Abadreaction: Acase Studyinimmunology

ABadReaction: ACase StudyinImmunology

by

JamesA.Hewlett

ScienceandTechnologyDepartment

FingerLakesCommunityCollege,Canandaigua,NewYork

PartI

Youhavebeenawardedagrantin theamount of$1200.Yourresearchteamistousethisgranttocoverthecostsof examiningthecasehistoriesofthreepatients.Yourgoalistomakeadiagnosisfromtheserecordsanddesignatestable experimentthatcanbeusedtoobtainfuturefunding.Youwillnotbegivenmuchtimetoexaminethethreepatient histories,sobepreparedtotakenotesandrecordasmuchinformationasyoucanin thetimeallowed.

Diagnosis

Yourteammustdeliver:

• AdiagnosisforPatient#1andthemajorpiecesofevidencethatyouused.

• AdiagnosisforPatient#2andthemajorpiecesofevidencethatyouused.

• AnexplanationforwhyPatient#3appearsnormal.What arethemajorpiecesofevidencethatyouusedto accountforthis?

Eachpatientrecordcontainsareferencenumber.When recordingapieceofevidencetobackupyourdiagnosisofa patient,youmustreferencetherecordnumberthatyouusedtoobtainthatpieceofevidence.

ExperimentProposal

Yourteammustalsoproduce:

• Atestablehypothesistobackupyourdiagnosisofthethreepatients.

• Adescription ofanexperimentthatcanbeperformedtotestyourhypothesis.

ContentsandCostsofRecords

Individualrecordscost$200.00.Thisiswhatisavailableforeachpatient:

• MedicalHistory—information onlifestyle,surgeries,allergies,andpastmedicalproblems.

• Interviewtranscripts—transcriptstakenfrominterviewswiththepatientsafterbeingadmittedtothehospital.

• Vitalsandtests—Blood pressure,heartrate,bloodcounts(CBC),bloodgasesandresultsfromanyteststhatwererun.

• Organassesment—assesmentsofkidney,liver,andpancreaticfunction.

Youhavebeenprovidedwithasheetthatdescribesthecontentsofeachoftherecords.Yourgrantprovidesyouwith enoughmoneytopurchasesixofthe12recordsthatareavailableforthesethreepatients.

EvaluationCriteria

Theperformanceofyourgroupwillbeevaluatedonthefollowingcriteria:

• Yourdiagnosisforthethreepatientsandthevalueoftheevidencethatyouhaveused.

• Yourproposalforyourexperiment.

• Residualgrantfunds(spendinglessmoneygivesyouahigherscore).

TimeLimitations

• Allinformationshouldberecordedonthedatasheetsprovided.

• Yourapplicationsaredueat[TIME].

PartII

Transfer ofsymptomaticpeanutallergytotherecipientofacombinedliverandkidneytransplant

Miss. Ross, DirectorofGrantsandResearchatNYU, wouldliketoacknowledgeDr.ChristopheLegendreandhis teamofdoctorsfortheirworkonidentifyingthecausativeagentofa symptomaticpeanutallergyacquiredbya35-year-oldmalerecipient ofacombinedliver-and-kidneytransplant.Thefollowingreport summarizestheirworkonthiscase.

A.Introduction

Peanutsareoneofthemostcommoncausesoffoodallergyin the United StatesandEurope.Theyarealsoaleadingcause offood- inducedanaphylaxisanddeath,whichusuallyfollowinadvertent exposures.AllergytopeanutsisanIgE-mediated,mast-cell-dependent, immediate-hypersensitivityreaction.Therearenumerous reportsofthetransferofallergen-specificIgE-mediated hypersensitivitybybonemarrowtransplantation.Wereportacaseof peanutallergytransmittedthroughcombinedliver-and-kidneytransplantation.

Questions

A1. What isthedifferencebetweenan“allergen”andan“antigen”? A2. What ismeantby“anaphylaxis”?

A3. What arethedifferentclassesofantibodiesthatourbodiesproduce?Whichclassisassociatedwiththepeanut allergy?

