disorders of the immune response
DESCRIPTION
just part of the notes on the immune system.. chapter 19 was a big chapter. Immunodeficiencythese notes gave me trouble when my laptop crashed and i had to recover them.. i rushed through them in order to finish them by tonight 10/3/09 -- i have an exam to study for.. let me know if things need to be corrected. thanks ^__^TRANSCRIPT
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Chapter19:DisordersoftheImmuneResponse 1
EinaJane&Co.2009.
I. AlterationsoftheImmuneSystemA. ImmunodeficiencystatesB. AllergicorhypersensitivityreactionsC. TransplantationrejectionD. Autoimmunedisorders
II. ImmunodeficiencyDisordersA. Abnormalityintheimmunesystemthatrendersapersonsusceptibleto
diseasesnormallypreventedbyanintactimmunesystemB. Classifications
1. Primarycongenitalorinherited2. Secondaryacquiredlaterinlife
a. Malnutritionb. InfectionHIV,AIDSc. Disseminatedcancersneoplasticdiseaseslymphomad. Immunosuppressivetherapycorticosteroidsortransplant
rejectionmedicationsC. WarningSignsofImmunodeficiencybyJeffreyModellFoundation/Immune
DeficiencyFoundation1. Eightormorenewearinfectionswithin1year2. Twoormoreserioussinusinfectionswithin1year3. Twoormoremonthsonantibioticswithlittleeffect4. Twoormorepneumoniaswithin1year5. Failureofaninfanttogainweightorgrownormally6. Recurrent,deepskinororganabscesses7. Persistentthrushinmouthorelsewhereonskin,after1yearofage8. Needforintravenousantibioticstoclearinfections9. Twoormoredeep‐seatedinfections10. Afamilyhistoryofprimaryimmunodeficiency
III. FourMajorCategoriesofImmuneMechanismsA. Humoralorantibody‐mediatedimmunityBlymphocytesB. Cell‐mediatedimmunityTlymphocytesC. ComplementsystemD. Phagocytosisneutrophilsandmacrophages
IV. HumoralImmunodeficienciesA. HumoralimmunodeficienciesinvolveB‐cellfunctionandimmunoglobulin
productionB. IncreasetheriskofrecurrentpyogenicinfectionsC. Humoralimmunityusuallyisnotasimportantindefendingagainst
intracellularbacteria(mycobacteria),fungi,andprotozoaD. Virusesusuallyarehandlednormally,exceptfortheenterovirusesthatcause
gastrointestinalinfectionsV. PrimaryHumoralImmunodeficiencyDisorders
A. GeneticdisorderofBlymphocytesB. Approximately70%ofprimaryimmunodeficiencies
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Chapter19:DisordersoftheImmuneResponse 2
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C. MaturationcycleinitiallyinvolvestheproductionofsurfaceIgM,migrationfromthebonemarrowtotheperipherallymphoidtissue,andswitchingtotheproductionofspecializedIgM‐,IgA‐,IgD‐,IgE‐,orIgG‐secretingplasmacellsafterantigenicstimulation
D. Immunoglobulinproductiondependson1. DifferentiationofstemcellsintomatureBlymphocytes2. Antigen‐dependentgenerationofimmunoglobulin‐producingplasma
cellsE. Caninterrupttheproductionofoneoralloftheimmunoglobulins
VI. CombineT‐CellandB‐CellImmunodeficienciesA. AffectallaspectsofimmunefunctionB. Severecombinedimmunodeficiencyrepresentsalife‐threateningabsenceof
immunefunction1. AbsenceofallT‐andB‐cellfunctionand,insomecases,alackofNKcells2. AffectedinfantshaveadiseasecoursethatresemblesAIDS,withfailureto
thrive,chronicdiarrhea,andopportunisticinfections3. X‐linkedSCID
a. Boys>girlsb. Causedbyageneticdefectinthecommongamma‐chainsubunit(γc)
ofcytokinereceptorsC. Combinedimmunodeficiency(CID)isdistinguishedfromSCIDbythe
presenceoflow,butnotabsent,T‐cellfunction1. Althoughantibody‐formingcapacityisimpairedinmostcases,itisnot
absent2. Autosomalpatternofinheritanceiscommon
a. Ataxia‐telangiectasiai. Complexsyndromeofneurologic,immunologic,endocrinologic,
hepatic,andcutaneousabnormalitiesii. Autosomalrecessivedisorderiii. Characterizations
o Cerebellarataxiapoormusclecoordinationo Appearanceoftelangiectaseslesionsconsistingofdilated
capillariesandarteriolesontheskinandconjunctivalsurfacesoftheeye
b. Wiskott‐Aldrichsyndromei. X‐linkedrecessivedisorderthatbecomessymptomaticduringthe
firstyearoflifeii. Plaguedbyeczema,lowplateletcounts,andsusceptibilityto
bacterialinfectionsiii. Bleedingepisodesorsymptomsduetoinfectionusuallybegin
withinthefirst6monthsoflifeiv. Pronetosepticemiaandmeningitis,lethalvaricellav. Management:treatmentofeczema,controlofinfections,and
managementofbleedingepisodes,antimicrobialtherapy,bonemarrowtransplantation,splenectomy
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Chapter19:DisordersoftheImmuneResponse 3
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D. RequiresbonemarroworstemcelltransplantationforsurvivalVII. DisordersofComplementSystem
A. Primary1. Mostlytransmittedasautosomalrecessivetraits2. Caninvolveoneormorecomplementcomponents3. Onlysupportivemeasuresareavailablefortreatmentofprimary
disordersofthecomplementsystema. Preventbacterialinfectionb. ImmunizedwithvaccinesforS.pneumoniae,H.influenzae,andN.
