1、医学免疫学,Medical Immunology,个人简介,高美华, 国家二级教授、青岛大学一层次特聘教授。博士生及硕士生导师。曾留学于美国哈佛大学做博士后研究工作，并先后赴德国、法国、荷兰等进行学术交流。享受国务院政府特殊津贴专家；山东省有突出贡献的中青年专家；山东省千名知名专业技术专家；青岛市资深专家；全国模范教师；全国优秀教师；山东省十大优秀教师；山东省优秀共产党员；承担国家自然基金等课题项,获得省级科研奖励6项，重点进行肿瘤及糖尿病分子免疫机制研究。,Chapter IIntroduction to Immunology第一章 免疫学概论,Medical immunology is t
2、he subject forefront in Life science and the support in modern medicine.,Medical immunology is very important course for a medical student. Because many human diseases pathogenesis associated with immune abnormal and diseases diagnosis need a lot of immune methods.This disease prevention and treatme
3、nt need many immunothrapy. In addition to immunology test for reseach work construct good platform, I hope every student to study hard for medical immunology,医学免疫学既是生命科学的前沿学科，也是紧密联系临床实际的重要医学支撑学科，是医学生必读且具有重要应用价值的课程。,因为免疫学可以帮助解释多种疾病的发病机理如AIDS，自身免疫病，肿瘤等。可以帮助临床诊断疾病如肿瘤、肝炎、早孕。可以帮助防治疾病如亚单位疫苗、新型免疫疗剂。可以说人类的“
4、生老病死”均与免疫密切相关。希望同学们能努力学好免疫学。,此外，免疫学检测技术为科研搭建良好平台。Immunolabling techniques-,Immunofluorescence 免疫荧光技术 Enzyme immunoassay,EIA 酶免疫标记技术 Radioimmunoassay, RIA 放射免疫技术 Immunohistochemistry 免疫组化技术 Gene chip and Antibody chip 基因及抗体芯片,Enzyme immunoassay,EIA; 免疫酶标技术,Immunofluorescence technique 免疫荧光技术,流式细胞技术,R
5、adioimmunoassay, RIA 放射免疫技术,Gene and antibody chip 基因及抗体芯片技术,Study Content of Medical Immunology 医学免疫学研究内容：,1. Structure and function of immune system 免疫系统结构与功能（2-11章） 2. Types and process of immunoresponse免疫反应类型及过程（12-16章） 3. Immunity diseases pathogenesis免疫性疾病发病机制（17-21章） 4. Immunity diagnosis ， p
6、revention and treatment 免疫病诊断、预防和治疗（22-23章）,Section 1,Brief introduction of medical immunology第一节 医学免疫学简介,免疫性疾病 免疫学应用,Conception of immunity: 免疫的概念：,The original term “immunity”,meaning exempt epidemic situation and the state of protection from disease. It is the source of the word “immunitas”.原意：罗马
7、时代即免除劳役、免除疫情、免除感染Now, immunity is process that antigen are recognized, neutralized and eliminated by immune system 概念： 免疫是指免疫系统识别、中和、清除抗原性异物（病原微生物、肿瘤细胞）的过程,抗肿瘤免疫（Anti-tumor）,肿瘤免疫和免疫逃逸机制,免疫平衡状态,抗感染免疫（Anti-infectious）,免疫系统是人体的健康卫士、守护神 Immune system is the health guards and patron saint of human body,一
8、、Basic Function of Immune System 免疫系统的功能,Historically, immunity meant protection from disease and, more specially, infectious disease. Immunology help us understanding how the body distinguishes between what is “self” or “nonself ” , and eliminated nonself。识别自我与非我,Come to light,human live in a world
9、 filled with infectious agents.Our bodies have many mechanisms that permit us to defend foreign organisms.This defensive ability is called Immunity. This defensive system is called immune system,（一）Composition of Immune System 组成 1. organsthymus、bone marrow、 spleen、lymph node、mucosal-associated lymp
