Medical Microbiology

andalternativeactivation,butisnotnecessarilyessentialsincethereleased

chemotaxinsandopsoninsareoftenaloneenoughtomediatethefunctions

ofmicrobeneutralizationandelimination.Somevirusescanactivatethe

complementsystemwithouttheinterventionofantibodiesbyvirtueoftheir

abilitytodirectlybindC1q.Thisappearstobelargelyrestrictedtoretro-

viruses(includingHIV).Importantly,withoutastringentcontrolmechanism

complementwouldbeactivatedinanuncontrolledmanner,resultinginthe

lysisofthehostsowncells(forinstanceerythrocytes).

ComplementControlProteins

Thefollowingregulatoryproteinsofthecomplementsystemhavebeencharacter-

izedtodate:

C1inhibitor,preventsclassiccomplementactivation.

DAF(decayacceleratingfactor),preventstheassociationofC3bwithfactorB,orof

C4bwithC2,onthecellsurface.DAFcanalsomediatethedissolutionofexisting

complexes,andisresponsiblefortheregulationofclassicandalternativeCactivities.

MCP(membranecofactorprotein),enhancestheactivityofthefactorwhichde-

gradesC3btoiC3b.FactorHandCR1(complementreceptor1)havesimilareffects.

HRF(homologousrestrictionfactor).Synonyms:MAC(membraneattackcomplex),

inhibitoryprotein,C8-bindingprotein.HRFprotectscellsfromC5-9-mediatedlysis.

Thisproteinislackinginpatientssufferingfromparoxysmalnocturnalhemoglobinuria.

CD59.Synonyms:HRF20,membraneattackcomplex(MAC)-inhibitingfactor,protec-

tin.ThisisaglycolipidanchoredwithinthecellsurfacewhichpreventsC9frombinding

totheC5b-8complex,thusprotectingthecellfromlysis.

Thosecomplementcomponentswiththemostimportantbiologicaleffects

include:

&C3b,resultsintheopsonizationofmicroorganismsandotherantigens,
eitherdirectlyorintheformofimmunecomplexes.“C-marked”microorgan-
ismsthenbindtotheappropriatereceptors(R)(e.g.,CRIonmacrophagesand
erythrocytes,orCR2onBcells).

&C3aandC5a,contributetothedegranulationofbasophilsandmastcells
andarethereforecalledanaphylatoxins.Thesecretedvasoactiveamines(e.g.,
histamine)raisethelevelofvascularpermeability,inducecontractionofthe
smoothmusculature,andstimulatearachidonicacidmetabolism.C5ainiti-
atesthechemotacticrecruitmentofgranulocytesandmonocytes,promotes
theiraggregation,stimulatestheoxidativeprocesses,andpromotesthere-
leaseofthethrombocyteactivatingfactor.

&“Early”Cfactors,inparticularC4,interactwithimmunecomplexesand
inhibittheirprecipitation.

&Terminalcomponents(C5–9),togetherformtheso-calledmembraneat-
tackcomplex,MAC,whichlysesmicroorganismsandothercells.

ImmuneResponsesandEffectorMechanisms 89

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Kayser, Medical Microbiology © 2005 Thieme

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