Blood types are determined by the presence, or absence, of certain markers on the surface of red blood cells, called antigens. An antigen is a molecule that is of sufficient size and complexity that the body can recognize it as “not self” and mount an immune response to destroy it as a potential invader. There are actually many antigens that can define various blood types but the most important come in two groups; 1) A, B, O, and 2) Rh.
Let’s look at ABO first. A and B are antigens that humans may or may not carry on their red blood cells, but the important thing about A and B is that they are also abundant in our environment, in microorganisms, pollen, and in animal dander. We are constantly exposed to the antigens and as a result, we develop antibodies that will attack and destroy red blood cells that are unlike our own.
We get one gene from each of our parents to determine our ABO type. The gene for A codes for the A antigen, the gene for B codes for the B antigen, there really is no gene for O, it’s more of a blood banker’s placeholder, it doesn’t code for anything at all. If you inherit two A genes you’ll be type A, but you’ll still type as A if you only get one gene for A and one for O.
Whichever way you get there, if you are type A you will carry in your bloodstream antibodies that will fiercely attack red blood cells displaying the B antigen. It goes the same way for people of type B. One copy of the B gene will make you type B if your other one is also a B or if your other is for O. Either way you’ll carry antibodies that will attack any cells showing the A antigen. Of course, you could get genes for both A and B and your type comes out AB and you don’t make antibodies against either antigen. People who are type O make both Anti-A and Anti-B antibodies.
Once they got the ABO grouping sorted out transfusions got a lot safer but still, people occasionally died in obvious transfusion reactions. Something else was going on. For the safety of the humans involved the search for the mystery antigen causing these reactions was done in Rhesus monkeys. People to whom the Rhesus monkey’s blood reacted to were dubbed Rhesus Positive, which got shortened to Rh+. People to whom the monkeys did not react are of course Rh-. Modern blood bankers refer to the Rh antigen as D.
The D antigen is uniquely human, it is not abundant in our environment, the only way for a person to become sensitized to, and develop antibodies to attack the D antigen is to actually be exposed to Rh+ red cells when they themselves are Rh-. The most common way for this to occur is not via transfusions it often occurs in childbirth. When a Rh- woman gives birth to a Rh+ child there is a risk the fetal red blood cells that make get into her bloodstream will be recognized as “not self” and an immune response will soon destroy all of the Rh+ cells, and any such cells her body may encounter in the future.
An ABO mismatch transfusion can be quickly fatal. An Rh- Rh+ mismatch is an entirely different matter. Of course, a Rh- woman of childbearing age should never be given Rh+ cells for the sake of the safety of future pregnancies, but in a life threatening emergency situation there is no reason a man of Rh- blood type couldn’t safely be transfused with Rh+ cells in sufficient quantity to reverse a trend towards death. This would be a once in a lifetime deal. Over several weeks all of the recipient’s transfused Rh+ cells would be destroyed for being “not self” and an enduring immune response would remain.