免疫系统紊乱immunedisorders+aids埃文斯维尔大学(美国)

ImmuneSystemDisordersImmuneSystemDisordersHypersensitivity(Allergy):Anabnormalresponsetoantigens.FourTypesofHypersensitivityReactions:TypeI(Anaphylactic)ReactionsTypeII(Cytotoxic)ReactionsTypeIII(ImmuneComplex)ReactionsTypeIV(Cell-Mediated)ReactionsTypeI(Anaphylactic)ReactionsOccurwithinminutesofexposuretoantigenAntigenscombinewithIgEantibodiesIgEbindstomastcellsandbasophils,causingthemtoundergodegranulationandreleaseseveralmediators:Histamine:Dilatesandincreasespermeabilityofbloodvessels(swellingandredness),increasesmucussecretion(runnynose),smoothmusclecontraction(bronchi).Prostaglandins:Contractionofsmoothmuscleofrespiratorysystemandincreasedmucussecretion.Leukotrienes:Bronchialspasms.Anaphylacticshock:Massivedropinbloodpressure.Canbefatalinminutes.MastCellsandtheAllergicResponseMastCellsandtheAllergicResponseTypeII(Cytotoxic)ReactionsInvolveactivationofcomplementbyIgGorIgMbindingtoanantigeniccell.Antigeniccellislysed.Transfusionreactions:ABOBloodgroupsystem:TypeOisuniversaldonor.Incompatibledonorcellsarelysedastheyenterbloodstream.RhBloodGroupSystem:85%ofpopulationisRhpositive.ThosewhoareRhnegativecanbesensitizedtodestroyRhpositivebloodcells.•Hemolyticdiseaseofnewborn:Fetalcellsaredestroyedbymaternalanti-Rhantibodiesthatcrosstheplacenta.TypeIII(ImmuneComplex)ReactionsInvolvereactionsagainstsolubleantigenscirculatinginserum.UsuallyinvolveIgAantibodies.Antibody-Antigenimmunecomplexesaredepositedinorgans,activatecomplement,andcauseinflammatorydamage.Glomerulonephritis:Inflammatorykidneydamage.Occurswithslightlyhighantigen-antibodyratioispresent.ImmuneComplexMediatedHypersensitivityTypeIV(Cell-Mediated)ReactionsInvolvereactionsbyTDmemorycells.Firstcontactsensitizesperson.Subsequentcontactselicitareaction.Reactionsaredelayedbyoneormoredays(delayedtypehypersensitivity).DelayisduetomigrationofmacrophagesandTcellstositeofforeignantigens.Reactionsarefrequentlydisplayedontheskin:itching,redness,swelling,pain.•Tuberculosisskintest•Poisonivy•Metals•Latexinglovesandcondoms(3%ofhealthcareworkers)Anaphylacticshockmayoccur.AllergicContactDermatitisResponsetoPoisonIvyHaptenAutoimmuneDiseasesLossofself-toleranceleadstoproductionofantibodiesorTcellsthatreactagainstone’sownantigens.Immunesystemresponsetoselfantigenscausesdamagetoorgans.Threetypesofautoimmunedisorders:Cytotoxic(TypeIIreactions)Immunecomplex(TypeIIIreactions)Cell-mediated(TypeIVreactions)AutoimmuneDiseasesA.TypeII(Cytotoxic)AutoimmuneReactionsInvolveantibodyreactionstocellsurfacemolecules,withoutcytotoxicdestructionofcells.Grave’sDisease:Antibodiesattachtoreceptorsonthyroidglandandstimulateproductionofthyroidhormone.Symptoms:Goiter(enlargedthyroid)andbulgingeyes.Myastheniagravis:Progressivemuscleweakness.Antibodiesblockacetylcholinereceptorsatneuromuscularsynapse.Affects25,000Americans(mainlywomen).Todaymostpatientssurvivewhentreatedwithdrugsorimmunosuppressants.AutoimmuneDiseasesB.TypeIII(ImmuneComplex)AutoimmuneReactionsSystemicLupusErythematosus:Affectsabout200,000Americans(90%women).Namederivedfromredskinrashonface.AutoantibodiesreactagainstDNA,bloodcells,neurons,andothertissues.Whencellsdie,immunecomplexesformanddepositunderskin,joints,inkidneys,bloodvessels,andcentralnervoussystem.Inflammationinterfereswithnormalfunctionofthesesites(arthritis,rash,kidneydamage).Mostpatientsdiefromkidneydamage.Nocure.Symptomstreatedwithanti-inflammatoryandimmunosuppressivedrugs.AutoimmuneDiseasesB.TypeIII(ImmuneComplex)AutoimmuneReactions(Continued)RheumatoidArthritis:Affectsabout2millionAmericans(70%+women).Causeunknown,butmicrobialmimicrymaybeinvolved.IgMautoantibodies(rheumatoidfactors)againstIgGformcomplexesinjoint,leadingtoinflammationandcartilagedamage.Oftencausesfingerandjointdeformities.Nocure.Symptomstreatedwithanti-inflammatory(aspirin)andimmunosuppressivedrugs.Physicaltherapykeepsjointsmovable.Surgicalreplacementofjointsmaybenecessary.AutoimmuneDiseasesC.TypeIV(Cell-Mediated)AutoimmuneReactions(Continued)Insulin-dependent(TypeIorJuvenile)DiabetesMellitus:Diabetesaffectsupto5%ofAmericans.IntheU.S.,35,000peopledieeveryyearfromalltypesofdiabetesmellitusandcomplications(gangrene,kidneyandcardiovasculardisease,dehydration,andnervedamage).InsulinDependent(TypeIorJuvenile)Diabetes:Makesup10%ofdiabetescases.Characterizedbyinsufficientinsulinproductionduetoimmunologicaldestructionofinsulin-secretingcellsofthepancreasbyTcells.Usuallydevelopsbeforetheageof15.Treatedwithinsulininjections.AcquiredImmunodeficiencySyndrome(AIDS)History1950s:BloodsamplesfromAfricahaveHIVantibodies.1976:FirstknownAIDSpatientdied.1980:Firsthumanretrovirusisolated(HTLV-1).1981:Firstreportsof“AcquiredImmuno-deficiencySyndrome”inLosAngeles.1983:VirusfirstisolatedinFrance(LAV).1984:VirusisolatedintheU.S.(calledHTLV-IIIandAIDS-RelatedVirus,ARV).1985:Developmentandimplementationofantibodytesttoscreenblooddonors.AcquiredImmunodeficiencySyndrome(AIDS)History(Continued)1986:ConsensusnameHumanImmunodeficiencyVirus(HIV-1).Relatedvirus(HIV