《遗传学概论》PPT课件教案资料.ppt

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1、遗传学概论遗传学概论PPTPPT课件课件 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 by the body as protection against environmental agents t

2、hat 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 by the Chinese in the 1200 a technique called variolation

3、 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)Pasteurcalledtheattenuatedstrainas“Vaccine”.Thelatinword“vacca=c

4、ow”inhonorofJennerswork.Attenuatedvaccinesforcholera,anthrax,andrabiesOnJuly4,1886,9-year-oldJosephMeisterwasbittenrepeatedlybyarabiddog，Pasteurtreatedhimwithhisattenuatedrabiesvaccinetwodayslater.Meistersurvived.JosephMeisterlaterbecomeagatekeeperforthePasteurInstitute.In1940,whenhewasorderedbytheG

5、ermanoccupierstoopenPasteurscrypt,JosephMeisterrefusedandcommittedsuicide!RobertKoch(1843-1910)Germanphysician;alsostartedtoworkonAnthraxin1870s.Identifiedthesporestage.Firsttimethecausativeagentofaninfectiousdiseasewasidentified.Discoveredthetuberclebacillusandtuberculin.Detailedtuberculinskintest(

6、DTH).Awarded1905NobelPrize.EmilAdolfvonBehring(18541917)AStudentofKochWithKitasatoandWernike,discoveredanti-toxinforDiphtheriaandTetanusandappliedastherapy.AwardedfirstNobelPrizeinphysiology,1901PaulEhrlich(18541915)Developedaseriesoftissue-stainingdyesincludingthatfortuberclebacillus.WorkedwithKoch

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

8、ee.LaterhefoundafungalsporeattachedtoaphagocyteofDaphnia.Formedthebasisofleukocytephagocytosis.BirthofcellularimmunologySharedNobelPrizewithEhrlichin1908SirFrankMacfarlaneBurnet(1899-1985)Importantworkoninfluenza.Discoveryofaninfluenzaviralenzymewiththespecificityforparticularformsofneuramicacid.Use

9、dtodayfordetection.Clonalselectiontheorytoexplaintolerance1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.GeraldM.Edelman1929-RodneyR.Porter1917-19851972NobelPrizefortheirdiscoverie

10、sconcerningthechemicalstructureofantibodies.BARUJBENACERRAFJEANDAUSSETGEORGED.SNELLDiscoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980NobleprizeNielsK.Jerne(1912-1994)AntibodyaviditymaturationPlaqueformingassayPre-existingrepertoire(inhostDNA)theoryhel

11、pedtheformationofclonalselectiontheory.HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.*IdiotypenetworkNobelPrize,1984,fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryoftheprincipleforproductionofmonoclonalantibodies.Milstein(b.1927)a

12、ndKhler(1946-1995)MonoclonalantibodySusumuTonegawa(b.1939)CloningoftheImmunoglobulingene1987Nobelprizeforhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity.PeterC.DohertyandRolfM.ZinkernagelTwosignals1996NobelPrizefortheirdiscoveriesconcerningthespecificityofthecell-mediatedimmunedefe

13、nse.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,mucociliary escalator,vomiting,flow of urine/tears,coughingCell

14、ularandhumoraldefenceslysosyme,sebaceous/mucous secretions,stomach acid,commensalorganisms,complement proteins,phagocytosis,NK cellsCellularandhumoraldefencesAntibodies,cytokines,T helper cells,cytotoxic T cellsImmuneresponsesBarriersInvasion&infectionInnateimmunityAdaptiveimmunityInflammationImmune

15、 Responses innate immune response natural immune response non-specific immune response adaptive immune response acquired immune response specific immune responseThe innate and adaptive immune responseCharacteristicsCellsMolecularsInnateimmunityRespondsrapidlyNomemoryPhagocytes(PMNsandmacrophages)Nat

16、uralkillercellsMastercellsDendriticcellsCytokinesComplementAcutephaseproteinsAdaptiveimmunitySlowtoostartHighlyspecificMemoryTcellsBcellsDendriticcellsAntibodiesCytokinesinnate immune response Physiological barriers skin mucous membranes Phagocytosis polymorphonuclear leukocytes(PMN)macrophages Natu

17、ral 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 of lymphocytes B cell-cytokines T cell-Antigen-TCR;co-s

18、timulatory 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 antigenic peptides to T cells distribution:Kupffer cells i

19、n 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:lysosomes;lactoferrin;lysozymeNeutrophilLymphocytes1.Lymphoc

20、ytes 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 the thymus.B Lymphocytes BCR:a surface receptor specifi

21、c 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 immunityAntigen presenting cells Macrophage:antigen processing h

22、igh 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 systemPrimary lymphoid organs the bone marrow the thymus

23、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 lymphoid progenitor cells are transported by circulating bloo

24、d 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 is the site of T cell maturation;It determines the specif

25、icity 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 granulocytes;destroy the Ag,aged platelets spleenDownloaded

26、 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.non-encapsulated lymphoid tissue2.in the lamina propria

27、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结束结束