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1、Chapter 20 Hypersensitivity 超敏反应,(Allergy, 变态反应) (Anaphylaxis, 过敏反应),Concept,Allergen (Anaphylactogen) 过敏原secondly enter sensitized host. Immune responses (too strong!) that result in tissue injury or physiological dysfunction.,History,At first,0.1ml of the glycerin extract of tentacles of Actiniari
2、a(sea anemone)海葵甘油提取物 22 days later, a second injection of the same amount,the dog not ill,the dog anaphylaxis,Richet & Portier, 1902,Hypersensitivity,Type I -Immediate 速发型 Type II - Cytolytic 细胞溶解型 Type III - I C 免疫复合物型 Type IV - Delayed 迟发型,Type I Hypersensitivity (Immediate速发型 ，Anaphylaxis过敏反应),I
3、 Features,quick various, serious IgE mediated no complement involved Obvious individual variation & genetic factors,II Mechanisms,Proteins 蛋白 Foods 食物 foreign serum 异种血清 nuts 坚果 vaccines 疫苗 seafood 海鲜 (fish,shrimp,shellfish,crab) (鱼，虾，贝，蟹) Plant Pollens 植物花粉 peas 豌豆 rye grass 黑麦 beans 菜豆 ragweed 豚草属
4、 eggs 蛋 timothy grass 梯牧草 milk 牛奶 birch trees 桦树 mushroom 磨菇,(i) Allergens 过敏原(Anaphylactogens),Insect Products 昆虫产物 bee venom 蜂毒 wasp venom 黄蜂毒液 ant venom 蚂蚁毒液 cockroach calyx 蟑螂萼 dust mites 尘螨 Drugs 药物 penicillin 青霉素 sulfonamides 磺胺 local anesthetics 局麻药 salicylates 水杨酸盐 Mold Spores 霉菌孢子 Animal Ha
5、ir and Dander 动物毛及皮屑,(i) Allergens (Anaphylactogens),(ii) Ab: IgE,Th1: IL-2,IFN-g,TNF-b, IL-12 Th2: IL-4,5,6,10,13 IL-4BIgE (IFN-g inhibit IL-4) (IL-12 inhibit IgE),2.Biological characteristics of IgE,1.Generation of IgE,(1) IgE (2) Ach (3) Th2 (4) SIgA (5) C1INH (C2a ),Allergic Individual过敏体质,(iii)
6、 IgE-FceR+ cells,mast cell, basophil Distribution: mast cell: skin and submucosa; basophil: blood. 2) IgE-FceR 3) activation of mast cell,Biological activities of mast cell and basophil,basophil,1.preformed mediators (1)Histamine 组胺 (2)Kinnogenase 激肽原酶 2.newly synthesized mediators (1)LTs 白三烯 (SRS-A
7、) (2)PGD2 前列腺素 (3)PAF 血小板活化因子,(iv) Biological Mediators,III Common Diseases in Clinical,1 Anaphylactic shock过敏性休克 1) Medicine (i.e., penicillin) Penicillin (372, hapten) In tissue, blood (pH7.27.6) 624h penicilloyl, penicillenic acid (青霉噻唑醛酸、青霉烯酸)+protein IgE 2) Xenogenic serum异种动物血清,2 Allergy of re
8、spiratory tract,Asthma,1) Bronchia asthma 支气管哮喘,2)Allergic rhinitis 过敏性鼻炎,Rhinitis,Allergy of digestive tract 胃肠道过敏反应,Hives荨麻疹,Allergy of skin 皮肤过敏反应,Reactions of immediate hypersensitivity,The wheal can involve an area of skin as large as several centimeters in diameter.,The wheal and flare respons
9、e typically subsides after about 15 to 20 minutes.,IV Diagnosis,skin test IgE detection,skin test,Skin tests with Grass pollen allergen植物花粉 in a patient with typical summer hay fever枯草热,Read at 20 min,Skin tests with different allergens,IgE detection,V Prevention&treatment of Hypersensitivity,Preven
10、tion Identify the offending allergen, avoid contact if possible! （找出变应原，避免接触）！ 1)Penicillin skin test 2)Xenogenic serum skin test,(ii) Treatment,1. Desensitization 脱敏 1)Xenogenic anti-serum 2)Allergen 2. Anti-hypersensitivity 抗过敏,2 Type Hypersensitivity,(Cytotoxic type 细胞毒性 Cytolytic type 细胞溶解型) Fea
11、ture: Ab: IgG、IgM Complement involved Cell: M、NK Reaction on cell,一、机制,二、Common Diseases in Clinical:,(一) Blood transfusion reaction 输血反应,ABO blood groups and serum antibodies,(二) Hemolytic disease of the newborn 新生儿溶血症 (erythroblastosis fetalis) 胎儿红细胞增多症,1.Hapten type: i.e: penicillin degrade BPO(h
12、apten)+RBC Anti-BPO penicillin again RBC-BPO-Anti-BPO Complement hemolytic anemia,(三) Immune Hemolytic Anemia 免疫溶血性贫血,2.IC type:,Medicine (Hapten) + tissue pro Ab medicine again Hapten + Ab IC C3b, Fc RBC, Platelet, neutrophil (hemolytic anemia 溶贫, thrombocytopenia 血小板减少性紫癜, neutropenia 中性白细胞减少症),1.
