Much research has been done to investigate why the fetus in most pregnancies, in spite of being semi-allogenic, is not rejected by the immune system. Experiments in transgenic mice have suggested that dysfunctions in both the innate immune system (NK cells) and the adaptive immune system (T-cells and T regulatory cells) result in increased fetal loss rate. Many studies have suggested that women with pathological pregnancies such as
recurrent miscarriages have signs of generally exaggerated inflammatory immune responses both before and during pregnancy and signs of breakage of tolerance to
autoantigens and fetal
antigens. In addition, several abnormalities of innate immune responses seem to characterize women with pathological pregnancies. These abnormalities involve disadvantageous interactions between uterine NK cells and
HLA-G and
HLA-C on the trophoblast that may have pro-inflammatory effects. Also, humoral factors belonging to the innate immune system such as
mannose-binding lectin seem to be associated with pregnancy outcome probably by modifying the level of
inflammation at the feto-maternal interface. The pro-inflammatory conditions at the feto-maternal interface characterizing pathological pregnancy are suggested to predispose to adaptive immunological processes against
alloantigens on the trophoblast that may further increase the risk of pathological pregnancy outcome. The best documented adaptive immune reaction against fetal
alloantigens is directed against male-specific minor histocompatibility (HY)
antigens. Anti-HY immunity seems to play a role especially in women with secondary
recurrent miscarriage.