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Immunology
Theimmunesystem
- Processof“awareness”and“recognition”
- Discriminationof“self”and“selfenvironment”
- Protectionandregulationmechanisms(ifitdoesn’tbelong,itisbadregardlessofwhatitis)
- Advantagesanddrawbacks(tissuedamageiscausedbytheimmunesystem,alsocauseinflammation)
InnateImmuneSystem-nonspecific“firstline ofdefense” highorlow specificityofthe response.
Majorcells:Phagocyticcells,antigen-presentingcells
NaturalKiller(NK)cells-cytotoxictotumors, virally-infectedcells
Monocyte/Macrophages-Phagocytic,antigenpresentation
Dendriticcells-antigenpresentation(piecesandbring tohelp tcells)
MastCells-anti-parasitic,allergy
Neutrophils-phagocytic,inflammatory(firsttothesiteofinfection)
Eosinophils-Phagocytic,anti-parasitic
Basophils-workwithEosinophils,allergy
AdaptiveorAcquiredImmuneSystem-Hasmemoryandadaptstoparticulardiseasesalready
encountered
MajorCells:TandBcells
Cellsoftheinnateimmunesystemwarnthecellsoftheadaptiveimmunesystemthataforeignantigenis
present.Adaptivecellsproducesignals that enhancethe effectivenessofthe innate response
BCells( reactto the antigenwhenitfirst comesin & presentpiecesofantigento T cell)
- Origininantibodies/humoralimmunity
- Antibodiesactdirectlytoneutralizeinvadersandtriggerpotentcell-mediatedimmunity
- ProducedinBoneMarrow
- Actagainstextracellularinvadersortoxins
TCells(regulatetheimmuneresponse,choosesweaponry)
- Producedinbonemarrow,maturein Thymus
- Originofcell-mediatedimmunity
- CoordinatetheImmunesystem, actagainstinfected cells
Thelpercells (TH):Providehelp informofsecretedcytokinesor cell-cellinteractiontoB, Tc, &
macrophages(decision-makingcell;whatcells to activateandwhat weaponto use)
Tcytotoxiccells(Tc):killinfectedcellsby lysis
Tregulatorycells(TR):Maintainself-tolerance(monitorsituationandmakesure youkillantigenwithout
causingtissuedamage)
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SpecificImmuneResponses
HumoralImmunity:1901NobelPrize(EmilyvonBehring, Germany)
- SERUMfromimmunizedanimalstransferimmunityto non-immunizedanimals
- “Anti-Toxin”wasfoundtobeinthegammaglobulinfractionofserum“IMMUNOGLOBULIN” &
“ANTIBODY”
- Sinceantibodieswereintheblooditiscalled HumoralImmunity
2MajorFunctionsofantibodies
- Specificbindingtothe antigen(makeantigenmorevisibletophagocyticcells)
- Afterbindingantigen,theyactivatedtheimmunemechanismlikeallergicreactions,
complement ThesetwofunctionsarecarriedoutbydifferentpartsoftheAbmolecule
Complement
- Directlysisofsusceptiblecellsby insertionofappropriatemembraneattackcomplex(putting
aholein the membrane of acell thatis foreign)
-Opsonizationisaterm thatrefersto an immuneprocesswhereparticles suchas bacteria
aretargetedfordestructionbyan immunecellknownas aphagocyte
-C3e-mediatedreleaseofmaturePMNfromthebonemarrow.
Cytokines:Peptidemediatorsreleasedbystimulatedcells.The first celltellsthe secondcell whatto do.
(radiosignalsofanimmunearmy)(Communicatedwithincellsaredone by cytokines).
