During the late 19th and early 20th centuries, the impetus of the new science of bacteriology led to research into immunity. The most important figures were the Russian naturalist Elie Metchnikoff, who developed the theory of phagocytosis, the destruction of foreign materials in the blood, and the German bacteriologist and chemist Paul Ehrlich, who evolved a theory of antibody formation. In the first decade of the 20th century, German physician and chemist Paul Ehrlich began experimenting with the synthesis of organic compounds that would selectively attack an infecting organism without harming the host organism.
His experiments led to the development, in 1909, of salvarsan, a synthetic compound containing arsenic, which exhibited selective action against spirochetes, the bacteria that cause syphilis. 16(pp424-448) 1) Karl Landsteiner’s Blood Group Typing of red blood cells is a prerequisite for blood transfusion. In the early part of the 20th century, physicians discovered that blood transfusions often failed because the blood type of the recipient was not compatible with that of the donor. In 1901 the Austrian pathologist Karl Landsteiner classified blood types and discovered that they were transmitted by Mendelian heredity.
The four blood types are known as A, B, AB, and O. Blood type A contains red blood cells that have a substance A on their surface. This type of blood also contains an antibody directed against substance B, found on the red cells of persons with blood type B. Type B blood contains the reverse combination. Serum of blood type AB contains neither antibody, but red cells in this type of blood contain both A and B substances. In type O blood, neither substance is present on the red cells, but the individual is capable of forming antibodies directed against red cells containing substance A or B.
If blood type A is transfused into a person with B type blood, anti-A antibodies in the recipient will destroy the transfused A red cells. Because O type blood has neither substance on its red cells, it can be given successfully to almost any person. 5 2) Opsonization Antibodies also help destroy antigens by preparing them for ingestion by macrophages in a process called opsonization. In opsonization, antibodies coat the surface of antigens. Since macrophages have receptors that stick to the base of the antibody’s Y structure, antigens coated with antibodies are more likely to stick to the macrophages and be ingested5(p38).
Opsonization is especially important in helping the body resist bacterial diseases. 3) Anaphylaxis Anaphylaxis, the malevolent kingpin of allergic reactions, makes a mockery of a patient’s assertion that “it’s just allergies. ” Anaphylaxis is a misguided attack by the body’s immune system against a generally benign foreign substance—usually a food, drug, or insect venom. In this type of relentless allergic reaction, an overzealous immune system seeks to expel a harmless intruder by burning down the house.
It is so overwhelming that it can leave virtually every body system in a state of collapse, and so ferocious that a patient can be dead in minutes despite the best medical treatment. Anaphylaxis occurs when the body recognizes the presence of a foreign intruder, or antigen, that it has seen before and for some unknown reason has deemed henceforth unwelcome. During the first encounter there is no outward reaction to the antigen. But the body takes an irrational dislike to the substance, creating immune molecules called antibodies that remember its chemical structure.
If and when it intrudes again, these scouts detect its presence and sound a chemical alarm. Cells called mast cells release powerful chemical messengers—histamines—that pour into the bloodstream and cause smooth muscle to contract and blood vessels to open wide and become leaky. Tissues become swollen as fluid leaks from the vessels. And this inflammation occurs not only externally—causing hives—but internally as well. 6 4) Antigens Ehrlich suggested that antigens interact with receptors borne by cells7(pp424-428), 8 and this results in the secretion of excess receptors (antibody).
He differed from his contemporary Metchnikoff who ascribed the production of antibodies to macrophages. Ehrlich did suggest that erythrocytes would not have this function and that the function might be a specialized characteristic or “haemopoietic tissue. ” He also implied that some tissues might respond better to certain antigens than others. Thus, his collaborator Von Dungern wrote, “the most varied cells, according to the kind of side-chains [receptors] they possess and the affinities thereby brought about, are probably able to produce immune body [antibody]”.
8 The key feature of Ehrlich’s “selective” model was that there was a pre-existing repertoire of specificities for a variety of antigens. The antigens then would act to select from among the specificities. Ehrlich appreciates that some antibody (natural antibody) might be released without the necessity of previous interaction of the cell with antigen. Furthermore, he appreciated that this free antibody might serve to buffer receptor-bearing cells against interaction with antigen.
He understood that antibody molecules would have a distinct structure, and that parts of the molecule that react with complement might differ from parts reacting with specific antigen. He also recognized that antibodies themselves are potential antigens and that distinct anti-antibodies might be raised against different parts of the antibody molecule. He also introduced the idea of a mechanism of self/not-self discrimination: “which prevents the production within the organism of ambo ceptors [antibodies] directed against its own tissues. In this horror autoxicus, we are dealing with a well-adapted regulatory contrivance.