淋巴系統(tǒng)與免疫備課講稿

淋巴系統(tǒng)與免疫OrganizationandFunctionsoftheLymphaticSystemInthelymphaticsystemthereare:Lymphaticfluid,lymph,thatcontainslymphocytesVesselsthattransportlymphAndsiteswherelargecontentsoflymphocytesareheld:lymphnodes,spleen,andthymus.FunctionsofthelymphaticsystemThelymphsystemhasthreemajorfunctions:1.FluidBalance.Circulatingbloodreleaseabout30Loffluidintointerstitialspaceeachday.Ofthe27Larereturnedtothecirculation.Theremaining3Lwillenterthelymphaticsystemaslymph.Thelymphpassesthroughthelymphaticsystemandenterbacktothebloodvessels.Inadditiontowater,lymphcontainssubstancesasinplasmaandsubstancesextractedfromcells.2.FatAbsorption.Fatsandothersubstancesareabsorbedfromthedigestivetractandcarriedthroughthelymphaticsystem.3.Defense.Immunesystem(lymphocytes,B-cells,T-cells)LymphaticVesselsLymphaticvesselsarespreadoutthroughoutthebodyexceptintheCNS(Fig22.1)Theyoriginatefromwithinlymphocyteproducingorgansandemptyintothethoracicduct.Theycontainmanylymphaticnodesandnodules.Likebloodvessels,theyhavesmallvesselscalledlymphaticcapillarieswhichlayclosetothebloodcapillaries.Lymphsolublefluidwillbepickedupthroughthecapillariesandpushedbacktolargertruck.Theyevenhavevalvestocontroltheflowoflymphthroughverylowpressureoffluid.LymphaticOrgansDiffuselymphatictissueDispersedlymphocytes,macrophagesandothercells.Noclearboundaries.(Fig.22.2)LymphoidNodulesPackedwithlymphocytes.FlexibleinsizedependinguponthenumberoflymphocytesSpreadinlooseC.T.ofthedigestive,respiratoryandurinarysystems.LargerpatchesinintestinalsystemcallPeyer’spatches.Inlymphnodestheyarecalledfollicles,theretheycontainagerminalcenter,wherelymphocytesdivide.Thoughfilledwithlymphocytes,lymphoidnodulescouldbeinfected:tonsillitis,appendicitis.Tonsils

Largegroupsoflymphnodulesanddiffuselymphatictissuelocatedintheoralcavity(Fig.22.3)Protectionagainstbacteria,etc..Inthenoseandmouth.Threetypesoftonsils:pharyngeal,palatine,andlingualEnlargedpharyngealtonsiliscalledadenoid.LymphNodes(Fig.22.1andFig.22.4)Foundthroughoutthebodyexceptinthebrain.Theyareencapsulationoflymphocytes,macrophagesandreticularcellswithbloodvessels1-25mmindiameterandaresubdividedintotworegionscalled,amedullaandcortex.Withinthecortexgerminalcentersarefound.Thisiswherelymphocytedivisiontakesplace.Actassieveandremovalof99%ofantigenswhilereactivatingT-cellsandB-cells.TheSpleenUpperandposteriorpartoftheabdominalcavity.Largestofthelymphatictissue,160g.(Fig.22.5)Containstwotypesoflymphatictissue:whitepulp(arterialsupply)andredpulp(venoussupply).Thespleendetectsandrespondstoforeignsubstancesintheblood,destroysworn-outRBC’sandactsasabloodreservoir.ThymusGlandOntopoftheheartT-cellsmaturehereBecomeslargeduringthefirstorsecondyear.Intrinsicsizeislargestatpubertyandthendecreases.Produceslymphocyteswhichthenmovetootherlymphatictissues.Blood-thymicbarrier-reticularcellswraparoundcapillariesandpreventlargemoleculesfromenteringthecortexofthethymus.ImmunityHowthehumanbodydefendsitselfagainstdamagefromforeignsubstancessuchasmicroorganismsandharmfulchemicalastoxins.Innate(non-specific)andadaptive(specific)immunity.Thesetwotypesaredistinguishedbythewaytheyrespondtospecificstimulationsandhowtheymemorizetheevents.Specificity.Innateimmunitycanactagainstbacteriaingenera.(nomemory)Memory.Adaptiveimmunitycandistinguishamongdifferentkindsofbacteriaandgenerallygetmoresensitivewitheachnewencounter.InnateImmunityMechanicalMechanismPhysicalbarriers,suchastheskinandmembranesChemicalMediators(Table22.1)Moleculeswhichcontributetodevelopimmunity.Killbacteria:lysozymeandsebummucusOthers:histamineandkininsbyvasodilation;interferonproduction,etc..ComplementIsagroupofapproximately20proteinsthatmakesupapproximately10%oftheglobulinpartofserum.Theyareagroupofproteinsactivatedintheformofacascadeandprovideprotectionbyattackingthebacterialmembrane.Theyattachtoandformholesinthemembranes.Theproteinscanalsoattachtobacteriamembraneandstimulatemacrophagestophagocytizethebacteria.Interferons:proteinsthatprotectthebodyagainstviralinfectionandpossiblycancer.CellsforInnateImmunityReviewthemajorfunctionsof,neutrophils,monocytes,macrophages,basophils,mastcells,eosinophils,andnaturalkillercells.