免疫耐受-免疫学信息网.ppt

免疫耐受 Immunological Tolerance 概论 免疫耐受是机体对抗原刺激表现为“免疫不应答”的现象 免疫耐受具有免疫特异性 自身耐受可以避免自身免疫病的发生 第一节 免疫耐受的形成及表现 一、胚胎期及新生期接触抗原所致免疫耐受 Owen的观察 于1945年首先报道了在胚胎期接触同种异型Ag所致的免疫耐受现象 免疫耐受实验的诱导 嵌合体（chimaeric）小鼠 二、后天接触抗原导致的免疫耐受 适宜的抗原刺激，可产生特异性免疫应答 不适宜的抗原量，特殊的Ag表位及Ag表位的变异，均会导致免疫耐受 T细胞活化缺乏第二信号；缺乏生长及分化因子，使T细胞克隆不能扩增，可导致免疫耐受 抗原因素与免疫耐受 Factors affecting tolerancerole of antigen Factors affecting tolerancethe role of host Immunologic features of tolerance It is an antigen-induced, active process Like immunologic memory, it is antigen specific Like immunologic memory, it can exist in B cells, T cells or both Like immunologic memory, its easier to induce and lasts longer in T cells than in B cell Tolerance in T and B cells High and low dose tolerance Host age and antigen dose affect tolerance 第二节 免疫耐受机制 Mechanism of tolerance induction Clonal deletion Thymus: negative selection Bone marrow: IgM+, IgD- B cells encountering self antigen Clonal anergy Lack of co-stimulatory(B7) molecules Exposure to large amounts of antigen Improper antigen presentation Lack of antigenic stimulus Receptor editing Anti-idiotype antibodies Suppressor T cells Clonal deletion:negative selection in the thymus Negative selection of B cells inbone marrow Clonal anergy in T cells Clonal anergy in B cells Tolerance due to lack of helper T cells Receptor editing among B cells Antiidiotype antibody in tolerance Breakdown of tolerance Immunosuppression Lack of antigen during differentiation of new clones Lack of antigen exposure As above Cross reactive antigens 第三节 免疫耐受与医学 口服免疫原，建立全身耐受 静脉注射抗原，建立全身耐受性 移植骨髓及胸腺，建立或恢复免疫耐受 脱敏治疗，防止IgE抗体产生 防止感染 诱导产生特异拮抗性免疫细胞，抑制效应免疫细胞对靶细胞的攻击 自身抗原肽拮抗剂的使用 免疫原及免疫应答分子用于肿瘤患者的治疗 细胞因子及其抗体的合理使用 多重抗感染措施，防止病原体产生抗原拮抗分子 打破免疫耐受 Introduction: Tolerance refers to the specific immunological non-reactivity to an antigen resulting from a previous exposure to the same antigen. While the most important form of tolerance is non-reactivity to self antigens, it is possible to induce tolerance to non-self antigen