第一章免疫學(xué)

1、Medical ImmunologyMedical Immunology授課教師：胡雪梅授課教師：胡雪梅 xue-mei-濱州醫(yī)學(xué)院免疫學(xué)教研室濱州醫(yī)學(xué)院免疫學(xué)教研室醫(yī)學(xué)免疫學(xué)醫(yī)學(xué)免疫學(xué)（Medical Immunology）研究人體免疫系統(tǒng)研究人體免疫系統(tǒng)（immune system）的的結(jié)構(gòu)和功能結(jié)構(gòu)和功能免疫應(yīng)答免疫應(yīng)答（immune response）的規(guī)律的規(guī)律免疫功能異常與疾病免疫功能異常與疾病為診斷、預(yù)防和治療免疫相關(guān)疾病奠定基礎(chǔ)為診斷、預(yù)防和治療免疫相關(guān)疾病奠定基礎(chǔ)*免疫學(xué)的地位：當(dāng)今生命科學(xué)的前沿學(xué)科和免疫學(xué)的地位：當(dāng)今生命科學(xué)的前沿學(xué)科和現(xiàn)代醫(yī)學(xué)的支撐學(xué)科之一現(xiàn)代醫(yī)學(xué)的支撐

2、學(xué)科之一教教學(xué)學(xué)教材教材( (雙語雙語) )授課教師授課教師考試考試( (理論、實驗）理論、實驗）理論理論實驗實驗學(xué)習(xí)目的學(xué)習(xí)目的Reference booksReviews Trends in Immunologyhttp:/ Review of Immunology /loi/immunolNature Review ImmunologyImmunological Reviews http:/www.blackwell- Opinion in Immunologyhttp:/ Books & JournalsBasic I

3、mmunologyCellular and Molecular ImmunologyImmunobiologyAnnual Review of ImmunologyScienceNatureTrends in ImmunologyCurrent opinion in ImmunologyImmunityJournal of Experimental MedicineJournal of Clinical Investigation單位：免疫學(xué)教研室單位：免疫學(xué)教研室辦公地點：實驗樓辦公地點：實驗樓A411 免疫學(xué)主任辦公室免疫學(xué)主任辦公室實驗室地點：實驗樓實驗室地點：實驗樓A A三層三層辦公電

4、話：辦公電話：6913364Introduction of Immunology1.History of Immunology2.Research and Development Strategies of Modern Immunology3.General Introduction to the Immune system4.Antigens(抗原抗原)*免疫接種與抗感染免疫免疫接種與抗感染免疫第一章第一章 免疫學(xué)發(fā)展的歷史回顧免疫學(xué)發(fā)展的歷史回顧Chapter 1 History of the Immunology* *免疫學(xué)科學(xué)試驗與理論研究免疫學(xué)科學(xué)試驗與理論研究* *免疫學(xué)免疫學(xué)一

5、個獨立學(xué)科的誕生一個獨立學(xué)科的誕生Vaccination and immunity against Infection DiseaseExperimental and Theoretical Studies of ImmunologyImmunology-An Independent Discipline Came into BeingImmunology developed as humans continued fighting against infectious diseases (感染性疾病感染性疾病) . 霍亂弧菌霍亂弧菌流感病毒流感病毒第一節(jié)第一節(jié) 免疫接種與抗感染免疫免疫接種與

6、抗感染免疫Vaccination and immunity against Infection Disease* *人痘苗及其應(yīng)用人痘苗及其應(yīng)用(variolation and its application)* *牛痘苗的發(fā)明牛痘苗的發(fā)明(Invention of cowpox vaccination)* *減毒活疫苗減毒活疫苗(Live-attenuated vaccine)Figure 1-1 Historical review of the influenza(a) The influenza epidemic (b) Vaccination of influenza in New Y

