Karl Landsteiner discovered the main human blood group systems in 1901. He found that mixing blood from two individuals can cause clumping of red blood cells. This occurs due to antibodies in the plasma that target antigens on red blood cells. There are four main blood groups - A, B, AB and O - determined by the presence or absence of A and B antigens on red blood cells and antibodies in the plasma. Understanding blood groups made blood transfusions safer by avoiding incompatible blood.