The Immunologic Response to Plasmodium

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  • Department of Chemical Pathology, Guy's Hospital Medical School, London SE1 9RT, Great Britain
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Summary and Conclusions

The species and strain specificity which characterizes acquired immunity to many malarial infections indicates that specific antibody plays a primary role in the response. The importance of serum antibody has been established by passive transfer tests in man and experimental animals. Immune serum has also been shown to inhibit the cyclical growth of P. knowlesi maintained in vitro. Studies on this system have revealed that immune serum has no effect upon the growth of intracellular parasites, but acts upon mature schizonts or free merozoites to inhibit the cycle of growth that follows schizogony. The inhibitory antibodies appear to be distinct from the schizont agglutinins present in immune sera and are associated with IgG and IgM, but not with IgA or IgE; their action is species-specific, but not complement-dependent and requires at least two combining sites per antibody molecule. The similarity between protective malarial antibody and some viral neutralizing antibodies is apparent from these experiments. Claims that cell-mediated immunity (i.e., a reaction mediated by sensitized lymphocytes of thymic origin, such as those responsible for graft rejection) play an effector role in malarial immunity are at present based upon inconclusive evidence.

Although serum antibody appears to play a primary role in acquired malarial immunity its clinical effectiveness may be dependent upon a synergistic action with the macrophage system. Malarial antibody is present in two Ig classes (IgG and IgM) which are known to have cytophilic properties and can therefore promote phagocytosis of antibody-bound antigen. The phagocytic activity of macrophages during malarial infection has long been recognized on morphological grounds and the role of specific antibody in promoting macrophage ingestion of parasites has been demonstrated in vitro. The importance of a primed macrophage system in malarial immunity may explain certain discrepant results observed in passive immunization experiments. Thus, although immune IgG produced a rapid elimination of parasites in West African children with severe infections, equivalent doses of immune rhesus IgG did not consistently inhibit parasitemia in normal monkeys challenged with only 50 P. knowlesi parasites.

The mechanisms which lead to the state of “premunition,” i.e., clinical immunity associated with continued low-grade infection, have long been a subject of speculation. This characteristic response could be attributable to relatively poor immunogenicity of the plasmodium, the immuno supressive effect of malarial infection, the presence of enhancing antibody, or the occurrence of antigenic variation. Available facts indicate that antigenic variation in P. knowlesi is fundamental for parasite survival in the immunized host and constitutes the basic mechanism which underlies chronicity of infection. In vitro assays have shown that protective antibody is predominantly specific for those variants which have produced patent infections. However, antibody against other variants is also present at lower titer and is associated with clinical immunity on challenge with such variants. This explains why P. knowlesi parasites which arise by antigenic variation during the course of chronic infection produce mild parasitemia in the host and yet are fully virulent in normal monkeys.

The state of “sterilizing” immunity, such as follows P. berghei infections in rats, has not been studied in detail. It is clearly a matter of interest and importance to elucidate the nature of the immune response in such infections and to establish the features which distinguish it from the less effective, “non-sterilizing” responses characteristic of many monkey and human malarias.