10、hoid tissue 2. cellsMacrophages（M） 、 Natural Kill Cell 、 Dendrtic cell 、 T cell 、 B cell 3. moleculesmembrane type molecules:CD、 AM、 MHC secretion type molecules:antibody、cytokine、complement,（二）Function of Immune System （免疫系统的功能）,Function Normally AbnormityDefense eliminated infectious Hypersensitiv
11、ityorganisms ImmunodeficiencySuveillance eliminated tumor cell Tumor virus infectionHomeostasis eliminated self death cell Autoimmune diseases,防御功能过高：超敏反应- 荨麻疹,防御功能过低:免疫缺陷-AIDS,免疫自稳功能异常自身免疫病类风关 SLE,免疫监视功能降低-肿瘤,二、Classification and Characteristics of Immune response：免疫应答的种类和特点,Immune response may be
12、divided into Innate and adaptive immunity(固有免疫和适应性免疫）I. Innate immunity (non-specific immunity)：固有免疫/非特异免疫,1.Composition ：组成,(1) Barriers：屏障结构 第一道防线1） skin and mucosa barrier 皮肤粘膜屏障 Physical barrier : skin and mucosa structure Chemical barrier: antimicrobial substances in secretion of skin and mucos
13、a Biotic barrier: normal flora existing on the surface of skin and mucosa 2） blood- brain barrier 血脑屏障3） blood- placental barrier 血胎屏障 胎盘是母子间物质 交换的中转站.,纤毛定向项运动 皮脂腺分泌的脂肪酸,正常菌群的拮抗作用,（2） molecules ：固有免疫分子 complement， lysozyme 补体、溶菌酶,（3） Cell ：固有免疫细胞,Macrophage（巨噬细胞）、NK cell、neutrophil 、 DC（树突状细胞） 、NKTp
14、attern-recognition receptor,PRR（模式识别受体）+pathogen associated molecule pattern,PAMP（病原体相关分子模式）.such as, G-菌LPS+ Toll-like receptor（果蝇蛋白样受体）,TLR4， G+菌肽聚糖+TLR2,巨噬细胞（Macrophage）的吞噬作用,树突状细胞-DC,2. The characteristics :特点(1)non-specific (2)no memory (3) early effect (4) genic acquired,II Adaptive immune：适应免
15、疫/特异免疫,specific immunity or acquired immunity：1.Type 类型 ：T cell and B cell induce both majorimmune response:humoral immunity and cellular immunity （体液免疫与细胞免疫）2. Process 过程 ：分为识别、活化、效应三个阶段 Recognition Phase:TCR BCR+MHC-Ag/APC Activation Phase: double signal（1）specific signal（2）co- stimulatory signal
16、Effector Phase: Antibody and effect T kill Ag,1）Recognition Phase: 识别阶段、BCR TCR,2）Activation Phase 活化阶段：双信号/Ag及协同刺激信号,3）Effect Phase 效应阶段/抗体及CTL,3.The characteristics of Adaptive immunity:,(1) specific 特异性: TC+BC/1012(2) memory 记忆性:Bm Tm(3) tolerogenic 耐受性：自身耐受(4) later 迟缓性: 7-10 day(5) acquired 获得性
17、:出生后获得 :,相辅相成，彼此协作，独立交叉,Comparison of Innate and Adaptive Immunity 固有免疫与适应免疫的区别,Innate adaptive receptor PRR TCR / BCR specific no yes Memory no yes Time early later Mode genic acquired Cell NK DC MQ T B Molecule C lysozyme Ab CK,三、Immune diseases（免疫病） Immune is rapier（双刃剑） Advantages（有利） ：anti-tumo
