Cytokines(Interleukins)andAdhesion................
Cytokinesarebioactivehormones,normallyglycoproteins,whichexercisea
widevarietyofbiologicaleffectsonthosecellswhichexpresstheappropriate
receptors(Table2. 6 ).Cytokinesaredesignatedbytheircellularoriginsuch
thatmonokinesincludethose interleukinsproducedbymacrophages/
monocytes,whilstlymphokinesincludethoseinterleukinsproducedby
lymphocytes.Theterminterleukinsisusedforcytokineswhichmostlyin-
fluencecellularinteractions.Allcytokinesarecyto-regulatoryproteinswith
molecularweightsunder 60 kDa(inmostcasesunder 25 kDa).Theyarepro-
ducedlocally,haveveryshorthalf-lives(amatterofsecondstominutes),and
areeffectiveatpicomolarconcentrations.Theeffectsofcytokinesmaybe
paracrine(actingoncellsneartheproductionlocus),orautocrine(the
samecellbothproduces,andreactsto,thecytokine).Bywayofinteraction
withhighlyspecificcellsurfacereceptors,cytokinescaninducecell-specific
ormoregeneraleffects(includingmediatorrelease,expressionofdifferen-
ImmuneResponsesandEffectorMechanisms 77(^3) Fig.2. 13 Forthesakeofsimplicity,theprinciplesillustratedherearebasedon
anantigen(1)whichonlycontainsasingleBepitopeandasingleTepitope.As
anexample,thestructuralBepitope(blue)ispresentonthesurfaceoftheanti-
gen;whilstthelinearTepitope(red)ishiddeninsideit.Anantigen-presenting
cell(APC),ormacrophage,takesuptheantigenandbreaksitdowninanon-
specificmanner.TheT-cellepitopeisthusreleasedandloadedontoMHCclassII
moleculeswhicharepresentedonthecellsurface(2).AThelpercellspecifically
recognizestheTepitopepresentedbytheMHCclassIImolecule.Thisrecogni-
tionprocessactivatestheAPC(3a)(orthemacrophages).Tcells,APC,and
macrophagesallproducecytokines(Fig.2. 14 ),whichthenactonTcells,Bcells,
andAPCs(causingup-regulationofCD40,B7)(3).Thisinturnstimulatesthe
Tcellstoproliferate,andencouragesthesecretionofadditionalsignalingsub-
stances(IL-2,IFNc,IL-4,etc.).ABcellwhosesurfaceIghasrecognizedand
boundaBepitopepresentontheintactantigen,willpresenttheantigenic
TcellepitopecomplexedtoMHCclassIIonitscellsurface,inamannersimilar
tothatdescribedfortheAPC(4).Thisenablesdirectinteractionbetweenthe
ThelpercellandthespecificBcell,resultingininductionofproliferation,dif-
ferentiation,andB-cellclassswitchingfromIgMtootherIgclasses.TheBcell
finallydevelopsintoanantibody-producingplasmacell.Theantibody-binding
siteoftheproducedantibodythusfitstheBepitopeontheintactantigen.The
inductionofcytotoxiceffectorcellsbypeptidespresentedonMHCclassI
molecules(violet)isindicatedinthelowerpartofthediagram(5).Thecytotoxic
Tcellprecursorsdonotusuallyreceivecontact-mediatedThelp,butarerather
supportedbysecretedcytokines(mainlyIL-2)(6).(Again,intheinterestof
simplicity,theCD3andCD4complexesandcytokinesarenotshownindetail;
seeFig.2. 8 ,p. 61 formoreonantigenpresentation.)
2
Kayser, Medical Microbiology © 2005 Thieme