Protective immunity to malaria and anti-erythrocyte autoimmunity.
The intraerythrocytic development of malaria parasites results in considerable modification and destruction of erythrocytes. This may lead to the breaking of tolerance such that immune recognition of 'self' or 'modified self' erythrocyte antigens by B or T lymphocytes occurs. Such recognition may be a vital factor in the induction of protective immunity even though it may also cause immunopathology. Serological and immunocytochemical assays have been used to demonstrate, in the serum of Plasmodium berghei-infected or immune rats, antibodies to isoantigenic determinants on infected erythrocytes. Absorption studies indicated that antigens specifically associated with parasitized erythrocytes and erythrocyte isoantigens were closely associated at the surface membrane. Extensive erythrocyte modification and destruction, artificially generated by phenylhydrazine treatment, significantly enhanced immunity against rodent malaria. In contrast, the generation of an incomplete anti-erythrocyte autoantibody response in mice by the injection of cross-reacting rat erythrocytes failed to augment protective responses to P. chabaudi. The reinjection of rat erythrocytes into mice previously injected with rat erythrocytes suppresses further autoantibody synthesis and the mice revert to the normal (Coombs-negative) state. Spleen cells from rat erythrocyte-treated mice transfer this suppression when injected into syngeneic recipients. Coombs-negative mice reinjected with rat erythrocytes failed to show enhanced protective responses to P. chabaudi. Spleen cells from such Coombs-negative mice, injected into sublethally irradiated recipients, increased the protective effects of concurrently transferred spleen cells from malaria-immune donors when the recipients were challenged with P. chabaudi.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D006384:Hemagglutination; D007109:Immunity; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010962:Plasmodium berghei / Q000276:immunology*; D051381:Rats; D012156:Reticulocytes / Q000276:immunology