Naked Science Forum
Life Sciences => Physiology & Medicine => Topic started by: george on 31/10/2006 23:13:17
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I was reading about foetal development the other day and came across something that I couldn't understand; I hope someone here can explain.
From 30 weeks gestation, the placenta begins to transfer immunoglobulins (antibodies) of the IgG class from the mother's bloodstream to the baby. The aim is to provide the baby with "passive" protection against infection until its own immune system begins to work properly.
I know that the B cells that produce antibodies are "checked" to make sure that they aren't auto-reactive (don't lock on to our own tissues) before they are allowed to mature. But the antibodies are not checked against the developing baby's tissues, only the mother's.
So why don't the maternal IgG's start to bind onto foetal tissue and damage it?
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Hi George,
sometimes IgGs from the mother do bind and damage foetal tissues.
It is the case of Rh-antigens immunization: when the RhNEG mother had met foreign Rh-Ag in a previous pregnancy or abortion, her IgG anti-Rh cross the placenta and are actively passed to the foetus.
Maternal immunoglobulins bind Rh-Ag on foetal red blood cells (Rh-Ag is on rbc ONLY)and destroy them. Foetuses may die from acute anemia because of that.
Intrauterine transfusion of RhNEG red cells is the standard treatment.
So a crucial mechanism designed (selected!) to defend newborn babies may damage them when something goes wrong (it happens quite rarely anyway).
ikod
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Thanks Iko.
I knew about Rhesus disease, and should have mentioned it, but I was more thinking of all of the other IgGs naturally present in maternal circulation. Surely some of them must recognise foetal epitopes?
George
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Hello George,
There are other rbc antigens capable of doing the same trick: Kell, Kidd and even ABO system Ags. ABO antigens are present also on many other tissues apart from blood, so any bad effect is 'diluted'. Maternal natural anti-A and anti-B IgM do not cross the placenta, so previous immunization is required to produce IgGs anti-A or B.
Most of the IgGs are just good for the baby and developing IgG anti-HLA tissue antigens is quite rare and, still...
Basically IgG from a normal person do not affect receiving patients: think of the use of concentrated IgG infusion for a variety of diseases (immunodeficiencies, viral diseases, thrombocytopenia etc.). Even plasma infused for coagulation deficiencies contains IgG that are just fine.
Cellular immunity would hit quite hard foreign HLA-Ags in the foetus, but special hormonal-immune mechanisms (mostly uknown, to me at least) seem to keep it at large. Few maternal lymphocytes manage to reach the foetus through placental vessels as some foetal cells manage to circulate in maternal blood: this could be part of the trick.
Take care,
ikod
The placenta is an allograft
One of the greatest unsolved mysteries in immunology is how the placenta survives for 9 months without being rejected by the mother's immune system. Every cell of the placenta carries the father's genome (a haploid set of his chromosomes); including one of his #6 chromosomes where the genes for the major histocompatibility antigens are located.
One partial exception: none of the genes on the father's X chromosome are expressed. While X-chromosome inactivation is random in the cells of the fetus, it is NOT random in the cells of the trophoblast. In every cell of the trophoblast — and its descendants — it is the paternal X chromosome that is inactivated. [Discussion of X-chromosome inactivation.] But this does not solve our problem because the genes for all the major histocompatibility antigens are located on chromosome 6, which is not inactivated.
Discussion of the human major histocompatibility complex (MHC)
Thus the placenta is immunologically as foreign to the mother as a kidney transplant would be.
Yet it thrives.
Despite a half-century of research, the mechanism for this immunologically privileged status remains uncertain. But one thing is clear:
The mother is not intrinsically tolerant of the father's antigens.
Some evidence:
She will promptly reject a skin transplant from the father.
She develops antibodies against his histocompatibility antigens expressed by the fetus. In fact, women who have borne several children by the same father are often excellent sources of anti-HLA serum for use in tissue typing.
So what accounts for the phenomenon? Some possibilities:
The placenta does not express class II histocompatibility antigens. Discussion of the role of class II antigens in immunity.
Nor does it express the strongly-immunogenic class I histocompatibility antigens (HLA-A, HLA-B). It does express HLA-C, but this is only weakly immunogenic.
The cells of the placenta secrete progesterone, which is immunosuppressive.
In lab rats, at least, the embryos (and the mother's endometrium) secrete corticotropin-releasing hormone (CRH). This hormone induces the expression of Fas ligand (FasL) on the cells of the placenta. Activated T cells express Fas so any threatening T cells would commit suicide by apoptosis when they encounter FasL on their target. Link to more of the story of the role of Fas and FasL in apoptosis. (but note: the example you will see is the reverse of the story here; that is, the cytotoxic T cell is using its own FasL to kill a target cell that is expressing Fas but not FasL.)
In laboratory mice, at least, the cells of the placenta degrade the amino acid tryptophan. Tryptophan is essential for T-cell function. When mice are treated with an inhibitor of the Trp-degrading enzyme, their fetuses are promptly aborted by the action of the mother's lymphocytes. (D. H. Munn, et. al., Science, 281: 1191, 21 Aug 1998.)
from: http://home.comcast.net/~john.kimball1/BiologyPages/S/Sexual_Reproduction.html