(Table22.2)InflammatoryResponseTissuedamagecausedbybacteriaorothersmayinduceinflammationoftissueasitreleaseshistamine,prostaglandins,kinins,etc…Vasodilationattractschemotaticphagocytesandotherleukocytestotheregionaswellasfibrinogentoformfibrininordertolocalizedamage.AdaptiveImmunitySubstancestostimulateadaptiveimmunityareantigens,ofwhichmoleculeweightscouldbeaslargeas10,000ormore.(produceantibodies)Haptensaresmallmoleculescapableofcombiningwithlargermoleculestostimulateadaptiveimmunityresponse.Twotypeofantigens:foreignantigens(allergen)arefromoutsideofthebody,andselfantigens(auto-immune)aremoleculesofitsownbody.Forexample.Allergicreactionisbyforeignantigens,whileautoimmunediseaseisfromselfantigens.Immunityhasbeendividedintotwotypes:humoral(bodyfluid)immunityandcellmediatedimmunity.Specificity:recognitionofantigenThespecificityisestablishedbecauseofthespecificreceptorslocatedonthesurfaceofTandBcells.Versatility:therearemanyantigens.Andtherearemanydifferentformsoflymphocytesthataremadeagainstthem.Memory:theadaptiveimmunesystemhasamemory.Withthepresenceoftheforeignbody,lymphocytesrespondingtoitbegintoinitiatecelldivisions.Thepresenceofantigenleadstotheformationofactiveandmemorycells.Theactivecellsrespondtoantigens,whilethememorycellswaituntilthenextonslaught.Inthismanner,thesecondresponsetothesameantigenwillbefast.Lymphocytes25%ofcirculatingwhitecells.Themajorityoflymphocytesareinperipheraltissues.TypesoflymphocytesWehavealreadyseenthattherearethreetypesoflymphocytes.(Fig.22.9)Tcells:80%ofcirculatinglymphocytes(cellmediatedimmunity)Bcells:10-15%,plasmacellsproduceantibodies(immunoglobulins)andreactantigenicpathogens.(antibody-mediatedimmunity)Naturalkillercell:theremainder:theyattackforeigncells,normalcellsinfectedwithvirusesandcancercells.Theyimmunologicallysurveyperipheraltissues.CytotoxicTcellsattackforeigncellsorcellsinfectedwithviruses.Providecell-mediatedimmunity.HelperTcellsstimulatetheactivitiesofTcellsandBcells.SuppressorTcellsinhibitTcellsandBcells.OriginanddevelopmentoflymphocytesLymphocytestravelaroundtheentirebodyandhavesignificantlylonglifespan.80%surviveupto4yearsandsometo20years.Aswehaveseen:lymphocytesaremadeintheredbonemarrowandsomecontinuetodevelopinthethymus.(Fig.22.9)Pre-Bcellsandpre-Tcellsareintheredbonemarrow.Pre-BcellsmatureintheredbonemarrowintoBcells.Tcellsmatureinthethymus.Apositiveselectionprocesskeepcellscapableofimmuneresponse.Thosewhichareincapablewilldie.EachgroupofBorTcellscapableofrespondingtoaspecificantigenisacloneEachcloneiscapableofrespondingtoaparticularantigenandtherearemanydifferentclones.Whentheclonesrespondtoself-antigens,negativeselectioneliminatessuchclones.Mostofthisprocessoccursduringprenataldevelopment,butcontinuesthroughoutlife.ActivationofLymphocyteLymphocytesaremadeinresponsetoaspecificantigenandinalargequantity.AntigenicDeterminantsandAntigensReceptorsAnantigenmayhavemanyantigenicdeterminants(epitopes)(Fig.22.10)towhichlymphocytescanrespond.Eachantigenicdeterminatecanactivateaspecificlymphocyte.Thusispossiblethatanantigenwithmanyepitopescanactivatemanydifferent(clones)lymphocytes.Eachlymphocytefromthesameclonewillhavethesameantigenreceptor.Forexample,atcellreceptorhasavariableandconstantregions.(Fig.22.11).Thevariableregionwillhavespecificantigenbindingsites.ThusacloneofTcellscanbindaspecificantigenicdeterminant.TheotherTcellswithinthesameclonecouldhavedifferentantigenbindingsites.TheB-cellreceptorissimilar,butlarger.MajorHistocompatibilityComplexAntigensSomearedirect,butmostlymphocyteactivationinvolvesglycoproteinsonthesurfaceofcellscalledMHCmolecules.AllcellmembraneshaveMHC>MHCclassImolecules

