Medical Microbiology

ImmunopathologicalDamageandAIDS

CoulditbethatimmunopathologicaldamageresultingfromTcellimmunere-

sponsesplayaroleinAIDS?

ThegeneralassumptionatthepresenttimeisthatthecausalHIVvirusdestroys

thoseThelpercellsitinfects,yetnounequivocalin-vivoproofofthisassumption

hasbeenobtained.Thelpercellsdodisappear,buthowandwhytheydisappear

remainsunclear.AnimalmodelsemployingvirusessimilartoHIVsuggestthatAIDS

mightalsodevelopbyalternativemeans:

AssumingthatHIVisanoncytopathic,oronlymildlycytopathic,virus—infectionof

macrophages,dendriticcells,and/orThelpercellswillnotcauseanimmediateout-

breakofdisease.Soon,however,thevirus-infectedmacrophagesandThelpercells

willbedestroyedbyspecificallyreactingcytotoxicCD8+Tcells.Becausetheim-

muneresponsealsoactstoinhibitvirusproliferation,theprocessofcellulardestruc-

tionisgenerallyagradualprocess.However,overtimetheimmunesystemitself

maybecomedamagedandweakened.Paradoxically,theprocessofimmunological

celldestructionwouldhelpthevirussurviveforlongerperiodsinthehostandhence

facilitateitstransmission.Fromthepointofviewofthevirusthiswouldbeanas-

tounding,andhighlyadvantageous,strategy—butonewithtragicconsequencesfor

thehostfollowing,inmostcases,alengthyillness.IfproliferationofHIVcouldbe

slowedorevenhalted,theviruswouldinfectfewerlymphocytes,andthusfewer

cellswouldbedestroyedbythecytotoxicT-cellresponse.Preventionorreductionof

HIVproliferation,eitherbypharmacologicalmeansorbybolsteringtheearlyim-

munedefensesthroughothermeans,thereforerepresentsanimportantobjective

despitethelikelihoodthatHIVisnotverycytopathic.

InfluenceofProphylacticImmunization

ontheImmuneDefenses

Vaccinesprovideprotectionfromdiseases,butinmostcasescannotentirely

preventre-infection.Vaccinationnormallyresultsinalimitedinfectionby

anattenuatedpathogen,orinducesimmunitythroughtheuseofkilledpatho-

gensortoxoids.Theformertypeofvaccineproducesaverymildinfectionor

illnesscapableofinducinganimmuneresponseandwhichsubsequently

protectsthehostagainstre-infection.Thesuccessfuleradicationofsmallpox

intheseventiessofarrepresentsthegreatestsuccessstoryinthehistoryof

vaccination.Thefactisthatvaccinationsneverofferabsolutesecurity,but

insteadimprovethechancesofsurvivalbyafactorof 100 to 1000 0.Aspecial

situationappliestoinfectionswithnoncytopathicagentsinwhichdisease

resultsfromtheimmuneresponseitself(seeabove).Undercertaincircum-

stances,andinasmallnumberofvaccinatedpersons,thevaccinationpro-

ceduremaythereforeshiftthebalancebetweenimmunedefenseandinfec-

tiontowardsanunfavorableoutcome,suchthatthevaccinationwillactually

strengthenthedisease.Rareexamplesofthisphenomenonmayincludethe

106 2 BasicPrinciplesofImmunology

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Kayser, Medical Microbiology © 2005 Thieme

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