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INNATEIMMUNITYNon-SpecificImmuneResponse
PhysiologyUnit3
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InPhysiologyToday
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ResistancetoDisease
• Bodydefensesagainstinfectiousdisease• Immunesystemhas2arms:– Innateornon-specificimmunity– Adaptiveorspecificimmunity
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ImmuneCells
• Diversecollectionofcellsthatarefoundinblood,lymphandtissuesthroughoutthebody
• Cytokines– Chemicalmessengerssecretedbyimmunecells
• Cells– Leukocytes– Plasmacells– Macrophages– Dendriticcells– Lymphocytes– Mastcells
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ImmuneCells
• Leukocytes– Usebloodprimarilyfortransportandmigratetothetissueswheretheyfunction
• Plasmacells– Foundintissues(lymphnodes)wheretheydifferentiatefromBlymphocytes
– Synthesizeandsecreteantibodies
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ImmuneCells
• Macrophages– Foundinallorgansandtissuesstrategicallyplacedwheretheywillencountertheirtargets• Epitheliaincontactwiththeoutsideofthebody
– skin,liningofdigestiveandrespiratorytract– Linebloodandlymphvessels
– Tissuespecificresidentpopulations– Derivedfrommonocytes,transformintomacrophages– Passthroughwallsofcapillariestoentertissues
• Diapedesisandextravasation
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Macrophage
• KupferCells(liver)• MesangialCells(kidney)• SatelliteCells(PNS)• Microglia(CNS)• DendriticCells(skin)• Monocytes• DustCells(lungs)• Histocytes(c.t.)• Osteoclasts(bone)
• Macrophagearelonglived(severalmonths)
• APCrole• Removalofcellulardebris
• Inflammatoryresponse• Tissuerepair• Woundhealing
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DiapedesisorExtravasation
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ImmuneCells
• Dendriticcells– Epitheliumincontactwiththeexternalenvironment,
– Macrophagefunction– Migratetolymphnodes
• APC’s• PresenttoTCells• Messengersbetweeninnateandadaptiveimmunity
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LymphocytesRecognitioncellsinspecificimmunedefensesandareessentialfor
allaspectsofspecificimmuneresponses
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ImmuneCells
• Mastcells– Foundinconnectivetissues(especiallybelowepithelialsurfacesofthebody)
– Moveintotissueswheretheydifferentiateanddivide
– Containvesiclesthatcontainhistamineandheparin
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Cytokines
• Immunecellssecretemorethan100proteinmessengersthatregulatehostcelldivision
• Involvedinnon-specificandspecificimmunedefenses
• Mostoftheiractionsactlocally– Paracrine/autocrineagents– Somewillcirculateinbloodandactashormonesondistantorgans
• Allowcommunicationbetweendifferentimmunecellsandtimingofcascadereactions
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NonspecificImmuneDefensesInnateImmuneResponse
• Againstall“non-self” cells• Recognizesomegeneralpropertymarkingtheinvadersasforeign– Antigens
• Notdependentuponexposuretodisease• Include:defensesatthebodysurfaces,theinflammatoryresponse,interferons
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DefensesattheBodySurfacePhysicalBarriers
• Skin–Watertightbarrier– Keptcleananddry– Sweatglandssecreteantibodies,lysozyme–Mostlyimpermeabletomicrobes
• Certainmicrobesdrillthrough(syphillis,hookworms,manyarthropodbornepathogens)
• Coughandsneezereflex• Hairsattheentranceofthenose
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DefensesattheBodySurfacePhysicalBarriers
• Mucousmembranes• Nonkeratinizedepithelialmembranes,oftenciliated
• Linedwithmucus• Containantimicrobialchemicals
• Excellentfortrappingmicrobesforexpulsion
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DefensesattheBodySurfacePhysicalBarriers
• Serousmembranes• Lubricatedwithserumfrom“leakycapillaries”
• Internalphysicalbarriertoinfectionofvitalorgans
• Heart,lungs,andabdominalviscera• Similarprotectionbythemeningesofthebrainandspinalcord
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NonspecificChemicalDefenses
• pHlevels– Gastricjuice,vaginalsecretions,urine
• Lysozyme– Intears,saliva,sweat– Bindstomicrobesandpunchesholesinthecellwall
– Foundingranulesofneutrophilsandmacrophages
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NonspecificCellularDefenses
• Neutrophils• FirstWBCataninfectionsite
• Voraciousphagocytes• Microphage• Uselysozymesandoxygenradicalstodissolvemicrobes
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NonspecificCellularDefenses
• Eosinophils• Slightlyphagocytic• Majorroleininfectionsinvolvingeukaryoticparasites(worms)
• Alsoinvolvedincertainallergies,dissolvingclots,detoxifyingforeignsubstances
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NonspecificCellularDefenses
• Basophils• Similartomastcellsoflooseconnectivetissue
• Granulescontain– Heparin– Histamine
• vasodilator,increasescapillarypermeability
• Importanttoinflammation,especiallyrelatedtoallergies
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NonspecificCellularDefenses• Monocytes• Transformwhenactivated
tomacrophages• “Eat”microbesand
cellulardebris• Storedintheredpulpof
thespleen• Linknonspecificbody
defensestothespecificimmuneresponses– APC
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NonspecificCellularDefenses
• NaturalKillers• NKCells• “lymphocytelikecell”,butnotimmunologicallyspecific
• Performstumorsurveillance
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Inflammation
• Localresponsetoinfectionorinjury• Functions– Todestroyforeigninvaders– Preparefortissuerepair
• Keymediatorsarephagocyticcells– Neutrophils,macrophages,dendriticcells
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Inflammation• Inflammationaccompaniesmanyimmuneresponses
• Involvesphagocytosisandmanyimmuneprocesses
• FirstWBCatinfectionsite:neutrophil• Stimulatedbythepresenceofinfectionorallergen
• Signs:pain,heat,swelling,redness
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Inflammation
1. Infectionorinjurycausesreleaseofchemicals2. Localvasodilation3. Increaseinproteinpermeabilityresultingin
diffusionofproteinandfiltrationoffluidintointerstitialfluid
4. Diapedesis:movementofleukocytesfromvenulesintointerstitialfluidofinfected/injuredarea
5. Destructionofbacteria6. Tissuerepair
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• A“suite” (orfamily)ofplasmaproteins• Extracellularkillingofbacteriawithoutphagocytosis• Sequentiallybindtobacteria,formingapore,causinglysis
• Antibodiesactivatethefirstcomplementprotein(C1)
• Someformopsonins– Makemicrobes“tasty”– Chemicalattractantforphagocytes– Moleculethatenhancesphagocytosis
ComplementPathway
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Complement
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Complement
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Interferons
• Nonspecificchemicaldefensesinplasma• Interferon familyofcytokines• Nonspecificallyinhibitviralreplicationincells– Protectionforhealthycellsagainstnewlyreleasedviruses
– Host(tissue)specific,notvirusspecific• Releasedbyvirusinfectedbodycells
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InterferonAction