A4. What isamastcell?What roledomastcellsplayin theimmuneresponse?

A5. Hypersensitivitiescanbedescribedasimmediate,sub-acute,ordelayed.How dothesesensitivitiesdiffer?What evidencedidthedoctorsusetodeterminethatthepeanutallergywasanimmediatehypersensitivity?

B.CasePresentations

A22-year-old manwithahistoryofallergicreactionstopeanutswasadmittedtoourhospitalin acoma.After inadvertentlyingestingsataysauce,whichcontainspeanuts,duringaChinesemeal,hehadbecomeunwellandhad hadacardiorespiratoryarrestthatresultedin cerebralanoxia,coma,andbraindeath.Ahighlevelofpeanut-specific IgEwasdetectedin hisserum... multipleorgansweresubsequentlyprocured.Thedonor’s HLAphenotypewas A1, 24; B8, 44; DRB1*03, 13.

...thedonor’sliverandrightkidneyweregivenin transplantationtoa35-year-oldman,andtheleftkidneyand pancreasweregiventoa27-year-oldwoman.Theman(HLAphenotype,A2, 19; B12,-; DRB1*07, 13)hadend-stage renalfailure....Thewoman(HLAphenotype,A1, 24; B8, 44; DRB1*03, 04)hadchronicrenalfailure....

Bothtransplantrecipientsreceivedimmunosuppressiveinduction therapywithmuromonab-CD3(OKT3)and corticosteroids,azathioprine,andcyclosporine.Neitherhadeverhadanyallergytopeanuts.

Threemonthsaftertransplantation,therecipientoftheliver-kidneytransplantreportedaskinrashandlaryngeal dyspneaaftereatingpeanuts.Allergytopeanutswasdiagnosedonthebasisoftheclinicalfindings;theabsenceof specificIgEantibodiesbeforetransplantation,theirpresenceatthetimethesymptomsappeared,andtheirdecline thereafter;andapositivebasophildegranulationtest.

Questions

B1. What doesHLAstandfor?What isanHLAphenotype?

B2. How doesHLArelatetoMHCin immunephysiology?

B3. Whyisitimportanttounderstandthe“HLAphenotypes”oftheindividualsin thiscase?

B4. Fromwhatyouknowaboutthestructureofanantibody,explainhowanIgEcanbe“peanut-specific.”

B5. Onewaytotestforanallergyistomixaspecificallergenwithbasophilsandmastcellsfromapatientandlook for“degranulation.”What isoccurringwhenthesecellsdegranulate?How doesthisbecomeapositivetestfora specificallergy?

B6. Whywerethepatientsputonanimmunosuppressivetherapyaftertheirtransplantations?

C.Discussion

Thetransferofallergen-specificdonor lymphocytesisalikelypossibility....TheproductionofIgEbyBcellsdepends

onthepresentationofallergensbyantigen-presentingcellsandoncooperationbetween BcellsandregulatoryT-helper lymphocytesoftheTh2type.Inourpatienttheremayhave beentransferofpeanut-specific IgE-producingBcellsor

ofpeanut-specificTh2lymphocytesthatinducedtherecipient’s Bcellstoproducepeanut-specificIgE.

Questions

C1. BrieflydescribetheroleofBcellsandT-helperlymphocytesin immunephysiology.

C2. What isan“antigen-presenting cell”andwhatroledoesthistypeofcellplayin animmuneresponse?

C3. ExplaintheinteractionthatoccursbetweenaT-helperlymphocyteandaBcellwhentheBcellisbeinginduced toproducepeanut-specificIgE.Inyourexplanation,explaintherolethatthepeanutallergenplays in this interaction.

C4. Inimmediatehypersensitivity,theinitialexposuretoanallergenusuallydoesnotproduceanysymptoms.The symptoms,suchasthoseinvolvedin anaphylaxis,usuallyappearin thesecondexposure.What eventsare occurringduringthisinitialexposurethatsensitizesapersontoanallergen.Inyourdescriptionincludetherole ofBcells,Tcells,IgE,mastcells,basophilsandtheallergen.

