There was a story on NPR this morning about chimerism, which is essentially a condition where a person has two distinct sets of DNA as a result of “fraternal twin” embryos fusing together very early on in the pregnancy to form a single person. They say the person could have one set of DNA in their blood, for example, but a completely different set of DNA in a hair or skin sample, or organ tissue.
My wife was trying to figure out how the embryo could even survive, why there wouldn’t be some kind of mutual tissue rejection going on. My initial guess would be because the body doesn’t recognize either one as being “foreign tissue”, like you would have in the case of an organ transplant rejection. But it was just a WAG and I’m sure there is a more detailed medical explanation for how this situation is possible without being fatal.
Nah, you’re pretty much correct. During early development the immune system isn’t yet primed to recognise self and non-self. You can stick anything into a developing embryo and it won’t be rejected, although it may cause serious deformities. When you think about it, it would be unworkable if embryos did recognise foreign tissue, since they would reject the uterine lining as soon as they implanted.
In general whatever tissue an embryo/foetus is infused with up to a certain stage of development is recognised as self. I can’t remember when the cut off point is, but it’s quite late in development. This has been proposed as a way of getting around the rejection issues with animal transplants. If a human foetus were infused with tiny amounts of material from an individual pig emryo and vice versa, then the two should mutually accept each other for life. Ideal for organs transplants. I imagine the ethical and health problems assocaited with tampering with devleopng embryos has made this solution impractial so far.
There have been quite a few synthetically chimeral animals produced, including cross species chimeras.
I found this article from Nature that talks about it a bit, although it does not directly answer your question. It also has a linked bibliography that might provide more help.
Firstly, the body would have to actually make the proteins coded for by the “foreign” DNA, which may or may not happen. It’s the protein that provokes an immune response, not the DNA.
Secondly, during the maturation of lymphocytes (B and T cells), they go through a step where they have to sort of pass a test. If a cell reacts with any proteins that the body recognizes as “self”, that cell dies off. Presumably, anything coded for by the foreign DNA would still be recognized as “self”, since it’s been around since the embryonic stage.
The proteins are indisputably produced. These individuals contain whole, functioning cells from the aborted twin. That incudes the surface proteins and any other proteins that cell type normally makes. If they have some hair folicles form the aborted twin the keratin for example will be a “foreign protein”. If skin fibroblasts then the collagen will be foreign and so forth.
Precisely.
"during the late first and second trimester, this therapeutic window overlaps the time period when the fetus is immunologically tolerant to foreign antigens, presenting the ideal opportunity for tissue transplantation without requiring immunosuppression….
By exploiting the immune “naïve” window in the fetus, when there is no immune distinction between self and non-self, cells which contain the missing gene may be placed in the defective fetus without the need for immunosuppression. Such transplantation would also occur prior to the need for functional gene products within the fetus. Postnatally, these transplanted cells would produce enough product to maintain normal or near-normal functional levels. In addition, if the fetus has become tolerant to the donor cells, but there is attrition of these cells, a boost infusion of same-donor cells may be feasible in the early neonatal period should the fetus have been made tolerant by the initial transplant."
So this perosn could commit a crime and leave a hair sample behind, but it couldn’t be matched to a DNA sample taken from a throat swab or blood sample? Sounds like a plot point for CSI!
Interestingly, this is not necessarily the case. The maternal adaptive immune system is fully aware of the fetus. Somehow (via incompletely understood mechanisms) the fetus is not generally spontaneously aborted. Fetal allograft survival is not thought to be due to antigenic immaturity of the fetus.
Incidentally, the concept of chimerism is used extensively in biotechnology. Perhaps the most well-known use of chimeras is in the production of monoclonal antibodies (antibodies that recognize only a single epitope of a particular antigen). During this procedure, B cells are forced to fuse with myeloma cells. This immortalizes the B cells, of which clones can be selected to produce certain monoclonal antibodies. The end result is the production of a whole lotta money.
That isn’t the issue. I was pointing out that embryos that has the capacity to react to foreign tissue “would reject the uterine lining”. Whether the maternal immune system reacted to the infant would be irrelevant if the infant reacted to the uterus and began to destroy it.
Sorry, should’ve made my point clearer. What I meant was this: if the fetus recognized the uterine lining as foreign tissue, the fetus would not necessarily reject it. I used the maternal adaptive immune response as an example of recognition without destruction.
That is exactly the point they made in the NPR story. The woman who was featured in the story, learned about her condition because they were doing some kind of blood tests on her and her family (I don’t recall the exact reason) and the doctors told her that there was no way that two of her sons were hers because the DNA didn’t match. But they also extended the scenario to someone leaving one set of DNA at a scene of a crime (blood, for example) and getting away because the DNA in, say, a throat swab was the other set. Yeah, the whole situation is, as they said, “mind-bending”.