Functions:
- Mediatorsofnaturalimmunity(canturn oninnate cells)
- Regulatorsoflymphocyteactivation,growth,anddifferentiation(T cells)
- Activatorsofinflammatorycells(macrophages)
- Stimulatorsofimmatureleukocytegrowthanddifferentiation
Cell-MediatedImmunity: Phagocytes-whiteblood cellscouldingestmicroorganisms
OrgansoftheImmuneSystem
● Anatomicbarriers
- Skininamechanicalbarrier,acidic
- Mucousmembranes-trappathogens,ciliapropelforeignmaterialsoutward
- Normalflora-competeforniches
● Primarylymphoidorgans
- Originofimmunecells
● Secondarylymphoidorgans
- Bringstogetherpathogensandimmunesystems
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Primaryorgans-BoneMarrow(sourceofallcells)
- Allbloodcellsoriginatehere(fetalliver=bonemarrowfunctionally)
- AllhematopoieticcellsexceptTcellsmaturehere
- Perfusedwitharteriesto allowexchangewith bloodand marrow
- Stromalcells-providematurationsignalsto HSC’s,primarilyviacytokines
PrimaryOrgans-Thymus
- SiteofTcellmaturation
- ImmatureTcells(thymocytes)migratefrombonemarrow
- 95%ofthymocytesdie(preventsself-reactivity)
- MatureTcellsemergeandenterbloodandlymphatics
- Asweage,sizeandfunctiondecline
SecondaryOrgans-Lymphatics
- Designedtotrapantigens,initiateimmuneresponses
- Lymphfluid
- Afluidcompartmentofblood(plasma)
- Seepsacrosscapillarywalls
- Returnstoeitherthebloodorto anetworkofcapillaries(lymphaticvessels)
LymphNodes
- HighlyOrganized
- Locatedatpointsofconvergenceoflymphaticvessels
- Collectfluidsfromtissues,promotesantigenpresentationtoThelper
cellsCortex-Bcellsorganizedinfollicles,proliferating
Paracortex-T cells and dendriticcells (antigen-presentation)
Medulla-Macrophagesandplasma(B)cells
SecondaryOrgans-Spleen
- Locatedbehindstomach
- Collectsantigenfromblood
- SimilarroletoLymphNodes
- Alsothesiteofdisposalof RedBlood Cell
RedPulp:Redblood cells aredisposed
WhitePulp:lymphocyte
SecondaryOrgans:Malt,Galt
● Mucosal associatedlymphoidtissue
- Diffuseaggregationoflymphoidtissuethatprotectsmucosalsurfaces,
respiratoryepithelia
● Gut-associatedlymphoidtissue
- Tonsils -Appendix
- Adenoids -Peyer’spatches(smallintestines)
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Chemotaxis
- Directedmovementofleukocytesalongaconcentrationgradientofchemoattractants
- Chemoattractantsmaybederivedfromthe tissueorfrom infectingorganisms
- Stimulateleukocytesbybindingto receptorsontheneutrophilsurface
- Phagocytosis
- Internalizationofparticulatematterbycells
- Phagocytes→usuallyneutrophilsand macrophages
- Particles→usuallybacteria
Hematopoiesis
- “Hematopoiesis”-processofmaturationofbloodcells(bonemarrowgeneratesall cells)
- “Lymphopoiesis”-maturationofTandBlymphocytes
- “Erythropoiesis”-maturationofredbloodcells
GeneralPrinciples(Solidershowsofficerpiecesof theenemy)
- Firststepin infectionisthe activationofINNATEIMMUNERESPONSE,causeinflammation
(majorclearanceofinvadingorganisms,cell-mediated)
- Thesecondstepis toalert theADAPTIVEIMMUNERESPONSE(Antigenpresentation,both
cell-mediatedand humoralcomponents)
Phasesoftheimmuneresponse
● Cognitive-Antigenrecognitionandbinding,internalizingantigenandbreakingitdown
● Activation-Followsantigenexposure,characterizedbylymphoproliferation,celldivision
(whentcelldecide whattodo withthe antigen)
● Effector-Antibodyproductionandcell-mediatedeffectorfunctions(Actonthe decisionthat
wasmade)
ImmunologicalRecognition
- Usuallyachievedbymoleculesonthesurfaceof immunecells
- Alsoachievedbyimmune moleculesincirculation(ex: antibodies)
- Dependent onhavingalargerepertoireofallthesemoleculescapableofrecognizing
differentspecificities
Antibodydiversity
- Over10billionestimatedAntibodyspecificities
- EachBcellproducesonlyonesetofantibodymoleculestoonespecificity
- DifferentBcellsproducedifferentspecificities
- Informationneededforthesespecificitiesiscontainedin germlineDNA
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AntigenicDeterminants(Epitopes)
- Restrictedportionsofamoleculewhichare involvedin theactualbinding withcombiningsiteof
aparticularimmunoglobulin
- Thenumberofdistinctantigenicdeterminantsonanantigenmoleculevarieswithitssize
andchemicalcomplexity
Cross-reactivity
- Anyantibodyraisedagainst aparticularantigenmay“cross-react” withanotherantigenif
thesecondantigencontains antigenicdeterminants foundin thefirst
- Thesedeterminantsmustbetheonesrecognizedbytheantibodyonthefirstantigen
TheBigPicture
- Thelpercellsthen secretecytokineswhich:
- TriggerAPC’stopresentandphagocytosemoreeffectively
- CauseThelper cellsto multiply
- EnableBcellstoproduceantibodies
- TriggerTcytotoxiccellstokillinfectedcells
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