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

A cell-ELISA was developed using monolayers of glutaraldehyde-fixed normal as well as Plasmodium berghei-infected mouse erythrocytes for quantification and characterization of anti-erythrocytic autoantibodies in murine malaria. Testing normal (NMS) and peak parasitaemic sera (PPS) on erythrocyte monolayers treated with trypsin, sodium meta periodate, neuraminidase or heat, and competitive inhibition of antibodies with soluble sialic acid, revealed that some anti-erythrocytic antibodies (which increase during the parasitaemic phase of infection) recognize N-acetyl neuraminic acid (NANA) residues on host erythrocytes. High levels of antibodies to NANA covalently conjugated to bovine serum albumin (BSA) were detectable in PPS. Such antibodies could be significantly absorbed out by preincubation of PPS with mouse erythrocytes (MRBC). Antibodies in PPS, when affinity-purified on a column of Fetuin-Agarose, were found to be reactive to normal as well as parasitized erythrocyte monolayers. Immunoglobulin isotyping and IgG subgroup typing revealed that most of the anti-erythrocytic autoantibodies in NMS were IgM and IgA, while in PPS there was an appreciable increase in IgG2a and IgG3. Affinity-purified anti-NANA antibodies reacted with DNA when tested in an ELISA. There was a significant positive correlation between anti-erythrocytic antibody and DNA-binding levels in NMS as well as PPS. The DNA-binding antibodies in PPS could be effectively absorbed out by preincubation of sera with fresh MRBC. Affinity determination of anti-erythrocytic antibodies eluted from MRBC revealed binding characteristics in the following order: MRBC > single-stranded DNA > double-stranded DNA.
 ...
PMID:Murine malaria: anti-erythrocytic antibodies recognize N-acetyl neuraminic acid residues. 750 18

Mice lacking T cells with alpha beta TCR (TCR beta-/-) or gamma delta TCR (TCR delta-/-) were infected with the erythrocytic stages of the malaria parasite, Plasmodium chabaudi chabaudi (AS). Mice without gamma delta T cells could control and reduce a primary infection of P. chabaudi with a slight delay in the time of clearance of the acute phase of infection and significantly higher recrudescent parasitaemias compared with control intact mice. TCR delta -/- mice had higher levels of both serum Ig and malaria-specific antibodies of the isotypes IgG3 and IgG1 compared with control mice. TCR beta -/- mice, despite a striking increase in NK1.1+ cells and the presence of gamma delta T cells, were unable to clear their infection. Although the plasma of TCR beta -/- mice contained all Ig isotypes before and during a primary infection, they were unable to produce significant levels of malaria-specific IgG antibodies, suggesting that in the absence of alpha beta T cells gamma delta T cells are not able to provide efficient help for antibody production.
 ...
PMID:alpha beta and gamma delta T cells in the immune response to the erythrocytic stages of malaria in mice. 757 94

The development of antidisease immunity in children infected with Plasmodium falciparum is thought to be related to their immunologic responses to certain soluble parasite-derived exoantigens. We have assessed both cellular and humoral responses to these antigens in a cross-sectional study of a cohort of Gabonese schoolchildren who live in an area where malaria is holoendemic and perenially transmitted, in an attempt to identify immunologic markers of this early developing protective immunity. Concurrent parasitemia was found to have a significant influence on lymphoproliferative and antibody responses to the exoantigens. Individuals with higher levels of parasitemia had significantly lower proliferative and IgG isotype responses. Higher concentrations of specific IgG1 and IgG3, in particular, were associated with lower or no parasitemia, suggesting a possible protective role for these isotypes, whereas the level of IgM antibodies showed a trend towards higher concentrations in those with parasitemia, perhaps indicative of an exoantigen-induced T cell-independent response. Cytokine responses were unaffected by either the presence or the intensity of parasitemia and were dissociated from both proliferative and antibody response to the exoantigens. However, the mitogen-stimulated production of tumor-necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 was positively correlated with the corresponding lymphoproliferative responses. At the individual level, mitogen-stimulated TNF-alpha, interferon-gamma, IL-2, and IL-6 responses were positively correlated, as were mitogen- and exoantigen-induced TNF-alpha. The results are discussed in the light of current knowledge of immune responses to the exoantigens and the development of protective immunity to P. falciparum.
 ...
PMID:Immunologic responses to soluble exoantigens of Plasmodium falciparum in Gabonese children exposed to continuous intense infection. 781 Aug 4

