The role of intrauterine immune privilege in perinatal infectious diseases
The pregnant uterus provides an immunologically "privileged" environment in which a genetically mismatched fetus typically thrives without deleterious allogeneic immune response. The mechanisms by which the fetus is protected from maternal immune attack are still incompletely understood but are undoubtedly multifactorial. Simple evasion of immune detection is no longer considered to be involved. There is now good evidence that the maternal immune system recognizes and responds to the presence of the fetus. However, maternal cellular and soluble immune responses, and those of the immunologically active, fetally derived trophoblast cells, generally support rather than harm the pregnancy. Gestational hormones and placenta-derived substances actively modulate maternal immunity and promote tolerance of the fetus. Still, the maternal immune system must continue to serve its protective role against pathogen invasion during pregnancy. Dramatic, pregnancy-related shifts in systemic and local immune responsiveness in the mother could compromise her ability to control infectious insults. To this point, clinical data indicate that pregnant women are more susceptible to specific types of viruses and parasites than their nonpregnant female counterparts. In this chapter, we will review the molecular mechanisms involved in creating the immunologically privileged intrauterine environment during pregnancy and discuss its costs to mother and fetus in terms of increased infectious disease risk.