Immunology of Pregnancy

The principal role of the immune system is to defend the integrity of the host by preventing infectious disease, tumor development, and contamination of the host genome. Mammalian pregnancy, which features gametes and embryos expressing proteins derived from disparate maternal and paternal genes, presents a serious challenge to the maternal immune system. A combination of strategies is involved in negotiating and preventing fetal immune rejection. Specific aspects of the immune response are circumvented, while others are engaged and persuaded to permit the intimate associations between maternal and fetal cells that characterize embryo development, implantation, and placental development. In this chapter, features of the female reproductive organs and specific strategies that protect against immune-mediated embryonic loss are described. Key concepts are that both the mother and the fetus contribute to successful pregnancy, that multiple immune evasion and tolerogenic mechanisms are deployed, and that immune adaptations to permit internalization of the fetus depend on ovarian steroid hormones and are initiated from the time of conception. Major features include (1) specific structural elements of the reproductive tissues that support immune accommodation, (2) characteristic features of resident leukocyte subpopulations, (3) immune suppressive and pro-tolerogenic molecules produced by maternal and fetal cells, (4) restricted fetal trophoblast expression of major histocompatibility molecules, and (5) a critical role for T-regulatory cells which suppress inflammation and inhibit maternal immunity to the fetus.