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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of long term in vivo administration of IL-4 on the induction of antigen-specific B cells, the splenic microenvironment and the yield of antigen-specific antibody producing hybridomas was studied. Immunization with DNP-KLH, followed by 12 weeks continuous IL-4 treatment resulted in increased numbers of total splenic (non-DNP) IgM and IgG AFC (antibody forming cells) on day 5 after booster, whereas the DNP-specific IgG and IgG1 AFC were reduced compared to age-matched control animals not treated with IL-4. In addition, an almost 300-fold increase in non-DNP IgE was found while the IgE anti-DNP response was minimal.When the splenic cells were used in a fusion protocol, a relative decrease in yield of antigen-specific hybridomas was found in the long term IL-4 treated mice. Immunohistological staining of spleen sections from mice treated with IL-4 up until the time of booster revealed reduced B-cell follicle area and germinal centre numbers. These results show that extensive IL-4 treatment reduced antigen-specific B-cell formation and suggests a reduction in the number of B cells entering the memory B-cell pathway in the spleen.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The immunological processes in early life and their relation to allergic sensitization leading to a Th2 cytokine profile are still not well understood.Objective To analyse the environmental and genetic risk factors and immunological responses at birth in relation to the development of atopic disease at 12 months of age in a longitudinal study of high-risk children.Methods High-risk children were followed from birth till 12 months of age. Mononuclear cells obtained at birth and 6 and 12 months thereafter were analysed for their proliferative and cytokine responses after polyclonal and allergen-specific stimulation.Results At 12 months of age 25% children had developed an atopic disease. Two atopic parents, parental smoking and atopic dermatitis of at least one of the parents were significant risk factors. In cord blood of newborns who developed atopy, an increased percentage of CD4+CD45RO+ cells and an increased polyclonal-stimulated proliferation were observed. Furthermore, an impaired allergen-induced, but not polyclonal-stimulated IFN-γ production was found, suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile (characterized by increased levels of IL-4, IL-5, and IL-13) after both polyclonal and, to a lesser extent, allergen-specific stimulation was found in the children developing atopy. Allergen-induced IL-10 production at 12 months of age was only observed in the non-atopic children.Conclusion Our data indicate that the first 6 months of life represent a critical time window for the initiation of immunological changes resulting in the development of atopy. The selective development of a Th2 cytokine profile in high-risk children who develop atopy is due to increased production of Th2 cytokines, possibly caused by impaired allergen-induced IFN-γ production in the neonatal period. Furthermore, the decreased allergen-induced IL-10 levels observed in the atopic children at 12 months of age may result in a lack of down-regulation of the inflammatory process.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 55 (2000), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: During inflammation, membrane expression of adhesion molecules and tumor necrosis factor (TNF)-receptors (TNF-R) are increased, and soluble forms of these molecules are released. This study analyzed plasma levels ofsICAM-1 and sE-selectin as well as TNF-γ, sTNF-R55, and sTNF-R75 in nonallergic (NAA) and allergic asthma patients (AA), atopic dermatitis patients (AD), and healthy children (HC) by ELISA. Plasma levels of sICAM-1. sE-selectin. and sTNF-R, but not TNF-γ, were detectable, but were not significantly different between the patient groups and healthy children. In the AA group, a significant correlation (rs0.78, P=0.008) was found between sICAM-1 and sE-selectin levels. Furthermore, a significant correlation was found between sTNF-R55 and sTNF-R75 levels in the AA group (rs=0.70, P=0.025) and in the AD group (rs=0.69, P=O.O27). In AD patients, a significant correlation was observed between sE-selectin and the disease severity, as measured by the SCORAD index (rs=0.73. P=0.038). Our data demonstrate that plasma levels of sICAM-1. sE-selectin, TNF-a, sTNF-R55, and sTNF-R75 were not different between atopic and nonatopic children during a stable phase of the disease. In AD patients, levels of sE-selectin seemed to be related to clinical severity of the disease.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 40 (1994), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have recently developed a model in which mice were treated with 1L-4 after primary immunization, resulting in elevated total serum IgG1 and IgE levels, but decreased antigen-specific levels and memory formation for these isotypes. In this report, we describe that these effects of IL-4 are mediated at the B cell and not the T-cell level. Major changes occurred in the γ1ɛ-double positive B-cell population which is increased as a result of IL-4 treatment. Moreover, it is shown that γ1ɛ-double positive B cells can develop in vitro out of γ1-positive primed B cells and that these double positive cells can differentiate into IgG1- and IgE-secreting cells. The existence of γ1ɛ-double positive memory B cells can explain the differences in cytokine dependence of TNP-specific memory IgG1 and IgE responses found after adoptively transferring primed spleen cells into irradiated naive recipients. Whereas the IL-4 independent TNP-specific memory IgG1 responses could be blocked efficiently by neutralizing IL-5 and IL-6, TNP-specific memory IgE responses were virtually not susceptible to such treatment. These IgE responses were also not susceptible to IFN-γ, used in doses that could inhibit the primary IgE response. Inhibition of the TNP-specific memory IgG1 response by neutralizing IL-5 and IL-6 is accompanied by a 10-fold increase of the IL-4 independent TNP-specific IgE memory response. These data indicate that secondary IgE responses primarily result from B cells that are either switched to IgG1, or are double positive for IgG1 and IgE, thereby suggesting a minor role for ɛ-single positive B cells in secondary IgE responses.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 40 (1994), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: IL-4 is obligatory for primary IgE responses, whereas primary IgG, and secondary IgE responses are partially IL-4 independent. To investigate the effect of IL-4 on the antigen-specific memory formation for these isotypes, BALB/c mice were treated after primary TNP-KLH immunization with recombinant IL-4 for a period of 4 months. This prolonged presence of a high IL-4 level resulted in increased serum levels of total IgG1 and IgE, whereas total IgG2a did not change. The expression of CD23, but not J-Ad, increased on the splenic B cells. IL-4 treatment did not affect the IL-4 production by Con A stimulated spleen cells, whereas it did decrease the IFN-γ production. In the same mice the TNP-specific IgG1 and IgE serum levels, however, were decreased. Similar results were found when the antigen was continuously present during the IL-4 treatment. Furthermore, it was shown that IL-4 decreased the formation of IgG1, and IgE memory cells. These results point to different effects of IL-4 in regulating antigen-specific and bystander responses.
    Type of Medium: Electronic Resource
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