meningitidesB. Secondary
1. Occurinpersonswithfunctionallynormalcomplementsystemsbecauseofrapidactivationandturnoverofcomplementcomponentsasisseeninimmunecomplexdisease
2. Reducedsynthesisofcomponentschroniccirrhosisoftheliverormalnutrition
3. HereditaryangioneuroticedemaandlossofregulationVIII. PhagocyticSystems
A. Composedprimarilyofpolymorphonuclearleukocytes(neutrophilsandeosinophils)andmononuclearphagocytes(circulatingmonocytesandtissueandfixed[spleen]macrophages)
B. Actionofthesecells1. Migratetothesiteofinfectionchemo‐taxis2. Aggregatearoundtheaffectedtissueadherence3. Envelopeinvadingmicroorganismphagocytosis4. Generatemicrobicidalsubstancestokilltheingestedpathogens
C. DysfunctionofPhagocyticSystem1. Defectinanyofthesefunctionsorareductionintheabsolutenumberof
availablecellscandisruptthephagocyticsystem2. Pronetoinfections
a. BacteriaCandidaspeciesb. Filamentousfungi
3. Chronicgranulomatousdisease(CGD)a. Primarydisordersofphagocytosisb. Representsagroupofinheriteddisordersthatgreatlyreduceor
inactivatetheabilityofphagocyticcellstoproducetheso‐calledrespiratoryburstthatresultsinthegenerationoftoxicderivativesofoxygen(superoxideanionandhydrogenperoxide)createsanintracellularenvironmentthatkillsingestedmicroorganisms
c. Diagnosedbyexaminingtheabilityofaperson'sphagocytestoreduceayellowdyetoabluecompoundduringactiverespiration
d. Treatmenti. Bonemarrowtransplantationonlycureii. Supportivecarerecombinantinterferon‐gammaand
prophylacticantibiotictherapy
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Chapter19:DisordersoftheImmuneResponse 4
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D. StemCellTransplantation1. Manyoftheprimaryimmunodeficiencydisordersinwhichthedefecthas
beentracedtothestemcellcanbecuredwithallogeneicstemcelltransplantationfromanunaffecteddonora. SCIDb. Wiskott‐Aldrichsyndromec. Chronicgranulmatousdisease
2. Stemcellscanrepopulatethebonemarrowandreestablishhematopoiesisa. Tobeeffective,bonemarrowcellsofthehostaredestroyedby
myeloablativedosesofchemotherapyb. Chronicimmunoglobulintherapymaybenecessaryfortransplant
recipientswhoprimarilyretainBcellsofhostorigin3. Stemcellscanbecollectedfromthebonemarroworperipheralblood
a. HLA‐matchedsiblingsusuallyproducethebestresultsb. Stemcellaspirationfromthebonemarrowisthemostcommonform
ofallograftcollectionc. Umbilicalcordcollectedatthetimeofdeliverywithoutproducing
detrimentaleffectstothemotherandnewbornIX. AdaptiveImmunity
A. DevelopmentofresponsetoantigenB. SpecifichumoralandcellularrecognitionC. Memorycells
X. HypersensitivyDisordersA. ExcessiveorinappropriateactivationoftheimmunesystemB. Types
1. TypeI,IgE‐mediateddisorders2. TypeII,antibody‐mediateddisorders3. TypeIII,complement‐mediatedimmunedisorders4. TypeIV,T‐cell‐mediateddisorders
XI. TypeIHypersensitivityReactionsA. IgE‐mediatedreactionsbeginrapidly5‐30minB. Allergicreactionstoallergens
1. Proteininpollen,housedustmites,animaldander,foods,andchemicalsliketheantibioticpenicillin
2. Exposurethroughinhalation,ingestion,injection,orskincontact3. Reactionscanbelocal(atopic)orsystemic
C. TwotypesofcellsarecentraltoatypeIhypersensitivityreaction1. Type2helperT(TH2)cellswithtwosubsetsofhelperTcellsTH1and
TH2a. DevelopfromprecursorCD4+Tlymphocyteb. TH1cells
