BIO202 ImmuneDefensesPartIInnateDefenses VirusesandBacteria:AnIntroduction Virusesarenonlivingbiologicalagentsthatinvadecells Virusesconsistof o Anucleicacidcore EitherDNAorRNA o Acoatofproteinmoleculescalledthecapsid o Somemayhaveanadditionallipidenvelope Manybacteriaperformusefulfunctions,while otherscauseseriousdiseases(E.

ousdiseases(E.coli) Bacteriaareclassifiedlivingorganismsthat reproduceontheirownwithouttakingoverhost cells Bacteriaareprokaryotesanddonothaveanucleus GeneticmaterialconsistsofasingleDNA chromosome o Maycontainextrachromosomalplasmid DNA Bacteriatypicallydonotinvadecells Bacteriamayproducetoxins Bacteriarespondtoantibiotics;virusesdonot Immunity Resistancetodisease Immunesystemhastwointrinsicsystems o Innate(nonspecific)defensesystem o Adaptive(specific)defensesystem Antigens Substancesthattriggeranimmuneresponse Antigensareantibodygeneratingsubstances Largemolecularweightmolecules,particularlyproteins andpolysaccharides Smallmoleculesgenerallydonotgenerateanimmune response o Somemolecules(penicillin,formaldehyde,poisonivytoxin)willbindwithcellularproteinsformingunique (foreign)proteincomplexes Microbesandvirusescontainforeignproteinsandsugarsontheirsurfacesactasantigens Cellstransplantedfromonepersontoanotherelicitimmuneresponsesduetotheindividualcellularfingerprintof eachcell Cancercellsproduceslightlydifferentcellularfingerprints,causinganimmuneresponse

TheFirstLineofDefensePhysicalBarrier Thicklayerofepidermalcells Cellsareproducedfromthebaseoftheepidermisandcells moveoutward,becomeflattenedanddie Cellscontaintightjunctionsimpedemicrobialpenetration Deadcellscontainkeratinfairlywaterproof Passagespenetratingintotheinteriorofthebodyinclude: respiratory,digestive,andurinarytracts Thesepassagewayshaveepithelialliningswithcilia FirstLineofDefenseChemical Intheepitheliallinings o Mucus o Antibodies Digestiveenzymesintearsandsaliva(lysozyme) Stomachishighlyacidic UrinarytractismaintainedatalowpH SecondLineofDefenseInnateImmunity Combatsinfectiousagentsthatpenetratethefirstlineand consistsofcellularandchemicalresponses. Onceapathogenentersthebody,macrophagesengulfitand releasecytokinestoattractdendriticcells,neutrophils,andmoremacrophages Fourothernonspecificmechanismsinclude o Theinflammatoryresponse o Pyrogens o Interferons o Complement InflammatoryResponse Characterizedbyrednessandswelling Beginswiththereleaseofavarietyofchemicalsbytheinjuredtissues Somechemicalsattractmacrophages(tissues)andneutrophils(blood) Histamineisreleasedandstimulatesarteriolesintheinjuredtissuetodilate Thisincreaseinbloodflowisresponsiblefortheheatandredness o Heatincreasesthemetabolicratesofthecells,speedinghealing Plasmabringsoxygen,nutrients,andclotting factors o Resultsinswellingofaffectedtissues causingpain o Alsohelpstoimmobilizetheaffectedarea Prostaglandinsanotherpaincausingchemical o Aspirinworksbyinhibitingitssynthesis andrelease

 Pyrogens Moleculesreleasedprimarilybymacrophagesexposedtobacteria Theytraveltothehypothalamusandcauseanincreaseinbodytemperature Mildfevers o Causethespleenandlivertoremoveironfromtheblood o Increasescellularmetabolismspeedingcellulardefenses Highfever(over105F)candestroyourownproteins Interferons Agroupofproteinsreleasedbycellsinfectedby viruses, Theytraveltoothercells,wheretheytriggerthe synthesisofvariousantiviralproteins Interferonsdonotprotectcellsalreadyinfected withvirusestheyworkbystoppingthespreadof viruses Oncecellsareinfectedwithreplicatingvirusesthey killthemselvesthroughaprocessofprogrammed celldeath(apoptosis)

