道徳と幸福 : カント倫理思想の一考察

Asthma is a serious health problem and during the last decade various experimental models of asthma have been developed to study the pathogenesis of this disease. In this study we describe a new mouse model of asthma that uses the spores of Alternaria alternata and Cladosporium herbarum, two allergenic molds recognized as common inducers of rhinitis and asthma in humans. Here we demonstrate that A. alternata and C. herbarum spores are immunogenic when injected into BALB/c mice, and induce the production of specific IgM and IgG1 antibodies and strongly increase IgE serum levels. To induce the allergic response, mice were sensitized by two intraperitoneal (i.p.) injections and then intranasaly (i.n.) challenged with A. alternata and C. herbarum spores. Bronchoalveolar lavages (BALs) from these mice contained numerous macrophages, neutrophils, eosinophils and lymphocytes whereas neutrophils were the predominant BAL inflammatory cells in nonsensitized mice. Histological studies demonstrated an influx of eosinophils in peri-vascular and peri-bronchial areas and the presence of numerous epithelial goblet cells only in sensitized mice. Increased expression of mRNA specific for various chemokines (eotaxin, MIP-1α, MIP-2) and chemokine receptors (CCR-1, CCR-2 and CCR-5) was observed in the lungs of nonsensitized mice challenged with the spores. Expression of CCR-3 mRNA in the lungs and Th2 cytokine (IL-4, IL-5 and IL-13) secretion in the BAL was additionally observed in sensitized and challenged mice. Finally we demonstrate through whole-body plethysmography that mold spore sensitization and challenge induce the development of an airway hyperreactivity in response to nebulized methacholine

Polyclonal Activation of the Murine Immune-system By An Antibody To Igd .11. Contribution of Membrane Igd Cross-linking To the Generation of An Invivo Polyclonal Antibody-response

The injection of mice with a foreign, polyclonal antibody to IgD a polyclonal IgG1 response; 2) the cross-linking of B cell membrane Ig, their cell membrane (m) IgD; 2) B cell processing and presentation of the bound anti-IgD antibody to T cells; 3) activation of these T cells; and 4) T-dependent stimulation of B cell differentiation into IgG1 secreting cells. To determine whether the cross-linking of B cell membrane IgD and/or the resulting B cell activation that follows contribute to the generation of the polyclonal IgG1 response, we examined the abilities of three sets of anti-delta mAb or mAb fragments to stimulate polyclonal IgG1 production. Within each set mAb were matched for species and Ig isotypic determinants, but differed in avidity for IgD or in ability to cross-link IgD. In addition, experiments were performed to determine whether the anti-delta mAb had to be foreign to the immunized mouse to stimulate an IgG1 response. Results of these experiments indicate that: 1) recognition of the injected anti-delta antibody as foreign is required for the induction of a polyclonal IgG1 response; 2) the cross-linking of B cell membrane Ig, which directly activates B cells, can contribute considerably to the generation of in vivo IgG1 production; and 3) that even relatively weak cross-linking of membrane Ig by ligands that bind it with low avidity can make this contribution

In vivo study of mIgM and mIgD cross-linking on murine B cells

In this study, we have analysed in mice the effects on the immune response of in vivo treatment with different rat monoclonal antibodies (MoAb) against IgM and IgD. Although the effects of IgD cross-linking have been studied already, no attempt has been made to characterize the effects of in vivo IgM crosslinking, probably because of the higher IgM serum levels compared to IgD. We have used a panel of nine monoclonal rat anti-mouse IgM and three anti-IgD antibodies and we have characterized their isotypes, avidities, immunoglobulin (Ig) cross-linking and internalization abilities. Our results show that injection of mice with some rat MoAb against IgM led to an important decrease of IgM serum level and internalization of membrane IgM (mIgM) on almost all B cells. Similarly, treatment with a high-avidity anti-IgD antibody induced disapperance of mIgD on B cells. Treatment with rat MoAb against IgM or IgD led to a synthesis of specific antibodies and there was a direct relationship between the Ig internalization abilities of rat MoAb and the induction of specific antibody production. Finally, treatment with a high-avidity rat MoAb against IgD induced a polyclonal IgE and IgG1 secretion. The significance of these results on mIg receptor functions is discussed