A parasitological and immunological survey was carried out in an area in Papua New Guinea highly endemic for malaria. Two hundred fourteen adult individuals were selected for studies to assess their immune responses against the malaria vaccine candidate ring-infected erythrocyte surface antigen (RESA). Total immunoglobulin G (IgG) antibodies directed against RESA as well as specific IgG1, IgG2, and IgG3 antibodies were determined. Humoral responses directed against RESA were frequent in all IgG subclasses. Only IgG3 responses were found to be age dependent. Total anti-RESA IgG antibodies were not correlated with protection against malaria as measured by parasite prevalence, parasite density, or health center attendance. In contrast, cytophilic antibodies (IgG1 and IgG3) were associated with reduced Plasmodium falciparum prevalence and reduced health center attendance. T-cell proliferation in general was low and very infrequent. No correlation between humoral and cellular immune responses could be found. Parasite density, parasite prevalence, and health center visits tended to be reduced in individuals with good humoral and cell-mediated immune responses.
 ...
PMID:Humoral and cell-mediated immunity to the Plasmodium falciparum ring-infected erythrocyte surface antigen in an adult population exposed to highly endemic malaria. 782 28

We developed an ELISA test using leishmania antigenic extracts to detect antigen-specific antibody responses, including subclass and isotype analysis, in visceral leishmaniasis (VL) patients from the Sudan. A total of 92 parasitologically proven patients were compared with cutaneous leishmaniasis, schistosomiasis, malaria, onchocerciasis and tuberculosis patients, as well as with healthy endemic and non-endemic controls. Some VL patients were examined before and after chemotherapy. VL patients showed significantly higher IgG responses compared with all other groups (93.4% sensitivity, 93.7% specificity), and higher (but not significantly) IgM responses. All groups showed low IgA levels. All IgG subclasses, IgG1, 2, 3, and 4, showed higher levels in patients than all other groups, with IgG1 and IgG3 levels being significantly reduced following treatment. The rank order for specificity and sensitivity for IgG subclasses was IgG3 > IgG1 > IgG2 > IgG4.
 ...
PMID:The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients. 830 4

MRL-lpr/lpr mice spontaneously develop an autoimmune disease resembling systemic lupus erythematosus and rheumatoid arthritis. One of the unique serological abnormalities in this strain is remarkably high concentrations of cryoglobulins. Analysis of immunoglobulin components in their cryoglobulins has shown selective enrichment of a particular IgG subclass, IgG3. As IgG3 enrichment is also found in two other cryoglobulins, which are induced after injection with bacterial lipopolysaccharides or infection with malaria, IgG3 apparently represents a major source of murine cryoglobulins. Studies on murine IgG3 monoclonal antibodies (mAbs) have clearly shown that murine IgG3 have the unique physiochemical property to self associate through non-specific IgG3 Fc-Fc interaction, and that most of them can generate monoclonal cryoglobulins. Most strikingly, IgG3 monoclonal cryoglobulins with rheumatoid factor (RF) activity induce extensive pathological manifestations: skin vascular purpura and glomerulonephritis with 'wire loop' lesions. Although the cryoglobulin activity of IgG3 RF mAb is solely responsible for the generation of glomerular lesions (both RF and cryoglobulin activities are necessary for skin vascular lesions), the absence of nephritogenic activity by some IgG3 cryoglobulins supports the idea that qualitative features of cryoglobulins are critical to determine their pathogenic activity. The demonstration of a positive correlation between the production of IgG3 cryoglobulins and the development of lupus nephritis in MRL-lpr/lpr mice further substantiates the pathological importance of cryogenic autoantibodies. On the other hand, it should be emphasised that non-cryogenerating IgG3 autoantibodies may not be harmful, but even protective, as a result of their interaction with pathogenic IgG3 cryoglobulins. Finally, the development of an experimental model of cryoglobulinaemia associated with vascular and glomerular disease certainly represents an invaluable opportunity to study the molecular mechanisms responsible for the generation of cryoglobulins and their associated tissue lesions, and also to assess various therapeutic approaches. Our demonstration that anti-idiotypic mAb can prevent the pathogenic effects of the cryoprecipitable IgG3 RF mAb suggests strongly that such a therapeutic approach might be successful in similar diseases in man.
 ...
PMID:IgG3 cryoglobulins in autoimmune MRL-lpr/lpr mice: immunopathogenesis, therapeutic approaches and relevance to similar human diseases. 848 Oct 59

