Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TNF plays important roles in the protection and onset of malaria. Although mast cells are known as a source of TNF, little is known about the relationship between mast cells and pathogenesis of malaria. In this study, mast cell-deficient WBB6F1-W/W(v) (W/W(v)) and the control littermate WBB6F1+/+ (+/+) mice were infected with 1 x 10(5) of Plasmodium berghei ANKA. +/+ mice had lower parasitemia with higher TNF levels, as compared with W/W(v) mice. Diminished resistance in W/W(v) mice was considered to be due to mast cells and TNF. This fact was confirmed by experiments in W/W(v) mice reconstituted with bone marrow-derived mast cells (BMMCs) of +/+ mice or of TNF-/- mice. W/W(v) mice with BMMCs of +/+ mice exhibit lower parasitemia and mortality accompanying significantly higher TNF levels than those of W/W(v) mice. Parasitemia in W/W(v) mice with BMMCs of TNF-/- mice was higher than that in +/+ mice. Activation of mast cells by anti-IgE or compound 48/80 resulted in release of TNF and decrease of parasitemia. In addition, splenic hypertrophy and increased number of mast cells in the spleen were observed after infection in +/+ mice and W/W(v) mice reconstituted with BMMCs of +/+ mice as compared with W/W(v) mice. These findings propose a novel mechanism that mast cells and mast cell-derived TNF play protective roles in malaria.
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PMID:Protective roles of mast cells and mast cell-derived TNF in murine malaria. 1692 Sep 70

The purpose of this work was to test the immunogenicity in C57BL mice of two synthetic peptides derived from the constant region of 3D7 and FC27 Plasmodium falciparum MSP2 dimorphic proteins, either microencapsulated into poly-lactide-co-glycolide acid microparticles (PLGA MP) or delivered with the human compatible adjuvant Montanide ISA 720 for comparison. Potent and prolonged antibody responses were obtained for both peptides by using PLGA MP formulations after subcutaneous or intradermal injections. As compared to the subcutaneous route of immunization, the intradermal route induced greater immune responses. Montanide adjuvant was effective in eliciting antibodies against the 3D7 peptide but not against the FC27 peptide. Peptide-specific cytophilic antibodies (IgG2a) were detected after boosting with homologous peptide for all vaccine formulations. MP formulations elicited a lower IgE secretion as compared to that observed for both Montanide formulated vaccines. Our results demonstrate the ability of the polymer microparticles to overcome the lack of immunogenicity of FC27 MSP2 peptide in C57BL mice and their potential to induce desirable immune responses against malaria.
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PMID:Adjuvant activity of polymer microparticles and Montanide ISA 720 on immune responses to Plasmodium falciparum MSP2 long synthetic peptides in mice. 1707 Jun 28

The aim of this study was to assess the immunoglobulin (Ig)-subclass distribution of antimalarial antibody responses in 110 and 169 Thai patients with complicated and uncomplicated Plasmodium falciparum malaria, respectively. Antimalarial plasma IgG subclasses and IgE antibody levels against a crude malaria blood stages, and antigen preparation were determined using enzyme-linked immunosorbent assay (ELISA). On admission, the levels of anti-P. falciparum IgG1, IgG2 and IgG3 were significantly lower in patients with complicated malaria than uncomplicated malaria (IgG1, P < 0.0001; IgG2, P < 0.0001; IgG3, P < 0.0001). The levels of antimalarial IgE were slightly lower, but not statistically significant (P = 0.389) in the complicated malaria. After adjusting all antibody levels and age, anti-P. falciparum IgG3 levels remained significantly associated with complicated malaria. None of the other antibody concentrations showed statistically significant associations with complicated malaria. The anti-P. falciparum IgG3 levels were related to the IgG1 as well as IgG2 levels. A correlation between anti-P. falciparum IgG2 and IgE was observed in the complicated malaria group, and this may indicate their roles in the severity of disease. Our data suggest that anti-P. falciparum IgG3 is associated with a reduced risk of complicated malaria and that antimalarial Ig-subclasses are differently regulated in patients with complicated and uncomplicated malaria.
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PMID:Differential regulation of IgG subclasses and IgE antimalarial antibody responses in complicated and uncomplicated Plasmodium falciparum malaria. 1841 May 81