ComplementSystem Complementproteinscirculateinthebloodinaninactivestate Thebecomeactivatedonlywhenthebodyisinvadedbybacteria orothermicrobes Fiveproteinsinthecomplementsystemjointoformalarge proteincomplex,knownasthemembraneattackcomplex(MAC) Thiscompleximbedsintheplasmamembraneofthemicrobe creatinganopenchannelinwhichwaterflows Thiscausesthemicrobetoswellandburst ComplementSystem Otherfunctionsofthecomplementsystem o Stimulatethedilationandpermeabilityofbloodvessels o Actaschemicalattractantsformacrophages,monocytes, andneutrophils o Somecanbindtothesurfaceofmicroorganisms,formingaroughcoatwhichfacilitatestheirphagocytosis ThirdLineofDefenseTheImmuneSystem Designedtoeliminatevirusesandmicrobes Lymphocytescirculateinthebloodandlymphandtakeupresidenceinthelymphoidorgansandlymphoidtissues Adaptiveimmunityhasthreedefiningfeatures: o ItisspecificeachBandTcellonlyrecognizesoneantigen o ItisdiverseBandTcellscollectivelycanrecognizeatleastabilliondifferentthreats o Ithasmemory. Importantinthepreventionofemergingcancercells Antigensstimulatetwotypesoflymphocytes: o Tlymphocytes(Tcells) o Blymphocytes(Bcells) Asarule,Bcellsrecognizeandreacttomicroorganismssuchasbacteriaandbacterialtoxins,andafewviruses o Generallythoseorganisms/antigenscirculatingintheblood Onceactivated,Bcellsproduceantibodies Tcellsrecognizevirusinfectedcellsandourowncellsthathavechangedtheircellularfingerprint Canbeduetocancer,transplantedcells,virusinfection Tcellsalsorespondtolargerdiseaseorganismsfungiandparasites UnlikeBcells,Tcellsattacktheirtargetsdirectly

Immunocompetence Lymphocytesproducedinthebone marrowarereleasedintothe bloodstream TCells o ImmatureTcellswilleventually maketheirwaytothethymus, wheretheymatureinto functionalTcells Alymphoidorgan (gland)locatedabove theheart o FunctionalTcellshave developedtheabilityto recognizeaspecificantigen BCells o Bcellsmatureanddifferentiate inthebonemarrow o EachBcellrecognizesaspecific antigen Oncemature,bothBandTcellscirculateinthebloodandlymphlookingfortheirspecificantigen ImmuneDefensesPartIIAdaptiveImmuneResponse Red blood cells Platelets MHCProteins Monocytes, others ClassesofMHCproteins o ClassIMHCproteins,foundonvirtuallyallbodycells o ClassIIMHCproteins,foundoncertaincellsintheimmuneresponse MHCproteinsdisplaypeptides(usuallyselfantigens) Ininfectedcells,MHCproteinsdisplayfragmentsofforeignantigens,which helpmobilize B cells