7、ork 1918 (a) (b) vaccinationVaccineNothing known of microorganisms* *人痘苗及其應(yīng)用人痘苗及其應(yīng)用(variolation and its application)接種接種疫苗疫苗vaccinationEdward Jenner 1749-1822VaccineNothing known of microorganismsDiscovered in 1796 that cowpox, or vaccinia（牛痘）牛痘）, induced protection against human smallpox ( (天花天花) )

8、* *牛痘苗的發(fā)明牛痘苗的發(fā)明 (Invention of cowpox vaccination) 1796，Jennar: occupational exposure to cowpox prevents smallpox-vaccination/ vaccine經(jīng)驗免疫經(jīng)驗免疫學(xué)時期學(xué)時期18世紀(jì)They should be vaccinated first.Why do they not want to play with my kids?Figure 1-2Vaccination led to a world-wide eradication of smallpox by 1979Sm

9、allpox eradication World Health Organization Eradication effort began 1966 Last naturally acquired case 1977, SomaliaRobert Koch(1843-1910) :infectious diseases caused by microorganisms（微生物）；結(jié)（微生物）；結(jié)核桿菌核桿菌, 1905年年Nobel Prize Louis Pasteur(1822-1895): cholera cholera （霍亂）（霍亂）,anthrax,anthrax（炭疽）（炭疽）r

10、abies vaccine rabies vaccine （狂犬病疫苗）。（狂犬病疫苗）。免疫學(xué)作為一門科學(xué)誕生在免疫學(xué)作為一門科學(xué)誕生在PasteurPasteur的實驗室。的實驗室。Experimental immunology19世紀(jì)中葉世紀(jì)中葉Pauster isolate microorganisms and culture bacterial successfullyLouis Pasteur The chicken which were injected with fowl cholera bacterium (old culture) survived from a subse

11、quent injection of fresh culture of bacteria.- Aging had weakened the virulence of the pathogen.- An attenuated（減毒）（減毒） (weakened) strain could protect the chickens against the disease. Figure 1-6 Karl Landsteiner(18681943):epitope (表位表位)，20世紀(jì)初世紀(jì)初20世紀(jì)上葉世紀(jì)上葉奧地利科學(xué)家奧地利科學(xué)家抗原的特異性僅是由抗原抗原的特異性僅是由抗原分子中的特殊化學(xué)基

12、團所分子中的特殊化學(xué)基團所決定，這些化學(xué)基團稱為決定，這些化學(xué)基團稱為表位表位（ epitopeepitope ）紅細(xì)胞表型的特異性是由其紅細(xì)胞表型的特異性是由其表面糖蛋白分子末端寡糖結(jié)表面糖蛋白分子末端寡糖結(jié)構(gòu)所定，并根據(jù)其不同將紅構(gòu)所定，并根據(jù)其不同將紅細(xì)胞進行細(xì)胞進行ABO分型分型，提出了，提出了同型輸血的原則同型輸血的原則血型之父血型之父20世紀(jì)上葉世紀(jì)上葉Antibodies (抗體抗體)1890年，年，Von Brhring /Kitasato將白喉抗毒素用于臨床，將白喉抗毒素用于臨床，濟世成就濟世成就1901年年von Behring 獲得第一屆獲得第一屆諾貝爾生理學(xué)或醫(yī)學(xué)獎諾貝

13、爾生理學(xué)或醫(yī)學(xué)獎*抗體研究的發(fā)展抗體研究的發(fā)展 (Development of antibody research)1.免疫球蛋白（免疫球蛋白（Immunoglobulins)2.單克隆抗體（單克隆抗體（Monoclonal antibody)Ab is globin 1975年年Kohler and Milstein將產(chǎn)生抗體免疫鼠（接受抗原注射）的脾細(xì)胞（含抗體產(chǎn)將產(chǎn)生抗體免疫鼠（接受抗原注射）的脾細(xì)胞（含抗體產(chǎn)生細(xì)胞）與骨髓瘤細(xì)胞融合，形成了具有雙親細(xì)胞特點的生細(xì)胞）與骨髓瘤細(xì)胞融合，形成了具有雙親細(xì)胞特點的雜交瘤細(xì)胞。雜交瘤細(xì)胞。Elie MetchnikoffCellular The

