thegeneticallyengineeredinsertionofcostimulatorymoleculesintotumor
cells.Immunosuppressioncanbeinducedgloballyusingdrugs,orspecifi-
callyusingantibodies,interleukinsorsolubleinterleukinreceptors;thiscan
alsobeachievedbymeansoftoleranceinductionwithproteins,peptides,or
cellchimerism. &
ImmuneDefects
Themostimportantandfrequentimmunedefectsareacquired,e.g.,iatro-
genic(cytostatics,cortisone,irradiation,etc.),age-induced,ortheresultof
viralinfections(aboveallHIV).Congenitaldefectsarerare;examplesinclude
Bruton’sX-chromosome-linkedB-celldefect,thymichypoplasia(DiGeorge),
andcombinedT-andB-celldeficiencyresultingfromMHCdefects(bare
lymphocyte syndrome) or fromenzymedefects(adenosinedeaminase
[ADA]deficiencyor purinenucleosidephosphorylase[PNP]deficiency).
Thesedefectscanalsoberepairedbyreconstitution(thymictransplants),
orinsomecasesthroughtheuseofstemcells(genetherapy;oneofthe
veryfirstsuccessfulgenetherapieswasthetreatmentofADAdeficiency).
Morefrequentcongenitaldefectsinvolveselectivedeficiencies,forexample
arelative-to-absoluteIgAdeficiency,normallybeingmoreprominentinin-
fantsthanlaterinlife.Childrenwithsuchdeficienciesaremoresusceptibleto
infectionwithHaemophilusinfluenzae,pneumococci,andmeningococci.
Generalconsequencesofimmunedefectsincluderecurringandunusualin-
fections,eczemas,anddiarrhea.
Immunoregulation........................................
Thisareaofimmunologyisdifficulttodefineandremainselusive.Antigens
representthemostimportantpositiveregulatorofimmunity;sincethereis
simplynoimmunestimulationwhenantigenshavebeeneliminatedorare
absent.Otherimportantregulatorsincludeinterferongamma(IFNc)forTH1
responses,andIL-4forTH2responses.FurtherIL-dependentregulatoryfunc-
tionsareintheprocessofbeingdefined.TheexistenceofspecificCD8+Tsup-
pressorcells,capableofdownregulatingimmuneresponses,hasbeenpos-
tulatedandtheirrolewasassumedtobethatofcounteractingtheinflam-
matoryCD4+Tcellresponse.However,todatetherehasbeennoconvincing
proofoftheirexistence.ThetermCD8+Tsuppressorcells,whichisusedfre-
quently,isthereforemisleadingandinaccurate.Inrelativelyrarecases,cyto-
118 2 BasicPrinciplesofImmunology
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Kayser, Medical Microbiology © 2005 Thieme
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