《遗传学概论》PPT课件.ppt

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1、Introduction and History of Immunology Institute of immunology,ZJU Lecture 1 History of Immunology Immune system Innate immunity Adaptive immunity Text book:Medical Immunology 5th ed（金伯泉）References:Natural Review of ImmunologyAnnual Review of ImmunologyImmunityImmunity:refers to all mechanisms used

2、by the body as protection against environmental agents that are foreign to the body.The term“immunity”was first used in 1775 by Van Sweiten,a Dutch physician,as“immunitas”to describe the effects induced by an early attempt at variolization.Variolation To induce immunity deliberately were performed b

3、y the Chinese in the 1200 a technique called variolation Edward Jenner an English country doctor in 1798,took the scrab from Sarah Nelmes,a milkmaids and inserted into arm of James Phipps,a 8-year old boy.Eight weeks later,James was challenged with the deadly smallpox.LouisPasteur(1822-1895)Pasteurc

4、alledtheattenuatedstrainas“Vaccine”.Thelatinword“vacca=cow”inhonorofJennerswork.Attenuatedvaccinesforcholera,anthrax,andrabiesOnJuly4,1886,9-year-oldJosephMeisterwasbittenrepeatedlybyarabiddog，Pasteurtreatedhimwithhisattenuatedrabiesvaccinetwodayslater.Meistersurvived.JosephMeisterlaterbecomeagateke

5、eperforthePasteurInstitute.In1940,whenhewasorderedbytheGermanoccupierstoopenPasteurscrypt,JosephMeisterrefusedandcommittedsuicide!RobertKoch(1843-1910)Germanphysician;alsostartedtoworkonAnthraxin1870s.Identifiedthesporestage.Firsttimethecausativeagentofaninfectiousdiseasewasidentified.Discoveredthet

6、uberclebacillusandtuberculin.Detailedtuberculinskintest(DTH).Awarded1905NobelPrize.EmilAdolfvonBehring(18541917)AStudentofKochWithKitasatoandWernike,discoveredanti-toxinforDiphtheriaandTetanusandappliedastherapy.AwardedfirstNobelPrizeinphysiology,1901PaulEhrlich(18541915)Developedaseriesoftissue-sta

7、iningdyesincludingthatfortuberclebacillus.WorkedwithKoch.Developedanti-toxin(Diphtheria)andhemalysisSide-chaintheoryofantibodyformation:surfacereceptorsboundbylock&key;AgstimulatedreceptorsShared1908NobelPrizewithMetchnikoff.ElieMetchnikoff(1845-1916)Embryologiststudyingstarfishdevelopment.Foundphag

8、ocytosis.Phagocytesfromlarvastuckonthornfromatangerinetree.LaterhefoundafungalsporeattachedtoaphagocyteofDaphnia.Formedthebasisofleukocytephagocytosis.BirthofcellularimmunologySharedNobelPrizewithEhrlichin1908SirFrankMacfarlaneBurnet(1899-1985)Importantworkoninfluenza.Discoveryofaninfluenzaviralenzy

9、mewiththespecificityforparticularformsofneuramicacid.Usedtodayfordetection.Clonalselectiontheorytoexplaintolerance1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.GeraldM.Edelman1929

10、-RodneyR.Porter1917-19851972NobelPrizefortheirdiscoveriesconcerningthechemicalstructureofantibodies.BARUJBENACERRAFJEANDAUSSETGEORGED.SNELLDiscoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980NobleprizeNielsK.Jerne(1912-1994)AntibodyaviditymaturationPlaq

11、ueformingassayPre-existingrepertoire(inhostDNA)theoryhelpedtheformationofclonalselectiontheory.HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.*IdiotypenetworkNobelPrize,1984,fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryoftheprinci

12、pleforproductionofmonoclonalantibodies.Milstein(b.1927)andKhler(1946-1995)MonoclonalantibodySusumuTonegawa(b.1939)CloningoftheImmunoglobulingene1987Nobelprizeforhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity.PeterC.DohertyandRolfM.ZinkernagelTwosignals1996NobelPrizefortheirdiscove

13、riesconcerningthespecificityofthecell-mediatedimmunedefense.Why we need to study immunology?New emerging diseases are close to usResurrection of 1918 Flu From Sequenced FragmentsHIV and AIDSAutoimmunityAllergyGraftrejectionSkin&Mucousmembranesrapidly regenerating surfaces,peristalticmovement,mucocil

14、iary escalator,vomiting,flow of urine/tears,coughingCellularandhumoraldefenceslysosyme,sebaceous/mucous secretions,stomach acid,commensalorganisms,complement proteins,phagocytosis,NK cellsCellularandhumoraldefencesAntibodies,cytokines,T helper cells,cytotoxic T cellsImmuneresponsesBarriersInvasion&i