Bone marrow Stem cells

Thymus

T cells

Organs of lymphatic system Foreign invasion B cells T cells

Antibody-mediated immune response

Cell-mediated immune response

ImmuneDefenses BcellsandTcellsrespondtopathogensindifferentways. o Bcellsproduceantibodies(proteins)andareresponsibleforantibodymediatedimmunity o Tcellsdirectlyattackinvaders;theirresponseiscalledcellmediated immunity AntigenpresentingcellsintroduceantigenstoTcellsandBcells. o TcellsandBcellscanonlyseeantigensthathavebeenprocessedbyan antigenpresentingcell(APC) Macrophages,dendriticcells,andBcellscanallpresentantigen Theantigenisingestedanddigested;thenitsfragmentsdisplayed onthecellssurface BCellsandAntibodies AntibodiesdevelopwhileBcellsareinbonemarrow o Theyareaclassofproteinsknownasimmunoglobulins o AnantibodyhasaYshapedproteinstructure;antigens areboundbythetwoarmsoftheantibody. o NotwoBcellsmakeantibodiesthatarealike;thisallows bothdiversityandspecificity. o Bcellsmakemanycopiesoftheirantibodies,whichare insertedintheplasmamembrane,armsstickingoutand readytobindantigen.

Antibodies Plasmacellscanreleaseupto2,000antibodiesperminuteintothebloodstream;theseantibodiesflaginvaders fordestructionbyphagocytesandcomplement. Antibodiesdestroyantigensinoneoffourways: o Neutralization Antibodiesbindtovirusesorbacteriaandcompletelycoatthem,preventingthemtobindingtoour cells o Agglutination Antibodiesbindnumerousantigens,causingthemtoclumptogether o Precipitation Antibodiesbindtosolubleantigens,forminglarger,waterinsolublemolecules o Activationofthecomplementsystem

Tcells Tcellsattackforeigncellsdirectly Tcellsdifferentiateintoatleastfourcelltypes,eachwithaseparatefunctionincellmediatedimmunity o CytotoxicTcells Destroycellsinfectedwithviruses Attackandkillbacteria,fungi,parasitesandcancercells o HelperTcells CoordinatetheattackofbothBandTcells ProducefactorsthatstimulateBcellproliferationandantibodyproduction EnhancetheactivityofCytotoxicTcells o MemoryTcells Remaininthebodyawaitingreintroductionofpreviouslyintroducedantigen o SuppressorTcells Inhibittheimmuneresponse

 ImmuneDefensesPartIIIImmunity Immunity Twotypesofimmunityarepossible o Active Causesanactiveimmuneresponse, producingBandTcells Vaccinescontainingadeador weakenedvirus, bacterium,orbacterialtoxin Generallylonglastingdueto memoryimmunecells o Passive Immunecellsarenotactivated Canbeachievedbyinjecting antibodiesintoapatient Bythetransferofantibodiesfroma mothertoherbaby Generallyshortlived ImmunologicalMemory Memorycellsformduringtheprimary(first) responsetoanantigenandremaininthebloodfor yearsordecades Secondaryresponsestothesameantigenaremuch faster;plasmacellsandeffectorTcellsformsooner andingreaternumbers,preventinginfection

Allergies Anallergyisanimmuneresponsetoanormallyharmlesssubstancecalledanallergen o Allergensinclude:pollen,somefoodsanddrugs,dustmites,fungalspores,insectvenom,andcertain ingredientsincosmetics o Allergenstriggermildtosevereinflammationofvarioustissues AllergiesarecausedbyIgEantibodies,producedbyplasmacells IgEantibodiesbindtomastcells,whichcausesthemtoreleasehistamineandotherchemicalsubstancesthatinduce thesymptomsofanallergyproductionofmucus,sneezing,anditching. TissueRejection ThiscanoccurwhencytotoxicTcellsrespondtotissuethatisnotrecognizedasselftissue Thiscanbecontrolledbygivingpatientsimmunosuppressivedrugsandbytransplantingorgansthathavethesame MHCproteinsinthedonorandrecipient Currentlywearetryingtogroworgansinthelabthatcanbetransplantedwithlessrejection DisordersoftheImmuneSystem Autoimmunediseases: o AdiseaseinwhichcytotoxicTcellsorantibodiesattackthebodysowncellsasiftheywereforeign o Examples:multiplesclerosis,lupus,myastheniagravisandrheumatoidarthritis Immunodeficiencydisease: o Adiseaseinwhichtheimmunesystemiscompromisedandthusunabletodefendthebodyagainstdisease o Examples:AIDSandSCID