Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protective immunity to the parasitic nematode Onchocerca volvulus (Ov) appears to be directed against molecules of invading L3 larvae. In this study, the cellular immune reaction to such an Ov L3 protein (S1) which is protective in an animal model was analyzed using peripheral blood mononuclear cells (PBMC) of individuals from a hyperendemic area in West Africa who were exposed to Ov but remained free from disease ('putatively immune individuals'). Despite seronegativity of these individuals against S1, proliferation of PBMC was inducible, allowing generation of an S1-specific T cell line which produced IFN-gamma upon stimulation with both Ov lysate and S1. However, S1 induced significantly more IL-5 than Ov lysate. S1-specific, DQ6 (DQA1*0103/DQB1*0603)-restricted T cell clones were generated which reacted against synthetic peptides comprising amino acids 99-111 of S1. These clones, which are the first generated against a recombinant fllarial antigen, produced both IFN-gamma and IL-5 as well as little IL-4, suggestive of a Th0-like phenotype. In conclusion, in putative immunity, reactivity against a particular parasite protein can be detectable on the level of T but not B cells. Induction of both IFN-gamma and IL-5 by S1 suggests that it may trigger macrophage plus eosinophil dependent killing of L3 in vivo. The identification of a likely DQ6 (DQA1*0103/DQB1*0603)-restricted T cell epitope may be of more general relevance, given that allele combinations of DQ6, including DQA1*0103/DQB1*0603, are negatively associated with diabetes mellitus.
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PMID:Production of both IFN-gamma and IL-5 by Onchocerca volvulus S1 antigen-specific CD4+ T cells from putatively immune individuals. 918 17

Immunization of mice with irradiated Onchocerca volvulus infective stage larvae (L3) has been demonstrated to confer protection against challenge infections with these larvae. Additionally, cytokine level measurements and cytokine depletion studies have shown that both IL-4 and IL-5 are important in generating a protective immune response against O. volvulus challenge infections, thus suggesting a dependency of protective immunity on IgG1, IgE and/or eosinophils. In the present study, we examined the humoral responses of immunized mice to O. volvulus L3 antigens. ELISA measurements of total serum antibody levels indicated that IgE was the only antibody isotype elevated in mice immunized with O. volvulus L3. IgM from immunized mice was the only isotype that recognized surface antigens on intact O. volvulus L3. IgG1, IgG3, IgE and IgA recognized internal parasite antigens on O. volvulus L3 frozen sections. Western blot analysis of L3 proteins showed that in serum from mice immunized with O. volvulus L3 IgG1, IgG2a/2b, IgA, and IgE, as well as IgM, recognized unique L3 proteins. Antibodies in serum from L3 immunized mice were able to detect O. volvulus adult antigens in a pattern similar to the recognition found in O. volvulus L3. Some L3 antigens were shared by adults, while other antigens were L3 specific. The ELISA, immunohistochemistry and Western blot findings thus demonstrate a complex pattern of antigen recognition of parasite antigens by antibodies found in mice immune to the L3 of O. volvulus.
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PMID:Structural and molecular specificity of antibody responses in mice immune to third stage larvae of Onchocerca volvulus. 922 62

In order to determine whether infection with Onchocerca volvulus might modify the immune response to mycobacterial antigen, the proliferative and cytokine responses of peripheral blood mononuclear cells from 117 persons infected with O. volvulus and 36 non-endemic control subjects were compared. Tuberculin-stimulated cellular proliferative responses and production of Th1-type cytokines (interferon gamma) were reduced in persons infected with O. volvulus compared to controls. However, there was no evidence of polarization of the immune response towards a Th2-type phenotype (interleukin 5) in infected individuals compared to controls.
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PMID:Human infection with Onchocerca volvulus does not affect the T helper cell phenotype of the cellular immune response to mycobacterial antigen. 923 Dec 15