i. Differentiateinresponsetomicrobesii. StimulatedifferentiationofBcellsintoIgM‐andIgG‐producing
plasmacells
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Chapter19:DisordersoftheImmuneResponse 5
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c. TH2celli. Differentiationinresponsetoallergensandhelminths(intestinal
parasites)ii. StimulatedifferentiationofBcellsintoIgE‐producingplasma
cells,actasgrowthfactorsformastcells,andrecruitandactivateeosinophils
2. Mastcellsorbasophilsa. Derivedfromhematopoieticprecursorcellsb. Containgranulesthatreleasemediatorsduringreactionsc. Mastcellsdistributedthroughoutconnectivetissue
i. Beneaththeskinandmucousmembranesoftherespiratory,gastrointestinal,andgenitourinarytracts,andadjacenttobloodandlymphvesselssurfacesthatareexposedtoenvironmentalantigensandparasites
d. TypeIhypersensitivityreactionsbeginwithmastcellorbasophilsensitizationi. Allergen‐specificIgEantibodiesattachtoreceptorsonthesurface
ofmastcellsandbasophilsii. Withsubsequentexposure,thesensitizingallergenbindstothe
cell‐associatedIgEandtriggersaseriesofeventsthatultimatelyleadtodegranulationofthesensitizedmastcellsorbasophils,causingreleaseoftheirpreformedmediators
iii. Mastcellsarealsothesourceoflipid‐derivedmembraneproducts(e.g.,prostaglandinsandleukotrienes)andcytokinesthatparticipateinthecontinuedresponsetotheallergen
D. TypeI,IgE‐mediatedhypersensitivityreactionprocess1. ThestimulationofB‐cell
differentiationbyanantigenstimulatedtype2helper(TH2)TcellleadstoplasmacellproductionofIgEandmastcellsensitization
2. Subsequentbindingoftheantigenproducesdegranulationofthesensitizedmastcellwithreleaseofpreformedmediatorsthatleadstoaprimary,orearly‐phaseresponse
3. TH2T‐cellrecruitmentofeosinophils,alongwiththereleaseofcytokinesandmembranephospholipidsfromthemastcell,leadstoasecondary,orlate‐phaseresponse
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Chapter19:DisordersoftheImmuneResponse 6
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E. ManyTypeIhypersensitivityreactionshave2phases1. Primaryorinitial‐phaseresponseoccurswithin5‐30minutesof
exposure,subsideswithin60mina. Vasodilationb. Vascularleakagec. Smoothmusclecontractiond. Mediatedbymastcelldegranulation
i. Releaseofhistamine,acetylcholine,adenosine,chemotacticmediators,enzymessuchaschymaseandtrypsinthatleadtogenerationofkinins
ii. Histaminepotentvasodilatorincreasespermeabilitysmoothmusclecontraction,bronchialconstrictionsystemicshock
iii. Acetylcholinebronchialsmoothmusclecontraction,dilationofsmallbloodvessels
iv. Kininspotentinflammatorypeptidesactivatedbyenzymesvasodilationandsmoothmusclecontraction
2. Secondaryorlate‐phaseresponsea. Occursabout2to8hourslaterandlastsforseveraldaysb. Moreintenseinfiltrationoftissueswitheosinophilsandotheracute
andchronicinflammatorycellsc. Tissuedestructionintheformofepithelialdamaged. Resultsfromtheactionoflipidmediatorsandcytokinesinvolvedin
theinflammatoryresponsei. Derivedfrommastcellmembranephospholipidsthatarebroken
downintoarachidonicacidsynthesizeintoleukotrienesandprostaglandinsthatactsimilartohistamineandacetylcholinebutwithdelayedandprolongedeffects
ii. Mastcellscytokines,chemotacticfactorsinfluxeosinophilsandleukocytesinflammatoryresponse