14、ory: certain white blood cells, which hetermed phagocytes, were able to ingest (phagocytose) microorganisms and other foreign material1883,cell-mediated immunity細(xì)胞免疫學(xué)派的形成細(xì)胞免疫學(xué)派的形成1942年年Chase 等等 結(jié)核菌素的反應(yīng)結(jié)核菌素的反應(yīng)是致敏是致敏T淋巴細(xì)胞，不是淋巴細(xì)胞，不是Ab1962年切除雞的腔上囊后仍可移植排斥。年切除雞的腔上囊后仍可移植排斥。俄國科學(xué)家俄國科學(xué)家Figure 1-7 Frank Macfar

15、lane Burnet （18991985）19601960年獲得諾貝爾獎年獲得諾貝爾獎克隆選擇學(xué)說克隆選擇學(xué)說Clonal selection theory(1) There are various lymphocyte clones in our body, each of them bears a unique type of Ag receptor which can recognize Ag specifically. (2)The clones of lymphocytes that can be interacted with corresponding Ag will be s

16、elected and lead to activation, proliferation , produce antibody and specific memory cells. -clonal selection(3)The clones of lymphocytes that can recognize self-Ags will be destroyed or learn to tolerance (forbidden clones) at the early stage of their development. -clonal deletion(Formation of immu

17、nology sub-disciplines)19711971年：免疫學(xué)作為一獨立學(xué)科誕生年：免疫學(xué)作為一獨立學(xué)科誕生第二章第二章 現(xiàn)代免疫學(xué)研究及發(fā)展策略現(xiàn)代免疫學(xué)研究及發(fā)展策略Resarch and Development Strategies of Modern Immunology 免疫學(xué)的概念、功能與表現(xiàn)免疫學(xué)的概念、功能與表現(xiàn) 固有免疫及適應(yīng)性免疫固有免疫及適應(yīng)性免疫 現(xiàn)代免疫學(xué)研究的熱點與發(fā)展策略（自學(xué)現(xiàn)代免疫學(xué)研究的熱點與發(fā)展策略（自學(xué)) )Concept of Immunity and Its Functions and ManifestationsInnate Immuni

18、ty and Adaptive ImmunityHot Spots in Research and Strategies of Modern Immunology1. Concept of Immunity (p16)1) Historical concept-Immunity meant protection against from disease, usually infectious diseases.2) Modern concept-Immunity refers to the ability to respond to foreign substances, including

19、microbes and molecules. P390現(xiàn)代免疫是指機體現(xiàn)代免疫是指機體識別和排除抗原性識別和排除抗原性異物的功能異物的功能 p16Immune FuntionsNormal ManifestationsAbnormal ManifestationsImmune defenseImmune homeostasisImmune surveilanceresisting invasion of pathogensNeutralizing toxinsImmune tolerance to self componentsKilling transformed cellsControl

20、ling persistence infectionHypersensitivityImmunodeficiency diseasesAutoimmune diseasestumorPersistent viral infectionImmune functions and Menifestations免疫功能免疫功能免疫防御：免疫防御：指正常的免疫應(yīng)答可阻止和清除入侵的指正常的免疫應(yīng)答可阻止和清除入侵的病原體及其毒素等，即抗感染免疫的作用。病原體及其毒素等，即抗感染免疫的作用。免疫自穩(wěn)：免疫自穩(wěn)：指機體對自身成分的耐受、對自身衰老指機體對自身成分的耐受、對自身衰老和損傷的細(xì)胞的清除，通過免疫

