hypersensitivity-2.ppt

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Sensitization phase,Effector phase,Type I hypersensitivity,Type II hypersensitivity,由IgG或IgM类抗体与靶细胞表面抗原结合后，在补体、吞噬细胞和NK细胞参与下，引起的以细胞溶解或组织损伤为主的病理性免疫反应,Type II hypersensitivity cytotoxicity hypersensitivity),Features：,Ag is on surface of self-cell,Ab is IgG or IgM,Complements,macrophage,NK cells participated in,cell lysis or tissue injury,Type II hypersensitivity,The diseases caused by Type II hypersensitivity,输血反应（Transfusion reactions）,Produced by mismatched ABO blood types,2、新生儿溶血,Neonate hemolysis：Rh blood group antigen,新生儿溶血的预防,Rh,+,Rh,初孕,Rh,+,Rh,再孕,健康新生儿,健康新生儿,Rh抗体被动免疫,胎儿红细胞进,入母体即被破坏,（不能诱导母亲,抗Rh免疫反应）,anti-Rh antibodies(Rhogam),3.,药物过敏性溶血性贫血,Drug-induced hemolytic anemia,Drugs such as aspirin and antibiotics can bind to the antigen on the surfaces of RBC.,These interactions act similar to hapten-carrier conj.,Such complexes can trigger Ab-mediated cell lysis by complement activation or opsonization,Production of anti-penicillin antibodies,Lysis and phagocytosis of penicillin-modified RBC,病因：,溶血性链球菌感染（异嗜性抗原）,临床特点:,以肺出血和进行性肾功能衰竭为特征,发生机制:,肺泡基底膜抗原改变,呼吸道病毒或细菌感染,产生IgG类抗体,与肺泡基底膜和肾小球基底膜IV型胶原结合,肾、肺组织损伤,4.肺出血肾炎综合症,Goodpastures disease,5.自身免疫性受体病,Graves disease Myasthenia gravis,（甲状腺功能亢进）（重症肌无力）,功能亢进 功能抑制,导致细胞功能紊乱，但无炎症现象和组织损伤。,刺激型超敏反应,抑制型超敏反应,血液循环中的可溶性抗原与相应的抗体（IgG、IgM类）结合形成可溶性的免疫复合物，在一定条件下沉积于肾小球、皮肤或滑膜等组织的毛细血管壁中，通过激活补体并在血小板、中性粒细胞等其它细胞的参与下，引起以充血水肿,局部坏死和中性粒细胞浸润为主要特征的炎症反应和组织损伤。,Type III hypersensitivity immune complex hypersensitivity,Type III hypersensitivity immune complex disease,Features,Ig G or IgM participate in Type III hypersensitivity,Immune complex persist and eventually deposit in a range of tissues and organs.,The complement and effector cell mediated tissue damage.,自身抗原：变性,IgG,，核抗原,外来抗原：微生物、寄生虫感染,生物制剂：抗毒素血清、药物等,抗 原,免疫复合物的形成和沉积的影响因素,Phagocytosis by phagocytes,Discharged from circulation,Exist in circulation,and deposit,Clinical symptoms depend on size and localization of immune complexes,免疫复合物沉积的影响因素,机体清除免疫复合物的能力,吞噬细胞的功能缺陷,先天性补体缺陷,解剖和血流动力学因素,易沉积在肾小球、滑膜部位,炎症介质的作用,免疫复合物沉积后引起组织损伤的机制,1.,激活补体,C3a、C5a与肥大细胞或嗜碱性粒细胞上的C3a、C5a受体结合,炎性介质释放,毛细血管通透性增加、渗出增加,吸引中性粒细胞至免疫复合物沉积部位,2.中性粒细胞的作用：,释放溶酶体酶(包括蛋白水解酶、胶原酶和弹力纤维酶),水解血管及其周围组织。