chapter 16 obj 08
TRANSCRIPT
16.8Complement
Explaintheroleofcomplementininnateimmunity.a) Whatarethethreeeffectsonmicrobesby
complement?b) Whatisthecommonpathway/cascadeofcomplement?c) WhatarethethreepathwaysofacAvaAng
complement?d) WhatisananAgen?e) WhatisananAbody?f) WhatisalecAn?g) Whatare2waysbacteriamightevadecomplement?
RoleofComplementSysteminImmunity
• Complementsystemismadeupofover30proteinssynthesizedbytheliver,circulateintheblood
• ManycomplementproteinsareinacAveandmustbeacAvated.
• AcAvatedcomplementactsinacascadethatcauses1. inflammaAon:dilaAonofarterioles,releaseof
histamine&increasedpermeabilityofcapillaries2. opsonizaAon:proteinbindstomicrobemakingit
easiertophagocyAze3. cytolysis:acomplexofseveralproteinscanform
holesinmicrobemembranescausingleakinessandcellrupture
TheCommonPathway
• Step1–acAvateC3,promotesopsonizaAonandphagocytosis
• Step2–acAvateC5,promotesinflammaAon
• Step3–formMAC,promotescytolysis
Step1:Ac*vateC3
• C3issplitintoC3aandC3b,catalyzedbyC3
convertase
• C3bbindstosurfacetoenhancephagocytosis(opsonizaAon)
• C3bisalsoanenzymethatcatalyzesthenextstep
• C3apromotesinflammaAonbysAmulaAngmastcellstoreleasehistamine
Step2:Ac*vateC5
• C3bactsastheC5convertase,spliWngC5intoC5aandC5b
• C5apromotesinflammaAonby
sAmulaAngmastcellstoreleasehistamine(alongwithC3a)
• C5bisbeginsthechainreacAonofproteinsbindingtothesurfaceofamicrobe
Step3:Forma*onoftheMembraneA:ack
Complex• C5bbindstothesurface
ofthebacterialcell
• C6,thenC7andC8bindinsequence
• These4proteinsa[ractorrecruitC9tobind
• SeveralC9proteinsbindinapa[erntoformahugeporepuncturingtheplasmamembraneandallowingbacterialcytoplasmtoleakout‐cytolysis
3WaystoAcAvateComplement
• Classicalpathway–anAbodies(partofacquiredimmunity)
• AlternaAvepathway–a[racAonofcomplementproteinstomicrobialcellwalls
• LecAnpathway–proteinsthatbindtobacterialcarbohydrates
TheClassicalPathway:adapAveimmunity
• AspecificanAbodyrecognizesandbindstoabacterialcell
• C1bindstotheanAbodies– TheinteracAonacAvatesenzymaAcfuncAonofC1
• AcAveC1a[ractsandclipsC2andC4intoC2a,C2b,C4a&C4b
• C2acombineswithC4btoformanacAveC3convertase
AnAbodies&AnAgens
• AnAbodiesareproteinsproducedbyBcells• Partofouracquiredimmunity• AnAbodiesbindtosmallpiecesofmicrobes,calledanAgens,toiniAateavarietyofimmuneresponses
• AnAgensaresubstancesthatsAmulatetheproducAonofanAbodies…anAbodygenerators
• TheclassicalpathwayisiniAatedwhenananAbodybindstoitsanAgen
TheAlternaAvePathway:innateimmunity
• ComplementproteinsB,D&Fcirculatethroughoutthebody
• Bindtomicrobialcellwallcomponents(glycolipids)
• B,D&Fa[ractC3andactasaC3convertase
TheLecAnPathway:innateimmunity
• LecAnisaproteinthatrecognizesandbindstobacterialcarbohydrates
• LecAna[ractsC2&C4andcatalyzesthespliWngofbothproteinsintoC2a,C2b,C4a&C4b
• C2acombineswithC4btoformanacAveC3convertase
EvadingComplement
• Capsule– ThecapsuleisacoaAngsurroundingthecellwall– OnecomponentofthecapsuleissialicacidwhichcanpreventopsonizaAon(tooslipperyforC3b)
– AnothercomponentpresentforsomebacteriaisOpolysaccharidewhichblocksbindingoftheMACcomplex(C5b,C6,C7,C8,C9)
• Secretedenzymes– SomebacteriasecreteC5apepAdase,whichdestroysC5a–impairinflammaAonandrecruitmentofphagocytes