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Mechanisms of immune tolerance to allergens

机译:对过敏原的免疫耐受机制

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In allergic diseases, immune responses are induced by normally well-tolerated allergens, which result in chronic inflammation characterized by antibody secretion and T cell activation. For almost 100 years, allergen-specific immunotherapy (allergen-SIT) has been the potentially curative and antigen-specific method for the treatment of allergic diseases. Allergen-SIT alters the course of allergic diseases and can reduce allergic symptoms and medication use. The key mechanism behind allergen-SIT is the induction of peripheral T cell tolerance by altering the balance between Th cells and regulatory T cells. Both naturally occurring thymus-derived FOXP3 +CD4 +CD25 + regulatory T cells and inducible type 1 regulatory T cells suppress the development of allergic diseases via several mechanisms including suppression of dendritic cells, Th cells, mast cells, eosinophils and basophils; suppression of inflammatory cell migration to tissues; and decrease of the ratio between allergen-specific IgE and IgG4 antibodies. These effects are mainly mediated by the suppressive cytokines IL-10 and TGF-β. Knowledge of this molecular basis is crucial to understanding the regulation of the immune response and their possible therapeutic applications for allergic diseases.
机译:在变态反应性疾病中,免疫反应是由通常耐受性良好的变应原诱导的,从而导致以抗体分泌和T细胞活化为特征的慢性炎症。近一百年来,过敏原特异性免疫疗法(allergen-SIT)已成为治疗过敏性疾病的潜在治愈和抗原特异性方法。过敏原SIT可以改变过敏性疾病的病程,并可以减少过敏症状和药物使用。过敏原-SIT背后的关键机制是通过改变Th细胞与调节性T细胞之间的平衡来诱导外周T细胞耐受。天然产生的胸腺来源的FOXP3 + CD4 + CD25 +调节性T细胞和可诱导的1型调节性T细胞均通过多种机制抑制过敏性疾病的发展,包括抑制树突状细胞,Th细胞,肥大细胞,嗜酸性粒细胞和嗜碱性粒细胞。抑制炎症细胞迁移至组织;降低变应原特异性IgE和IgG4抗体之间的比例。这些作用主要由抑制性细胞因子IL-10和TGF-β介导。了解这种分子基础对于理解免疫应答的调节及其对过敏性疾病的可能治疗应用至关重要。

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