of History Immunology
Athenian Epidemic (430-426 BC) Thucydides noted that survivors of the disease had immunity. Immunization against smallpox known in China from at least the 10th century AD. Dried the matter from pustules and inserted in nostrils. Turkey variolation using crusts (scabs) from smallpox patient with mild form.
Smallpox 30% mortality rate. Late 1700's killed: 10% of population 20% in cities 33% of all child deaths
Lady Mary Wortley Montaque (1718) had her children infected with smallpox. Charles Maitland trial of smallpox variolation on six condemmed prisoners (August 1721). All survived after being exposed to smallpox. Repeated experiment on five orphaned children. Treated the daughters of the Prince of Wales. 2-3% of variolated persons died or contracted another disease (tuberculosis, syphilis). *case-fatality rate associated with variolation was 10 times lower than contracting the naturally
Edward Jenner
Cowpox milkmaids that developed cowpox did not get smallpox. Used fluid from cowpox pustule to inoculate 8-year old boy, James Phipps, subsequently innoculated boy with smallpox lesion (1798). Latin for cow = vacca, cowpox = vaccinia Jenner called new treatment - vaccination
In science credit goes to the man who convinces the world, not the man to whom the idea first occurs. --Francis Galton
Louis Pasteur
Louis Pasteur
Cholera used old cultures, chickens recovered, were resistant to disease. Attenuated vs. virulent Discovered methods to make attenuated forms of disease organisms = vaccines Anthrax in sheep (1881) Rabies in humans (1885)
Emil von Behring & Shibasaburo Kitasato
1890 Demonstrated that serum from immunized animals could transfer immunity to nonimmunized animals. "Antibodies" Immunity mediated by antibodies found in body fluids (humors) = humoral immunity. Led to practice of producing
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Elie Metchnikoff
Demonstrated (1883) that cells contribute to Using immunity. starfish larvae observed that cells migrated to splinter and could digest bacteria = phagocytes. Noted that phagocytes were more active in immunized animals. Cells not serum components were major
Cellular Immunity
Merrill Chase (1940's) demonstrated that immunity to tuberculosis could be conferred by transferring white blood cells between guinea pigs. Bruce Glick (1950's) Two types of Lymphocytes T cells Thymus (cellular immunity) B cells bursa of Fabricius (humoral immunity)
Antibody Antigen Interaction
Injection of animal with almost any organic chemical would produce production of specific antibodies. Almost unlimited range of reactivity Molecules differing in smallest detail react to different antibodies.
Antibody Antigen Interaction
Two theories: Selective Theory Paul Ehrlich (1900) Instructional Theory Breinl & Haurowitz (1930's) Linus Pauling (1940's)
Selective Theory
(1)
Cells in the blood expressed a variety of receptors that react with infectious reagents and inactivate them. Interaction with the infectious agent caused the cell to produce and release more of the same molecules. Specificity of the receptor was determine before its exposure to antigen and the antigen selected the appropriate receptor
(2)
(3)
Instructional Theory
(1)
Antigen plays a central role in determining the specificity of the antibody. Antigen serves as the template around which the antibody folds antibody assumes a configuration complementary to antigen template
(2)
Disproved in the 1960s
Clonal-Selection Theory F. Macfarlane Burnet (1959)
(1)
Individual lymphocytes express membrane receptors that are specific for distinct antigen. This unique receptor's specificity is determined before the lymphocyte is exposed to antigen. Binding of antigen to the receptor activates the cell, causing proliferation into a clone of cells that have the same receptor as the parent cell.
(2)
(3)
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