e. Playsaprotectiveroleinthecontrolofparasiticinfectionsi. IgEantibodiesdirectlydamagethelarvaeoftheseparasitesby
recruitinginflammatorycellsandcausingantibody‐dependentcell‐mediatedcytotoxicity
ii. Importantindevelopingcountrieswheremuchofthepopulationisinfectedwithintestinalparasites
F. ExamplesofTypeI1. Anaphylactic(Systemic)Reactions
a. Systemiclife‐threateninghypersensitivityreactionb. Characterizedbywidespreadedema,vascularshocksecondaryto
vasodilation,anddifficultybreathingsystemicshockc. Exposureofantigenfrominjection,insectsting,skin,GImucosa
levelofseveritydependsonthelevelofsensitizationd. Initialmanagement:establishmentofastableairwayandintravenous
access,andadministrationofepinephrine
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Chapter19:DisordersoftheImmuneResponse 7
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2. Atopic(local)Reactionsa. Geneticallydeterminedhypersensitivity
i. Positivefamilyhistoryofallergyisfoundinabout50%ofatopicindividuals
ii. HavehighserumlevelsofIgEandincreasednumbersofbasophilsandmastcells.
b. EnvironmentalallergensmediatedbyanIgE‐mastcellreactionc. Mostcommonatopicdisordersurticaria(hives),allergicrhinitis
(hayfever),atopicdermatitis,foodallergies,andsomeformsofasthma
d. Treatmentforseasonalallergy/allergicrhinitisdesensitizationi. Frequent(usuallyweekly)injectionsoftheoffendingantigensii. Antigens,whicharegiveninincreasingdoses,stimulate
productionofhighlevelsofIgG,whichactsasablockingantibodybycombiningwiththeantigenbeforeitcancombinewiththecell‐boundIgEantibodies
XII. TypeII(Cytotoxic)HypersensitivityReactionsA. TypeII(antibody‐mediated)hypersensitivityreactionsaremediatedbyIgG
orIgMantibodiesdirectedagainsttargetantigensoncellsurfacesorinconnectivetissues1. Endogenousantigensthatarepresentonthemembranesofbodycells2. Exogenousantigensthatareadsorbedonthemembranesurface
B. Threedifferenttypesofantibody‐mediatedmechanisms1. Opsonizationandcomplement‐andantibodyreceptor‐mediated
phagocytosisa. Deletionofcellstargetedbyantibodycanoccurbywayofeitherthe
complementsystemorbyantibody‐dependentcell‐mediatedcytotoxicity(ADCC),whichdoesnotrequirecomplement
b. Occurbecausethecellsarecoated(opsonized)withmoleculesthatmakethemattractivetophagocytesorbecauseoftheformationofmembraneattackproteinsthatdisrupttheintegrityofthecellmembraneandcausecelllysis
c. WithADCCdestruction,cellsthatarecoatedwithlowlevelsofIgGantibodyarekilledbyavarietyofeffectorcellsthatbindtotheirtargetbytheirreceptorsforIgG,andcelllysisoccurswithoutphagocytosis
d. Examplesi. Mismatchedbloodtransfusionreactions,hemolyticdiseaseofthe
newbornduetoABOorRhincompatibilityii. Certaindrugreactions
o Bindingofcertaindrugsordrugmetabolitestothesurfaceofredorwhitebloodcellselicitsanantibodyresponsethatlysesthedrug‐coatedcell
o Causestransientanemia,leukopenia,orthrombocytopenia,o Correctedbytheremovaloftheoffendingdrug
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Chapter19:DisordersoftheImmuneResponse 8
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2. Complement‐andantibodyreceptor‐mediatedinflammationa. Whenantibodiesaredepositedintheextracellulartissues,suchas
basementmembranesandmatrix,theinjuryistheresultofinflammationratherthanphagocytosisorcelllysis
