Medical Microbiology

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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