Anything that causes antibody production is an antigen. Antibodies are proteins produced and secreted by B cells in the immune system. Antigens are molecules, often cell surface proteins, capable of eliciting the formation of antibodies. However, the A and B antigens are actually carbohydrate groups that are bound to lipid molecules protruding from the membrane of the red blood cell. Three of the most important antigen's are called A, B, and Rh. A-B-O System The A-B-O blood groups, discovered by Karl Landsteiner in the early 1900s is a system characterized by the presence of antigens on the surface of red blood cells. In humans, if an antigen is present on the surface of the person's red blood cells, it would react with the corresponding antibody and cause agglutination of red blood cells. Upon this sort of testing four possible phenotypes may be revealed. These being the A antigen (A phenotype), B antigen (B phenotype), A and B antigens (AB phenotype), or neither antigens (O phenotype). Landsteiner's discovery has several practical applications. The knowledge of human blood types has been extremely important in the testing for compatibible blood types for use in blood transfusions. Another application involves cases of paternity tests, where a child's blood type can be matched to a fathers. Rh System In approximately 1940, Landsteiner, Levine, and others discoverd Rh antigens. Named after the rhesus monkey, Rh antigens are present on the surface of red blood cells. Rh antigens can be either positive or negative. These antigens have received a lot of attention due to their direct correlation in hemolytic disease of the newborn. This disease occurs if a mother is Rh-negative, carrying a Rh-positive fetus, because the father is Rh-positive. If fetal blood passes through the placenta at birth and enters the mother’s circulation, the mother’s immune system recognizes the Rh antigen as foreign and builds immunity by producing antibodies against it. If the mother becomes pregnant a second time, the antibody concentration becomes high enough that when mother’s antibodies pass across the placenta, they enter the fetus’s circulation and begin to destroy the fetus’s red blood cells causing the hemolytic anemia.