Subjects with generalized onchocerciasis (GEN), with the sowdah form, and with exposure but without onchocerciasis (endemic normal/putatively immune; EN/PI) were studied for cytokine responses to Onchocerca volvulus extract (OvAg) and recombinant Ov33 and OvL3-1 proteins. Higher levels of cytokines were produced in response to OvAgs in sowdah and EN/PI than in GEN subjects. Peripheral blood mononuclear cells did not produce interferon-gamma in response to antigens. OvAg induced interleukin (IL)-5, IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and soluble IL-2 receptor. EN/PI and sowdah persons produced significantly more IL-5 and IL-2 than GEN subjects, and EN/PI subjects had significantly higher GM-CSF levels than GEN persons. The low IL-5 and GM-CSF levels in GEN subjects were increased by addition of exogenous IL-2. Ov33 and OvL3-1 stimulated production of IL-10 and less IL-5 and IL-2. The study groups did not show a strict Th2-like cytokine response.
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PMID:Differences in cytokine responses to Onchocerca volvulus extract and recombinant Ov33 and OvL3-1 proteins in exposed subjects with various parasitologic and clinical states. 929 49

In onchocerciasis patients and in O. volvulus-exposed individuals without signs of onchocericiasis, T- and B-cell responses to two recombinantly expressed O. volvulus enzymes were analysed and compared to responses to total protein extract of adult parasites. The cytosolic enzymes Cu/Zn superoxide dismutase 1 (OvSOD1) and glutathione S-transferase 2 (OvGST2) represent 2 detoxifying molecules which may play an important role in parasite defense against host-induced oxidative stress. The T-cell response to the two recombinant proteins was analysed by investigating the cytokine responses of peripheral blood mononuclear cells. Induction of IL-5 at the mRNA level and IL-5 and IL-10 at the protein level was demonstrated in patients with the generalized form of onchocerciasis and endemic normals without clinical manifestations. IFN-gamma was not found to be induced by either antigen. This pattern of lymphokine expression is indicative of a Th2-type response. Compared to patients with the generalized form, a higher level of cytokine induction was observed in the group of endemic normals. Low but significant IgG levels were observed against OvSOD1 in patients with onchocerciasis; higher antibody levels were found against OvGST2 in patients and endemic normals. The highest IgG levels were detected against the crude O. volvulus extract. These results indicate that the two recombinant O. volvulus proteins induce moderate T and B cell responses.
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PMID:Characterization of human immune responses to the cytosolic superoxide dismutase and glutathione S-transferase from Onchocerca volvulus. 929 49

To shed clarity on the dichotomy of reported results relative to the significance of T helper-1 vs T helper-2 immune responses in onchocerciasis, we compared the survivability of Onchocerca volvulus third-stage larvae (L3) in immunized mice that had either a targeted disruption of the Interleukin-4 or Interferon-gamma gene. Treatment groups consisted of control mice and mice immunized with irradiated O. volvulus L3. All mice were challenged with diffusion chambers containing viable L3. Vaccinated IL-4-/- were unable to kill this larval target. In contrast, vaccinated INF-gamma-/- and C57BL/6 mice, exhibited high levels of killing, had elevated levels of IL-4 and significantly greater numbers of eosinophils in their diffusion chambers than the IL-4-/-. Whereas, levels of IFN-gamma in all three groups of immunized mice were equivalent to those of control mice, levels of IL-5 were elevated, even in the IL-4-/-, indicating that cytokines other than IL-4 were involved in its production. The protective immune response to third-stage larvae of O. volvulus in mice vaccinated with irradiated larvae has an absolute IL-4 requirement.
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PMID:Immune responses to third stage larvae of Onchocerca volvulus in interferon-gamma and interleukin-4 knockout mice. 971 93

