Trends in Parasitology
Volume 24, Issue 12, December 2008, Pages 578-584
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Review
Recent insights into humoral and cellular immune responses against malaria

https://doi.org/10.1016/j.pt.2008.08.008Get rights and content

Effective immunity to malaria has been clearly demonstrated among individuals naturally exposed to malaria, and can be induced by experimental infections in animals and humans. The large number of malaria antigens has presented a major challenge to identifying protective responses and their targets, and it is likely that robust immunity is mediated by responses to multiple antigens. These include merozoite surface antigens and invasion ligands, variant antigens on the surface of parasitized red blood cells, in addition to sporozoite and liver-stage antigens. Immunity seems to require humoral and cellular immune components, probably in co-operation, although the relative importance of each remains unclear. This review summarizes recent progress towards understanding the targets and mechanisms that are important for mediating immunity to malaria.

Section snippets

Immunity to malaria

The complexity of immune responses to malaria has been increasingly recognized over recent years, together with an appreciation that any single antigen-specific response is unlikely to afford much immunity on its own. This is reflected in the multiple life-stages in the life cycle of Plasmodium and the large genome. With around 5000 genes, there are myriad potentially important immune targets, making the identification of protective responses highly challenging. Furthermore, immune responses

Humoral immunity

The most direct evidence that antibodies are important mediators of immunity to malaria comes from passive transfer studies in which antibodies from malaria-immune adults were successfully used to treat patients with severe malaria 4, 5. Studies in mice deficient in Fcγ receptors further support an important role for antibodies [6]. Protective antibodies are thought to target primarily merozoite surface antigens, erythrocyte invasion ligands and variant surface antigens expressed by P.

Cell-mediated immunity

Our understanding of cell-mediated immunity (CMI) in malaria remains relatively poor, despite the recognition that CD4+ T-cell help is essential for most Plasmodium-specific antibody responses [44], and evidence that vaccine-induced P. falciparum-specific CD4+ T-cell responses might protect against malaria in humans [3]. A large body of research on interactions between Plasmodium pre-erythrocytic stages and the host has also identified important roles for memory CD8+ T cells in protection from

Conclusions

Recent findings have highlighted many important advances being made into dissecting and defining immune responses to malaria, despite its great complexity. Further research to define the mechanisms and targets of immunity, including humoral and cellular responses and how they interact, is crucial for vaccine development and evaluation and to further understand disease pathology (Box 1). Interactions between humoral and cellular immunologists, linking studies in humans and experimental animals,

Acknowledgements

The authors wish to thank Arlene Dent and Mirja Hommel for helpful comments and suggestions on the manuscript.

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