INNATEIMMUNITYNon-SpecificImmuneResponse

PhysiologyUnit3

InPhysiologyToday

ResistancetoDisease

• Bodydefensesagainstinfectiousdisease• Immunesystemhas2arms:– Innateornon-specificimmunity– Adaptiveorspecificimmunity

ImmuneCells

• Diversecollectionofcellsthatarefoundinblood,lymphandtissuesthroughoutthebody

• Cytokines– Chemicalmessengerssecretedbyimmunecells

• Cells– Leukocytes– Plasmacells– Macrophages– Dendriticcells– Lymphocytes– Mastcells

ImmuneCells

• Leukocytes– Usebloodprimarilyfortransportandmigratetothetissueswheretheyfunction

• Plasmacells– Foundintissues(lymphnodes)wheretheydifferentiatefromBlymphocytes

– Synthesizeandsecreteantibodies

ImmuneCells

• Macrophages– Foundinallorgansandtissuesstrategicallyplacedwheretheywillencountertheirtargets• Epitheliaincontactwiththeoutsideofthebody

– skin,liningofdigestiveandrespiratorytract– Linebloodandlymphvessels

– Tissuespecificresidentpopulations– Derivedfrommonocytes,transformintomacrophages– Passthroughwallsofcapillariestoentertissues

• Diapedesisandextravasation

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

DiapedesisorExtravasation

ImmuneCells

• Dendriticcells– Epitheliumincontactwiththeexternalenvironment,

– Macrophagefunction– Migratetolymphnodes

• APC’s• PresenttoTCells• Messengersbetweeninnateandadaptiveimmunity

LymphocytesRecognitioncellsinspecificimmunedefensesandareessentialfor

allaspectsofspecificimmuneresponses

ImmuneCells

• Mastcells– Foundinconnectivetissues(especiallybelowepithelialsurfacesofthebody)

– Moveintotissueswheretheydifferentiateanddivide

– Containvesiclesthatcontainhistamineandheparin

Cytokines

• Immunecellssecretemorethan100proteinmessengersthatregulatehostcelldivision

• Involvedinnon-specificandspecificimmunedefenses

• Mostoftheiractionsactlocally– Paracrine/autocrineagents– Somewillcirculateinbloodandactashormonesondistantorgans

• Allowcommunicationbetweendifferentimmunecellsandtimingofcascadereactions

NonspecificImmuneDefensesInnateImmuneResponse

• Againstall“non-self” cells• Recognizesomegeneralpropertymarkingtheinvadersasforeign– Antigens

• Notdependentuponexposuretodisease• Include:defensesatthebodysurfaces,theinflammatoryresponse,interferons

DefensesattheBodySurfacePhysicalBarriers

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

• Certainmicrobesdrillthrough(syphillis,hookworms,manyarthropodbornepathogens)

• Coughandsneezereflex• Hairsattheentranceofthenose

DefensesattheBodySurfacePhysicalBarriers

• Mucousmembranes• Nonkeratinizedepithelialmembranes,oftenciliated

• Linedwithmucus• Containantimicrobialchemicals

• Excellentfortrappingmicrobesforexpulsion

DefensesattheBodySurfacePhysicalBarriers

• Serousmembranes• Lubricatedwithserumfrom“leakycapillaries”

• Internalphysicalbarriertoinfectionofvitalorgans

• Heart,lungs,andabdominalviscera• Similarprotectionbythemeningesofthebrainandspinalcord

NonspecificChemicalDefenses

• pHlevels– Gastricjuice,vaginalsecretions,urine

• Lysozyme– Intears,saliva,sweat– Bindstomicrobesandpunchesholesinthecellwall

– Foundingranulesofneutrophilsandmacrophages

NonspecificCellularDefenses

• Neutrophils• FirstWBCataninfectionsite

• Voraciousphagocytes• Microphage• Uselysozymesandoxygenradicalstodissolvemicrobes

NonspecificCellularDefenses

• Eosinophils• Slightlyphagocytic• Majorroleininfectionsinvolvingeukaryoticparasites(worms)

• Alsoinvolvedincertainallergies,dissolvingclots,detoxifyingforeignsubstances

NonspecificCellularDefenses

• Basophils• Similartomastcellsoflooseconnectivetissue

• Granulescontain– Heparin– Histamine

• vasodilator,increasescapillarypermeability

• Importanttoinflammation,especiallyrelatedtoallergies

NonspecificCellularDefenses• Monocytes• Transformwhenactivated

tomacrophages• “Eat”microbesand

cellulardebris• Storedintheredpulpof

thespleen• Linknonspecificbody

defensestothespecificimmuneresponses– APC

NonspecificCellularDefenses

• NaturalKillers• NKCells• “lymphocytelikecell”,butnotimmunologicallyspecific

• Performstumorsurveillance

Inflammation

• Localresponsetoinfectionorinjury• Functions– Todestroyforeigninvaders– Preparefortissuerepair

• Keymediatorsarephagocyticcells– Neutrophils,macrophages,dendriticcells

Inflammation• Inflammationaccompaniesmanyimmuneresponses

• Involvesphagocytosisandmanyimmuneprocesses

• FirstWBCatinfectionsite:neutrophil• Stimulatedbythepresenceofinfectionorallergen

• Signs:pain,heat,swelling,redness

Inflammation

1. Infectionorinjurycausesreleaseofchemicals2. Localvasodilation3. Increaseinproteinpermeabilityresultingin

diffusionofproteinandfiltrationoffluidintointerstitialfluid

4. Diapedesis:movementofleukocytesfromvenulesintointerstitialfluidofinfected/injuredarea

5. Destructionofbacteria6. Tissuerepair

• A“suite” (orfamily)ofplasmaproteins• Extracellularkillingofbacteriawithoutphagocytosis• Sequentiallybindtobacteria,formingapore,causinglysis

• Antibodiesactivatethefirstcomplementprotein(C1)

• Someformopsonins– Makemicrobes“tasty”– Chemicalattractantforphagocytes– Moleculethatenhancesphagocytosis

ComplementPathway

Complement

Complement

Interferons

• Nonspecificchemicaldefensesinplasma• Interferon familyofcytokines• Nonspecificallyinhibitviralreplicationincells– Protectionforhealthycellsagainstnewlyreleasedviruses

– Host(tissue)specific,notvirusspecific• Releasedbyvirusinfectedbodycells

InterferonAction