Why The Fetus Is Not Rejected
Who is the alien?
Have you ever stopped to ask yourself why the fetus in the womb is not rejected? After all, the body defence (immune) system is geared towards getting rid of any foreign tissue that gets in the body and the baby, having 50% genetic material from the father is essentially foreign. Come to think of it, in case of surrogacy, the fetus is 100% foreign as the fetus growing in the womb has no genetic relationship at all to the woman carrying the pregnancy. Yet, the fetus stays happily, aided and abetted for 9 months, give or take. How? Let’s shed some light, shall we?
Mammals: The art of being a mother
Mammals, a group where we belong, are the only animals that give birth to their young. The clue is in the name. In science circles, they are also described as viviparous, meaning ‘they give birth to live young’ (as opposed to laying eggs). This evolutionary attainment required some dextrous adjustment to the normal immune defence mechanism to ensure the young, by all intents and purposes a distinct foreign body, does grow unharmed inside the mother until birth.
Mounting a defence
If a transplant of an organ from another individual is made, it will be swiftly rejected by the body unless something is actively done to suppress the immune reaction. This is why, even though a close genetic match as possible is sought in any transplant surgery, the recipient of the organ is put on medication to suppress that response for life. The fetus in the womb is biologically a graft. The reaction of the body’s immune system would be expected to be the similar to having an organ from another person.
During pregnancy, the fetus is connected to the mother via an umbilical cord which extends to the placenta (afterbirth). The placenta is entirely fetal in origin. The placenta is embedded in the inside wall of the womb. The blood of the mother and fetus are in entirely separate circulations and do not mix or even come into contact. However, the bloods come in close proximity at the placenta/womb interface where that all important exchange of gases (oxygen and carbon dioxide) and nutrients take place. The layer of placental cells known as ‘trophoblast cells’ in direct contact with the wall of the womb would be expected to trigger an immune response but, normally, this does not happen. It is an effective physical barrier which is tolerated by the mother’s immune system.
Mechanism of tolerance
The exact mechanism through which mother and fetus co-exist during pregnancy has been a subject of extensive scientific research and debate for well over a century now. It appears this remarkable state has been achieved through multiple adjustments, amounting to a localised down-regulation of the normal immune reaction allowing the fetus to flourish unperturbed. Below are just some of those.
- There is evidence that the layer of trophoblast cells of the placenta secrete specific proteins into the mother’s circulation. These proteins have the effect of inhibiting her Natural Killer (NK) cells and cytotoxic T lymphocytes, which are normally responsible for attacking and destroying the foreign tissue. This is believed to create an inert environment at the site where the normal immune reaction does not take place. This effect is strictly local, leaving the woman’s normal general immune capabilities intact.
- Progesterone is a hormone that is known to be crucial both for preparing the womb environment for implantation after conception has taken place and for the maintenance of pregnancy. Initially the progesterone is sourced from the cyst left behind after ovulation. The cyst goes by the name corpus luteum. A few weeks down the line, the placenta takes over the production of this important hormone. It transpires that progesterone produced by placental cells is crucial in preventing fetal rejection as it actively inhibits T-cell mediated foreign tissue rejection in the womb. One of the ways it achieves this is by inhibiting white cell (lymphocyte) activation and proliferation in the womb. What is impressive is that this effect is observed locally (in the uterus) only and lymphocytes in the rest of the body are not susceptible to this progesterone effect thus maintaining normal immune capabilities.
- Research in recent years has investigated the role of an enzyme known as IDO (Indoleamine 2,3-dioxygenase). This enzyme is found in much higher concentrations in the pregnant uterus. It turns out that it is actually produced by the fetus. IDO is responsible for breaking down the amino acid Tryptophan. This action has the effect of inhibiting the proliferation of the T cells which would otherwise be cytotoxic to the foreign tissue that is the fetus.
Looking after No. 1
What is clear is that the fetus does actively mount and maintain its own defence to survive in an otherwise hostile environment. The paradox of the mother-fetus happy co-existence has yet to be fully unravelled but, we know more about the numerous complex mechanisms via which this has been achieved than we knew a few years ago.
Some women suffer recurrent pregnancy loss, usually in the early trimester, which remain unexplained. It is now thought, for some at least, there may be a breakdown in the tolerance mechanisms described above resulting in the fetus being rejected, like any foreign tissue would. This has been a subject of extensive research, so far with no conclusive answers
Reason to be happy
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