Immunologic challenges of human reproduction: an evolving story

Characterization of the implanting human fetus as an allograft prompted a field of research in reproductive immunology that continues to fascinate and perplex scientists. Paternal- or partner-derived alloantigens are present in the maternal host at multiple times during the reproductive process. They begin with exposure to semen, continue through implantation and placentation, and may persist for decades in the form of fetal microchimerism. Changes in maternal immune responses that allow allogenic fertilization and survival of semiallogenic concepti to delivery must be balanced with a continued need to respond appropriately to pathogenic invaders, commensals, cell or tissue damage, and any tendency toward malignant transformation. This complex and sophisticated balancing act is essential for survival of mother, fetus, and the species itself. We will discuss concepts of alloimmune recognition, tolerance, and ignorance as they pertain to mammalian reproduction with a focus on human reproduction, maternal immune modulation, and the very earliest events in the reproductive process, fertilization and implantation.