医学免疫学英文版课件：Chapter 1 and 2 Introduction to immnunology

1、MEDICAL IMMUNOLOGYChapter 1-2 Introduction & Overview of Immunology 高成江, 教授, 泰山学者刘素侠，副教授王嘉宁，副教授 山东大学医学院免疫学研究所Chengjiang Gao，Professor88382292 (office), 88382113 (lab)Office: building 6, Rm 438Email: 梁晓红88382038Office: building 6, Rm 540Email: MEETINGS: Monday 56, East library, 201d Thursday 12, East

2、 library, 201dTEXTBOOKS:Sun Wensheng（孙汶生）， Medical Immunology. In Chinese with English abstractAbbas, Lichtman and Pillai, Cellular and Molecular Immunology. 6th ed. In English Immune system and immune moleculesImmune cells and immune responsesImmunity and clinicHistory of ImmunologyConcept of Immun

3、ity Traditional concept Modern conceptFunctions of Immunity Immune defense Immune surveillance Immune homeostasis Types of Immunity Innate immunity Adaptive immunityHistory of ImmunologyPathogens: VirusesBacteriaFungiParasite Infectious diseases Kalaazar/black fever disease（黑热病）： 3 times, 542-543, 1

4、/4 of population/ 25000 thousand diedPlague（鼠疫）：3 times, Europe/24000 thousand diedSmallpox（天花）：18th century，Europe/60000 thousand deathInfluenza：1918.3-1919.1，50000 thousand death，19000 thousand death for warKalaazar/ Visceral Leishmaniasis（利什曼原虫） Historical record of plague：鼠疫杆菌1793年云南师道南所著“死鼠行”：

5、东死鼠， 西死鼠， 人见死鼠如见虎。 鼠死不几日， 人死如圻堵。 InfluenzaSmallpoxExperiential Immunology periodVariolation（人痘苗）: 1670, Chinese medical practitioners Cowpox vaccination（牛痘苗）: 1796, Edward JennarLive-attenuated vaccines（减毒活疫苗技术）: 19 century Loius PasteurVariolation: 1670, Chinese medical practitioners Making childre

6、n resistant to smallpox by having them inhale powders made from the skin lesions of patients recovering from the disease.cowpox vaccination: 1796, Edward Jenner Injected the material from a cowpox pustule into the arm of an 8-year-old boy (vaccination) -Isolated and cultured bacteria successfully -I

7、nfectious diseases were caused by pathogens R. KochLive-attenuated vaccineAnti-cholera live-attenuated vaccineArtificial active immunityLouis Pasteur（18221895）Active immunity（主动免疫）: The form of adaptive immunity that is induced by exposure to a foreign antigen and in which the immunized individual p

8、lays an active role in responding to the antigen. Experimental Immunology periodAntigen and epitope（抗原与抗原表位）Antibodies and humoral immunity（抗体与体液免疫）T cells and Cellular immunity（ T细胞和细胞免疫）1. Antigen & antigenic epitope Antigen: substances that can induce a specific immune response and react with pro

9、ducts of immune response in vitro or in vivo specifically.20 century，Karl Landsteiner antigenic determinants/epitopesAntibody and passive immunity-Diphtheria (白喉）was caused by exotoxin produced by C.diphtheriae （白喉杆菌） -Roux and Yersin, in the late eighties of 19th century: the discovery of diphtheri

10、ae antitoxin and bactericindins Antitoxin-Antibody (Ab) Exotoxin-Antigen (Ag)2. Antibodies and humoral immunity-In 1890,Von Behring and Kitasato, diphtheriae antitoxin was applied in treatment of Diphtheria-Artificial passive immunity Passive immunity（被动免疫）: The form of immunity to an antigen that i

11、s established in one individual by transfer of antibody or lymphocytes from another individual who is immune to that antigen.Active immunity and passive immunity globulin : 1938，Tiselius and Kabat Abs produced by plasma cells: 1949，Astrid et al. Basic structure of Abs 1959, Rodney Porter和Gerald Edel

12、man Monoclonal antibodies 1975, Kohler and MilsteinGenetic control of antibody diversity 1978, Tonegawa，cloned V and C region of Ig, molecular immunology3. T lymphocytes and cellular immunity 1942, Chase, effector T cells1962, Warner and Szenberg, transplantation rejection 1970s, T cells subset: Th1