,3.,血小板的作用：,Deposition of the medium IC on basement membrane,The complements are activated by the IC,producing C3a and C5a,which mediate an local inflammation and tissue damage by activating mast cells and basophils and recruiting neutrophils,Mechanism of Type III hypersentivity,临床常见的III型超敏反应性疾病,局部免疫复合物病,全身性免疫复合物病/循环免疫复合物病,Arthus reaction（Arthus 反应）,The diseases caused by Type III hypersensitivity,经抗原反复免疫之后,注射抗原的皮下出现局部红肿、缺血性坏死等剧烈炎症反应。,Mechanism of Arthus reaction,IC 沉积在注射部位的小动脉壁上,大量注射抗毒素马血清后1-2周出现发热、全身荨麻疹、淋巴结肿大、关节肿痛，严重的可出现肝、肾等功能损害。,使用大剂量青霉素、磺胺类药物或治疗性单抗也能出现类似症状。,Clemens Pirquet 1903,Serum sickness（血清病）,血清病,Rheumatoid arthritis（风湿性关节炎）,自身抗体与可溶性自身抗原形成免疫复和物，沉积于关节滑膜处,风湿因子：抗自身变性,Ig抗体,Poststreptococcal glomerulonephritis,(免疫复和物型肾小球肾炎),SLE,：DNA/抗DNA/补体沉积物,肾原性链球菌引起的肾病：,链球菌感染后2-3周。抗体与链球菌可溶性抗原形成复和物，沉积于肾小球基底膜处。,免疫复合物性肾炎：,病毒慢性感染。（淋巴细胞性脉络丛脑膜炎病毒 LCM virus),Type IV:Delayed type hypersensitivity(DTH）迟发型超敏反应,a hypersensitivity reaction mediated by antigen-specific effector T cells(Th1),delayed reaction:arises in 2472 hours after encounter with the same antigen,pathological change is an inflammation characterized by infiltration of macrophage and lymphocyte,No antibody and complement attend,Characteristics:,The antigen that induce DTH,胞内细菌,胞内病毒,结核分枝杆菌,单纯疱疹病毒,麻风分枝杆菌,麻疹病毒,单核细胞增生李斯特菌,布氏杆菌,同种异体移植物,胞内真菌,接触性抗原,卡氏肺囊虫,2,4,6-三硝基氯苯,白色念珠菌,染发剂,荚膜组织胞浆菌,镍盐,新型隐球菌,常春藤毒素,胞内寄生虫,槲叶毒葛,利什曼原虫,Pathogenesis of DTH,Mechanism of DTH,Granuloma（肉芽肿）,肉芽肿是临床上最重要的迟发型超敏反应。,由病原体持续存在于M,f内，而,M,f又不能对其杀灭清除而引起的一种特征性炎症反应。,两周出现，4周时反应达到高峰。,肉芽肿的参与细胞：上皮样细胞，巨噬细胞和淋巴细胞。,Mechanism of granuloma,Granuloma from Chronic DTH Response,肉芽肿周围纤维母细胞增殖，胶原合成增加，因此又被认为是纤维化。,Three variants of DTH,接触性皮炎,结核菌素试验,肉芽肿,Contact dermatitis（接触性皮炎）,抗原：染料、药物、金属及植物等,由T细胞介导，环境中抗原所诱导的湿疹样皮肤病。,症状：急性皮损表现为红肿和水疱，重症可有剥脱性皮,炎，慢性为丘疹和鳞屑,The mechanism of contact dermatitis,致敏阶段：,Mostly small molecules attach to a protein in the skin,The Ag-protein complex is processed and presented,sensitize TH1 cells,The mechanism of contact dermatitis,效应阶段,Subsequent exposure activates TH1 cells 4872 hrs later M infiltrate,Activation of M causes the inflammation that characterizes the disorder,Tuberculin hypersensitivity（结核菌素反应）,结核菌素试验,阳性：红肿、硬结,正常皮肤,接触性皮炎,结核菌素型超敏反应,内皮层,微血管,角质层,上皮层,皮下硬结,炎性疹块,细胞浸润,细胞浸润,接 触 性 和 结 核 菌 素 型 超 敏 反 应,教学要求,型超敏反应的发生机制、特点及常见疾病；*,型超敏反应的发生机制、特点及常见疾病；*,型超敏反应的发生机制、特点及常见疾病。*,