dan@wystan.bsd.uchicago.edu (09/28/90)
binkley@boulder.Colorado.EDU (Jon Binkley) writes: >I would like to comment that I don't consider immunological responses >a barrier to interspecies crosses. The mother's immune system is >no more likely to attack the developing hybrid than it would a child >of her own species. Someone mentioned the response to Rh+; remember, >this response rarely occurs in the first Rh+ pregnancy of an Rh- mother. >This is because the mother's and child's blood do not come into direct >contact until birth. At this time, the mother develops anti-Rh antibodies >and subsequent Rh+ pregnancies are affected. I think that immune response may have some role here, for two important reasons: 1. Although the mother may not be exposed to the fetus' antigens before birth, her immune system is still capable of mounting a formidable attack on the foreign tissue. A very large number of circulating T-cells in a given host animal can respond against the major histocompatibility antigens of a foreign animal without prior exposure to the foreign tissue. This "immediate allogenic response" is probably the strongest response a host can mount and is very difficult to prevent (as witnessed by the difficulty of human-human transplantation). The key issue is how different the two animals are at the level of the major histocompatibility complex. Identical animals (identical twins or inbred strains) show absolutely no response to each other while animals of very distant heritage (humans and pigs, for example) show no immediate response but can reject later. However, cells from a given strain of mouse can react _immediately_ with no prior sensitization against cells from a different strain of mouse. Since humans and chimps have very similar MHC antigens, I suspect that chimp tissue would be subject to an immediate response. Fetuses can also be subjected to this type of "non-specific" T-cell reaction since they carry a different MHC type than the mother, but they are protected by an unknown mechanism at the uteral/placental interface. I don't know how the increased mismatch of MHC antigens from a human/chimp hybrid would affect the placental immunologic barrier, but if the protection mechanism broke down, the hybrid would surely be destroyed by the "mother's" T-cells. 2. While T-cell mediated immunity may be an important factor, experience with human/simian transplants casts an even darker shadow over a human/ chimp fetus. It seems that human/simian transplants (concordant xenographs for those who speak immunese) are rejected by a second mechanism having to do with _pre-formed_ anti-bodies against simian antigens in human serum. Just how an animal manages to make anti-body against a species its never been exposed to is a mystery, but it happens in every species. This problem has made human/simian transplants practically impossible up to now. Because anti-bodies can and do cross the placenta, I think the presence of pre-formed anti-bodies to other species makes hybrids pretty iffy. Any anti-chimp Ab's in a human "mother" (or vise-versa) would eat away at a hybrid fetus once the placenta had formed. Since the anti-bodies are present before impregnation (and would probably increase soon after) the normal immunological protection mechanism of the placenta would have little affect. There are ways of getting rid of the Ab's in serum, but I don't think that this discussion should involve "artificial" means (artificial insemination excluded, I sincerely hope). As a final word, I seem to remember that there was quite a big deal a few years ago about a horse carrying a zebra fetus to full term. Apparently it had never been accomplished before and the zoos were really hoping that it meant the beginning of "surrogate" mothering for endangered species. I haven't heard anything else about it since, but it could make an interesting model for this thread. -- Dan Rohwer-Nutter The University of Chicago Department of Neurology dan@wystan.bsd.uchicago.edu "Why does everybody put those stupid quotes at the end?" - my wife