INNATEIMMUNITYNon-SpecificImmuneResponsePhysiologyUnit3

ProtectionAgainstInfection

• Thebodyhasseveraldefensestoprotectitselffromgettinganinfection• Skin• Mucusmembranes• Serousmembranes• Chemicals

• Ifapathogendoesbreachthebarriersattheentrancestothebody,thenyourimmunesystemisactivated• 2branchesofyourimmunesystem

• Innateimmunity(non-specificimmuneresponse)• Adaptiveimmunity(specificimmuneresponse)

DefensestoPreventInfectionPhysicalBarriers

• Skin• Watertightbarrier• Keptcleananddry• Sweatglandssecreteantibodies,lysozyme• Mostlyimpermeabletomicrobes

• Certainmicrobesdrillthrough(syphillis,hookworms,manyarthropodbornepathogens)

• Coughandsneezereflex• Hairsattheentranceofthenose

DefensestoPreventInfectionPhysicalBarriers

• Mucousmembranes• Non-keratinizedepithelialmembranes,oftenciliated• Linedwithmucus• Containantimicrobialchemicals• Excellentfortrappingmicrobesforexpulsion

DefensestoPreventInfectionPhysicalBarriers

• Serousmembranes• Lubricatedwithserumfrom“leakycapillaries”• Internalphysicalbarriertoinfectionofvitalorgans• Heart,lungs,andabdominalviscera• Similarprotectionbythemeningesofthebrainandspinalcord

DefensestoPreventInfectionNonspecificChemicalDefenses

• pHlevels• Gastricsecretions• Vaginalsecretions• Urine

• LowpHisdamagingtomostcells

• Lysozyme• Foundinbodysecretions:• Tears• Saliva• Sweat

• Foundingranulesofneutrophilsandmacrophages• Bindstomicrobesandperforatesthecellwall

ResponsetoInfectionImmuneSystem

• Thebodiesdefenseagainstinfectiousdisease• 2branchesofyourimmunesystem• InnateImmunity:

• Non-specificimmuneresponse• Encounterandrecognitionofantigen• Includesmultipletypesofimmunecells• Includesinflammatoryresponse

• AdaptiveImmunity:• SpecificImmuneresponse• ActivatedafterpresentationofantigenbyanAPC• Responseoflymphocytestospecificantigen

ResponsetoInfectionCellSignaling

• Immunecellssecretemorethan100differentcytokines• Cytokinesmediateeverystepoftheimmuneresponse• Allowcommunicationbetweendifferentimmunecellsandtimingofcascadereactions• Mostcytokineshavelocalactions• Paracrine/autocrineagents

• Somewillcirculateinbloodtodistanttissues• Hormones

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Diversecollectionofcellsthatarefoundinextracellularfluid• Plasma• Lymph• Interstitium

• Non-specificImmuneResponseCells• Neutrophils,eosinophils,basophils,monocytes• Macrophage• Dendriticcells• Mastcells• NKCells• **Bcells

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Leukocytes(WBC’s)• Neutrophils,eosinophils,basophils,monocytes• DifferentWBC’shavedifferentactions• Transportedinplasmaandmigrateintothetissueswheretheyfunction

DiapedesisandExtravasation

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Neutrophils• Voraciousphagocytes• Opsonify pathogens

• Uselysozymesandsuperoxide(reactiveO2 species)todissolvemicrobesingested• Granulescontainanti-microbialagents

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Neutrophils• FirstWBCataninfectionsitemediatedbychemicalmessengers• Chemotaxis• Endothelium,mastcells,macrophage

• Shortlived• 5-90hoursincirculation• 1-2daysintissue

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Eosinophils• Slightlyphagocytic• Majorroleininfectionsinvolvingeukaryoticparasites(worms)• Alsoinvolvedin• Someallergicresponses• Dissolvingclots• Detoxifyingforeignsubstances

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Basophils• Actionsaresimilartomastcellsoflooseconnectivetissue• Granulescontain• Heparin• Histamine

• vasodilator,increasescapillarypermeability

• Importantininflammation,especiallyrelatedtoallergies

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

•Monocytes• Differentiateintomacrophageanddendriticcellsaftermigrationintolocaltissues• Storedintheredpulpofthespleen

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

•Macrophage• Derivedfrommonocytes• Activatetomacrophageininterstitium• Residentpopulationsfoundinalltissues• Strategicallylocated• Epitheliaincontactwiththeoutsideofthebody• Skin,liningofdigestiveandrespiratorytract