b. Depositedantibodiesactivatecomplement,generatingchemotacticbyproductsthatrecruitandactivateneutrophilsandmonocytesreleasedenzymescauseinflammationanddamagetissuesglomerulonephritis,vascularrejectioninorgangrafts,andotherdiseases
c. Goodpasturesyndromeantibodybindstoamajorstructuralcomponentofpulmonaryandglomerularbasementmembranes,causingpulmonaryhemorrhageandglomerulonephritis
3. Antibody‐mediatedcellulardysfunctiona. Antibodybindingtospecifictargetcellreceptorsdoesnotleadtocell
death,buttoachangeincellfunctionb. Gravesdiseaseautoantibodydirectedagainstthyroid‐stimulating
hormone(TSH)receptorsonthyroidcellsstimulatesthyroxineproduction,leadingtohyperthyroidism
c. Mmyastheniagravis,autoantibodiestoacetylcholinereceptorsontheneuromuscularendplateseitherblocktheactionofacetylcholineormediateinternalizationordestructionofreceptors,leadingtodecreasedneuromuscularfunction
C. TypeII,hypersensitivityreactionsresultfrombindingofantibodiestonormaloralteredsurfaceantigens1. Opsonizationandcomplement‐
orantibodyreceptor‐mediatedphagocytosisorcelllysisthroughmembraneattackcomplex(MAC)
2. Complement‐andantibodyreceptor‐mediatedinflammationresultingfromrecruitmentandactivationofinflammation‐producingleukocytes(neutrophilsandmonocytes)
3. Antibody‐mediatedcellulardysfunction,inwhichantibodyagainstthethyroid‐stimulatinghormone(TSH)receptorincreasesthyroidhormoneproduction
4. Antibodytoacetylcholinereceptorinhibitsreceptorbindingoftheneurotransmitterinmyastheniagravis
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Chapter19:DisordersoftheImmuneResponse 9
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XIII. TypeIIIImmuneComplexAllergicDisordersA. Mediatedbytheformationofinsolubleantigen‐antibodycomplexes,
complementfixation,andlocalizedinflammationB. Activationofcomplementbyimmunecomplexgenerateschemotacticand
vasoactivemediatorsthatcausetissuedamagebyalterationinbloodflow,increasedvascularpermeability,destructiveactionofinflammatorycells
C. Immunecomplexesformedinthecirculationproducedamagewhentheycomeincontactwiththevesselliningoraredepositedintissues,includingtherenalglomerulus,skinvenules,lung,andjointsynovium1. Vasculitisseenincertainautoimmunediseases2. Systemicimmunecomplexdisordersserumsickness
a. Triggeredbythedepositionofinsolubleantigen‐antibody(IgM,IgG,andoccasionallyIgA)complexesinbloodvessels,joints,andheartandkidneytissue
b. Mostcommoncauses:antibiotics(especiallypenicillin)andotherdrugs,variousfoods,andinsectvenom
c. S/S:urticaria,patchyorgeneralizedrash,extensiveedema(usuallyoftheface,neck,andjoints),andfever
d. Treatmentremovalofthesensitizingantigenandprovidingsymptomreliefi. Aspirinforjointpainandantihistaminesforpruritusii. Epinephrineorsystemiccorticosteroidsmaybeusedforsevere
reactions3. LocalizedimmunecomplexreactionsArthusreaction
a. Localizedtissuenecrosis(usuallyintheskin)causedbyimmunecomplexes
b. Producedbyinjectinganantigenpreparationintotheskinofanimmuneanimalwithhighlevelsofcirculatingantibody
c. Within4to10hours,ared,raisedlesionappearsontheskinatthesiteoftheinjectioni. Ulceroftenformsinthecenterofthelesionii. Injectedantigendiffusesintolocalbloodvessels,whereitcomes
incontactwithspecificantibody(IgG)toincitealocalizedvasculitis
D. TypeIII,immunecomplexreactionsinvolvingcomplement‐activatingIgGorIgMimmunoglobulinswith1. Formationofblood‐borneimmune