Immunisation with purified DNA is a powerful technique for inducing immune responses. The concept is very simple, involving insertion of the gene encoding the antigen of choice into a bacterial plasmid, and injection of the plasmid into the host where the antigen is expressed and induces humoral and cellular immunity. This technology can induce immunity to all antigens that can be encoded by DNA; this includes all protein, but not carbohydrate, antigens. DNA immunisation appears to result in presentation of antigens to the host's immune system in a natural form, similar to that achieved with live attenuated vaccines. The most efficacious routes for DNA immunisation are bombardment with particles coated with DNA (gene-gun), followed by intramuscular and intradermal administration. The efficiency of transfection of host cells is low, but sufficient to induce immunological responsiveness. The DNA plasmid is retained in the transfected cells in an unintegrated form for the life of the cell. The majority of transfected cells are eliminated, but residual expression has been detected for longer periods. In animal model systems, DNA immunisation has been shown to induce protective immunity to influenza, herpes, rabies, hepatitis B and lymphocytic choriomeningitis viruses, and to malaria and mycobacteria. However, strategies to induce protective immunity to HIV and other disease agents remain to be developed. DNA vaccines permit modulation of the immune response by altering the route or method of DNA administration, by including immunostimulatory sequences in the plasmid, and by co-administration of cytokine genes with the gene encoding the antigen of interest. A T helper 1 response provides cell-mediated immune killing of infected cells and neutralising antibody production, while a T helper 2 response induces IgE and allergic responses. The advantages of DNA immunisation are: similarity to live attenuated vaccination but without the possibility of contamination with undesirable agents;correct presentation of antigen;combinations of DNA-encoded antigens and/or cytokines may be administered;genetic stability;potential speed of making new vaccines with genetic identity;development of vaccines for agents that cannot be grown in culture;no need for a cold chain; andpossibility of modulation of the immune response. The perceived risks include: integration of the plasmid into the host genome;induction of anti-DNA antibodies and autoimmunity; andinduction of tolerance. The available information concerning safety is encouraging, with the risk of integration being considered to be orders of magnitude below the spontaneous mutation frequency in humans. DNA immunisation offers the possibility of extending the control of infectious diseases far beyond those that are currently controlled by conventional and recombinant vaccines, to include vaccines for parasites and cancer. However, it is currently too early to predict the future extent of use of DNA vaccines in human immunisation programmes because the initial clinical trials are still in progress.
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PMID:DNA vaccines: a review of developments. 1802 May 19

Previous studies have shown that antibodies from humans exposed continuously to malaria recognize the Plasmodium falciparum asexual blood-stage antigen Pf332. Here we analysed the antibody responses to a C-terminal fragment of Pf332, designated C231, in individuals from Senegal, by measuring the serum levels of immunoglobulin M (IgM), IgG class and subclass and IgE antibodies. IgG antibody reactivity with crude P. falciparum antigen was detected in all the donors, while many of the children lacked or had low levels of such antibodies against C231. The antibody levels increased significantly with age for both crude P. falciparum antigen and C231, and in the older age groups most of the donors displayed antibodies to C231. This was also true for IgM, IgE and IgG subclass reactivity against C231. Moreover, the ratio of IgG1/IgG2 was considerably lower for C231 than for crude P. falciparum antigen, and in age groups 10-14 and 15-19 years the levels of IgG2 against C231 even exceeded that of IgG1. The IgG2/IgG3 ratios suggest that C231 gives similar levels of IgG2 and IgG3, except for children aged 4-9 years, where IgG3 was higher. Raw IgM, IgG class and subclass and IgE antibody levels to C231 tended to be higher in those who did not experience a malaria attack, but following linear multivariate analysis the trends were not significant.
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PMID:Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite. 1827 41

In the many areas where human malaria and helminthiases are co-endemic, schoolchildren often harbour the heaviest infections and suffer much of the associated morbidity, especially when co-infected. In one such area, the Buea district, in south-western Cameroon, two cross-sectional surveys, together covering 263 apparently healthy schoolchildren aged 4-12 years, were recently conducted. The prevalences of fever, malarial parasitaemia and intestinal helminth infections, the seroprevalences of anti-Plasmodium falciparum IgG and IgE and anti-glycosylphosphatidylinositol (anti-GPI) IgG, plasma concentrations of total IgE, and the incidence of anaemia were all investigated. The mean (S.D.) age of the study children was 7.56 (1.82) years. Overall, 156 (59.3%) of the children were found parasitaemic, with a geometric mean parasitaemia of 565 parasites/microl. Parasitaemia and fever were significantly associated (P=0.042). The children who lived at low altitude, attending schools that lay 400-650 m above sea level, had significantly higher parasitaemias than their high-altitude counterparts (P<0.01). At low altitude, the children attending government schools had significantly higher parasitaemias than their mission-school counterparts (P=0.010). Of the 31 children (11.9%) found anaemic, 22 (70.4%) had mild anaemia and none had severe anaemia. A significant negative correlation (r=-0.224; P=0.005) was observed between haemoglobin concentration and level of parasitaemia. Infection with Plasmodium appeared to reduce erythrocyte counts (P=0.045), a condition that was exacerbated by co-infection with helminths (P=0.035). Plasma concentrations of total IgE were higher in the children found to be excreting helminth eggs than in those who appeared helminth-free, while levels of anti-P. falciparum IgE were higher in the children with low-grade parasitaemias than in those with more intense parasitaemias. Levels of anti-GPI IgG increased with age and were relatively high in the children who lived at low altitude and in those who were aparasitaemic. The survey results confirm that asymptomatic malarial parasitaemia frequently co-exists with helminth infections in schoolchildren and indicate links with fever, altitude and school type. Immunoglobulin E may play a role in immune protection against helminthiasis whereas anti-GPI antibodies may be important in the development of antimalarial immunity in such children. In Cameroon, as in other areas with endemic malaria, control programmes to reduce the prevalences of infections with intestinal helminths and malarial parasites in schoolchildren, which may effectively reduce the incidence of anaemia, are clearly needed.
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PMID:Febrile status, malarial parasitaemia and gastro-intestinal helminthiases in schoolchildren resident at different altitudes, in south-western Cameroon. 1831 32

