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Download 17 Specific Immune Response
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Physiology Unit3 ADAPTIVEIMMUNITY TheSpecificImmuneResponse InPhysiologyToday TheAdaptiveArmoftheImmune System • SpecificImmuneResponse • Internaldefenseagainstaspecificpathogen • Acquiredasyouareexposedtodiseases – Theimmunesystem“learns” – Memorycellsremainforeverypathogenyourare exposedto • Myadaptiveimmunityisnotthesameas yours! TheAdaptiveArmoftheImmune System • Controlledbythelymphaticsystem • Acoordinatedmechanisminvolvingalink betweenAPC’sandlymphocytes – APC’sarenon-specific – Lymphocytesarespecific • Identifiesspecific foreignantigens Lymphocytes • Lymphocytesmustrecognizethespecificpathogentobe attacked • Anyantigenthatthehostimmunecelldoesnot recognizeasself – Lymphocytesrecognizeantigens • • • • • Proteinsorlargecarbohydrates Proteincoatsofvirions Antigensonforeigncells Cancercells Transplantedcells • Lymphocytetraffickingincreasesthelikelihoodthat theywillcontacttheirspecificantigen • Lymphocytesarecirculatingthroughlymph,lymphorgansandtheblood allthetime BLymphocytes • MatureinBonemarrow • B-cellactivationoccursinthespleenorlymph nodes • APC tohelperT-cells • Produceplasmacellswhichsecreteantibodies TLymphocytes • MigrateandmatureintheThymusgland – HelperTcells • Necessaryforamplificationoftheimmuneresponse • ActivateB-cellsandKillerT-cellsandotherHelperTcells – Killer(Cytotoxic)Tcells • Attackandkillyourowncellsthathavebecome cancerousorinfectedordamaged RolesofLymphocytes StagesofSpecificImmuneResponse EncounterandRecognition • Encounterand recognitionofantigen bylymphocytes – – – Eachlymphocyteis specificforjustone typeofantigen ≈100milliondistinct antigenreceptors Progenyof lymphocytesarecalled clones StagesofSpecificImmuneResponse LymphocyteActivation • Lymphocyteactivation – Bindingofantigentoreceptoronlymphocyte – Triggersthelymphocytetoundergomultiple roundsofmitosistoproduceclones– clonal expansion – Somelymphocyteswillbeeffectorcellsandbe partoftheattackresponse – Somelymphocyteswillbesetasideasmemory cells forquickersubsequentresponsesinthe future StagesofSpecificImmuneResponse TheAttack • Theattacklaunchedagainstspecificantigenbythe activatedlymphocytes u ActivatedBcellsdifferentiateintoplasmacellsand secreteantibodiesintotheblood(butthemselves remaininlymphnodesorspleen) u ActivatedKillerTcells directlyattackandkillcells u ActivatedHelperTcells releaseIL-2whichamplifythe immuneresponse • Plasmacells,helperTcells,killerTcellsthat participatedintheattackdiebyapoptosis – Preventstheimmuneresponsefrombecomingexcessiveand potentiallydestroyingitsowntissues The5classesofAntibodiesProduced ByPlasmaCells • Immunoglobulins • 5classesbasedonthe aminoacidsequenceof constantends • Classes – – – – – IgA IgD IgE IgG IgM IgA ImmunoglobulinA • Mucosalimmunity – Secretedbymucus membranesliningdigestive, respiratory,UGtractand prostate – Foundinbodysecretions • Breastmilk • Sweat • Tears – Providesprotectionagainst microbesthatmultiplyin mucussecretions IgD ImmunoglobulinD • Littleknownregarding function IgE ImmunoglobulinE • Defenseagainst multicellular parasites • Implicatedinallergic responses • Activatesmastcells and/orbasophilsto secretehistamine • Foundinlungs,skin, mucusmembranes IgG ImmunoglobulinG • Mostabundantantibodyin bloodandECF – Bindstomanykindsof pathogens(bacteria,virions, fungi) – Causesagglutination – Neutralizestoxins – Activatesthecomplement pathway – Opsonizationforphagocytosis – Directsmarkedvirionstothe proteosomes • Crossestheplacentafor fetalimmunity IgM ImmunoglobulinM • ProducedprimarilybyBcellsinthespleen • Foundinplasmaand lymph • ToolargetomoveintoECF • Mostabundantuponfirst exposuretoaninfection • Naturalantibody • Causesagglutination • Activatesthecomplement pathway FunctionofHelperTCells • HelperTCells – ExpressCD4 proteinsintheirplasmamembranes – AmplifytheresponseofB-cellsandotherhelper T-cells – Activatedbybindingtoantigen • Onceactivated,theHelperT-cellsecretesIL-2 • IL-2 isacytokine thatthatactsonB-cellsandother T-cells • B-cellscannotfunctionadequatelyunlessthey arestimulatedbyIL-2 FunctionofKillerTCells • CytotoxicTcells – ExpressCD8 proteinsintheirplasmamembranes – Musttravelthroughthebloodandlymphtoseek outtheirtargets – Attackanddirectlykillcellsbysecretingchemicals – Attackhostcells(yourowncells): • Cancercells – Anydamagedordysfunctionalcell • Infectedcells – Cellsinfectedwithanypathogen CDClassificationofTCells • CDproteinsareinthe plasmamembraneof Tcells • CD4: – HelperTcells – Macrophages • CD8: – CytotoxicTcells • CD4populations decimatedbyHIV BCellReceptors • ThereceptoronBcells foritsspecificantigenis theantibodyitsecretes • Constantends • Determineantibodyclass • IgA,IgD,IgE,IgG,IgM • Bindtomacrophage • Variableends • Bindantigens • A nearinfinitevariety! TCellReceptors • Tcellreceptorsforantigensareintegral membraneproteins – StayboundtothemembraneofTcells • Tcellreceptorscannotbindantigenunless theantigenisfirstcomplexedwithMHC proteins – 2classesof“self” plasmamembraneproteins • Tcellreceptorthencombineswiththeentire complexofantigenandMHCprotein MHCProteins • Differentfrompersonto person • ActascellularIDtags– markersofbiologicalself • BindingtoMHCproteins – ClassIMHCproteins – BindtotheCD8proteinon killerTcells – ClassIIMHCproteins – BindtotheCD4proteinon helperTcells •A group of proteins: the major histocompatibility complex are called MHC proteins •Also called human leukocyteassociated antigens or HLA antigens AntigenPresentingCells(APC) • Tcellscanbindantigenonly whentheantigen appearsontheplasmamembraneofahost cellcomplexedwiththeMHCproteins • Hostcellsbearingthesecomplexesarecalled antigenpresentingcells(APC’s) – Macrophage – Dendriticcells – B-Cells • ProducetheMHCClass2proteins PresentationtoHelperTcells 1. Afteranantigenhasbeenphagocytizedbyan APC(non-specificresponse) itisbrokendown intosmallerpeptides 2. Thedigestedepitopes (fragments)bindtothe MHCClass2proteinswithinanendosomeof theAPC 3. Theepitope-MHCcomplexistransportedto thecellssurfaceanddisplayedintheplasma membrane DendriticCells • Mostlikelyderivedfrom monocytes • Madeinbonemarrow • Foundintissuesincontact withtheoutsideworld – Skin – Liningsof: • • • • Nose Lungs Stomach Intestines • Migratetolymphnodesand thespleentopresenttoTCells AntigenPresentationtoHelperTCells Lymphokines • APCbindingtothe helperTcelltriggersthe APC tosecretelarge amountsof lymphokines 1. IL-1 andtumornecrosis factor(TNF)secreted byAPCs 2. StimulatehelperTcells tosecreteIL-2 3. IL-2 activatesmore T-cellsandB-cells PresentationtoCytotoxicTcells • Anyhostcellcanactasan APCtoacytotoxicTcell 1. 2. 3. Anyhostcellthatis cancerous Anyhostcellthathas becomeinfected Anyhostcellthathasbeen damaged • APCsforCytotoxicTcells expresstheMHCClass1 protein • Hostcellssynthesizethe antigenthatcomplexeswith theMHCClass1protein Perforin • ActivatedKillerTcells secreteperforin • Perforincausesholes (perforations)toorm in thecellmembrane • Celldestructionresultsin thereleaseofvirions into theECFwheretheycan bedirectlyneutralizedby antibodies Antibody-MediatedResponse HumoralResponse • Humoralresponsesarethemajordefensesagainst – – – – Bacteriaintheextracellularfluid Virionsintheextracellularfluid Othermicroorganismsintheextracellularfluid Toxinsintheextracellularfluid • Onceboundtoanantibody,antigencannot infect otherbodycellsorreproduce – Becomesimmobilizedandistaggedfordestruction Antibody-MediatedResponse HumoralResponse • Communicationbyantibodiesintheblood andlymphwithotherimmunecells • Antibodiesinactivateantigensinplasma • Antibodiesbindtobacteriaforcomplement activation • Antibodiesrecruitandguideothercellsto performtheattack – Phagocyticcells AntibodiesAllowPhagocytestoBindto Pathogens ActiveImmunity • Immunitydevelopsovertime asaresultofthebody’s contactwithantigens • CausesBcellstosecretethe antibodiesfortheantigen • MemoryCells providelong lastingimmunity • NaturalActiveImmunity – Occurswhenyouarenaturally exposedtoantigen • AcquiredActiveImmunity HepA, TDAP vaccines – Occurswhenyouareinjected withtheantigen PassiveImmunity • Youreceivepreformedantibodies • Providesinstant,temporaryimmunity • Natural PassiveImmunity – Maternaltransferofantibodiestobaby – Breastfeeding(IgA) – Transplacentaltransfer(IgG) • Acquired PassiveImmunity – Occurswhenyoureceivepreformedantibodies(IgG) inaninjection • HepB,Rabies,Tetanus,Varicella-Zoster (chickenpox,shingles)vaccines AcutePhaseResponse • Manysystemicresponsestoinfection • Initiatedbylymphokines releasedby monocytesandmacrophage • IL-1,IL-6,TNF • Stimulatesactionsofthe • • • • • Brain,hypothalamus Liver Bonemarrow Adipocytes Muscle AcutePhaseResponse DisordersoftheImmuneSystem Immunodeficiency • Immunodeficiency • Maybecausedbyaging,stress,orviral infection • Mayleadto“opportunistic” diseasesor cancer(pneumonia,bronchitis) • Manifestedbyafailureoftheimmunesystem toprotectfromthesediseases DisordersoftheImmuneSystem Autoimmunedisorder • Autoimmunity – animmuneresponseismountedagainst“self” antigens • Hostantigensthataretransformedor previouslyhidden • Include – DiabetesmellitusTypeI – SystemicLupus – RheumatoidArthritis Hypersensitivities • Immuneresponsestoenvironmentalagents causeinflammation • Immediatehypersensitivities(allergies) – Antibody(IgE)productionandmastcellsecretionof histamine – Hayfever,allergies,penicillin,beesting • Delayedhypersensitivities – – – – Overstimulationoflymphocytesandmacrophages Take2-3daystodevelop Chronicinflammationandcytokinerelease Againsttuberculin,transplantrejection
