An antigen is any substance that provokes a response by the body's immune system. An antibody is a protein manufactured by the body to neutralize a specific invading antigen.
Before the 1880s, not much was known about the specific components and workings of the immune system. During the 1880s, researchers found that both diphtheria and tetanus were caused by a toxin produced by the disease bacillus and that the body responded by producing a neutralizer, or antitoxin. In 1890 Emil von Behring and Shibasaburo Kitasato, working in Robert Koch's laboratory in Berlin, Germany, showed that guinea pigs became immune to diphtheria or tetanus toxins if they had been injected with serum from an already immune animal. From this, von Behring concluded that immunity was conferred by protective substances in the blood, which he called antitoxins, or antibodies, and that these substances were very specific, protecting only against one particular disease. In 1901, Von Behring won the first Nobel Prize in medicine for his work.
Other properties of antibodies were discovered in the 1890s. A German bacteriologist showed in 1894 that cholera bacteria were destroyed by antibodies (a process called bacteriolysis). In 1898 a young Belgian bacteriologist, Jules Bordet, found that when cholera serum was heated to 131° F (55° C), it retained its antibodies but lost its ability to destroy bacteria. He concluded that the heated serum lost a bactericidal substance, originally called alexine but which became known as complement. This explained an important element of immunity: an antibody combines with an antigen, and only after the antibody reacts with complement is the antigen made harmless. Bordet also explained that antigens can be detected by their reaction to specific antibodies, and by the fact that antibody-antigen complexes precipitate out of a solution when they react to complement. These immune reactions became the basis for countless numbers of diagnostic tests, including the famous Wassermann test for syphilis.
The specific nature of the antigen-antibody reaction was used by Karl Landsteiner in 1900 to make his very important discovery of the human blood groups. Landsteiner also showed that individual antibodies react to the specific chemical structure of individual antigens. German medical scientist Paul Ehrlich developed the "side-chain" theory of immunity around 1900 explaining that antibodies and antigens fit together in very specific molecular ways, like a key in a lock.
Although much was now known about how antibodies worked, researchers still didn't know what these substances actually were. In the 1930s Arne Tiselius developed sophisticated new methods of electrophoresis that allowed the isolation of antibodies in blood sera. By 1938 Tiselius had identified them as proteins of the gamma globulin portion of plasma. (Antibodies are now also called immunoglobulins.) In 1948 Astrid Fagraeus showed that antibodies are produced by plasma cells in the bone marrow and lymph nodes.
The exact molecular nature of antibodies was difficult to discern, since the body produces about one million different antibodies, and they are all large molecules. A pioneer in this field was Linus Pauling, who published his first paper on antibody structure in 1940. By 1962 both Rodney R. Porter (1917-1985) in England and Gerald M. Edelman (1929-) in the United States had worked out the basic molecular structure of antibodies. In 1968 researchers discovered that there are two types of lymphocytes, and that it is the B-lymphocytes that produce the antibody-forming plasma cells. In 1975 Georges Kohler (1913-) and Cesar Milstein at the Laboratory of Molecular Biology in Cambridge produced exactly similar (monoclonal) antibodies outside the body, by fusing a B-lymphocyte with a myeloma (cancerous) cell. The resulting fused cell, like all cancer cells, divides indefinitely. Clones of the cell produce virtually unlimited amounts of identical antibodies, which can be used in the purification of viruses, bacteria, and interferons; and as weapons against cancer.
By virtue of their ability to interact with protein molecules in blood and urine, these agents are also useful in diagnostic tests known as immunoassays. For example, home pregnancy tests are one type of immunoassay which use a monoclonal antibody (MAb) to react with hCG (Human Chorionic Gonadotrophin) a hormone that is secreted during pregnancy.
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