Natural Killer Cells (NK Cells)
NK cells are a type of lymphocyte - an immune cell - normally circulating in blood. They make up a large part of the immune system and play a major role in the rejection of tumours and cells infected by viruses. There is evidence to suggest that an imbalance of activity of NK cells in the blood of some women could be contributing to miscarriage.
What are Natural Killer Cells?
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Natural Killer (NK) cells keep us alive.
NK cells are a type of lymphocyte - an immune cell - normally circulating in blood. Their job is to seek out and destroy cancerous or virus infected cells. Natural Killer Cells are an essential part of the human body. More Science... 
Blood contains immune cells called lymphocytes. About 5% of these lymphocytes have a special function: to recognise and rapidly kill cells that have either become cancerous or
have become infected with a virus. They are known as “Natural Killer cells” or NK cells. NK cells bind themselves to the diseased or infected target cells and release a potent
cytotoxic chemical called tumour necrosis factor (TNF) that kills these cells. |
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Uterine NK cells are found in the uterine lining.
Uterine Natural Killer cells are a special type of immune cell that can be found in the endometrial lining of the uterus. They are found particularly at the time of implantation of an embryo and during the early weeks of pregnancy. However, uterine NK cells are very different from the NK cells found in the blood. More Science...
No science just yet... [ x ] |
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The function of uNK cells remains unknown.
Despite much speculation, the function of uterine NK cells remains completely unknown. However, it is thought that uterine NK cells play an important role in implantation and in establishing the circulation of the early placenta. No evidence has been produced to show that uterine NK cells have a damaging effect on the embryo or developing baby. More Science...
Uterine NK cells (uNK cells) seem to help the placenta link up with the mother's blood vessels and so set up a healthy supply line to the fetus. However, scientists do not know exactly how they do it. (In mice that lack NK cells in the womb, development of the placenta is abnormal and the young are smaller than usual).
If uNK cells are not hostile to invading trophoblast (the outer layer of a blastocyst), it is possible that uNK cells may facilitate the implantation of abnormal blastocysts leading to the clinical presentation of recurrent miscarriage. [ x ] |
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uNK cells cannot be found in the blood.
Uterine NK cells remain in the endometrium and do not appear in the circulation. It is important to understand that levels of blood NK cells may not relate to any activity of uterine NK cells. Tests to measure blood NK cells may be pointless for women suffering from infertility and there may be no value in predicting the outcome of a future pregnancy. More Science...
Although the evidence regarding a link between blood and uterine NK cells is limited, it has recently been shown that NK cells in the blood could reflect changes in uterine NK cell levels (Park et al., 2010). [ x ] |
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uNK cells do NOT appear to attack embryo cells.
Whilst it is still believed that elevated uNK cells may cause recurrent miscarriage, the exact mechanism as to how this occurs remains unclear. It is however known that unlike blood NK Cells, Uterine NK Cells do not kill other cells. More Science...
At present, despite their compelling name, there is no evidence that uterine NK cells kill placental trophoblast cells. Instead, they probably have an essential, beneficial effect on trophoblast by secreting cytokines that alter the depth of placental invasion. Natural killer cells acquired their name as a result of the initial test used to identify them in vitro. Unlike T lymphocytes, NK cells are able to spontaneously kill cells in a non-MHC restricted manner. Regrettably, this is a misleading name in reproduction, and the powerful image of maternal cells attacking the fetus is emotive and easily exploited. [ x ] |
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A lack of uNK cells is bad.
NK cells present in the lining of the womb have been claimed to be beneficial for the development of pregnancy, by supporting the development of the placenta. A lack of such cells in experimental animals causes abortions or results in small babies. More Science...
No science just yet... [ x ] |
NK Cells and Fertility
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Elevated levels of NK cells may not be a problem.
There is currently no firm evidence to suggest that NK cells are implicated in causing infertility, IVF failure or recurrent miscarriage. Indeed NK cells are likely to play an important role in early pregnancy development.
However, a recent study has found that an imbalance in the presence of NK cells was also found in the blood of women whose embryos failed to implant in the womb. (Baltadzheiva et al., 2010). More Science...
No science just yet... [ x ] |
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Immune therapy treatment appears to work.
There is more and more emerging evidence that immune therapy improves pregnancy and fertility outcome. The use of prednisolone as well as other types of therapy such as intralipids appears to improve the success of IVF. More Science...
No science just yet... [ x ] |
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uNK cells may be a cause of recurrent miscarriage.
Studies have shown that higher numbers of uNK cells are found in the preimplantation endometrium of women with recurrent miscarriage compared to controls. Furthermore, women who had higher numbers of uNK cells were more likely to miscarry in subsequent pregnancy.
The latest research seems to indicate that the uterine NK cells make the lining of the womb produce an abundance of blood vessels. Whilst that sounds like a good thing, too many blood vessels could produce too much oxygen in the first few weeks of pregnancy, leading to a miscarriage. More Science...
Uterine NK cells are the most predominant leucocytes in the endometrium and their density varies throughout the menstrual cycle. uNK cell density increases in number towards the mid-luteal phase and peaks if implantation occurs. uNK cells accumulate as a dense infiltrate at the implantation site near stromal cells, glands, blood vessels and trophoblast cells in early pregnancy. In-vitro studies have also shown that extravillous trophoblast and uNK cells interaction occurs. These interactions may have an effect on trophoblast invasion. However, more recent evidence points to the role of uNK cells as one of controlling angiogenesis (the physiological process involving the growth of new blood vessels from pre-existing vessels).
It is possible that increased uNK cell density is associated with an increased number of spiral arteries which may lead to inappropriate blood flow to the developing foetal-placental unit causing oxidative stress and consequent miscarriage. [ x ] |
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Clinics that offer immune therapy appear more successful.
Whilst further studies are undoubtedly required to determine exactly how NK cells may impact on fertility, it does appear that the more successful fertility clinics test for and treat raised NK cell levels. More Science...
No science just yet... [ x ] |
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