants produced during pregnancy (eg., progesterone, cortisol, chorionic gonadotropins, pregnancy-specific globulins, alpha-fetoprotein [AFP], early pregnancy factor [EPF], PGE2, PAF) spare the fetus. Presumably immunosuppressive effects are localized to the uterine/placental interface (pregnant females are not more susceptible to disease). A combination of immunoreceptive mechanisms are undoubtedly responsible for survival of the unborn in what would seem to be a privileged environment.