Passivetransferofdonor IgEisunlikely,becausethehalf-lifeofIgEisonlyafewdays,whereastheallergicreaction occurredthreemonthsaftertransplantation. However,wecannotruleoutthepossibilitythatdonor IgEboundtothe recipient’s mastcellsandbosophilscouldhave persistedformorethanafewdays.

Questions

C5. DescribehowIgEbindsandreactswithbasophilsandmastcells.

C6. Asdescribedin questionC4,theinitialexposuretoanallergenusuallydoesnotproduceanysymptoms.The symptomsusuallyappearin thesecondexposure.What eventsareoccurringduringthissecondexposure?In yourdescriptionincludetheroleofIgE,basophils,mastcells,andtheallergen.

Itisrelevantthattheallergywastransferredfromtheliver-kidneytransplant,butnotfromthepancreas-kidney transplant.Pluripotenthematopoieticstemcellsanddendriticcellsareknowntobenormallyresidentin theliver. Thesepassengercellscanmigratefromthegrafttotherecipient’slymphoidorgans,andmultilineagehematopoiesis derivedfromdonor cellscanpersistforseveralmonthsafterlivergrafting.

Questions

C7. Describethenormalphysiologicalroleofa“pluripotenthemaotpoieticstemcell”in human physiology. C8. What ishappeningwhenthecellsyoudescribedin C7undergo“hematopoiesis?”

C9. Whyisitimportanttonotethepresenceofthesecellsin theliverwhentryingtounderstandthemechanismfor howthepeanutallergywastransferredtothepatient?

C10. Intheintroduction,thedoctorsnoted well-documentedtransfersofallergieswhenbonemarrowwasbeing transplanted.Whyisthisacommonoccurrencewiththistypeoftransplant?

D.RevisitingPatientRecords

Youhavebeensuppliedwiththerecordsofallthreepatientsinvolvedin thiscase.Inordertoconfirmtheconclusions ofDr.ChristopheLegendreandhisgroup,wewillrevisitthemedicalrecordsofthesepatientstoexploreevidencein supportoftheirclaims.

Questions

AlexanderKolineski,22-year-oldmaleorgandonor.

D1. ReviewtherecordsforMr.Kolineskiandsummarizetheevidencetosuggestthatdeathwas causedbyanaphylaxis. D2. Withoutreviewingtherecordsfromtheotherpatients,canyoupositivelyidentifythecausativeagentforthis

patient’sanaphylaxis?Whyorwhynot?

JonathanForken,35-year-oldmalerecipientofaliverandrightkidneyfromMr.Kolineski.

D3. ReviewtherecordsforMr.ForkenandsummarizetheevidencetosuggestthatMr.Forkenwashavingapeanut- specifichypersensitivityreaction.

MelissaJachowiz, 27-year-oldfemale recipientofapancreasandleftkidneyfromMr.Kolineski.

D4. ReviewtherecordsofMrs.Jachowizandsummarizetheevidencetosupportthefactthatshedidnotobtaina peanut-specifichypersensitivityfromhertransplant.

InternetResources

eAllergy.net—AdivisionofAllergyServicesInc.[Anextensivecollectionofallergyresources(bestviewed withInternetExplorer).]

AtAllergy.com[A resourceforunderstandingallergies;containsasearchabledatabaseofarticles.]

FoodAllergy,MayoClinic

AAAAIPatient/PublicResourceCenter-TipstoRemember:FoodAllergy

Anaphylaxis

Anaphylaxis:MedlinePlus,NationalLibraryofMedicine

Understandingthe ImmuneSystem,NationalInstituteofAllergyandInfectiousDisease

ClinicalDiagnosticfortheDeterminationofAllergenInducedBasophilDegranulation

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Photoofpeanuts © Yasonya|Dreamstime.com.CasecopyrightheldbytheNationalCenterforCaseStudyTeachinginScience, UniversityatBuffalo,StateUniversityofNewYork.OriginallypublishedFebruary27,2002.Pleaseseeourusageguidelines,which outlineourpolicyconcerningpermissiblereproductionofthiswork.