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      Oral tolerance induction with altered forms of ovalbumin

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          Abstract

          As a T cell-dependent phenomenon, oral tolerance is not expected to depend necessarily on native configuration of antigens. We investigated the induction of oral tolerance with modified ovalbumin (Ova). Oral administration of heat-denatured (HD-Ova) and cyanogen bromide-degraded ovalbumin was less effective than native Ova in inducing oral tolerance in B6D2F1 mice. HD-Ova was effective in suppressing delayed-type hypersensitivity (DTH) reactions but did not suppress specific antibody formation. Injection of Ova directly into the stomach, but not into the ileum or cecum, suppressed subsequent immunization to DTH reactions. Gavage with protease inhibitors (aprotinin or ovomucoid) before gavage with Ova was ineffective in blocking tolerance induction. Treatment with hydroxyurea to destroy cycling cells 24 h before gavage with Ova blocked oral tolerance induction and also the possibility to passively transfer tolerance to naive recipients with the serum of mice gavaged with Ova 1 h before. The implications of these findings about oral tolerance induction are discussed

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          Most cited references 26

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          Immunoprophylaxis of atopy: light at the end of the tunnel?

          Current research in the field of atopy is directed almost exclusively towards treatment of established allergic disease. In particular, treatment has concentrated on controlling the release and actions of various mediators, such as cytokines, from the allergy effector cells at the end of the immuno-inflammatory cascade. Here, Patrick Holt argues that a potentially more-effective and achievable goal may be the prevention of initial T helper 2 (Th2)-cell sensitization to environmental allergens during infancy. This might be achieved via amplification of the endogenous 'immune deviation' mechanism(s) that normally facilitate discrimination between pathogenic and non-pathogenic antigens at the mucosal surfaces of the body.
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            The influence of intestinal processing on the immunogenicity and molecular size of absorbed, circulating ovalbumin in mice.

            The presence of a tolerogen in mouse serum within 1 hr of antigen feeding prompted further study. Therefore, serum from mice fed with ovalbumin (OVA) was subjected to various immunochemical and biological tests. The appearance of tolerogen in serum was concomitant with the presence of OVA detected by a specific ELISA. Absorption of tolerogenic serum with anti-OVA antibody coupled to Sepharose beads effectively removed the tolerogenic moiety from the serum and confirmed that not only was tolerogenicity associated with the presence of antigen, but that binding sites for antibody were intact on this tolerogenic form of OVA. Finally, serum fractions from antigen-fed mice were assayed for total protein content, ELISA-detectable OVA and in vivo effect on systemic immunity. The only serum fraction in which immunoreactive OVA was detected contained proteins close to the molecular weight of native OVA and induced significant immune suppression in recipients. Serum fractions lacking immunoreactive OVA were not significantly tolerogenic in vivo. These experiments confirm that when OVA is absorbed across the gut mucosa it is subtly altered into a tolerogenic form. The recognition of gut-processed OVA by T-suppressor cells is discussed.
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              History of oral tolerance and mucosal immunology

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                Author and article information

                Affiliations
                [1 ] Universidade Federal de Minas Gerais Brazil
                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Braz J Med Biol Res
                Associação Brasileira de Divulgação Científica (Ribeirão Preto )
                1414-431X
                March 1998
                : 31
                : 3
                : 381-386
                S0100-879X1998000300009
                10.1590/S0100-879X1998000300009

                http://creativecommons.org/licenses/by/4.0/

                Product
                Product Information: SciELO Brazil
                Categories
                BIOLOGY
                MEDICINE, RESEARCH & EXPERIMENTAL

                Medicine, General life sciences

                ovalbumin, antigen, digestion, mouse, oral tolerance

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