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1、Introduction and History of Immunology Institute of immunology, ZJU Lecture 1n History of Immunologyn Immune systemn Innate immunityn Adaptive immunity Textbook:MedicalImmunology5thed（金伯泉）References:NaturalReviewofImmunologyAnnualReviewofImmunologyImmunityImmunity: refers to all mechanisms used by t
2、he 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
3、 by 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)P
4、asteurcalledtheattenuatedstrainas“Vaccine”.Thelatinword“vacca=cow”inhonorofJennerswork.Attenuatedvaccinesforcholera,anthrax,andrabiesOnJuly4,1886,9-year-oldJosephMeisterwasbittenrepeatedlybyarabiddog，Pasteurtreatedhimwithhisattenuatedrabiesvaccinetwodayslater.Meistersurvived.JosephMeisterlaterbecome
5、agatekeeperforthePasteurInstitute.In1940,whenhewasorderedbytheGermanoccupierstoopenPasteurscrypt,JosephMeisterrefusedandcommittedsuicide!RobertKoch(1843-1910)Germanphysician;alsostartedtoworkonAnthraxin1870s.Identifiedthesporestage.Firsttimethecausativeagentofaninfectiousdiseasewasidentified.Discove
6、redthetuberclebacillusandtuberculin.Detailedtuberculinskintest(DTH).Awarded1905NobelPrize.EmilAdolfvonBehring(18541917)AStudentofKochWithKitasatoandWernike,discoveredanti-toxinforDiphtheriaandTetanusandappliedastherapy.AwardedfirstNobelPrizeinphysiology,1901PaulEhrlich(18541915)Developedaseriesoftis
7、sue-stainingdyesincludingthatfortuberclebacillus.WorkedwithKoch.Developedanti-toxin(Diphtheria)andhemalysisSide-chaintheoryofantibodyformation:surfacereceptorsboundbylock&key;AgstimulatedreceptorsShared1908NobelPrizewithMetchnikoff.ElieMetchnikoff(1845-1916)Embryologiststudyingstarfishdevelopment.Fo
8、undphagocytosis.Phagocytesfromlarvastuckonthornfromatangerinetree.LaterhefoundafungalsporeattachedtoaphagocyteofDaphnia.Formedthebasisofleukocytephagocytosis.BirthofcellularimmunologySharedNobelPrizewithEhrlichin1908SirFrankMacfarlaneBurnet(1899-1985)Importantworkoninfluenza.Discoveryofaninfluenzavi
9、ralenzymewiththespecificityforparticularformsofneuramicacid.Usedtodayfordetection.Clonalselectiontheorytoexplaintolerance1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.GeraldM.Edel
10、man1929-RodneyR.Porter1917-19851972NobelPrizefortheirdiscoveriesconcerningthechemicalstructureofantibodies.BARUJBENACERRAFJEANDAUSSETGEORGED.SNELLDiscoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980NobleprizeNielsK.Jerne(1912-1994)Antibodyaviditymaturat
11、ionPlaqueformingassayPre-existingrepertoire(inhostDNA)theoryhelpedtheformationofclonalselectiontheory.HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.*IdiotypenetworkNobelPrize,1984,fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryofth
12、eprincipleforproductionofmonoclonalantibodies.Milstein(b.1927)andKhler(1946-1995)MonoclonalantibodySusumuTonegawa(b.1939)CloningoftheImmunoglobulingene1987Nobelprizeforhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity.PeterC.DohertyandRolfM.ZinkernagelTwosignals1996NobelPrizefortheir
13、discoveriesconcerningthespecificityofthecell-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
14、, mucociliary escalator,vomiting, flow of urine/tears, coughingCellularandhumoraldefenceslysosyme, sebaceous/mucous secretions,stomach acid, commensalorganisms,complement proteins,phagocytosis, NK cellsCellularandhumoraldefencesAntibodies, cytokines, T helper cells,cytotoxic T cellsImmuneresponsesBa
15、rriersInvasion&infectionInnateimmunityAdaptiveimmunityInflammationImmune Responses innate immune response natural immune response non-specific immune response adaptive immune response acquired immune response specific immune responseThe innate and adaptive immune responseCharacteristicsCellsMolecula
16、rsInnate immunityResponds rapidly No memoryPhagocytes (PMNs and macrophages)Natural killer cellsMaster cellsDendritic cellsCytokinesComplementAcute phase proteins Adaptive immunitySlow too startHighly specificMemoryT cellsB cellsDendritic cellsAntibodiesCytokinesinnate immune response Physiological
17、barriers skin mucous membranes Phagocytosis polymorphonuclear leukocytes(PMN) macrophages Natural killer(NK) cell cytokines and inflammationMacrophage attacking bacteria(Lung)MacrophageAttackingE.coliadaptive immune response The activation of lymphocytes antigen TCR(T cell receptor) BCR(B cell recep
18、tor) Proliferation and differentiation 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 an
19、tigens 2 take up,process and present antigenic 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
20、，兵工厂） of antibiotic protein granules:lysosomes;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 i
21、n the bone marrow. T lymphocytes develop in 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 ce
22、lls helper T cells,Th CMI,cell mediated immunityAntigen 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 receptorsCo
23、mponents of bloodTissues and organs of the immune systemPrimary 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 dev
24、elopment and maturation of B cells occur3. The lymphoid 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 th
25、ymocytes madulla-mature thymocytes M,TDC3.Function:It is 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 cord
26、s3.function:a reservoiv for platelets, erythrocytes and granulocytes; 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)
27、central medulla lymph nodeMucosal-associated lymphoid tissue(MALT)1.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
