Prevention of immune rejection of the fetus requires local immunologic adaptations within the mother, resulting in a state in which cytotoxic adaptive immune responses are diminished, bypassed, or even abrogated, while regulatory adaptive immunity is enhanced. In contrast, innate (natural) immunity remains intact, serving two purposes: one, to continue to provide host defense against infection, and two, to interact with fetal tissues to promote successful placentation and pregnancy.
●Trophoblast cells protect the embryo itself and certain components of the extraembryonic membranes. Multiple strategies are used by these cells to avoid maternal immune cells and antibody-mediated cell destruction, including altered human leukocyte antigen (HLA) expression, synthesis of immunosuppressive molecules, and expression of high levels of complement regulatory proteins that protect the extraembryonic tissues from maternal anti-paternal cytotoxic antibodies.
●Uterine changes during pregnancy also help contribute to maternal immune adaptation, including alterations in the relative proportions, phenotype, and functions of leukocyte subpopulations, induction of immunosuppressive molecules (progesterone, prostaglandins), and changes in cytokine profiles across gestation.
●Loss of potential pregnancies prior to or during implantation is common. Causes include genetic and endocrine abnormalities and autoantibodies, such as antiphospholipid antibodies (aPLs). It is unclear if any of these losses can be accurately attributed to infection. However, insults such as infection and aPLs can alter normal placental function and mechanisms of immune tolerance, and can disrupt the normal trophoblast-maternal immune system crosstalk, resulting in adverse pregnancy outcomes, such as preterm labor and preeclampsia.