Humoral Immunity - History

History

The concept of humoral immunity developed based on analysis of antibacterial activity of the components of serum. Hans Buchner is credited with the development of the humoral theory. In 1890 he described alexins, or “protective substances”, which exist in the serum and other bodily fluid and are capable of killing microorganisms. Alexins, later redefined "complement" by Paul Ehrlich, were shown to be the soluble components of the innate response that lead to a combination of cellular and humoral immunity, and bridged the features of innate and acquired immunity.

Following the 1888 discovery of diphtheria and tetanus, Emil von Behring and Kitasato Shibasaburō showed that disease need not be caused by microorganisms themselves. They discovered that cell-free filtrates were sufficient to cause disease. In 1890, filtrates of diphtheria (later named diphtheria toxins) were used to immunize animals in an attempt to demonstrate that immunized serum contained an antitoxin that could neutralize the activity of the toxin and could transfer immunity to non immune animals. In 1897, Paul Ehrlich showed that antibodies form against the plant toxins ricin and abrin, and proposed that these antibodies are responsible for immunity. Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy. The presence and specificity of compatibility antibodies became the major tool for standardizing the state of immunity and identifying the presence of previous infections.

Major discoveries in the study of humoral immunity
Substance Activity Discovery
Alexin(s)
Complement
Soluble components in the serum
that are capable of killing microorganisms
Buchner (1890),
Ehrlich (1892)
Antitoxins Substances in the serum that can neutralize
the activity of toxins, enabling passive immunization
von Behring and Kitasato (1890)
Bacteriolysins Serum substances that work with the
complement proteins to induce bacterial lysis
Richard Pfeiffer (1895)
Bacterial agglutinins
& precipitins
Serum substances that agglutinate bacteria
and precipitate bacterial toxins
von Gruber and Durham (1896),
Kraus (1897)
Hemolysins Serum substances that work with complement
to lyse red blood cells
Belfanti and Carbone (1898)
Jules Bordet (1899)
Opsonins serum substances that coat the outer membrane
of foreign substances and enhance the rate of
phagocytosis by macrophages
Wright and Douglas (1903)
Antibody formation (1900), antigen-antibody binding
hypothesis (1938), produced by B cells (1948),
structure (1972), immunoglobulin genes (1976)
Founder: P Ehrlich

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