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Chapter 3 : Filling the Churchyard with Corpses: Smallpox and the Immune Response
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The host is well defended against virus infections, for the immune system has several weapons at its disposal. The early story of the immune response includes smallpox vaccination and the phagocytosis-versus-humoral immunity debate with the joint award of the Nobel Prize to Elie Metchnikoff and Paul Ehrlich for their seminal work. When the opportunity presented itself to offer protection against smallpox by inoculation with smallpox material, a practice known as variolation, it was accepted in some European nations more successfully than in others. The procedure had been known elsewhere, including nasal insufflation, in which scabs from a mild case of smallpox were blown into the nostril. Hard on the heels of American independence came the description by Edward Jenner of vaccination against smallpox. It significantly reduced or eliminated the risks attendant to inoculation: illness and mortality and transmission of virulent disease to unfortunate and unsuspecting contacts. Inoculation with smallpox, or variolation, was to provide an essential link in the later demonstration of the protective action of cowpox against smallpox infection. This first experimental observation was the most beneficial medical public health intervention ever devised. In 1966 the WHO undertook the Global Eradication Programme to rid the world of smallpox, which was accomplished and certified in 1979, closing the magnificent chapter in smallpox history. Theories of humoral immunity, the basis of serological testing, were forged against Elie Metchnikoff’s theory of phagocytosis in host defense. In years to come, neutralization tests, with complement fixation assays, would become serological mainstays of diagnostic virology.
Lady Mary Wortley Montagu. Lady Montagu, an aristocrat of considerable intellectual sophistication and beauty, brought the practice of variolation against smallpox to England from Turkey. It consisted of inoculating smallpox material and preceded Jenner’s discovery of vaccination, the inoculation of cowpox to prevent smallpox. Lady Montagu is shown in a Turkish embellished costume with a jeweled turban in an illustration from The Letters of Horace Walpole. (Courtesy of the James Smith Noel Collection, Louisiana State University, Shreveport, LA.) doi:10.1128/9781555818586.ch3.f1
Edward Jenner. Jenner was an English physician with an intense interest in natural science. He demonstrated the truth in the folk belief that previous infection with cowpox prevented smallpox. The description of the inoculation of a boy, James Phipps, with material from a sore on the hand of a dairymaid, Sara Nelms, has achieved iconic status. Jenner published his results of vaccination in 1798. Vaccination eliminated the scourge of smallpox through the WHO Global Eradication Programme by 1979. (Courtesy of the National Library of Medicine.) doi:10.1128/9781555818586.ch3.f2
Triomphe de la Petite Vérole (Triumph of Smallpox). Vaccination was feared on the European continent as well as in England. This French caricature satirized that fear. It shows a woman with smallpox turning into a mermaid, a physician riding a cow, and an apothecary with a giant syringe pursuing frightened children. (Courtesy of the Wellcome Library, London, United Kingdom.) doi:10.1128/9781555818586.ch3.f3
Elie Metchnikoff. Metchnikoff’s studies of phagocytosis initiated the science of immunology, specifically cellular immunity. With Paul Ehrlich, who developed the theoretical basis for the action of antibodies or humoral immunity, Metchnikoff received the Nobel Prize in 1908. (Courtesy of Wikimedia Commons.) doi:10.1128/9781555818586.ch3.f4
Jules Bordet. With his brother-in-law, Octave Gengou, Bordet demonstrated the fixation of complement by reacting with bacteria and immune serum. The complement was then no longer available to participate in a hemolysis reaction. The assay, known as complement fixation, became a mainstay of diagnostic virology by demonstrating the development of antibodies in serum after infection. Bordet received the Nobel Prize in 1919. (Courtesy of the National Library of Medicine.) doi:10.1128/9781555818586.ch3.f5
Complement fixation. In stage 1, complement, antigen, and antibodies are mixed together. If antibody is present for the antigen, complement will be bound (fixed). In stage 2, if the complement has been fixed in the first stage, it will be unavailable to combine with antibody-coated erythrocytes. Therefore, a bull’s eye pellet of cells will appear in the bottom of the tube, as shown on the bottom left. However, if complement has not combined with antigen and antibody in the first stage, it will be available to lyse antibody-coated red cells. In that case, no bull’s eye pellet will be seen at the bottom of the tube, as shown on the bottom right ( 22a ). (From Diagnostic Virology, courtesy of the author, Diane S. Leland, Indiana University School of Medicine.) doi:10.1128/9781555818586.ch3.f6
Neutralization test in tissue culture. In the first stage, antibodies and live virus are mixed together. In the second stage, the mixture is added to susceptible cells in tissue culture. If antibodies specific for the virus are present, no cytopathic effects will occur; otherwise, the cells will be attacked and reveal cytopathic effects, as shown on the right ( 22a ). (From Diagnostic Virology, courtesy of the author, Diane S. Leland, Indiana University School of Medicine.) doi:10.1128/9781555818586.ch3.f7
Hemadsorption. Tissue culture cells infected with certain viruses produce receptors with an affinity for red blood cells which attach to the surface and are visible microscopically. In this illustration, influenza B virus has infected rhesus monkey kidney cells, facilitating the specific attachment of red blood cells which outline only the virus-infected cells. (Collection of Marilyn J. August.) doi:10.1128/9781555818586.ch3.f8