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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood mononuclear cells from forty-nine Thai adults infected with either Plasmodium falciparum or Plasmodium vivax were examined in order to determine the percentage of T, B, and Fc-receptor-bearing cells present. In comparison to healthy controls, both the percentage and concentration of peripheral T cells were decreased in the malaria-infected individuals as assessed by formation of rosettes with sheep red blood cells. The percentage of peripheral B cells was increased but their concentration was unchanged, as assessed by two techniques: the presence of surface immunoglobulin and the presence of a complement receptor. Both the percentage and concentration of lymphocytes bearing Fc receptors were unchanged in infected individuals. Finally, calculation of the changes in 'null' cells (defined either as non-T, non-B lymphocytes or as non-T, non-B, non Fc-receptor-bearing lymphocytes) revealed an increase in the 'null' cell percentage but a decrease in the absolute number of 'null' cells. These data indicate that in adult Thai patients naturally infected with malaria, there is a real loss of circulating T lymphocytes with no real change in B, Fc-receptor-bearing, or 'null' lymphocytes.
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PMID:Loss of circulating T lymphocytes with normal levels of B and 'null' lymphocytes in Thai adults with malaria. 37 35

Malaria infection in young rats is characterized by high parasitemia, severe anemia, and death. Parasitemia is lower in older rats, and the rats usually survive. This study was designed to investigate the immunological basis of this difference. T cell numbers in the thymuses and spleens of young (4 weeks old) and in adult (18 weeks old) infected and control rats were determined by killing with anti-theta serum and complement. The number of complement receptor lymphocytes (B cells) in spleens was determined after these cells had formed rosettes with sensitized, complement-coated sheep erythrocytes. Infection in young rats was characterized by progressive and severe thymic involution and by decreasing numbers of T and B cells in the spleen. In 18-week-old rats, T cell numbers in the spleen were slightly below those of controls early in infection but exceeded normal values by day 15. Progressive thymic involution was not a feature of infection in adult rats. The number of complement receptor lymphocytes in the spleens of adult rats decreased dramatically early in infection but were nearly normal by day 15. Severity of malarial infection in young rats is related to the inability of their lymphocytes to respond to Plasmodium berghei antigens early in infection in a way that leads to immunity.
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PMID:T and B cell population changes in young and in adult rats infected with Plasmodium berghei. 78 Feb 72

Immunity to malarial infection may be transferred with immune lymphocytes. This study was designed to determine which lymphocyte type is responsible for the adoptive transfer of immunity to malarial infection. In one set of experiments, the ability of immune T and B lymphocytes, separated by passage through nylon-wool columns, to transfer immunity to infection was determined. In another experiment, the effect of killing T lymphocytes with anti-theta serum on the transfer of immunity was determined. The effect on the ability of immune lymphocyte suspensions to transfer immunity after B lymphocytes were removed from such suspensions by centrifugation on Ficoll-Hypaque gradients, after they had formed rosettes with sensitized, complement-coated sheep erythrocytes, was also determined. The ability of lymphocyte suspensions to adoptively transfer resistance to malarial infection was greatly impaired by the removal from the suspensions of differentiated B-type lymphocytes. Our results indicate that it is the differentiated B cell, most probably an antibody-producing cell, which lacks both theta antigen and the complement receptor that is responsible for conferring immunity to malaria.
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PMID:Adoptive transfer of immunity to Plasmodium berghei with immune T and B lymphocytes. 78 Feb 73

We analyzed the role of adhesion molecules in the pathogenesis of experimental cerebral malaria (ECM), since tumor necrosis factor (TNF) plays a major role in this condition and has been shown to up-regulate in vitro expression of cell adhesion molecules (CAM), particularly intercellular CAM-1 (ICAM-1). We found increased expression of ICAM-1 on brain endothelial cells from mice with ECM. Treatment with monoclonal antibodies (mAb) directed against leukocyte function-antigen 1 (LFA-1, the ligand of ICAM-1) on days 6, 8 and 10 almost totally prevented ECM, while decreasing blood TNF levels. To exclude the possibility that the effects of anti-LFA-1 mAb resulted from an even partial inhibition of TNF overproduction, mice with signs of imminent death (hypothermia and neurologic defects) were treated with the anti-LFA-1 mAb, with dramatically protective effect. In contrast, injection of anti-ICAM-1 mAb on day 6 caused rapid death, while it was innocuous in normal mice. An mAb directed against complement receptor type 3 (CR3) was ineffective, as were injections of soluble human ICAM-1. These results suggest that adhesion of LFA-1+ cells to endothelial cells, stimulated by TNF to express high levels of ICAM-1, is critical in the pathogenesis of ECM. Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed.
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PMID:Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria. 167 17

