Immune tolerance in pregnancy

Placental mechanisms functions as an immunological barrier between the mother and the fetus. The placenta functions as an immunological barrier between the mother and the fetus, creating an immunologically privileged site. For this purpose, it uses several mechanisms: • It secretes neurokinin B containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host. • Also, there is the presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2. However, trophoblast cells do express the rather typical HLA-C. An immunoevasive action was the initial normal behavior of the viral protein, in order to avail for the virus to spread to other cells by simply merging them with the infected one. It is believed that the ancestors of modern viviparous mammals evolved after an infection by this virus, enabling the fetus to better resist the immune system of the mother. Still, the placenta does allow maternal immunoglobulin G (IgG) to pass to the fetus to protect it against infections. However, these antibodies do not target fetal cells, unless any fetal material has escaped across the placenta where it can come in contact with maternal B cells and make those B cells start to produce antibodies against fetal targets. The mother does produce antibodies against foreign ABO blood types, where the fetal blood cells are possible targets, but these preformed antibodies are usually of the immunoglobulin M type, and therefore usually do not cross the placenta. Still, rarely, ABO incompatibility can give rise to IgG antibodies that cross the placenta, and are caused by sensitization of mothers (usually of blood type O) to antigens in foods or bacteria that are homologous to A and B antigens. Other mechanisms Still, the placental barrier is not the sole means to evade the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier. The placenta does not block maternal IgG antibodies, which thereby may pass through the human placenta, providing immune protection to the fetus against infectious diseases. One model for the induction of tolerance during the very early stages of pregnancy is the eutherian fetoembryonic defense system (eu-FEDS) hypothesis. The basic premise of the eu-FEDS hypothesis is that both soluble and cell surface associated glycoproteins, present in the reproductive system and expressed on gametes, suppress any potential immune responses, and inhibit rejection of the fetus. As a fetus forms, it is seen similarly to an organ transplant due to it being semi-allogenic, having genetic material different to the mother. Since the fetus has partial paternal genetic material, it inherits paternal flags, called HLA alleles, that trigger the maternal adaptive immune system and are responded to by fighter Cytotoxic T cells and peacekeeping Regulatory T cells (Treg). In order for the foreign paternal fetal material to be accepted and unharmed by the maternal immune system, the Regulatory T-cells must keep a balance with the cytotoxic T-cells, overriding autoimmune attacks. Another participant in the balance of both T-cells is Indoleamine 2,3-dioxygenase (IDO) IDO is transformed by factors produced by Trophoblast cells and suppresses T-cell activation. ==Insufficient tolerance==

Many cases of spontaneous abortion may be described in the same way as maternal transplant rejection, Pregnancies resulting from egg donation, where the carrier is less genetically similar to the fetus than a biological mother, are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Infertility and miscarriage Immunological responses could be the cause in many cases of infertility and miscarriage. Some immunological factors that contribute to infertility are reproductive autoimmune failure syndrome, the presence of antiphospholipid antibodies, and antinuclear antibodies. Antiphospholipid antibodies are targeted toward the phospholipids of the cell membrane. Studies have shown that antibodies against phosphatidylserine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine target the pre-embryo. Antibodies against phosphatidylserine and phosphatidylethanolamine are against the trophoblast. These phospholipids are essential in enabling the cells of the fetus to remain attached to the cells of the uterus with implantation. If a female has antibodies against these phospholipids, they will be destroyed through the immune response and ultimately the fetus will not be able to remain bound to the uterus. These antibodies also jeopardize the health of the uterus by altering the blood flow to the uterus. ==Increased infectious susceptibility==

The increased immune tolerance is believed to be a major contributing factor to an increased susceptibility and severity of infections in pregnancy. Pregnant women are more severely affected by, for example, influenza, hepatitis E, herpes simplex and malaria. The evidence is more limited for coccidioidomycosis, measles, smallpox, and varicella. Pregnancy does not appear to alter the protective effects of vaccination. ==References==