Passive transfer of monoclonal antibodies (MAbs) against malaria circumsporozoite (CS) proteins protects animals against malaria. Active immunization with synthetic or recombinant peptides induces a level of polyclonal antibodies to sporozoites comparable to those found after passive immunization but does not provide comparable protection. In the Plasmodium yoelii system, synthetic or recombinant peptide-induced antibodies have never been shown to protect. The current studies were designed to determine whether immunogen structure (native protein versus synthetic peptide) or immunoglobulin G (IgG) subclass of antibodies was responsible for the absolute differences between protective, passively transferred MAbs and nonprotective, actively induced polyclonal antibodies. In this study we produced two MAbs, QGP-S1 (IgG1) and QGP-S2 (IgG2b), by immunization with a synthetic peptide based on the P. yoelii CS major repeat, (QGPGAP)4, conjugated to keyhole limpet hemocyanin. These MAbs were compared tp NYS1 (IgG3), an anti-CS protein MAb previously produced by immunization with irradiated P. yoelii sporozoites, which recognizes (QGP GAP)2. QGP-S1 and QGP-S2 passively transferred protection. However, when compared with NYS1, there was a hierarchy of protection, NYS1 > QGP-S1 > QGP-S2. There was no correlation between antibody level at challenge as determined by immunofluorescent antibody test against sporozoites or enzyme-linked immunosorbent assay against (QGPGAP)2 or apparent antibody avidity for (QGPGAP)2 by sodium thiocyanate elution assay. The data demonstrate that a synthetic peptide can induce protective antibodies and that a specific antibody subclass is not required for protection. Work to determine whether antibody affinity or fine specificity can explain the hierarchy of protection among the MAbs is under way.
 ...
PMID:Monoclonal antibodies of three different immunoglobulin G isotypes produced by immunization with a synthetic peptide or native protein protect mice against challenge with Plasmodium yoelii sporozoites. 850 Aug 85

Anti-phosphatidyl choline antibodies (alphaPC) have been measured in adult patients from Orissa, India with Plasmodium falciparum infection of varying clinical severity. Significantly raised levels of alphaPC were observed in infected individuals in comparison with controls. The IgG alphaPC were found to be generally more than IgM alphaPC in most cases. The IgG alphaPC levels were significantly more in those cases of cerebral malaria who recovered fully after quinine administration in comparison with fatal cases not responding to quinine therapy, indicating a role for alphaPC in prognosis of adult cerebral malaria. There was no significant difference in levels of alphaPC IgG between non-cerebral and fatal cerebral malaria patients, indicating an absence of a direct protective role in the development of cerebral manifestations. Subgroup typing of IgG with alphaPC activity indicated IgG3 to be the predominant type, followed by IgG2, IgG1 and IgG4. A significant inverse relationship between serum tumour necrosis factor-alpha (TNF-alpha) levels and IgG1 antibodies with alphaPC activity was found, emphasizing the importance of alphaPC in modifying disease severity. These observations appear to give credence to recent reports in the literature indicating that toxic malarial antigens consist of phospholipids and that antibodies to phospholipids (alphaPL) inhibit such antigens in experimental systems.
 ...
PMID:A prognostic role for anti-phosphatidyl choline antibodies in human cerebral malaria. 860 44

Three cross-sectional studies were conducted in a representative cohort of individuals living continuously in an area holoendemic for malaria in Senegal. Plasma from 145 children and adults were tested. The pattern of antimalarial immunoglobulin class (IgM and IgG) and subclass (IgG1 to IgG4) antibody distribution was determined by enzyme-linked immunosorbent assay using a crude blood-stage antigen of Plasmodium falciparum-infected red blood cells. Adults had higher levels of specific antibodies than children, and IgM, IgG2, and IgG3 accounted for the highest difference (2.9, 6.5, and 4.5 times, respectively). Differences in antibody levels were significant for IgG1 to IgG4 between the lowest and the highest transmission season. No particular isotype distribution pattern could be found associated with any given parasitemia level. The relationship between the optical density (OD) values of each isotype and the risk of clinical malaria attack was tested using a Poisson regression model. Only the IgG3 OD increases were found associated with a significantly reduced risk of malaria attack. These seroepidemiologic data suggest that whereas the total IgG-specific activity is not indicative of any given level of protection against malaria, the level of IgG3 was significantly associated with the relative susceptibility to clinical P. falciparum malaria attacks.
 ...
PMID:Pattern of immunoglobulin isotype response to Plasmodium falciparum blood-stage antigens in individuals living in a holoendemic area of Senegal (Dielmo, west Africa). 864 97

We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen.
 ...
PMID:Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1. 869


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>