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

To characterize the clinical and laboratory features of onchocerciasis in visitors to endemic areas and to compare them with those seen in endemic subjects, 20 returned visitors and 21 endemic subjects with onchocerciasis were evaluated. Dermatitis was the most frequent clinical finding among the returned visitors. None had nodules or eye disease and, in contrast to the endemic subjects, microfiladermia was often absent or of low density. All persons studied had antibody responses measurable by ELISA to both soluble Onchocerca volvulus antigen and a panel of diagnostic recombinant antigens. Eosinophil and IgE levels were significantly higher in the endemic group, as was the capacity of peripheral blood mononuclear cells from this group to produce the T helper cell-like cytokines interleukin-4 and -5. It is likely that the chronicity and intensity of infection in endemic subjects account for the clinical and immunologic differences observed between the 2 groups.
 ...
PMID:Onchocerciasis in endemic and nonendemic populations: differences in clinical presentation and immunologic findings. 807 40

Onchocerciasis is a chronic infectious disease caused by the filarial nematode Onchocerca volvulus. A minor population of human gammadelta T cells expressing Vdelta1 chains is preferentially stimulated by O. volvulus ligands in vitro. Therefore, the nature of the parasite ligand and the effector functions of Vdelta1+ T cells stimulated by O. volvulus was investigated. A 5- to 30-kDa ligand from the adult parasite lysate that is sensitive to proteinase treatment was identified. Presentation for preferential stimulation of Vdelta1+ T cells required processing. After in vitro stimulation with O. volvulus in the presence of interleukin-2, Vdelta1+ T cells produced interferon-gamma but not interleukin-4 and exhibited NK cytolytic activities. It is concluded that somatic 5- to 30-kDa protein ligands from O. volvulus stimulate Vdelta1+ T cells and that Vdelta1+ T cells play a role in immunity to O. volvulus.
 ...
PMID:Low-molecular-weight protein ligands from Onchocerca volvulus preferentially stimulate the human gammadelta T cell Vdelta1+ subset. 894 Feb 23

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.
 ...
PMID:Immune responses to third stage larvae of Onchocerca volvulus in interferon-gamma and interleukin-4 knockout mice. 971 93

Onchocerciasis is a debilitating parasitic infection caused by the filarial nematode Onchocerca volvulus. Infections are chronic, and persistence of the parasites for several years argues for highly adapted mechanisms of immune evasion. Due to the restricted host repertoire of O. volvulus, we have used the cattle parasite Onchocerca ochengi to investigate the nature of immunomodulation underpinning these long-term infections. Cattle were infected with a single inoculation of 350 infective-stage larvae under laboratory conditions (n = 6). Intradermal nodules containing immature adult worms were detected from 110 days postinfection, and microfilariae in skin were detected from day 280 postinfection. Parasite-specific responses during early infection were nonpolarized with respect to the major Th cytokines (interleukin-4 [IL-4], IL-2, and gamma interferon [IFN-gamma]) produced by antigen-stimulated peripheral blood mononuclear cells (PBMC) or serum antibody isotypes. Antigen-induced proliferation of PBMC peaked shortly after exposure and remained high during the prepatent infection. As the parasites matured and animals developed patent infections, there was a profound down-regulation of lymphoproliferation, accompanied by sharp falls in the expression of both IL-4 and IFN-gamma and a gradual decline in IL-2. Levels of immunoglobulin G2 (IgG2) fell, while those of IgG1 remained high. We conclude that neither a classical Th2 response nor a simple Th1-to-Th2 switch is sufficient to explain the immunomodulation associated with patent Onchocerca infections. Instead, there is an initial Th0 response, which matures into a response with some, but not all of the features of a Th2 response. The natural host-parasite relationship of O. ochengi in cattle may be useful as both a descriptive and predictive tool to test more refined models of immunomodulation in onchocerciasis.
 ...
PMID:Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis. 1140 68

Toll-like receptor 4 (TLR4) has been shown to be important for the induction of Th2-dependent immune responses in mice. Protective immunity against larval Onchocerca volvulus in mice depends on the development of a Th2 immune response mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains the rickettsial endosymbiont Wolbachia, which has molecules with lipopolysaccharide-like activities that also signal through TLR4. We therefore hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a decreased Th2 response to the larvae or because of the absence of a response to Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated third-stage larvae, and it was observed that Th2 responses were elevated based on increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific IgG1 response, and eosinophil recruitment. Protective immunity, however, did not develop in the TLR4-mutant mice. The Th1 response, as measured by gamma interferon production from spleen cells, was comparable in both wild-type and TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in both wild-type and TLR4-mutant mice. Therefore, the defect in the development of a protective immune response against O. volvulus in TLR4-mutant mice is not due to loss of Th2 immunity or the response to Wolbachia but is due to an unidentified TLR4-dependent larval killing mechanism.
 ...
PMID:Protective immunity to the larval stages of onchocerca volvulus is dependent on Toll-like receptor 4. 1629 26