13、, Th2, Treg, Th171984, T cell receptor: Mark Davis and Chien Satio, cloned genes encoding TCRStudy on immune systemIn 1957,Glick Fabricius and Xianguang Zhang-Chicken without bursa can not produce Ab -B cellIn 1961,Good and Miller -cell mediated immunity of new born mice whose thymus were taken away

14、 are defective-T cell Modern Immunology periodImmune organsImmune cells： T cellcellular immunity B cellhumoral immunity NK cell DC Monocyte/MacrophageImmune molecules：antibody、complement、cytokines et al.2. Clonal selection theory (Burnet)There are various lymphocyte clones in our body, each of them

15、bears a unique type of Ag receptor which can recognize Ag specifically.The clones of lymphocytes that can recognize self-Ags will be destroyed or learn to tolerance to self Ags (forbidden clones) at the early stage of their development.Forbidden clones can be revival and cause autoimmunity.The clone

16、s of lymphocytes that can be interacted with corresponding Ag will be selected and lead to activation, proliferation , produce Ab and specific memory cells.3. Research on immune tolerance No positive response to specific AgIn 1945, Oven found natural immune toleranceIn 1953, Medawar and Burnet set u

17、p animal model of acquired immune tolerance in newborn period. cattle of dizygotic twin4. Study on molecular mechanisms of immune response BCR and TCRDiscovery of MHC5. Cytokines and cytokine receptors1980,s，cloned many genes encoding cytokines1990,s ，human genome project and BioinformaticsClinical

18、treatment with cytokines2011 Nobel Prize in Physiology/Medicine Bruce A. Beutler Jules A. Hoffmann Ralph M. Steinman Concept of Immunity1) Traditional concept- refers to protection against different types of pathogenic microorganisms.2) Modern concept- refers to the capacity of a individual to recog

19、nize and eliminate antigenic foreign substances. It is normally beneficial, but sometimes, it is injurious. Functions of ImmunityImmune defense: defense against infectious microbesImmune surveillance: eliminate transformed cells, dying cells Immune homeostasis: immune tolerance and immune regulation

20、Immune functionsNormal manifestationsAbnormal manifestationsImmune defenseResisting invasion of pathogens Neutrolizing toxins (Anti-infection)Hypersensitivity ImmunodeficiencyImmune homeostasisClearance of foreign substancesTolerance to self-componentsImmune dismodulationAutoimmune diseasesImmune su

21、rveillancedestroy transformed cells (anti-tumor) Prevent from persistent infection Tumor Persistent viral infectionFunctions and Manifestation of ImmunityTypes of ImmunityInnate Immunity (native immunity/non-specific immunity) Adaptive Immunity (acquired immunity/specific immunity) 1. Innate immunit

22、y ( natural immunity/ non-specific immunity )Innate immunity: Protection against infection that relies on mechanisms that exist before infection, are capable of a rapid response to microbes, and react in essentially the same way to repeated infections.Features of innate immunityExists naturally and

23、before birthBe the first line of defense against infection Nonspecific No immune memory (innate immunity cant be enhanced by the second stimulation of the same antigen) Immune memory: Exposure of the immune system to a foreign antigen enhances its ability to respond again to that antigen.Hereditable

24、 No racial differenceInnate immunityComposition BarriersPhysical barrier : skin and mucosaChemical barrier: antimicrobial substances in secretion of skin and mucosa Anatomic barrier . blood- brain barrier . blood- placental barrier . blood- thymus barrier Innate immunity Humoral components Complemen

25、t LysozymeCytokines Cells participating in innate immunity Phagocyte: endocytosis and phagocytosis mononuclear phagocytes -Monocytes, Macrophages (M )-PRR polynuclear phagocytes -NeutrophilsNature killer cells (NK)KAR/KIR, IgG Fc receptorDentritic cells (DC) T cellsB1 cellsOther cells participating

26、in innate immunityMacrophagesNeutrophilsDendritic Cell (DC)Natural Killer cell (NK cell)2. Adaptive immunity( acquired immunity/specific immunity)Adaptive immunity: The form of immunity that is mediated by T or B lymphocytes and stimulated by exposure to infectious agents.Take effect after innate immune responseBe the second line of defense against infectionTypes of adaptive immune responseCell-mediated immunity (CMI): T cellHumoral immunity(HI) or antibody-mediated immunity: B cell Adaptive immunityFeatures of adaptive immunity Specificity and diversityAcquired (set up after bi