18、ranti-infection Disadvantages（有害）：Diseases,1）Hypersensitivity:I-IV超敏反应 I-III B细胞功能异常 IV T细胞功能异常,2）Immunodeficiency disease (AIDS) 艾滋病,3）Tumor 肿瘤,4）Autoimmune disease 系统性红斑狼疮(SLE),SLE发生机制：,细胞核DNA变性 自身抗原自身B细胞浆细胞抗核抗体+细胞核DNA 表皮、心、肝、肾细胞损伤,5). Transplantation rejection HVGR GVHR 移植排斥反应,(一)、 Immunodiagnosi
19、s 免疫诊断 ：minim,auto,celerity, 微量、快速、敏感、特异，Pg， ELISA， FACS - ABO typing, infectious disease, tumor marker, HBV,HIV，pregnancy ，leukemia. 传染病、肿瘤、早孕法医鉴定血迹。白血病及淋巴瘤、自身免疫病 (二)、 Immunotherapy 免疫治疗：Cytokine-EPO GM-CSF;MAb;HSC、DC-tumor、chronic infectious disease and Auto-immune disease 单抗、细胞因子、DC CIKHSC,四、Appl
20、ication of Immunology免疫学应用,(三)、 Immunoprophylaxis： 免疫预防 抗原疫苗：牛痘苗天花绝迹。脊髓灰质炎减毒活疫苗-消灭婴儿瘫已指日可待。重组疫苗应用降低乙肝及结核病的发病率。21世纪由于新型抗原疫苗的不断问世，人类疾病谱发生变更，传染病已得到有效控制，而心脑血管病、肿瘤、糖尿病成为危害人类健康的重大疾病。,Section 2 History of Immunology 第二节 免疫学发展史,The development of immunology has experienced 3 stages: 1) Experience immunology
21、 phase 经验免疫学 (16-18 century) 2) Scientific immunology phase 科学免疫学 (19-20 century) 3) Modern immunology phase 现代免疫学 (20 century middle-now),一、Experienced Phase of Immunology(16-18th)：经验免疫学时期chinesehuman pox（人痘）smallpox(天花）Jennercowpox vaccine（牛痘）smallpox,“以毒攻毒”,WHO declare to destroy smallpox in 1980
22、 1980年世界卫生组织宣布已经消灭天花,二、Scientific Phase of Immunology(19-20 century)科学免疫学时期,Koch Pasteur 1、discovery of pathogens and application of vaccines :病原菌的发现及疫苗研制成功 2、discovery of humoral immunity and cellular immunity：体液免疫及细胞免疫学派的形成,2)、Discovery of antibody（Antitoxin）:,Behring 1890年发现抗毒素， 1901 年获首枚诺贝尔奖3)、A
23、ntibody is r immunoglobulin :Tiselius Kabat 1937 4)、Antibody is four-peptide chain structure:Porter 19595)、Structure of antigen and antigenic specificity: Landsteiner 1930,1) 、 Discovery of Macrophage, Metchnikoff，1883年,3、 Important Immune theory （1）Burnet-clonal selection theory克隆选择选择学说，1957年,monoc
24、lonal antibody，mAb 单抗Kohler Milstein,2）Jeme-独特型网络学说,3）模式识别理论及危险信号学说,4）discovery of immune tolerance Owen 自身免疫耐受学说,4、 Overall Know to immune system：对免疫系统的全面认识： T主宰细胞免疫，B-主宰体液免疫，T B协同效应-TDAg development of new immune cell:T cell/CTL Th, Treg特异性免疫 M1 M2，NK,DC, B-1B NKT, r+T非特异免疫,Achievement scientist突出
25、贡献科学家,Jennercowpox vaccinesmallpox Koch and Pasteur- vaccine（疫苗） Behring - antibodyAntitoxin （抗毒素） Burnet -clonal selection theory-克隆选择Kohler and Milstein mAb（单克隆抗体）,三. Modern Immunology Phase(1970-Now) 现代免疫学时期：随着人类基因组计划的完成(2050024500)，遗传信息携带者-DNA双螺旋结构被揭秘，新型免疫分子基因不断被证实及克隆化，分子免疫学进入了快速发展时期,（一）Clarify
26、Diversity mechanism of BCR and antibody BCR及抗体多样性机制 It is the result of rearrangement and diversity by Variable and Constant genes,somatic hypermutation。VDJ基因分隔，V基因重排决定BCR及抗体结合抗原的多样性，C基因不同决定抗体类型。 多样性机制：胚系基因多样性，重排连接多样性，基因高频突变造成BCR及抗体多样性,（二）TCR gene clone,TCRa=IgL TCR=IgH,（三）MHC restriction 约束性的发现 360
