Effector mechanisms against asexual erythrocytic stages of Plasmodium.
Evidence for a role for macrophages/monocytes is largely based on in vitro not in vivo observations. Products of activated macrophages particularly tumor necrosis factor-alpha (TNF alpha) are implicated in the killing of parasites. Access of cytokines and other factors might be through intracellular channels in the infected red blood cell. The cytotoxic elements in 'crisis' serum are uncertain but may include TNF, gamma-interferon (IFN gamma), and lipid peroxidases. TNF alpha in excess, contributes to pathology. TNF, acting as a pyrogen and raising body temperature, may moderate parasite density by killing late asexual stages. Nitric oxide and other nitrogen intermediates, products of activated macrophages and a number of other cell types, have been demonstrated both in vitro and in vivo to have a protective role. Phagocytosis of infected erythrocytes and merozoites, enhanced by the presence of immune serum in some systems, has been reported. Killing of parasites by neutrophils is enhanced by immune serum and cytokines TNF alpha, IFN gamma and lymphotoxin. A role for natural killer cells has been suggested. Evidence for antibody-dependent cellular cytotoxicity (ADCC) is controversial. Antibody-dependent cellular inhibitory activity (ADCI) (blood monocytes plus immune IgG) has been described for P. falciparum. Evidence for an important role for complement is conflicting; an involvement in the protective activity of phagocytic cells is reported. Antibody isotypes have been relatively little studied. In murine systems IgG2a may have a role early in the protective immune response followed by IgG1. In P. falciparum ADCI activity is mediated by IgG1 and IgG3, two cytophilic isotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
Phillips
S
S
Department of Zoology, University of Glasgow, Scotland, UK.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010961:Plasmodium / Q000254:growth & development / Q000276:immunology*
D000953:Antigens, Protozoan; D007132:Immunoglobulin Isotypes; D003165:Complement System Proteins