PDF File - The Indian Society for Parasitology

Malaria and macrophages119presence of C3b on IE has not yet been confirmed avian (Soni and Cox, 1975), simian (Ward and Conran,(Shear et al., 1979; Topley et al., 1973; Abdalla et al., 1966; Shephard et al.,1982) and human (Houba et al.,1983). Thus, it appears certain that the phagocytosis of 1976) malaria hosts has been well documented;IE by MØs is mediated by FcR. Furthermore, the however, their precise functions still remain obscure.cross-linking of MØ FcR by parasite derived antigens Brown and Kreier (1982), in P. berghei/rat model,and cytophilic or opsonic antibodies present in observed that ICs formed by soluble malarial-antigensmalarious plasma may promote the clearance of and immune serum, and those precipitated from theopsonized IE (Leslie, 1985).acute-phase serum (APS) of infected rats, inhibitedthe in vitro antibody-mediated binding of IE withFollowing attachment of an IE with a MØ, it isperitoneal MØs. Using the same model, Packer andinternalized along with the phagosome producedKreier (1986) demonstrated that pretreatment of MØsaround it. The phagosome containing IE is then fusedwith APS inhibited the phagocytosis of IE. Almostwith lysosome, which contains lysosomal acidsimilar findings have been reported by Shear et al.hydrolases. Finally, after fusion, the phagolysosome is(1979) by using the mouse model. The ICs preparedformed containing IE and acid hydrolases. Thiseither by mixing total parasite antigens soluble inprocess is accompanied by a decrease in the size andculture medium or those precipitated (by polyethylenenumber of acid phosphatase-positive granules inglycol) from APS of P. knowlesi-infected monkeys,MØs. In the phagolysosome, IE are biodegraded intoinhibited the binding of IE with MØs, and thus enabledsmaller peptide fragments (8–15 amino acids long).them to evade the host destructive mechanisms (SinghThe malarial pigment along with various substances ofand Dutta, 1989a). The ICs not only inhibit thehost and parasite origin (including protein aggregates,binding, attachment and phagocytosis of IE by MØs,lipids and phospholipids), induce the production andbut they also modulated the phagocytic activities ofrelease of several inflammatory cytokines byMØs. Packer and Kreier (1986) have clearlymonocytes and MØs (Bate et al., 1989; Pichyangkul etdemonstrated that early in the infection, ICs inhibitedal., 1994; Jakobson et al., 1995; Hommel, 1997). Theerythrophagocytosis, but over time, induced changesprocessed products of IE are then exocytosed onto thein MØs which ended-up in the enhanced phagocytosissurface of MØ, which, in turn, functions as an antigenofIE. Singh and Dutta (1988) demonstrated a similarpresenting cell and subsequently presents thesephenomenon in P. knowlesi-infected monkeys,surface-bound processed antigens to T-lymphocytes.wherein APS from infected monkeys, soluble antigensThese antigen-sensitized T-lymphocytes then triggerand ICs precipitated from APS, inhibited the in vitroin motion the whole cascade of immune response.phagocytosis of IE by blood monocyte-derivedFACTORS THAT INTERFERE WITH MØ-IE (BMD) and splenic MØs. Incubation of MØs withINTERACTION: ROLE(S) OF IMMUNEculturein serum-free medium for 18 h, activated MØsAPS, heat-aggregated APS or ICs for 6 h, followed byCOMPLEXESfor the enhanced phgocytosis of IE. The blockage ofThe presence of normal erythrocytes and/or IE in phagocytosis by 2-deoxy-glucose in thesemononuclear phagocytes and MØ hyperplasia in experiments suggested the mediation of FcR. Thesemalaria-infected hosts, very convincingly suggests findings, in general, indicated that during the acutetheirrole(s) in the destruction and elimination of phase of P. knowlesii infection in monkeys, ICs maymalaria parasites (Taliaferro and Connan, 1936; inhibit the MØ-mediated parasite destruction,Langhorne et al., 1979; Dutta and Singh 1980; Dutta et whereas later during the convalescent phase ofal., 1982; Barnwell et al., 1983). Therefore, any infection, may promote their destruction by activatingmechanism(s) that may interfere with the interaction MØs.between IE and MØs, might eventually prevent orreduce the clearance of parasites by the host (Singh PRODUCTION OF CYTOKINES IN MALARIA:and Dutta, 1989a), and may also impede the onset of THE ROLE(S) OF ANTIGEN-PRESENTINGthe ensuing immune response, which otherwise would MØs AND LYMPHOKINE-ACTIVATED MØs INhave been initiated by MØs containing ingested IE THE DESTRUCTION OF MALARIA(Singh and Dutta, 1989b; Ockenhouse and Shear, PARASITES1983; Ockenhouse et al., 1984). The presence ofFrom the aforementioned account, it is now clear thatimmune-complexes (ICs), formed by antigens andMØs phagocytose IE, and then present the processedantibodies, in the plasma of murine (June et al., 1979),