Chapter 8 : Immunological Memory: Ingenuity and Serendipity

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The continuing expansion of the diagnostic virologist’s armamentarium by electron and fluorescence microscopy resulted in a progressive unmasking of the virological causes of disease and more rapid diagnosis. The distinction between hepatitis A and B was made in the 1940s, yet identification of a cause of serum hepatitis, hepatitis B, awaited a serendipitous finding by serology in the 1960s. The diagnosis of hepatitis B virus (HBV) in particular, and viruses in general, took a great leap forward with adaptation of a diagnostic technique known as radioimmunoassay (RIA), developed by Solomon Berson and Rosalyn Yalow to measure very small amounts of insulin. Both achievements, the discovery of the Australia antigen and the development of RIA, yielded Nobel prizes. Subsequently, enzyme immunoassays (EIA), enzyme-linked immunosorbent assays (ELISA), and other immunological assays had major impacts on virological diagnosis. Yellowing of skin and conjunctivae must have been among the most observable signs of illness for millennia. A new form of jaundice, homologous serum jaundice, later termed serum hepatitis, was recognized as a complication of yellow fever vaccination in the 1930s. The remarkable excess of stable antigen conferring antigenic specificity, variably called Australia antigen, hepatitis-associated antigen, and HBV surface antigen (HBsAg), offered unique diagnostic possibilities. When combined with the remarkable sensitivity of isotope-labeled reagents and the exquisite specificity of immunological recognition, the way was opened to establish sufficiently sensitive assays to screen the blood supply.

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 1

Jaundice. Yellowing of the skin and the whites of the eyes can be an indication of disease of the liver. Viral hepatitis, due to any of several agents, has been progressively defined as newer diagnostic techniques have been developed. In this photograph, yellowing of the sclerae (whites of the eyes) is evident. (Courtesy of the CDC, Public Health Images Library.) doi:10.1128/9781555818586.ch8.f1

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 2

F. O. MacCallum. A pioneer in diagnostic virology, MacCallum set up the first general virus reference laboratory in Britain at Colindale in 1946 and coauthored the textbook in 1950. With G. M. Findlay, he made essential observations on homologous serum hepatitis and later devised the nomenclature which divided hepatitis into virus A (infectious) and virus B (homologous serum) hepatitis. (Courtesy of Health Protection Agency, United Kingdom.) doi:10.1128/9781555818586.ch8.f2

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 3

Winston Churchill (left) with Franklin Delano Roosevelt (center) and Joseph Stalin at Yalta in 1945. Previously, F. O. MacCallum was asked to offer an opinion as to whether Winston Churchill should receive immunization against yellow fever on a trip through the Middle East to Moscow. MacCallum counseled against the immunization, based on inadequate time for immunity to develop. He may have spared the Prime Minister exposure to hepatitis virus as a contaminant of the vaccine with potential consequences for impairing his capacity to lead the war effort. (Courtesy of Wikimedia Commons.) doi:10.1128/9781555818586.ch8.f3

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 4

Baruch Blumberg. While seeking polymorphisms of proteins in human sera, he and his colleagues encountered a unique antigen which they termed the Australia antigen because of its origin from an Australian aborigine. It was later determined to be the key to unlocking the puzzle of a major type of serum hepatitis. (Image credit: NASA.) doi:10.1128/9781555818586.ch8.f4

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 5

Rosalyn Yalow and Solomon Berson. Working as an intensely collaborative team, Yalow and Berson devised the RIA with the capacity to measure remarkably small amounts of antigen. It revolutionized many fields in biomedicine, including the capacity to measure the Australia antigen and the antibody against it. Yalow received the Nobel Prize alone in 1977, Solomon Berson having passed away in 1972. (Courtesy of the Mount Sinai Archives, New York, NY.) doi:10.1128/9781555818586.ch8.f5

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 6

Creators of the ELISA, Eva Engvall and Peter Perlmann, and the EIA, Anton Schuurs and Bauke van Weemen. Standing left to right: Engvall, Schuurs, Perlmann, and van Weemen with Johannes Buttner, President of the German Society of Clinical Chemistry. (Courtesy of .) doi:10.1128/9781555818586.ch8.f6

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 7

Creators of the Western blot, Harry Towbin and Julian Gordon. With T. Staehelin, Towbin and Gordon developed immunoblotting, or Western blotting. It combined the resolving power of electrophoretic separation of proteins in gels and the sensitivity of immunochemical reactions. Immensely useful in many scientific fields, the technique was applied to diagnostic virology, such as for diagnosis of HIV. In this photograph of Julian Gordon’s group in 1979, Julian Gordon is center front and Harry Towbin is at the rear on the right. (Courtesy of Julian Gordon.) doi:10.1128/9781555818586.ch8.f7

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 8

Immunoglobulin class responses to viral infection. Shown is Fred Brown of the Institute for Animal Health (now the Pirbright Institute). With J. H. Graves, F. Brown determined that different types of antibodies developed in cattle at various times after infection with foot-and-mouth disease. Acute viral infections induce IgM, 19S antibodies, which are replaced later in the infection by IgG, 7S antibodies. (Courtesy of the Pirbright Institute.) doi:10.1128/9781555818586.ch8.f8

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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Figure 9

Georges Kohler (left) and Cesar Milstein (right), creators of monoclonal antibodies. Despite what seemed to be insuperable theoretical barriers, Kohler and Milstein succeeded in fusing an antibody-producing cell with a myeloma cell line. Refinements led to the capacity to produce enormous quantities of highly specific antibodies. The advent of monoclonal antibodies was a great boon to diagnostic virology. (Courtesy of the Albert and Mary Lasker Foundation.) doi:10.1128/9781555818586.ch8.f9

Citation: Booss J, August M. 2013. Immunological Memory: Ingenuity and Serendipity, p 249-292. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch8
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