21、調(diào)節(jié)達(dá)到維持機體和損傷的細(xì)胞的清除，通過免疫調(diào)節(jié)達(dá)到維持機體內(nèi)環(huán)境的穩(wěn)定的功能。內(nèi)環(huán)境的穩(wěn)定的功能。免疫監(jiān)視：免疫監(jiān)視：免疫系統(tǒng)識別、殺傷并清除體內(nèi)突變的免疫系統(tǒng)識別、殺傷并清除體內(nèi)突變的細(xì)胞，防止腫瘤的發(fā)生。細(xì)胞，防止腫瘤的發(fā)生。Bone marrowspleenBCRConstitute of the immune systemMATLCDTCRImmune organ centralperpheralImmunocytesImmune moleculemembrancesecretorythymusBursa of fibriciusLymph nodeSATLinnateadaptiv

22、eMHCCKRCAMIgcomplementcytokineTBmonocytesmacrophageDCneutrophilseosinophilsbasophilsMast cells erythrocytesplatelets免疫應(yīng)答的種免疫應(yīng)答的種類和特點類和特點固有免疫固有免疫 Innate immunityNatural or native immunity Non-specific immunity Congenital immunity 適應(yīng)性免疫適應(yīng)性免疫 Adaptive immunity Acquired immunity Specific immunity HOST D

23、EFENSE= Innate + adaptive immunity第二節(jié)第二節(jié) 固有免疫及適應(yīng)性免疫固有免疫及適應(yīng)性免疫Innate immunity and Adaptive immunity 固有免疫細(xì)胞的識別特點固有免疫細(xì)胞的識別特點模式識別受體（模式識別受體（pattern recognition receptor, PRR病原相關(guān)分子模式（病原相關(guān)分子模式（ pathogen associated molecular pattern ，PAMP ）3.3.Types of ImmunityI. Innate Immunity：機體先天具備的免疫防御功能：機體先天具備的免疫防御功能

24、(or natural immunity/ non-specific immunity )II. Adaptive Immunity：機體受抗原激發(fā)后而獲得的：機體受抗原激發(fā)后而獲得的免疫能力免疫能力 (or acquired immunity/specific immunity) 細(xì)細(xì)胞胞免免疫疫體體液液免免疫疫moleculesFigure 2-13Infection of host epithelial cells by Salmonella typhi傷寒沙門菌Salmonella typhi樹突狀細(xì)胞樹突狀細(xì)胞Dendritic cell（DC）Figure 10-1 Recogni

25、tion and cytolysis mechanisms of NK cells(a)Recognition of normal self tissue cells; (b)Recognition and cytolysis of virus-infected cells; (c)Recognition and cytolysis of target cells that are coated with antibodyNatural killer cells, NK cells適應(yīng)性免疫應(yīng)答適應(yīng)性免疫應(yīng)答 adaptive immunity識別階段識別階段活化增殖階活化增殖階段段效應(yīng)階段效

26、應(yīng)階段 Innate immunityAdaptive immunityManner of acquiringPhase of effectImmune memoryCongenital,exist with bornPRRNoAcquired by antigen stimmulation after birth TCR BCRHave immune memory cells producedComparison of innate immunity and adaptive immunityNo antigen specificityPromptDevelops slowly,Antige

27、n specificityAntigen recognition receptorFeatures of Innate immunity Rapid response to a microbe (hours) Lack of memoryFeatures of Adaptive immunity Slower response (days) Strong memory response More specific Transferred Self-restriction Acquired (set up after birth )summary病原體入侵早病原體入侵早期，發(fā)揮免疫期，發(fā)揮免疫防

28、御作用防御作用慢慢特異性強特異性強免疫記憶、防止再感染免疫記憶、防止再感染Questions1. Compare the characteristics of innate immunity and adaptive immunity.2. What is the new concept of immunity? Please explain the functions of immunity?中樞免疫器官中樞免疫器官（central immune organcentral immune organ）組成：胸腺、骨髓組成：胸腺、骨髓功能：免疫細(xì)胞發(fā)生、分化、發(fā)育和成熟的場所功能：免疫細(xì)胞發(fā)生、