13、Autoimmune (hemolytic) anemia -Methyldopa甲基多巴 RBC 2.Goodpastures syndrome肺肾综合征 3.Glomerulonephritis(20%)肾小球肾炎 Commom Ag(streptococcus and glomerular basement membrane) 4.Anti-hormone-Ab,(四) Autoimmune Diseases:, Graves Disease 甲状腺功能亢进 LATS长效甲状腺刺激素Thyroid 甲状腺Thyroxine甲状腺素 Myasthenia gravis重症肌无力: Anti
14、-AchR Diabetes Mellitus of Insulin Resistance胰岛素抗性糖尿病: Anti-Insulin R,5. Autoimmune receptor disease:,Type Hypersensitivity,一、Pathogenesis: (一) IC formation and deletion:,(IC mediated, vasculitis type血管炎型),1.Size of IC:,soluble Ag IgG(mainly) Ag Ab Ratio: Ag : Ab IC AgAb 19s Ag Ab 19s,2.Amount of IC
15、,ICcomplement C3a、C5a 、C3b neutroplil vasculitis血管炎,1.Golmerular basement membrane of the kidney 肾小球基底膜 2.Synovial membrane of joints 关节滑膜 3.Choroid plexus of the brain 脑脉络丛,(二) local deposition of IC,(三) Pathogenesis of IC:,(一) local IC diseases: 1. Arthus reaction 2. Allergic pneumonitis变应性肺泡炎 3.
16、IgA nephropathy肾病,二、Common Diseases in Clinical:,(二) Systemic IC diseases: 1.Serum sickness: Xenogenic serum injection7 14dsickness,2.Post streptococcal glomerulonephritis 链球菌感染后肾小球肾炎 Streptococcal infection 23w IC deposites in glomerular basement membrane and subepithelium上皮细胞 80% glomerulonephriti
17、s(by IC),(三) Chronic IC diseases: 1. SLE系统性红斑狼疮：抗核抗体 2. RA类风湿性关节炎：抗变性IgG抗体 (四) Allergic shock reation 1. Animal test: IC (iv) 2. Hexheimer reaction:,Type Hypersensitivity (Delayed type迟发型, Cell-Mediated细胞介导型),Feature: 1. Ag again: 24h,reation; 4872h, peak 2. TDTH(CD4+) secret CK M/ Mo, LC Inflammati
18、on 3. Ab， complement are not involved in ,一、Pathogenesis:,TD - Ag sensitized T cell : TC (CD8+) specific killing TDTH(CD4+) CK inflammation (一) Time for T cell sensitization: 23 weeks,(二) Cell-mediated tissue damage 1.CK: for LC : IL-2、IFN-、TNF- for M : MCF 、MIF、 MAF 2. Activating of M 3.Tc: specifi
19、c killing,61,临床常见病,传染性变态反应：（胞内寄生菌、病毒） 接触性皮炎 移植排斥反应,62,结核菌素反应,63,64,Contact dermatitis接触性皮炎 reaction to mango sap芒果汁,65,型 别,参加成分,发病机理,临床常见病,I型 （速发型）,IgE （IgG4） 肥大细胞、嗜碱性粒细胞,IgE粘附于肥大细胞或嗜碱粒细胞表面的FcR上，变应原与细胞表面的IgE结合，靶细胞脱颗粒，释放生物活性介质，作用于效应器官,过敏性休克、支气管哮喘、花粉症、过敏性鼻炎、荨麻疹、食物过敏症等,II型 （细胞毒型）,IgG、IgM、补体、巨噬细胞、NK细胞,在
