Comprehensive immunogenetics / W.H. Hildemann, E.A. Clark, R.L. Raison.

  • Hildemann, W. H., 1927-
Date:
[1981], ©1981
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Comprehensive immunogenetics / W.H. Hildemann, E.A. Clark, R.L. Raison. Source: Wellcome Collection.

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    82 Microbial Antigens and Serotype Patterns genes obviously has inherent restrictions in this serotype system. Apparent lack of sexual reproduction in trypanosomes precludes direct analysis of gene- antigen correlations. Antigenic Variation in Malaria Malaria, still the worst blight of the tropics, each year strikes 150 million peo¬ ple and in Africa alone kills more than 1 million children. Malarial parasites, transmitted to humans by the female Anopheles mosquito, multiply in the liver and then invade erythrocytes, producing fever, chills, and weakness. About one-fourth of the adult population of Africa suffers recurrent bouts of the dis¬ ease, and an estimated 2 billion people reside in endemic areas. Widespread resurgence of malaria has occurred in recent years because mosquitoes have developed resistance to insecticides such as DDT and the parasites have evolved resistance to chloroquine, the standard drug for prevention and treat¬ ment of the disease. Serotype variation analogous to that in trypanosomes has been conclusively shown in chronic erythrocytic malaria caused by at least six species of Plasmo¬ dium. Such variation occurs with high frequency in chronic P. knowlesi infec¬ tions in monkeys. Parasites isolated at seven-day intervals were found to possess different serotypes. Each strain appears to carry a distinct genetic rep¬ ertoire yielding new variants during infections of many months' duration. Variant-specific antibodies are demonstrable by agglutination of infected red cells or by opsonization correlated with in vivo protection. The molecular na¬ ture of the intraspecific surface antigens is unknown. Whether the antigenic variation appears in a sequential or predictably ordered manner during the course of mammalian and mosquito vector infections is also unknown. Since genetic recombination has been demonstrated among strains of malarial par¬ asites, both sexual and asexual sources of serotype variation may operate. Although onset of protective immunity is characterized by a sudden drop in numbers of blood parasites, antigenic variation continues during subclinical phases. Serotype transformations can also proceed in the absence of protection or effective parasite destruction. However, most experiments suggest that phe- notypic change is induced in these protozoans by the presence of specific non- lethal antibody. According to this view, low affinity antibodies are variation- inducing, while high affinity antibodies tend to be parasiticidal. Antigenic drift of influenza virus mutants by immunoselection has similarly been attrib¬ uted to low affinity antibodies. K. N. Brown has suggested a mechanism of selective gene activation and repression in response to environmental pres¬ sures, including combination of extracellular malarial merozoites (forms re¬ leased after red cell rupture) with specific antibody. The antigenic change itself may not take place until nuclear division at schizogony (asexual repro¬ duction by multiple division) a supposition in accord with the finding that ser¬ otype changes in Paramecium are correlated with mitosis. As with trypanosomes, the most probable working hypothesis is that serotype genes at