Medical Microbiology

cells—oronlyrequiresthesecellsindirectly.However,shouldtheantigenstim-

ulusandtheaccompanyinginflammationbeofalow-levelnature,thequan-

tityofcytokinessecretedbythecytotoxicTcellsthemselvesmaynotsuffice,in

whichcasetheinductionofaCD8+Tcellresponsewillbereducedunless

additionalcytokinesareprovidedbyhelperTcells.Thecytotoxicactivity

ofCD8+Tcellsismediatedviacontactandperforinrelease(perforinrenders

themembraneofthetargetcellpermeableresultingincellulardeath).CD8+T

cellsalsofunctionininterleukinrelease(mainlyofIFNc)bywhichtheyme-

diatenon-cytotoxiceffectorfunctions(Fig.2. 15 ).Theroleofperforinincon-

tact-dependentdirectcytolysisbynaturalkiller(NK)cellsandcytotoxicT

cells(seealsoFig.2. 17 ,p.88)hasbeeninvestigatedingeneknockoutmice.In

theseanimalstheperforingenehasbeenswitchedoffbymeansofhomolo-

gousrecombination,andasaresulttheycannolongerproduceperforin.Per-

forin-dependentcytolysisisimportantforthecontrolofnoncytopathicviruses,

tumors,andtransformedcells,butalsoplaysalargeroleinthecontrolofhighly

virulentvirusesthatproducesyncytia(e.g.,thesmallpoxvirus).Releaseof

noncytolyticeffectormoleculesbyCD8+cells,mostlyIFNc,playsamajor

roleincontrolofcytopathicvirusesandintracellularbacteria.Cytolyticeffector

mechanismsmayalsocontributetoreleaseofintracellularmicro-organisms

andparasites(e.g.,tuberculosis)fromcellsthatonlyexpressMHCclassI.

76 2 BasicPrinciplesofImmunology

LymphocytesandAPCsinthePrimaryImmuneResponse

2

Kayser, Medical Microbiology © 2005 Thieme