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Blood transfusions are an essential and safe part of modern medicine, but it wasn’t always that way. In medieval times, transfusions often caused terrible, fatal reactions. Then in 1901, Karl Landsteiner discovered blood types and that humans had four—A, B, AB and O. Because of this discovery, we now know that the secret to a safe blood transfusion is understanding how to mix and match them.

Why can people die if they receive the wrong type of blood? Blood type is determined by molecules called antigens that decorate the surface of a person’s red blood cells. There are three antigens that determine blood type: A, B and RhD. Those with A antigens on their red blood cells has blood type A, while those with B antigens on their red blood cells have blood type B. Those with both A and B antigens are blood type AB, and those with neither A nor B antigens have blood type O. Blood types are further divided into “+” or “-”, such as O+ and O-. The “+” sign means that the red blood cells also have the RhD antigen and “-“ means they do not.

Blood also has proteins called antibodies that patrol for antigens that don’t belong. When the antibody sees such an antigen, it sets off a chain of reactions to kill the invader. For example, a person with blood type A will have antibodies that recognize B antigens as not belonging and will attack blood types B and AB. This reaction can be fatal. Matching blood types correctly, however, can get around the antibody reaction. Giving type A or O blood to a person with type A blood will not induce a reaction because neither A nor O blood have the B antigen. The “+” or “-“ also have to be matched. People with Rh- blood will have antibodies that attack Rh+ blood, so they can only donate to other Rh- individuals. People with Rh+ blood, though, can donate to both Rh- and Rh+ individuals.

Can you figure out the combinations? Check your answers with this infographic from the American Red Cross, and test your blood-matching knowledge with this transfusion game.

-Emily Johnson and Maggie Kuo

Emily Johnson, PhD, is an APS member and a former volunteer editor for the I Spy Physiology blog.

Maggie Kuo, PhD, is the former Communications and Social Media Coordinator for APS. Catch more of her writing in the Careers Section of Science Magazine.