(Fig.22.12a)Onnucleatedcells,foreignorselfproteinsarefragmentedinthenucleatedcellsandbecomeantigens.TheycombinewithMHCclassImoleculeinthecellandthecomplexaretransportedonthesurfaceofthecell.Atthesurfaceofthecellmembrane,theforeignantigen/MHCIcomplexwillattractTcellsandthecellwillbedestroyed.(cellmediatedimmunity),whileselfantigen/MHCIwillnot.MHCclassIIMolecules

(Fig22.12b)ThemorecomplexandadvancedlymphocytesstimulationuseMHCIImolecules.Thesemoleculesarefoundinantigen-presentingcells,suchasBcells,macrophages,monocytesanddendriticcells.Antigen-presentingcellsphagocyticallyingestunprocessedantigens,processthemandletthemcombinewithMCHIImolecules.thecomplexwillbepresentedonthesurfaceofthecells.Theystimulatetheother(lymphocytes)immunecellstodivideandtocausethedestructionoftheantigen.CostimulationInadditiontotheinteractionbetweenthepresentedMHCII/antigenandantigenreceptor,costimulation,withcytokininsforexample,isneeded(Fig.2213a)Anothercostimulation(Fig.23.13b)isachievedcrosslinkingtwocellswithothermoleculessuchasCD4,B7,CD28,etc.OtherexampleofcytokininsarelistedinTable22.4.Noteinterferonsandinterleukins.HelperTCellsEnhancesmoreproductionofTandBcellsOnactivationhelperTcellsproduceavarietyofcytokinsthatcoordinatedspecificandnonspecificdefensesandstimulatecellmediatedimmunity.StudyFig.22.14and22.15tofindhowproliferationofhelperTcellcanbeachieved.Inshort,withthehelpofcytokinins,suchasinterleukins,thenumberofhelperTcellsincreaseandthusstimulateBcellsoreffectorTcells,whichreleaseperforin,producesholeininfectedcells.InhibitionoflymphocytesInhibitionoflymphocytesproliferationagainstitsownself-antigenisachievedbytolerance.Deletionofself-reactivelymphocytesDuringprenataldevelopmentwhenimmaturelymphocytesareexposedtotheselfantigens,theydie.Thus,nolymphocyteswhichrespondtotheselfantigenwillbefoundasthesubjectmatures.PreventingactivationoflymphocytesBylackofcostimulationActivationofsuppresserTcell.Thisisnotwellunderstood.ThesuppressorTcellsreleasesuppressivecytokins.Antibody-mediatedImmunityWhenexposedtoanantigen,thebodyactivatesBcellsandproducesantibodies.theantibodiesarefoundinbodyfluidsthusrespondtoextracellularantigens.AntibodiesAntibodiesareproducedinBcellsinresponsetoanantigenandarefoundinplasma.Plasmaproteinshavefourmajorcomponents:albumin,alpha,betaandgammaglobulins.Antibodiesarefoundingammaglobulinsgroup,thussometimesarecalledgammaglobulinsorimmunoglobulins(Ig).Therearefivetypes(Table22.5)IgG,IgM,IgA,IgE,andIgDTheyallconsistoffourpeptides.(Fig22.16)connectedwithdisulfidebondsandhaveaconstantregionandaantigenbindingvariableregion.Theconstantregionmayattachtocells,suchasmacrophages,basophils,etc..EffectsofAntibodiesThefunctionofantibodyistofindantigenanddestroyit.Neutralization,agglutinationandprecipitation,activationofcomplement.Attractionofphagocytes,enhancementofphagocytes,andstimulationofinflammation.Antibodiescancounteracttheactionofantigensinseveralways(Fig.22.17)Uponbindingwithanantigen,theantibodyinactivatestheantigen.Inactivationmayleadtoco-precipitationofantigenandantibodies.Bindingoftwomaystimulatephagocyticactivitiesandthereleaseofinflammationchemicals.AntibodyproductionTheprimaryResponseThefirstencounterwithanantigen,anBcelldividesanddifferentiateleadingtoantibodiesproduction(Fig.22.18a).Antibodies,IgMandIgD,areonthesurfaceofBcells.Bcells,whicharesmalllymphocytes,activatedbyantigenstartscelldivisions.Somebecomelargeplasmacells,whichproduceantibodiesandotherbecomesmallmemoryBcells.Theprimaryprocesstakes1-14days,theantigenmaycausetissuedamageduringthisperiod.Th