Onchocerca volvulus and the human immunodeficiency virus (HIV) are two immunocompromising infectious agents of major public health concern in Uganda. To examine the effect of coinfection with O. volvulus and HIV on cellular immune responses, lymphocyte proliferative responses and cytokine production of peripheral blood mononuclear cells (PBMC) from persons infected with O. volvulus with and without HIV type 1 infection were compared. Proliferation of PBMC to PHA and tuberculin (PPD) in coinfection was less (P = 0.08, P < 0.01) than in O. volvulus infection. O. volvulus extract stimulated lymphocyte proliferation in microfilaria-negative and HIV-negative O. volvulus infection while only an inconspicuous response was observed in microfilaria-negative coinfection. After stimulation of PBMC with PPD, the production of interferon-gamma (IFN-gamma), interleukin (IL)-4 and IL-5-demonstrated in O. volvulus infection-were reduced in coinfection with HIV (P < 0.01). While both groups failed to produce IFN-gamma in response to O. volvulus extract, only O. volvulus infected persons generated pronounced IL-5 and low IL-4 levels (0.01 > P = 0.02). The cellular immune responses in coinfection suggested an HIV-related lack of specific reactivity to O. volvulus antigen and impairment of IL-4 and IL-5 production in addition to the lack of IFN-gamma response on antigenic stimulation.
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PMID:T cell responses in coinfection with Onchocerca volvulus and the human immunodeficiency virus type 1. 976 10

To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin. Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment. Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P<.001), whereas circulating levels of IL-5 (P<.01) and EDN (P<.05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P<.01). High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions.
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PMID:Eosinophil sequestration and activation are associated with the onset and severity of systemic adverse reactions following the treatment of onchocerciasis with ivermectin. 995 90

Cellular and humoral immune responses of mice to Onchocerca volvulus glutathione S-transferase (OvGST) presented via in vivo expression in attenuated Salmonella typhimurium were examined and compared with the same antigen administered by subcutaneous injection with Freund's adjuvant. After infection with recombinant S. typhimurium, maximal numbers of bacteria were recovered from the mesenteric lymph nodes and spleens during the second week postinfection. By weeks 3-4, bacteria were absent from these tissues. Splenocytes from mice infected with S. typhimurium expressing OvGST showed significant and specific proliferative responses to OvGST, whereas the non-recombinant S. typhimurium controls and those which received the antigen by subcutaneous injection with Freund's adjuvant did not. Mice infected with recombinant S. typhimurium had elevated IFN-gamma levels over non-recombinant S. typhimurium and placebo controls. but IL-4 and IL-5 levels were low and did not differ significantly between these groups. Antibody responses to OvGST antigen expressed by a recombinant Salmonella vaccine or delivered in a purified form with Freund's adjuvant were moderate to high. These data suggest that Salmonella can be used as a vaccine delivery vector that induces specific cellular and humoral immune responses to Onchocerca volvulus antigens. This is the first report to describe the successful application of a filarial antigen in a live-vector delivery system as well as the first recombinant based filarial vaccine to elicit a cellular immune response similar to that described for putative immune endemics.
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PMID:Induction of specific cell-mediated immunity in mice by oral immunization with Salmonella expressing Onchocerca volvulus glutathione S-transferase. 1007 5

This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly elevated in infected mothers and their infants. One year post partum, O. volvulus-specific IgG4 was strongly reduced in children of infected mothers, while IgG1 responses weakened only slightly. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the bacterial antigens streptolysin-O (SL-O) or purified protein derivative (PPD). UCBC from neonates born to O. volvulus-infected mothers responded lower (P < 0.01) to Con A (at 5 micrograms/ml), PPD (at 10 and 50 micrograms/ml) and O. volvulus-derived antigens (OvAg) (at 35 micrograms/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers positive for O. volvulus. Several Th1-type (IL-2, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2-type (IL-4, IL-5, IL-10, IL-13) cytokines were secreted by UCBC and PBMC in response to OvAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mitogens or antigens induced production of IL-4 in neonates. In response to OvAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced by UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low levels of IL-5 and IL-13, while higher amounts of IL-10 were found (P < 0. 01) in newborns from onchocerciasis-free mothers. In conclusion, maternal O. volvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines.
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PMID:Prenatal immune priming in onchocerciasis-onchocerca volvulus-specific cellular responsiveness and cytokine production in newborns from infected mothers. 1040 26


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