complexesthatare2. depositedintissues.Complement
activationatthesiteofimmunecomplexdeposition
3. leadstoattractionofleukocytesthatareresponsibleforvesselandtissueinjury
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Chapter19:DisordersoftheImmuneResponse 10
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XIV. TypeIVHypersensitivityReactionsA. Cell‐mediatedratherthanantibody‐mediatedimmuneresponse
1. Principalmechanismofresponsetoavarietyofmicroorganisms,includingintracellularandextracellularpathogens
2. Canleadtocelldeathandtissueinjuryinresponsetochemicalantigens(contactdermatitis)orself‐antigens(autoimmunity)
B. MediatedbyspecificallysensitizedTlymphocytesdividedintotwobasictypes1. Directcell‐mediatedcytotoxicity
a. CD8+cytotoxicTlymphocytes(CTLs)directlykilltargetcellsthatexpresspeptidesderivedfromcystosolicantigensthatarepresentedinassociationwithclassIMHCmolecules
b. ViralinfectionsCTLresponsescanleadtotissueinjurybykillinginfectedtargetcellsevenifthevirusitselfhasnocytotoxiceffects
c. CTLscannotdistinguishbetweencytopathicandnoncytopathicviruseskillvirtuallyallinfectedcellsregardlessofwhethertheinfectionisharmful
d. HepatitisthedestructionoflivercellsisduetothehostCTLresponseandnotthevirus
2. Delayed‐typehypersensitivitya. Occurinresponsetosolubleproteinantigensandprimarilyinvolve
antigen‐presentingcellssuchasmacrophagesandCD4+helperTcellsoftheTH1type
b. DuringthereactionTH1cellsareactivatedandsecreteanarrayofcytokinesthatrecruitandactivatemonocytes,lymphocytes,fibroblasts,andotherinflammatorycells
c. Requirethesynthesisofeffectormoleculesandtake24to72hourstodevelop,whichiswhytheyarecalled“delayed‐type”hypersensitivitydisordersi. Best‐knownDTHresponseisthereactiontothetuberculintest,in
whichinactivatedtuberculinorpurifiedproteinderivativeisinjectedundertheskinareaofrednessandindurationdevelopswithin8to12hours,reachingapeakin24to72hours
ii. Allergiccontactdermatitiso Inflammatoryresponseconfinedtotheskinthatisinitiatedby
reexposuretoanallergentowhichapersonhadpreviouslybecomesensitized
o Erythematous,papular,andvesicularlesionsassociatedwithintensepruritusandweeping
o Affectedareaoftenbecomesswollenandwarm,withexudation,crusting,anddevelopmentofasecondaryinfection
o Severityofthereactionassociatedwithcontactdermatitisrangesfrommildtointense
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o BecausethisconditionfollowsthemechanismofaDTHresponse,thereactiondoesnotbecomeapparentforatleast12hoursandusuallymorethan24hoursafterexposure
o Diagnosis:patchtesto Treatment
Removeirritant Topicalpreparationsointments,corticosteroidcreams
torelievesymptomaticskinlesionsandpreventsecondarybacterialinfections
Severereactionssystemiccorticosteroidsiii. Hypersensitivitypneumonitis
o Exposuretoinhaledorganicdustsorrelatedoccupationalantigens
o InvolveasusceptiblehostandactivationofpulmonaryTcells,followedbythereleaseofcytokinemediatorsofinflammation
o Produceslaboredbreathing,drycough,chillsandfever,headache,andmalaise
o “Farmer'slung,”aconditionresultingfromexposuretomoldyhay
o Diagnosis:obtainagoodhistory(occupationalandotherwise)ofexposuretopossibleantigens
o Treatmentconsistsofidentifyingandavoidingtheoffendingantigensorsystemiccorticosteroids
C.
