Advent Science Day Twenty-One
So, yesterday I casually mentioned tissue matching in organ transplantation. What's going on there, I hear you ask. That it is genetic should be pretty obvious, given that close relatives are far more likely to be able to provide transplantable tissue, and that unrelated transplant donors are generally of the same race as the recipient.
The answer lies in a set of cell surface proteins called antigens, which are expressed from a group of genes called the Major Histocompatibility Complex (MHC). There are quite a lot of these genes; in humans, there are 140 known genes in the MHC, spanning 3.6 million base pairs (that's about 0.1% of your entire genome).
These genes are known for being highly polymorphic, ie there are hundreds of different alleles of them known in the population- so many that other than identical twins the odds of two individuals having the same set are far, far higher than the number of people on the earth. They also recombine (swap bits around between the maternal and paternal chromosomes) far more often than other cells, when making gametes (sex cells).
So, every human has a unique pattern of these things, and the closer yours are to your transplant donor, the less strong the immunosuppressant drugs you need to stop you rejecting it. Huzzah!
So why doesn't a pregnant mother reject her foetus? Well, the placenta doesn't express the most prevalent antigens at all, thus avoiding detection by the mother's immune system (placental tissue is made by the baby, not the mother) and only expresses just enough of some others to avoid being tagged as a foreign object by the mother for having no MHC proteins at all. And then it forms a syncitium, a thick barrier made of layers of maternal and foetal cells which blocks any migratory immune cells from crossing between mother and baby.
It's not perfect; you may have heard of rhesus disease, which is caused when a rhesus-negative mother (see day 11) gives birth to a rhesus-positive baby. It is highly likely that during the birth, the mother and baby's blood will meet, which causes the mother's body to raise antibodies against the rhesus protein in the baby's blood. This is usually fine for the *first* baby, which is no longer inside the mother by the time the antibodies are there in sufficient concentration to do any damage, but subsequent pregnancies with a Rh+ baby can end up with anaemia in the baby due to small numbers of anti-rhesus antibodies managing to cross the placenta. Happily, modern medicine can deal with this, with Rh- women in developed countries routinely being given an injection of anti-rhesus antibodies towards the end of pregnancy so that these antibodies will destroy the foetal red blood cells before the mother's immune system has time to discover them and react.
So basically it's a balancing act that usually works.
The answer lies in a set of cell surface proteins called antigens, which are expressed from a group of genes called the Major Histocompatibility Complex (MHC). There are quite a lot of these genes; in humans, there are 140 known genes in the MHC, spanning 3.6 million base pairs (that's about 0.1% of your entire genome).
These genes are known for being highly polymorphic, ie there are hundreds of different alleles of them known in the population- so many that other than identical twins the odds of two individuals having the same set are far, far higher than the number of people on the earth. They also recombine (swap bits around between the maternal and paternal chromosomes) far more often than other cells, when making gametes (sex cells).
So, every human has a unique pattern of these things, and the closer yours are to your transplant donor, the less strong the immunosuppressant drugs you need to stop you rejecting it. Huzzah!
So why doesn't a pregnant mother reject her foetus? Well, the placenta doesn't express the most prevalent antigens at all, thus avoiding detection by the mother's immune system (placental tissue is made by the baby, not the mother) and only expresses just enough of some others to avoid being tagged as a foreign object by the mother for having no MHC proteins at all. And then it forms a syncitium, a thick barrier made of layers of maternal and foetal cells which blocks any migratory immune cells from crossing between mother and baby.
It's not perfect; you may have heard of rhesus disease, which is caused when a rhesus-negative mother (see day 11) gives birth to a rhesus-positive baby. It is highly likely that during the birth, the mother and baby's blood will meet, which causes the mother's body to raise antibodies against the rhesus protein in the baby's blood. This is usually fine for the *first* baby, which is no longer inside the mother by the time the antibodies are there in sufficient concentration to do any damage, but subsequent pregnancies with a Rh+ baby can end up with anaemia in the baby due to small numbers of anti-rhesus antibodies managing to cross the placenta. Happily, modern medicine can deal with this, with Rh- women in developed countries routinely being given an injection of anti-rhesus antibodies towards the end of pregnancy so that these antibodies will destroy the foetal red blood cells before the mother's immune system has time to discover them and react.
So basically it's a balancing act that usually works.