In this study, 2-Cys Plasmodium berghei ANKA (PbA) peroxiredoxin (Prx) was identified as an antigenic protein recognized by an anti-PbA IgE antibody using two-dimensional polyacrylamide gel electrophoresis and proteomic analysis. Innate immune responses to PbAPrx were examined using cells from mice deficient in Toll-like receptors (TLR) or related molecules, and it was demonstrated that responses were severely impaired in TLR4(-/-), MyD88(-/-) and MD-2(-/-) mice, but not in Toll/IL-1 receptor domain-containing adaptor inducing IFN-gamma (TRIF)(-/-), TLR2(-/-) or radioprotective 105 (RP105)(-/-) mice. An association between PbAPrx and TLR4 was observed following immunoprecipitation and immunoblotting, suggesting that PbAPrx was associated with TLR4/MD-2. Interactions between Prx and TLR4/MD-2 were also examined by flow cytometry using TLR4/MD-2- or TLR2-expressing cells. NFkappaB/GFP activity was observed in TLR4/MD-2- but not in TLR2-expressing cells following stimulation with Prx. However, this effect was not observed after treatment with proteinase K, suggesting that PbAPrx is a protein ligand for TLR4 and that the PbAPrx activity observed in this study is not due to contamination with LPS. These findings indicate that malarial Prx induces IgE-mediated protection through FcepsilonRI on mast cells and innate immunity through TLR4 with MyD88 and MD-2, suggesting a novel function for malarial Prx in innate and acquired immune responses in malaria.
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PMID:Mast cell-mediated immune responses through IgE antibody and Toll-like receptor 4 by malarial peroxiredoxin. 1839 34

Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM, we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrollment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3.11, 95% CI 1.01-9.56, P = 0.05). Total IgG ICs (OR = 2.84, 95% CI 1.08-7.46, P = 0.03) and IgE-containing ICs (OR = 6.82, OR 1.88-24.73, P < or = 0.01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.
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PMID:Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia. 1914 73

This study aimed to assess correlations between anti-malarial antibody levels and differences in malariometric characteristics, seen between two sympatric ethnic groups, the Fulani and the Dogon, living in Mali. Plasma levels of anti-malarial IgE, IgG, IgG1-4 and total IgE were determined in asymptomatic individuals, of the above mentioned groups, and were correlated to malariometric indexes. Significantly higher levels of anti-malarial IgE, IgG, IgG1-3 and total IgE were detected in the Fulani individuals as compared to the Dogon. No difference in plasma levels of malaria specific IgG4 was noted between the two groups. Within the Fulani, an increase in total IgE levels was associated with the presence of infection. As the IgG4 level increased, the number of clones decreased in the Fulani individuals. A positive correlation between elevated levels of anti-malarial IgG and IgG3 and splenomegaly was noted only within the Fulani group. No other correlations between antibody levels and parasite prevalence, clone numbers or spleen rates were observed in any of the communities. These results suggest that the magnitude of antibody response against Plasmodium falciparum may not be as important as it is believed to be. Instead, the fine specificity or function of the response might be more critical in protection against malaria disease.
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PMID:Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali. 1883 54

Immune complexes (ICs) are believed to play an important role in malaria pathology, and an interesting article by Mibei et al. recently published by Parasite Immunology suggests that IgG4 and IgE are particularly important. However, researchers should be aware of potential pitfalls to current assays aimed at measuring plasma ICs and correlating these to deposition in tissues.
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PMID:When is a malaria immune complex not an immune complex? 1846 1


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