We have studied the effect of infection with the blood-stage of Plasmodium yoelii 17X, a nonlethal parasite, on plasma membrane antigens, receptors, and secretory properties of macrophages (M phi) in murine liver, spleen, and blood. mAb F4/80 (M phi specific), F7/4 (a marker for immature and immunologically activated M phi, as well as neutrophils), and Mac-1, which binds to the type 3 complement receptor, were used to measure the distribution and total content of antigens in situ and to assay surface expression of antigens on M phi isolated by collagenase perfusion-digestion and adherence. We also examined respiratory burst activity after stimulation with PMA, FcR activity, Ia antigen expression, and binding of 125I-mannose-BSA and unopsonized sheep erythrocytes by isolated M phi. In the normal animal, spleen M phi expressed Mac-1 and F7/4 antigens and relatively high levels of respiratory burst activity, in contrast to Kupffer cells in liver, where all three features were virtually absent. The introduction of parasitized erythrocytes into the circulation resulted in a large influx of F4/80+ M phi into the blood, liver, and spleen, where local M phi proliferation could also contribute. Liver M phi during malaria infection showed increased Mac-1 and 7/4 antigen and an increased respiratory burst potential compared with uninfected controls. Increases in total, but not specific activity of FcR, Ia antigen, and binding of unopsonized sheep erythrocytes were found in spleen and liver M phi populations after infection. In both populations, there was an early but persistent marked reduction in specific binding and uptake of 125I-mannose-BSA. These results confirm and extend observations that normal Kupffer cells are relatively homogeneous in morphology, surface markers, and anatomical location, in contrast to M phi in normal spleen, and that both of these populations differ from resident M phi elsewhere, including the peritoneal cavity. In the course of infection by P. yoelii, M phi with high levels of opsonic receptors (CR3, FcR) and respiratory burst potential are mobilized in large numbers at specific sites such as liver and spleen, in accordance with an important role for M phi in the clearance of parasitized erythrocytes from blood.
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PMID:Macrophage plasma membrane and secretory properties in murine malaria. Effects of Plasmodium yoelii blood-stage infection on macrophages in liver, spleen, and blood. 300 Dec 15

The phagocytosis of erythrocytes may contribute to the increased susceptibility to life-threatening infections in patients with burn injury, sickle cell anemia, and malaria. The phagocytosis of immunoglobulin G-coated erythrocytes (EIgG) is followed by a transient depression of several macrophage functions including phagocytosis, respiratory burst capacity, and killing of bacteria. The present study suggests the possibility that after erythrophagocytosis hemoglobin-derived iron conspires with reactive oxygen products of the macrophage respiratory burst to cause oxidant damage to the phagocyte. Challenge of elicited peritoneal macrophages with EIgG phagocytosis was followed by an increase in lipid peroxidation as assessed by thiobarbituric acid-reactive substances (TBARS). Doses of EIgG associated with increased TBARS also caused a depression of Fc receptor-mediated phagocytosis and phorbol myristate acetate (PMA)-stimulated hydrogen peroxide production. Time course experiments demonstrated that the increase in TBARS coincided with the depression of macrophage function. There was no increase in TBARS following the phagocytosis of IgG-coated erythrocyte ghosts, suggesting that hemoglobin iron is involved in the generation of TBARS. The phagocytosis of erythrocyte ghosts did not depress macrophage function. Since complement receptor-mediated phagocytosis does not stimulate the respiratory burst, the role of the respiratory burst in causing lipid peroxidation was assessed using the phagocytosis of complement-coated erythrocytes. Phagocytic challenge with complement-coated erythrocytes caused neither an increase in TBARS nor a depression of macrophage function. However, there was an increase in TBARS when the respiratory burst was stimulated with PMA following complement receptor-mediated phagocytosis of erythrocytes. These results suggest that hemoglobin iron and phagocyte-generated oxidants collaborate to cause the depression of macrophage function following EIgG phagocytosis.
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PMID:Macrophage dysfunction following the phagocytosis of IgG-coated erythrocytes: production of lipid peroxidation products. 860 13

IgG and IgM antibodies were detected on non-parasitized as well as parasitized erythrocytes (E) from mice surviving over 15 days after infection with rodent malaria, Plasmodium berghei, whereas C3 was detected exclusively on parasitized E. Parasitized E, however, were quite resistant to the haemolytic activity of guinea pig complement and effectively inactivated human C3b to iC3b on their surface. Similarly, parasitized E were extremely resistant to homologous complement as assessed by haemolysis and C3 binding even when regulatory proteins (decay-accelerating factor, DAF; complement receptor related gene y, Crry; heat-stable antigen, HSA) were blocked with specific antibodies. DAF and Crry were equally expressed on both normal E and parasitized E from mice within a week post-infection; therefore, molecules that inhibit the haemolysis or C3 binding of parasitized E appear to be independent of DAF and Crry. Unexpectedly, the molecular forms of HSA and DAF in parasitized erythrocyte membranes were found to be different from those of normal erythrocyte membranes: DAF was detected as three bands (85,000, 64,000 and 30,000 MW) by immunoblotting. HSA was detected as more highly glycosylated forms than normal HSA. These alterations of DAF and HSA could be explained by the modification of membrane proteins and polysaccharides induced by parasitization, and we hypothesize that these changes of membranes or membrane proteins are involved in the resistance of parasitized E against homologous complement.
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PMID:The serum resistance of malaria-infected erythrocytes. 920 59

