The immunology of pregnancy

Pregnancy is an immunological balancing act in which the mother's immune sy stem has to remain tolerant of paternal major histocompatibility (MHC) anti gens and yet maintain normal immune competence for defense against microorg anisms. The placenta separates fetal and maternal blood and lymphatic syste ms and it is fetal trophoblast that plays the major role in evading recogni tion by the maternal immune system. Trophoblast cells fail to express MHC c lass I or class II molecules and the extravillous cytotrophoblast cells str ongly express the nonclassic MHC gene encoding HLA-G, which may downregulat e natural killer (NK) cell function. In addition, the trophoblast expresses Fas ligand, thereby conferring immune privilege: maternal immune cells exp ressing Fas will undergo apoptosis at the placenta/decidua interface. A thi rd protective mechanism exploited by the trophoblast is the expression of t he complement regulatory proteins CD46, CD55, and CD59. Uterine decidual an d placental cells produce a huge array of cytokines which, in part, contrib ute to the deviation of the immune response from Th1 to Th2. This may leave the mother more open to infection whose control is Th1-dependent, but incr eased production of Th1 cytokines has been linked to spontaneous abortion a nd small-for-dates babies. This bias in cytokines and hormonally mediated e ffects on the thymus and on B cells may also contribute to the suppression of autoimmune responses and changes in circulating and local T-cell subsets in pregnancy.