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XV. HypersensitivityReactionsA. Exposuretolatexmayoccurbycutaneous,mucousmembrane,inhalation,
internaltissue,orintravascularroutes1. Mostseverereactionshaveresultedfromlatexproteinscomingin
contactwiththemucousmembranesofthemouth,vagina,urethra,orrectumcondoms
2. Allergicreactionstolatexproductscanbetriggeredbythelatexproteinsorbytheadditivesusedinthemanufacturingprocessa. Cornstarchglovepowderhasanimportantroleintheallergic
responselatexproteinsreadilyabsorbedbyglovepowderandbecomeairborneduringremovaloftheglove
b. High‐exposureareassuchasoperatingroomswherepowderedglovesareusedcontainsufficientlyhighlevelsofaerosolizedlatextoproducesymptomsinsensitizedpersons
B. TypeofLatexAllergies1. TypeI,IgE‐mediatedhypersensitivityreaction
a. Occurinresponsetothelatexproteinsb. Urticaria,rhinoconjunctivitis,asthma,oranaphylaxisc. Diagnosis:serumIgGlevels
2. TypeIV,Tcellmediatedresponsea. Mostcommontypeofreactionb. Contactdermatitisusuallydevelops48to96hoursafterdirect
contactwithlatexadditivesaffectsthedorsumofthehandsandischaracterizedbyavesicularrashglovecontactiscontinued,theareabecomescrustedandthickened
c. Diagnosis:serumTH1C. Treatment
1. Avoidinglatexexposure,medicalbracelet,skinmoisturizer2. Useofpowder‐freeglovescanreducetheamountofairbornelatex
particles3. Healthcareworkerswithsevereandlife‐threateningallergymaybe
forcedtochangeemployment4. Allsurgicalorotherproceduresonpersonswithlatexallergyshouldbe
doneinalatex‐freeenvironmentinwhichnolatexglovesareusedintheroomorsurgicalsuiteandnolatexaccessories(e.g.,catheters,adhesives,tourniquets,andanesthesiaequipment)comeincontactwiththepatient
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D. XVI. TransplantationImmunopathologies
A. Processoftakingcells,tissues,ororgans,calledagraft,fromoneindividual,andplacingthemintoanotherindividual
B. Theindividualwhoprovidedthetissueiscalledthedonor,andtheindividualwhoreceivesthegraftiscalledeithertherecipientorthehost
C. Rejection:processinwhichtherecipient'simmunesystemrecognizesthegraftasforeignandattacksit
D. Typesoftransplants1. Allogenicdonorandrecipientarerelatedorunrelatedbusharesimilar
HLAtypes2. Sygeneicdonorandrecipientareidenticaltwins3. Autologousdonorandrecipientarethesameperson
E. CellsurfaceantigensthatdeterminewhetherthetissueoftransplantedorgansisrecognizedasforeignaretheMHCorhumanleukocyteantigensMajorHistocompatibilityComplex1. Lymphocyterecognition2. Antigenpresentation3. Controltheimmuneresponsethroughrecognitionofselfandnonself4. Themoredifferenttheyare,thehigherchancethebodywillrejectthe
donor
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F. Rejectionisacomplexprocessthatinvolvescell‐mediatedimmunityandcirculatingantibodies
G. BasicPatternsofTransplantRejection1. Hyperacutereaction
a. Occursalmostimmediatelyaftertransplantationb. Producedbyexistingrecipientantibodiestograftantigensthat
initiateatypeIII,Arthus‐typehypersensitivityreactioninthebloodvesselsofthegraft
c. Antibodiesusuallyhavedevelopedinresponsetopreviousbloodtransfusions,pregnanciesinwhichthemothermakesantibodiestofetalantigens,orinfectionswithbacteriaorvirusespossessingantigensthatmimicMHCantigen
d. Veryveryraremismatch,seriouscomplicationproblemwithsamplehandling(humanerror)
2. Acuterejectiona. Occurswithinthefirstfewmonthsaftertransplantationandis
evidencedbysignsoforganfailureb. Mayoccursuddenlymonthsorevenyearslater,after
immunosuppressionhasbeenusedandterminatedc. Tlymphocytesplayacentralroleinacuterejection,respondingto
antigensinthegrafttissueactivatedTcellscausedirectlysisofgraftcellsandrecruitandactivateinflammatorycellsthatinjurethegraft
d. Canbecontrolledbyimmunosuppressanttherapye. TypeIVreaction
3. Chronicrejectiona. Occursoveraprolongedperiodb. Manifestswithdenseintimalfibrosisofbloodvesselsofthe
transplantedorganc. Renaltransplantcharacterizedbyagradualriseinserum
creatinineoveraperiodof4to6monthsd. Common
XVII. Graft‐Versus‐HostDiseaseA. Occurswhenimmunologicallycompetentcellsorprecursorsare
transplantedintorecipientswhoareimmunologicallycompromisedB. InvolvesactivatedCD4+andCD8+Tcellswithultimategenerationofatype
IV,cell‐mediatedDTHandCTLreactionsC. ThreebasicrequirementsarenecessaryforGVHDtodevelop