• Linebloodandlymphvessels

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Residentpopulationsofmacrophage• Kupfer Cells(liver)• MesangialCells(kidney)• SatelliteCells(PNS)• Microglia(CNS)• DendriticCells(skin)• DustCells(lungs)• Histocytes (c.t.)• Osteoclasts(bone)

• Macrophagearelonglived• Severalmonths

• Multipleactionsofmacrophage• Phagocytosis• Removalofcellulardebris• Tissuerepair• Woundhealing• Inflammatoryresponse

•APC

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• Dendriticcells• Locatedinepitheliumincontactwiththeexternalenvironment• Macrophagefunction

•APC

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

•Mastcells• Foundinlooseconnectivetissue• Areimmatureincirculation• Migrateintotissueswheretheymature• Undergodegranulationwhenactivated• Granulescontain• Histamine• Eicosanoids• Chemokines

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

CellsoftheInnateImmuneResponseNon-specificImmuneResponse

• NKCells• NaturalKillers• Lymphocytelikecell• Notimmunologicallyspecific• Performstumorsurveillance

ResponsetoInfectionInflammatoryResponse

• Inflammationaccompaniesmanyimmuneresponses• Localresponsetoinfectionorinjury• Manyimmuneprocesses

• Stimulatedbythepresenceofinfectionorallergen• Keymediatorsarephagocyticcells• Neutrophils,macrophages,dendriticcells

• Functions• Todestroyforeigninvaders• Preparefortissuerepair

• Signs:pain,heat,swelling,redness

ResponsetoInfectionInflammatoryResponse

Stepsoftheinflammatoryresponse1. Infectionorinjurycausesreleaseofchemicals2. Localvasodilation3. Increaseinproteinpermeabilityresultingindiffusionofproteinand

filtrationoffluidintointerstitialfluid4. Diapedesisandextravasationofleukocytesfromvenules into

interstitialfluidofinfected/injuredarea5. Destructionofbacteria6. Tissuerepair

ResponsetoInfectionAntigenPresentation

• Onceantigenhasbeenencounteredandrecognizedbythecellsofthenon-specificimmuneresponse• Theantigenmustbepresentedtoalymphocytetoinitiateadaptivebranchoftheimmunesystem(specificimmuneresponse)• AntigenPresentingCells(APC’s)• Macrophage• Dendriticcells• Bcells

ResponsetoInfectionDestructionofAntigen

• Oncethespecificimmuneresponsehasbeeninitiated,antibodiesareproducedfortheantigen• Antibodiesneutralizeantigen• Theantigenthatisboundbyantibodymustbedestroyed• Therearedifferentwaystodestroyantigen,dependingonwhattheantigenis• Destructionofantigenisonlyspecifictothetypeofantigen• Bacteria,virus,etc

ResponsetoInfectionDestructionofAntigen

• DestructionofBacteria• ComplimentPathway• Macrophage

• DestructionofVirus• Interferons(**)• Proteosomes• Macrophage

• ComplimentPathway(classicalpathway)• Extracellulardestructionofbacteriawithoutphagocytosis• Asuite(orfamily)ofplasmaproteins

• Sequentialactivationofcomplimentproteins• C1mustbeactivatedfirst

• Antibodiesactivatethefirstcomplementprotein(C1)• Caninvolveopsonization bytheantibody• C1bindstotheconstantarmofanantibody• Thevariablearmsoftheantibodyareboundtoabacterium

• Theendresultistheformationofaporeinthemembraneofthebacterium• Thecontentsofthebacterialcellleakout• Thebacteriumdies

ResponsetoInfectionDestructionofBacteria

Opsonization isachemicalattractant“Tomaketasty”

ResponsetoInfectionDestructionofBacteria

ResponsetoInfectionDestructionofBacteria

ResponsetoInfectionDestructionofVirus(**)

• Interferons• Interferonfamilyofcytokines• Releasedbyvirusinfectedbodycells• Actasparacrineagents• Interferonreleasedbyacellinfectedwithvirus• Interferonbindstocellsincloseproximity• Nonspecificallyinhibitsviralreplicationincellsbeforetheybecomeinfected• Protectionforhealthycellsagainstnewlyreleasedviruses• Host(tissue)specific,notvirusspecific

ResponsetoInfectionDestructionofVirus

ResponsetoInfectionDestructionofVirus

• Proteosomes• Proteincomplexes• Degradeun-needed,damaged,viralproteins

• Non-specificallydestroyproteins• Virushaveaproteincoat• Proteasescleavepeptidebonds• Proteolysis