15、nfectionInnateimmunityAdaptiveimmunityInflammationImmune Responses innate immune response natural immune response non-specific immune response adaptive immune response acquired immune response specific immune responseThe innate and adaptive immune responseCharacteristicsCellsMolecularsInnateimmunity

16、RespondsrapidlyNomemoryPhagocytes(PMNsandmacrophages)NaturalkillercellsMastercellsDendriticcellsCytokinesComplementAcutephaseproteinsAdaptiveimmunitySlowtoostartHighlyspecificMemoryTcellsBcellsDendriticcellsAntibodiesCytokinesinnate immune response Physiological barriers skin mucous membranes Phagoc

17、ytosis polymorphonuclear leukocytes(PMN)macrophages Natural killer(NK)cell cytokines and inflammationMacrophage attacking bacteria(Lung)Macrophage Attacking E.coli adaptive immune response The activation of lymphocytes antigen TCR(T cell receptor)BCR(B cell receptor)Proliferation and differentiation

18、 of lymphocytes B cell-cytokines T cell-Antigen-TCR;co-stimulatory signal Effective cell B cell-Antibody;T cell-CTL Memory celladaptive immune responseadaptive immune responseImmune ResponsePhagocytic cellsMonocytes/Macrophages functions:1 remove particulate antigens 2 take up,process and present an

19、tigenic peptides to T cells distribution:Kupffer cells in the liver microglial cells in the brainPhagocytic cellsmonocytePhagocytic cellsNeutrophils 1.neutrophils are short-lived phagocytic cells multilobed nucleus;10-20m 2.neutrophils have a large arsenal（军火库，兵工厂）of antibiotic protein granules:lyso

20、somes;lactoferrin;lysozymeNeutrophilLymphocytes1.Lymphocytes are wholly完全的 responsible for the specific immune recognition of pathogens,so they initiate adaptive immune responses.2.Lymphocytes are derived from bone-marrow stem cells.3.B lymphocytes develop in the bone marrow.T lymphocytes develop in

21、 the thymus.B Lymphocytes BCR:a surface receptor specific for a particular antigen B cells antigen plasma cells secrete antibody humoral immunity B LymphocytesT Lymphocytes TCR:T-cell antigen receptor TCR+95%TCR+15%CTL,cytotoxic T cells regulatory T cells helper T cells,Th CMI,cell mediated immunity

22、Antigen presenting cells Macrophage:antigen processing high antigen presenting lowDentritic cell(DC):antigen presenting highAntigen presenting cellsNatural killer cells(NK)15%of blood lymphocytes express neither T-cell nor B-cell antigen receptorsComponents of bloodTissues and organs of the immune s

23、ystemPrimary lymphoid organs the bone marrow the thymus glandSecondary lymphoid organs the spleen lymph nodes Mucosal-associated lymphoid tissueFunctions of lymphoid organs 1.the place in which proliferation of HSC take place2.the place in which development and maturation of B cells occur3.The lymph

24、oid progenitor cells are transported by circulating blood to the thymus and differentiate into fuctional T lymphocytesBone marrow Thymus 1.Cells:thymic stromal cells(TSC)thymocytes T cell (+)monocytes,macrophage,TDC2.Structure:cortex-immature thymocytes madulla-mature thymocytes M,TDC3.Function:It i

25、s the site of T cell maturation;It determines the specificity of the TCR expressed on the T cells released to periphery thymus gland spleen1.adult spleen:13*8cm 180-250g2.the white pulp:lymphoid cells the red pulp venous sinuses cellular cords3.function:a reservoiv for platelets,erythrocytes and gra

26、nulocytes;destroy the Ag,aged platelets spleenDownloaded from:StudentConsult(on 1 June 2006 02:08 PM)2005 Elsevier lymph node1.Human:2-10mm in diameter2.round and kidney shaped3.Consists of:B-cell area(cortex)T-cell area(paracortex)central medulla lymph nodeMucosal-associated lymphoid tissue(MALT)1.

27、non-encapsulated lymphoid tissue2.in the lamina propria and submucosal areas of the gastrointestinal,respiratory and genitourinary tracts.3.tonsil,appendix,Peyers patches4.B cell IgA IEL Adaptive immuneMucosal-associated lymphoid tissue(MALT)Peyers patchesM cellLymphocyte recirculation1.Lymphocytes leave the blood via high-walled endothelium of the post-capillary venules2.Lymphocyte trafficking exposes antigen to a large number of lymphocytes Lymphocyte recirculation