Medical Microbiology

toxicCD8+TcellsdoexercisearegulatoryeffectbylysinginfectedAPCsorB
cells(seealsop. 1 06).ItisunclearwhetherCD4+Tcellscouldhavesimilar
effects.Regulationviaidiotypic/anti-idiotypicantibodynetworks(i.e.,anti-
bodiesdirectedagainsttheABSofotherantibodies),oranti-TCRnetworks,
havealsobeenpostulated—butremainhypothetical.Althoughattractive
hypothesis,formostcasessuchregulatorypathwayshaveonlyproveddis-
appointingtheoreticalconcepts,andassuchshouldnolongerbeemployedin
theexplanationofimmunoregulation.Inisolatedcases,anti-idiotypic,or
anti-TCRpeptide-specificfeedback,mechanismscan bemodeledunder
forcedexperimentalconditions.Howeversuchconditionsprobablyfailto
modelnormalsituations,thereforetheycannotaccuratelyindicatewhether
thesefeedbackmechanismshavearoleinregulatingtheimmunesystemasa
whole.

Immunostimulation...................................

Theaimofimmunologicaltreatmentofinfectionsandtumorsistoenhance
immuneresponsivenessviatheuseofthymichormones(thymopoietin,pen-
tapeptides),leukocyteextracts,orinterferons.Derivativesorsyntheticana-
logsofmicroorganismssuchasBCG,componentsofCorynebacteriumparvum
andpeptidoglycans(e.g.,muramylpeptide),oroligonucleicacids(CpG),are
usedasadjuvants.ComponentsofstreptococciandStreptomyces,eluatesand
fractionsofbacterialmixtures,andtherelatedsyntheticsubstancelevami-
solearealsoused.TheroleofToll-likereceptorsintheseadjuvanteffectsis
becomingincreasinglyunderstood,withamajorroleofthesemolecules
beingtolinknon-specificinnateresistancetospecificimmunity..
Recentlydevelopedimmunetherapystrategiesaimtoimproveantigen
presentation.Forinstanceinterleukins,orcostimulatorymoleculessuchas
B7orCD40,havebeeninsertedintotumorcellsbymeansoftransfection.
Hybridantibodieshavebeenconstructedinanattempttoimproveantigen
recognitionandphagocytosis(onesuchexampleisthecouplingofananti-
CD3antibodywithtumorantigen-specificantibodies).Otherideastested
successfullyinmodelexperimentsincludesystemictreatmentwithinterleu-
kins(thispresentswithfrequenttoxicityproblems)ortargetedinsertionof
GM-CSF,TNF,orIL-2.Alternatively,theproductionofIFNcorIFNbbycells,or
theuseofmoleculescapableofpolyclonalT-andB-cellstimulationhasbeen
employed.Thisconceptutilizeslocalchronicoracuteinfectionswiththeaim
ofachievinginflammationsurrounding,ordirectinfectionof,tumorcellsre-
sultingintheircytolyticdestruction.Suchconceptshavealsobeenusedto
forcephagocytosisanduptakeofantigensbyAPCswiththeaimofinducing
orenhancingtumorimmunity(e.g.,BCGinfectionsinbladdercarcinoma
treatment).

ImmuneDefectsandImmuneResponseModulation 119

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