Mechanisms
Placental mechanisms
The placenta 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 presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.
The placental trophoblast cells do not express the classical MHC class I isotypes HLA-A and HLA-B, unlike most other cells in the body, and this absence is assumed to prevent destruction by maternal cytotoxic T cells, which otherwise would recognize the fetal HLA-A and HLA-B molecules as foreign. On the other hand, they do express the atypical MHC class I isotypes HLA-E and HLA-G, which is assumed to prevent destruction by maternal NK cells, which otherwise destruct cells that do not express any MHC class I.However, trophoblast cells do express the rather typical HLA-C.
It forms a syncytium without any extracellular spaces between cells in order to limit the exchange of migratory immune cells between the developing embryo and the body of the mother (something an epithelium will not do sufficiently, as certain blood cells are specialized to be able to insert themselves between adjacent epithelial cells). The fusion of the cells is apparently caused by viral fusion proteins from endosymbiotic endogenous retrovirus (ERV). 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 IgG antibodies to pass from 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 of the IgM type,and do not cross the placenta.
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.
In any case, 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 . The eu-FEDS model further suggests that specific carbohydrate sequences (oligosaccharides) are covalently linked to these immunosuppressive glycoproteins and act as “functional groups” that suppress the immune response. The major uterine and fetal glycoproteins that are associated with the eu-FEDS model in the human include alpha-fetoprotein, CA125, and glycodelin-A (also known as placental protein 14 (PP14)).
Regulatory T cells also likely play a role.
Also, a shift from cell-mediated immunity toward humoral immunity is believed to occur.
Insufficient tolerance
Many cases of spontaneous abortion may be described in the same way as maternal transplant rejection. Other examples of insufficient immune tolerance in pregnancy are Rh disease and pre-eclampsia:
Rh disease is caused by the mother producing antibodies (including IgG antibodies) against the Rhesus D antigen on her baby's red blood cells. It occurs if the mother is Rh negative and the baby is Rh positive, and a small amount of Rh positive blood from any previous pregnancy has entered the mother's circulation to make her produce IgG antibodies against the Rhesus D antigen. Maternal IgG is able to pass through the placenta into the fetus and if the level of it is sufficient, it will cause destruction of Rhesus D positive fetal red blood cells leading to development Rh disease. Generally Rhesus disease becomes worse with each additional Rhesus incompatible pregnancy.
One cause of pre-eclampsia is an abnormal immune response towards the placenta. There is substantial evidence for exposure to partner's semen as prevention for pre-eclampsia, largely due to the absorption of several immune modulating factors present in seminal fluid.
Increased infectious susceptibility
The immunologic changes in pregnancy alters the susceptibility to and severity of infectious diseases. For example, pregnancy may increase susceptibility to toxoplasmosis and listeriosis and may increase severity of illness and increase mortality rates from influenza and varicella.
Xenopregnancy
If the mechanisms of rejection-immunity of the fetus could be elucidated, it could avail for xenopregnancy, having, for example pigs carry human fetuses to term as an alternative to a human surrogate mother, providing a sober, drug-free and nonsmoking carrier.
All about pregnancy:
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- Gestational hypertension
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- Maternal physiological changes in pregnancy
- Prenatal development
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