27、0kb ,128/224gene seat，多基因性，多态性。MHCI，MHCII与抗原提呈（不同个体对同种抗原免疫应答能力不同）及移植排斥反应有关,(4).Cytokine and CKR,（5）Discovery of signal transduction 信号转导 Signal translation to the nucleus active transcription factors of specific genes. -cell active. BCR TCR CKR，不同信号通路激活相同转录因子 Cross talking串流，all road lead to rome 殊途
28、同归. 2011年诺贝尔奖得主-固有免疫学家。,discovery of signal transduction on Apoptosis（凋亡） Fas+FasLcaspase- DNA part-apoptosis,Section 3 Development tendency of Immunology,一、 Study of basic immune 基础免疫学1 Clarify the Mechanisms of immune response2 Study of Function gene（ 2450020500） : genome sequencesfunction gene-an
29、imal test to validate,transduction gene,knockout gene3 Study of New immune molecular:computer simulation(CD AM MHC CK C Ab)4 HSC/ESC direct differentiation,二、Study of clinical Immunology 临床免疫学,1 Diagnosis :诊断 Immunolabling techniques Immunofluorescence technique Enzyme immunoassay,EIA Radioimmunoass
30、ay, RIA Gene antibody and Protein chip. Micro-quickly-automation 微量、快速、自动化,2 Prevention ：预防 Subunit vaccine,DNA vaccine,Plant vaccine, recombination vaccine-HIV,TB, SARS New antigen vaccine： AIDS HCV Tumor vaccine,（1）Subunit vaccine（亚单位疫苗),HBsAg亚单位疫苗,（2） Conjugate vaccine（结合疫苗）,pneumococcus coating
31、polysaccharide vaccine。肺炎球菌荚膜多糖疫苗,（3）Synthetic peptide vaccine （合成肽疫苗),B epitope,Th CTL epitopeHI,CMI Such as HBSAg polypeptide vaccine,（4）Gene engineering vaccine (基因工程疫苗),1）Recombinant antigen vaccine（重组抗原疫苗）： DNAE coliexpression Such as recombine HBSAg vaccine,2）DNA vaccine（核酸疫苗）：,Immunogenic Gen
32、e+plasmid body,3）Plant vaccine (植物疫苗),3 Treatment ：治疗,New immunothrapy MAb ，human antibody，Genetic engineering antibody， Cytokine(EPO GM-CSF IFN） -Tumor，HVGR，Autoimmune Disesis， HSCLeukaemia，MDS，DC-Tumor,Recent development in immunology are opening up a huge region of potential new approaches of pre
33、vention and therapy of disease.One promising area is vaccine development using DNA recombination technology .Immunity not only against pathogens,but also against cancer and diabetes.Aim of immunology is for human benefit 我们应以基础免疫为亮点，临床免疫为特色，用发展的眼光去窥见免疫学这个五彩缤飞的世界，使免疫学造福于人类,point 本章重点,1.Function of im
34、mune system免疫的功能 2.Classification and characteristics of Immune response免疫的类型及特点 3.Immune disease 免疫性疾病的类型 4.The station and action of immunology in medicine 免疫学在医学中的地位及作用 5.Achievement in of Modern Immunology Phase 现代免疫学时期的新进展 6.Achievement scientist in empirical and scientific immunology stages为 为免疫学做出突出贡献的科学家？,