The expression of intercellular adhesion molecule-1 (ICAM-1), the ligand leucocyte function antigen-1 (LFA-1, CD11a), and complement receptor type 3 (CR3, or Mac-1, CD11b) has been studied in murine kidneys acutely infected with the fatal malaria parasite Plasmodium berghei ANKA. Thirty-six kidney sections from five groups of C57BL/6J mice on day 5, 10, 15, and 20 post-infection, and normal controls, were stained with monoclonal antibodies against ICAM-1, LFA-1, and Mac-1. There was markedly enhanced expression of ICAM-1 in the glomerular mesangium and the endothelium of blood vessels from day 10 post-infection. ICAM-1 was also found in the proximal tubular epithelial cells in an apical location, with a linear pattern. In addition, the glomeruli showed positive staining for LFA-1 and Mac-1 on day 10 post-infection, mainly in the infiltrating inflammatory cells. Mesangial cells and inflammatory cells in the cortical tubulointerstitium showed positive staining for ICAM-1, LFA-1, and Mac-1 at the later stages of infection. There were strong correlations between ICAM-1 expression on endothelial cells of glomerular/peritubular capillaries with inflammatory cells positive for LFA-1 and Mac-1, which correlated with proteinuria. These findings show that several adhesion molecules are up-regulated in murine malaria-associated nephritis. The expression of ICAM-1 on endothelial cells correlated with the severity of inflammatory responses, indicating the relationship between the expression of adhesion molecules and cell-mediated immune renal injury. It is suggested that adhesion molecules play an important role in the pathogenesis of murine nephritis. Better knowledge of the function of these molecules in malaria infection may open new approaches to antimalarial therapy.
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PMID:In situ analysis of adhesion molecule expression in kidneys infected with murine malaria. 971 51

Since the identification, in 1954, of the first gene associated with resistance to Plasmodium falciparum, several genes, some of them being implicated in the regulation of the immune response, have been described as possible influences on cerebral pathology. This pathology depends primarily on the capacity of infected red blood cells to adhere to the endothelia of micro-vessels, leading to their occlusion. The major players of cerebral malaria potentially include: receptors expressed on the surface of the endothelial cell and known to interact with infected red blood cells, cytokines modulating the expression of these adhesion molecules, nitric oxide (NO) and Fc epsilon RII/CD23. Cells other than infected red blood cells, such as platelets, monocytes and lymphocytes, have the ability to adhere to these endothelial receptors and to one another, via different ligands, leading to a more complex situation and an increase in the degree of vessel occlusion. The polymorphism of all these molecules, implicated either in adhesion, in modulation of this adhesion or activation of the expression of diverse endothelial mediators should be an important field of study. Polymorphism of five of these molecules has been explored so far: ICAM-1, TNF-alpha, IL-1 beta, iNOS2 (inducible NOS) and CR-1 (complement receptor-1). To these studies, can be added those concerning mannose binding protein (MBP), a protein playing a role in innate immunity, and the class-I antigen HLA-B53. To date the only clear-cut result concerns TNF-alpha. With the other polymorphisms, either no association is found (IL-1RA, CR-1, MBP), or results are geographically heterogeneous (ICAM-1, HLA-B53), or contradictory (iNOS2). Most often, the approach followed has been the candidate gene approach, as part of case control studies. One of the main problems in this approach is the difficulty of establishing the control cohort. This difficulty disappears in family studies, which include their own controls. So far, the only results based on complex segregation analysis have been focused on parasite multiplication and not on cerebral malaria.
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PMID:[Immunogenetics and cerebral malaria]. 1057 60

The malaria parasite Plasmodium falciparum induces a number of novel adhesion properties in the erythrocytes that it infects. One of these properties, the ability of infected erythrocytes to bind uninfected erythrocytes to form rosettes, is associated with severe malaria and may play a direct role in the pathogenesis of disease. Previous work has shown that erythrocytes deficient in complement receptor (CR) 1 (CR1, CD35; C3b/C4b receptor) have greatly reduced rosetting capacity, indicating an essential role for CR1 in rosette formation. Using deletion mutants and mAbs, we have localized the region of CR1 required for the formation of P. falciparum rosettes to the area of long homologous repeat regions B and C that also acts as the binding site for the activated complement component C3b. This result raises the possibility that C3b could be an intermediary in rosetting, bridging between the infected erythrocyte and CR1. We were able to exclude this hypothesis, however, as parasites grown in C3-deficient human serum formed rosettes normally. We have also shown in this report that rosettes can be reversed by mAb J3B11 that recognizes the C3b binding site of CR1. This rosette-reversing activity was demonstrated in a range of laboratory-adapted parasite strains and field isolates from Kenya and Malawi. Thus, we have mapped the region of CR1 required for rosetting and demonstrated that the CR1-dependent rosetting mechanism occurs commonly in P. falciparum isolates, and could therefore be a potential target for future therapeutic interventions to treat severe malaria.
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PMID:Mapping of the region of complement receptor (CR) 1 required for Plasmodium falciparum rosetting and demonstration of the importance of CR1 in rosetting in field isolates. 1108 71


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