Placenta and the immunological barrier

The fetus is not rejected even though its set of chromosomes differs from that of its mother and halfway represents an allogenic transplantation to the maternal organism (two individuals of the same kind, but genetically only half identical). This phenomenon remains an enigma. After birth the maternal organism rejects any tissue of the newborn, even though the same tissue (''natural allogeneic transplantation'') was accepted, protected and nourished for nine months. During pregnancy, the mother developed a tolerance to her child. This phenomenon is based on the specific antigen property of the embryo and the placenta as well as on the transitory changes of the maternal immune system during pregnancy.

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Antigenic properties of the embryo and placenta

On its surface cells, an embryo exhibits HLA proteins that differ from those of the mother, since it has received half of its genes from the paternal pronucleus. Thus for the maternal immune system the embryo consists of foreign, ''not-self'' material and would be eliminated if no protective mechanism was present.

Fetal tissue and especially that of the placenta (syncytiotrophoblast and cytotrophoblast of the villi) that stand in direct contact to the maternal organism produce no tissue antigens (HLA-A , -B, -C complexes = main complexes of the histocompatibility). Nevertheless, HLA -G antigens, which do not distinhuish between individuals, occurs through the extravillous cytothrophoblast. The HLA-G antigen takes over anti-viral and immunosuppressive functions as well as non-immunologic tasks.

In addition, the placenta blocks cytotoxic maternal cell effects by secreting various factors. The insufficiency of these mechanisms may be responsible for immune-dependent miscarriages. Besides these factors some steroid hormones (e.g., progesterone) have an immunosuppressive effect on the lymphocytes of the pregnant woman. Pogesterone (the concentration of which is especially elevated during pregnancy) seems to play an important immunosupressive role that is mediated by the PBIF protein (Progesterone Induced Blocking Factor).

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Reminder concerning immunologic reactions related to the rejection of fetal allogenic transplants

The cytotoxic T-lymphocytes control the cell population of the organism and, through cytolysis, destroy foreign cells (foreign to the body, "not self") or those cells of the organism that present a foreign antigen ("self, but modified "). Trophoblast cells would therefore have to be destroyed as foreign tissue. Since the recognition of an antigen presupposes its binding at a HLA (identity marking) protein and since trophoblast cells do not produce classical HLA, they cannot be recognized by the T-lymphocytes as foreign tissue and so escape destruction.

The NK cells (Natural Killer, non-B-non-T-lymphocytes) attack cells that do not possess classical HLA markers, e.g., trophoblast cells. NK-cells, though, are outfitted with a system that detects the HLA-G marker on throphoblast cells, inhibiting their cytolytic activity. The fetus is thus protected from the maternal immune defense system.