29、分化、發(fā)育和成熟的場所外周免疫器官外周免疫器官（peripheral immune organperipheral immune organ）組成：淋巴結(jié)、脾、粘膜免疫系統(tǒng)組成：淋巴結(jié)、脾、粘膜免疫系統(tǒng)功能：成熟的細(xì)胞、細(xì)胞定居的地方，也是功能：成熟的細(xì)胞、細(xì)胞定居的地方，也是 產(chǎn)生免疫應(yīng)答的部位產(chǎn)生免疫應(yīng)答的部位第三章第三章 免疫系統(tǒng)概述免疫系統(tǒng)概述Chapter 3 General Introduction to the Immune SystemSites of generation of all circulating blood cells(各類血細(xì)胞和免疫細(xì)胞發(fā)生的場所各類血細(xì)胞和

30、免疫細(xì)胞發(fā)生的場所)(B(B分化成熟的場所分化成熟的場所) )*體液免疫應(yīng)答的場所體液免疫應(yīng)答的場所The functions of bone marrowSites of generation of all circulating blood cells and immune cellsSites of maturation of B cellsSites of secondary humoral immune response occurIn birds B cells mature in the bursa of Fabricius胸胸 腺腺 （thymus）Thymus stroma

31、cells,especially epithelial cells(nurse cells) : cell to cell interactioncytokine and thymulin-like molecules (Thymosin胸胸腺肽，腺肽，thymulin- 胸腺素胸腺素， thymopoietin胸腺生成胸腺生成素素)produced by thymus epithelial cells: To promote the proliferation , differentiation of thymus cellsExtracellular matrix: enhance the

32、 interactionMicro-environments of thymus lymphocytes selected in thymus T cells are selected through a process of thymic education before being released into the peripheral lymphoid organs as mature lymphocytes positive selection (recognize MHC) negative selection (no response to self-Ag) Scanning e

33、lectron micrographof thymusDeveloping T cellThymic stromaFunctions of thymus: Sites of T cell maturation Immune regulation:cytokines and thymulin-like molecules (Thymosin，thymulin- ， thymopoietin ) Barrier function: 組成：淋巴結(jié)、脾、粘膜免疫系統(tǒng)組成：淋巴結(jié)、脾、粘膜免疫系統(tǒng)第二節(jié)第二節(jié) 外周免疫器官外周免疫器官（peripheral immune organ）Lymph node

34、Spleen Mucosal Associated Lymphoid Tissue ( MALT) 功能：成熟的細(xì)胞、細(xì)胞定居的地方，功能：成熟的細(xì)胞、細(xì)胞定居的地方， 也是產(chǎn)生免疫應(yīng)答的部位也是產(chǎn)生免疫應(yīng)答的部位The sites where mature T and B cells residence. The sites where adaptive immune responses to foreign antigens are initiated and develop.數(shù)量：數(shù)量：500600個個分布：廣泛分布于分布：廣泛分布于全身非粘膜部位的全身非粘膜部位的淋巴通道上淋巴通道上I

35、. Lymph node ( LN) 淋巴結(jié)淋巴結(jié) Structure:CortexLymphoid follicle ( Thymus-independent area)Paracotical area (Thymus-dependent area)medulla medulla cords: macrophage and plasma cells medulla sinus Figure 1-8 part 1 of 2Function of lymph node*Sites of mature T and B residence*Sites of immune response initi

36、ated*Participate in lymphocyte recirculation*Filter and discharge of antigenLymphatic System淋巴系統(tǒng)淋巴系統(tǒng) 脾（脾（spleen）- 人體最大的免疫器官人體最大的免疫器官動脈周圍淋巴鞘動脈周圍淋巴鞘紅髓紅髓白髓白髓初級濾泡初級濾泡中央動脈中央動脈脾的結(jié)構(gòu)脾的結(jié)構(gòu)(Structure of Spleen)Functions: 1) site of T and B cells residence 2) undergo immune response 3) produce IFN, complement 4) filter the blood皮膚黏膜相關(guān)淋巴組織皮膚黏膜相關(guān)淋巴組織皮膚相關(guān)淋巴組織皮膚相關(guān)淋巴組織（Skin-associated lymphoid tissue）（S