A common source of exposure to other blood proteins is pregnancy.  This is a  particularly common concern when an Rh- women carries an Rh+ child (since the D antigen is dominant, this is a common occurrence).  As we've already noted, we do not "innately" have the antibodies against the D protein.  During a first pregnancy with an Rh+ child, there are usually few problems related to the blood type disparity (as shown in the picture below). 

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With the first pregnancy, the mother will be exposed to the D protein for the first time.  During the pregnancy itself, little fetal blood makes it into the mother's system and there is generally no problem.   However, at labor and delivery, there is significant exposure of the mother's system and the fetal blood.  This exposure will cause the mother to make antibodies directed against the D protein.  Since the baby has been born by the time this occurs to any major extent, neither mother or child are affected adversely.  

The problems begin if the mother becomes pregnant again with an Rh+ child (see second picture).

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With the second pregnancy, the mother's body had already started making antibodies and has a memory cell for those antibodies in "storage".  A nice thing about the immune system is that the second time we are exposed to a foreign protein, the immune response is much more sensitive (i.e. it takes less exposure), much stronger (more antibodies will be produced) and much quicker.  If this is a virus we are running into, this is a good thing.   However, in the case of an Rh+ baby, this is a bad thing.  With the second pregnancy, the little bit of fetal blood that enters the maternal system is sufficient to produce an immune response (since the Mom's immune system is now more sensitive to that protein), and antibodies to the D protein begin to attack the fetal RBC's.  This results in erythroblastosis fetalis.

In the neonate suffering from an Rh incompatibility (erythroblastosis fetalis), a transfusion may be required to maintain normal oxygen carrying capacity in the fetus.  However, the neonate has a problem:  Mom's antibodies (directed against the D protein) may persist in the baby's circulation far longer than would happen in an adult.  This means that if we transfuse the baby with Rh+ blood (which would match it's blood type), there will be more antibodies around to cause more problems for us.  Therefore, a neonate suffering from erythroblastosis fetalis of a degree sufficient to require a transfusion is transfused with Rh- blood.   Remember that we don't respond to the absence of a protein, so the neonate won't be bothered at all by this disparity, but the mother's antibodies will no longer find the D protein to bind to.  Thus, there is no further activation of the complement system, sparing the baby the resulting hemolysis, jaundice and potential tissue damage.  

Erythroblastosis fetalis can be prevented by injecting the mother with a substance called "rho-gam" (the antibodies against the D protein) after each exposure.   This appears to work by "fooling" the mother's immune system into believing that a memory cell for the Anti-D has already been created.  Therefore, the next time the mother is exposed to the D antigen, her body does not have the memory cell available to start rapidly producing the antibodies and it behaves as if this were the first exposure.  As noted above, this must be repeated with each exposure (pregnancy).  

Similar reactions can also occur when the infant expresses an antigen that the mother is negative for.  The symptoms in the fetus are identical to those described above and all of these can cause hemolytic disease of the newborn.  This can result from ABO incompatibility or the presence of other antigens as discussed in transfusion reactions.  In these cases, prevention is generally not possible because by the time it is caught (i.e. a baby is born suffering from hemolytic disease of the newborn), the mother has already established the memory cells.  It is these cases that lead to the old (but accurate) piece of medical wisdom that a woman should never receive a transfusion from her husband if she is of child-bearing age.  


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