20、补体、巨噬细胞、NK细胞等协同作用下溶解靶细胞。,输血反应、新生儿溶血症、免疫性血细胞减少症、Graves病,III型 （免疫复合物型）,IgG、IgM、IgA 补体、中性粒细胞,中等大小的免疫复合物沉积于血管壁基底膜激活补体，吸引中性粒细胞、释放溶酶体酶，引起炎症反应,血清病、免疫复合物型肾小球性肾炎、系统性红斑狼疮等,IV型 （迟发型）,T细胞,致敏T细胞再次与抗原相遇，直接杀伤靶细胞或产生各种淋巴因子，引起炎症。,传染性超敏反应、接触性皮炎,四型超敏反应要点比较,Prevention & Treament of Hypersensitivity,Identify the offendin
21、g allergen and avoid contact if possible! 找出变应原，避免接触！ Allergen avoidance is the best treatment! 避免接触变应原是最佳治疗！,一、Ask case history & find the allergen,1. PC skin test 2. Xenogenic serum skin test,三、 Anti-hypersensitivity:,二、De-hypersensitivity:,1. Xenogenic anti-serum 2. Vaccine,Immunological Detectio
22、n,1 Ag or Ab Detection,一、Characteristics of Ag-Ab reaction in vitro (一) High specificity (二) Reversible (三) At certain concentration and ratio (四) Two stages (五) Influencing factors 1. electrolyte 2. temperature 3. pH,二、Significant 三、Methods of Ag-Ab Detetion (一)Precipitation Reaction 1.ring precipi
23、tation test 2.single immunodiffusion 3.immunonephelometry 4.double immunodiffusion 5.counter immunoelectrophoresis 6.immunoelectrophoresis 7.immunoblotting,(二) Agglutination 1.Direct 2.Indirecrt 3.Antiglobulin test (Coombs test) (三)Complement involved Ag/AbReaction CFT (四) Neutrolization (五) Immunol
24、abelling technic 1.Immunofluorescence technic 2.Enzyme immunoassay, EIA,ELISA: Sandwich assay: Absample (Ag)Ab-Enzyme Indirect ELISA: Ag sample (Ab) Anti-Ig-Enzyme BAS-ELISA Avidin + 4 Biotin Ab.E. Fluorescein 3.Radio immunoassay, RIA,2 Detection of Humoral Immune Function,一、Quantification of Ig 1.S
25、erum IgG 2.SIgA 二、Common Ab Detection 三、B cell 1.B cell number 2.B cell Function,3. Detection of Cellular Immune Function,一、DTH in vivo: 1. skin test 二、Detection of CI in Vitro 1.T cell number 2.T transformation 3. Cytotoxicity 4.MLR,Immuno-prophylaxis 免疫预防,一.Artificial active immunization 人工主动免疫：给机
26、体接种具有免疫原性的疫苗等抗原性物质，刺激机体产生特异性免疫力，从而预防疾病的措施，也称预防接种。 1. inactivated vaccine 2. live-attenuated vaccine 3. toxoid,死疫苗与活疫苗的比较,制剂特点 死，强毒株 活，无毒或弱毒株 接种量及次数 量较大，23次 量较小，1次 保存及有效期 易保存有效期约1年 不易保存4冰箱内数周 免疫效果 较低维持数月2年 较高维持35年甚至更长 不良反应 较大 较小 制品类型 可多种疫苗混合使用 一般单独使用,区别点 死疫苗 活疫苗,二.Artificial passive immunization 人工被动免疫：给机体注射含特异性抗体的免疫血清或细胞因子等制剂，以治疗或紧急预防疾病的措施。 1. antitoxin 2. Ig 3. CK 4. mAb,人工免疫的比较,自动免疫 被动免疫 过继免疫 输入物质 抗原 抗体 免疫细胞 疫苗、类毒素 抗毒素、丙种球蛋白 骨髓细胞、TIL等 免疫力出现时间 14周后生效 注入后立即 较快 免疫维持时间 数月数年 23周 不能确定 用途 多用于预防 多用于治疗或紧急预防 多用于治疗,