Immune effector mechanisms in malaria

Abstract

That humans in endemic areas become immune to malaria offers encouragement to the idea of developing protective vaccines. However natural immunity is relatively inefficient, being bought at the cost of substantial childhood mortality, and current vaccines are only partially protective. Understanding potential targets and mechanisms of protective immunity is important in the development and evaluation of future vaccines. Some of the problems in identifying such targets and mechanisms in humans naturally exposed to malaria may stem from conceptual and methodological issues related to defining who in a population is susceptible, problems in defining immune responsiveness at single time points and issues related to antigenic polymorphism, as well as the failure of many current approaches to examine functional aspects of the immune response. Protective immune responses may be directed to the pre erythrocytic parasite, to the free merozoite of the blood stage parasite or to new antigens induced on the infected red cell surface. Tackling the methodological issues of defining protection and immune response, together with studies that combine functional assays with new approaches such as allelic exchange and gene knock out offer opportunities for better defining key targets and mechanisms.

Involvement of CD8+ T cells in protective immunity against murine blood‐stage infection with Plasmodium yoelii 17XL strain

“…RBC were lysed with NH 4 Cl, and the cells were washed twice in fresh medium. CD4 1 or CD8 1 T cells were purified with positive selection using a MACS cell separation system (Miltenyi Biotech) according to the manufacturer's protocols; in some experiments negative and positive selection were done.…”

“…Splenic CD11b macrophages (10 6 cells/well) were seeded with CFSE-labeled pRBC or normal RBC in a 1:20 ratio, at a final volume of 200 mL for 4 h at 371C. Following co-culture, non-ingested RBC were removed by lysis with NH 4 Cl lysing buffer, and the remaining macrophages were washed twice with PBS, FcR-blocked and then stained with PE-labeled anti-CD11b mAb, in sorting buffer consisting of PBS with 1% FBS and 0.05% sodium azide (Sigma-Aldrich, St. Louis, MO, USA ). The capacity of macrophages to uptake CFSE-labeled pRBC or normal RBC was analyzed by a FACS Calibur cytometer (Becton Dickinson), and the data were analyzed using CellQuest Pro software (Becton Dickinson).…”

“…Antibodies specific for merozoites prevent invasion of those parasites into RBC [2][3][4][5]. These antibodies, attached to the parasites or parasitized RBC, lyse the parasites and RBC in a complement-dependent manner.…”

“…These antibodies, attached to the parasites or parasitized RBC, lyse the parasites and RBC in a complement-dependent manner. Another function of these antibodies is to mediate phagocytosis and digestion by monocytes/macrophages [3][4][5]. CD4 1 T cells act as Th cells for B-cell differentiation and antibody production; on the other hand, Th cells activate phagocytosing macrophages and kill the parasites.…”

“…CD8 1 T cells have been proposed to be essential for protective immunity against liver-stage malaria [2][3][4][5]. On the other hand, several studies have concluded that CD8 1 T cells do not contribute to protective immunity against blood-stage parasites, mainly because of the absence of MHC class I molecules on infected erythrocytes, by which antigens are presented to CD8 1 T cells [7][8][9][10].…”