Trends in Parasitology
ReviewRecent insights into humoral and cellular immune responses against 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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