Immunity

Abstract

Of the four species of Plasmodium responsible for essentially all naturally acquired malaria in man, only P. falciparum is frequently the direct cause of fatal disease. In the absence of specific treatment, the lethality of this infection, and the morbidity of malaria in general, is considerably influenced by the extent of the individual’s previous exposure to the malaria species in question. Other important factors influencing the outcome of infection, but not to be considered here, may include the size of infective inoculum, concurrent disease, nutritional status and the host’s possession or lack of any of the innate characteristics which reduce his susceptibility (for example, sickle cell trait). The transmission of malaria in a population provides a potent evolutionary selection pressure for such characteristics, which disadvantageously alter the parasites’ milieu within the host by mechanisms independent of the host’s acquired immune response, even when a proportion of carriers of the gene in question suffer severe disease as a consequence of it (e.g. sickle cell anaemia). Such innate resistance mechanisms have been recently reviewed by Miller and Carter (1976) (see also Chaps. 2 and 15). It would be unjustified to suppose that the transmission of malaria in a population does not also select for efficiency at countering malaria in the acquired immune response itself. Immune response genes are associated with the major histocompatibility complex (HLA system, in man), and Ceppellini (1973) showed differential rates of expression of HLA D antigens between lowland (recently malarious) and highland village populations (climatically protected from malaria transmission) in Sardinia.