1. Transplantmusthaveafunctionalcellularimmunecomponent2. Recipienttissuemustbearantigensforeigntothedonortissue3. Recipientimmunitymustbecompromisedtothepointthatitcannot
destroythetransplantedcellsD. AcuteGVHD
1. Developswithindaystoweeksaftertransplantation2. Involvestheepithelialcellsoftheskin,liver,andgastrointestinaltract
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a. Skindevelopmentofapruritic,maculopapularrash,whichbeginsonthepalmsandsolesandfrequentlyextendsovertheentirebody,withsubsequentdesquamation
b. Gastrointestinalsymptomsincludenausea,bloodydiarrhea,andabdominalpain
c. Liverpainlessjaundice,hyperbilirubinemia,andabnormalliverfunctiontestresultsi. Progresstodevelopmentofveno‐occlusivedisease,drugtoxicity,
viralinfection,ironoverload,extrahepaticbiliaryobstruction,sepsis,andcoma
ii. Veno‐occlusivediseaseobliterationofthesmallhepaticveinsandvenulescentrilobularcongestionandhepatocellularnecrosis
E. ChronicGVHD1. Whensymptomspersistorbegin100daysormoreaftertransplantation2. MayfollowacuteGVHDoritmaydevelopinsidiously3. Developskinlesionsresemblingsystemicsclerosisandmanifestations
mimickingotherautoimmunediseasesF. Treatmentblockanyofthe3stepsofpathogenesisTcellactivationand
actionofcytokines1. Immunosuppressivedrugscyclosporine,tacrolimus2. Anti‐inflammatorydrugsorglucocorticoids
XVIII. AutoimmuneDiseaseA. Self‐toleranceabilityoftheimmunesystemtodifferentiateselffrom
nonself1. HLAantigensencodedbyMHCgenesthatserveasrecognitionmarkersof
selfandnonselffortheimmunesystem2. Autoimmunityresultsfromlossofself‐tolerance
B. Systemic1. Mixedconnectivetissuedisease2. Polymyositis‐dermatomyositis3. Rhematoidarthritis4. Scleroderma5. Sjögrensyndrome6. Systemiclupuserythematosus
C. Blood1. Autoimmunehemolyticanemia2. Autoimmuneneutropeniaandlymphopenia3. Idiopathicthrombocytopenicpurpura
D. Otherorgans1. Acuteidiopathicpolyneuritis2. Atrophicgastritisandperniciousanemia3. Autoimmuneadrenalitis4. Goodpasturesyndrome5. Hashimotothyroiditis
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6. Type1DM7. Myastheniagravis8. Prematuregonadal(ovarian)9. Primarybiliarycirrhosis10. Sympatheticopthalmia11. Temporalarteritis12. Thyrotoxicosis(Gravesdisease)13. Crohndisease,ulcerativecolitis
E. Mechanismsofautoimmunedisease1. Inheritanceofsusceptibilitygenesthatcontributetothemaintenanceof
self‐tolerance2. Gender
a. SLEoccurmorecommonlyinwomenthanmen,suggestingthatestrogensmayplayaroleinthedevelopmentofautoimmunedisease
b. Estrogensstimulateandandrogenssuppresstheimmuneresponse3. Environmentalfactorsthatpromotetheactivationofself‐reactive
lymphocytesa. Infectiousagentsb. BreakdownofT‐cellanergy(stateofunresponsivenesstoantigen)
prolongedorirreversibleinactivationoflymphocytes,suchasthatinducedbyanencounterwithself‐antigens
4. FailuresofSelftolerancea. DisordersinMHC‐antigencomplex‐receptorinteractionsb. Molecularmimicrymicrobesharesanimmunologicepitopewith
thehostc. Superantigensfamilyofsubstancesabletoshort‐circuitthe
normalsequenceofeventsinanimmuneresponse,leadingtoinappropriateactivationofCD4+helperTcells
F. Summary Autoimmune diseases represent a disruption in self-tolerance that results in damage to body tissues by the immune system. Autoimmune diseases can affect almost any cell or tissue of the body. The ability of the immune system to differentiate self from nonself is called self-tolerance. Normally, self-tolerance is maintained through central and peripheral mechanisms that delete autoreactive B or T cells or otherwise suppress or inactivate immune responses that would be destructive to host tissues. Defects in any of these mechanisms could impair self-tolerance and predispose to development of autoimmune disease. The ability of the immune system to differentiate foreign from self-antigens is the responsibility of HLA encoded by MHC genes. Antigen is presented to receptors of T cells in combination with MHC molecules. Among the possible mechanisms responsible for development of autoimmune disease are failure of T-cell-mediated immune suppression; aberrations in MHC-antigen-TCR interactions; molecular mimicry; and superantigens. The suggested criteria for determining that a disorder results from an autoimmune disorder are evidence of an autoimmune reaction, determination that the immunologic findings are not secondary to another condition, and the lack of other identifiable causes for the disorder.