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ALLERGYHYPERSENSITIVITYLecture28:Hypersensi1vityTypeII,III&IV

3thYEARM.B.B.S.PHASEII

ProfessorSohailRao

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Hypersensi=vityTypeII

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TypeIIHypersensi=vity

Alsoknownascytotoxichypersensi3vity

Affectsavarietyoforgansand3ssues

An3gensarenormallyendogenous

Exogenouschemicals(haptens)arealsoinvolved(suchasdinitrophenol)

Drug-inducedhemoly3canemia,etc.

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TypeIIHypersensi=vity

Reac3on3meisminutestohours

Primarilymediatedbyan3bodiesoftheIgMandIgGsubclass

Complementac3va3onplaysamajorroleinthepathogenesis

PhagocytesandKcellsarealsoinvolved

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TypeIIHypersensi=vity

Thelesioncontainsan3bodies,neutrophilsandcomplement

Diagnosis:Detec3onofcircula3ngan3bodyagainstthe

3ssueinvolved

Presenceofan3bodyandComplementinabiopsyofthelesion

Byimmunofluorescence

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GoodpasturesSyndrome

Arareautoimmunediseasethataffectslungsandkidneys

E3ology?UnknownHereditary?Exposuretocertainchemicals

Hydrocarbonsolvents(suchaskerosene,benzene,etc.) WeedKiller(Paraquat)

ViralInfec3ons

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Goodpasture'sSyndrome

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Goodpasture'sSyndrome

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PemphigusVulgaris

Arareblisteringautoimmunediseaseaffec3ngskinandmucousmembrane

Autoan3bodiesaregeneratedagainstDESMOGLEIN

An3body-mediatedcomplement-dependentdestruc3onofdesmoglein

Dissocia3onofepidermalcells-acantholysis Genera3onofblisters

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PemphigusVulgaris-E=ology

Unknown Gene3cFactors:Highincidenceinindividuals

withHLADR4(DRB1*0402)andHLADRw6

(DQB1*050)

Peakageofonset:50-60years

Highassocia3onwithotherautoimmunediseasespar3cularlymyastheniagravisand

thymoma

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PemphigusVulgaris

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PemphigusVulgaris

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PemphigusVulgaris

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Treatment

ImmunosuppressiveDrugsPrograf,Cyclophosphamide,Cyclosporin,etc.

An3-inflammatorySteroids

Plasmaphersis

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Hypersensi=vityTypeIII

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Hypersensi=vityTypeIII

ImmuneComplexDiseasemediatedbysolubleimmunecomplexes

Reac3onmaytakeupto-10hourspost-Agexposure

An3genmaybe:Exogenous(suchaschronicbacterial,viralorparasi3c

infec3ons)

Endogenous(non-organspecificautoimmunity) An3genisalwayssoluble(notaachedtothe

organinvolved)

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Hypersensi=vityTypeIII

Primarycomponentsofreac3on:SolubleAg-IgcomplexesComplement(Ca,4a,and5a)

Tissuedamageiscausedbyplateletsandneutrophils

Macrophagesmaybeiden3fiedinthelesioninlaerstagesmostlyinvolvedwithrepair

Lesionbiopsyshowsinfiltra3onofneutrophilsanddeposi3onofimmunecomplexes

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Hypersensi=vityTypeIII

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Hypersensi=vityTypeIII

Reac3oncouldbe:Generalized(e.g.serumsickness)Organ-specific

Skin(SLE,ArthusReac3on,etc.) Kidney(LupusNephri3s) Lungs(Aspergillosis)

BloodVessels(Polyarteri3s)Joints(RheumatoidArthri3s)

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Hypersensi=vityTypeIII

Diagnosis:Examina3onof3ssuebiopsiesfor:

DepositofIgandcomplementbyimmunofluorescencemicroscopy

StainingisgranularasopposedtoTypeIIwherethestainingislinear

Detec3onofIg-AgcomplexesinseraDeple3oninserumcomplementlevels

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SystemicLupusErythematosus

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SystemicLupusErythematosus

Courseisunpredictablewithflaresandremissions

Effectswomen9xmoreoenthanmen Veryhighincidenceinwomenaged15-5

years

Mayhaveagene3clinkGenesonHLAregiononChromosome6

EnvironmentalfactorsmaytriggerSLEUVlight,extremestress,infec3ons,etc.

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SystemicLupusErythematosus

Diagnosis:History&PhysicalAn3-nuclearAn3body(ANA)inseraAn3-ExtractableNuclearAn3genAn3body(an3-

ENA)insera

Treatment:NoknowntreatmentnocureTreattheorgan-specificclinicalsymptomsImmunosuppressivedrugsandsteroids

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Hypersensi=vityTypeIV

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Hypersensi=vityTypeIV

Cell-mediatedorDelayed-typehypersensi3vity Involvedinthepathogenesisofmany

autoimmunediseasesandinfec3ousdiseases

e.g.tuberculosis,leprosy,leishmaniasis,etc. Alsoinvolvedingranulomasduetoinfec3ons

andforeignan3gens

Anotherformiscontactderma33se.g.,poisonivy,etc.

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Hypersensi=vityTypeIV

Classifiedintothreecategoriesbasedon3meofonset&clinical&histologicalpresenta3on

TypeReac=on

=me

Clinical

appearance

Histology An=genandsite

Contact 48-72hr eczema

lymphocytes,followedby

macrophages;edemaof

epidermis

epidermal(organicchemicals,

poisonivy,heavymetals,etc.)

Tuberculin 48-72hrlocal

indura=on

lymphocytes,monocytes,

macrophages

intradermal(tuberculin,

lepromin,etc.)

Granuloma 21-28days hardeningmacrophages,epitheloidand

giantcells,fibrosis

persistentan=genorforeign

bodypresence(tuberculosis,

leprosy,etc.)

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Hypersensi=vityTypeIV

Diagnosis:History&PhysicalsInvivo:

Montouxtest(tuberculosis) Patchtest(forcontactderma33s)

Invitro: ResponseofTcellstomitogens Produc3onofIL-2

Treatment: Cor3costeroidsand/orImmunosuppressivedrugs

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MontouxTest

InvitrotesttodetermineexposuretoMycobacteriumtuberculosis

An/genusedistuberculinapurifiedproteinderiva/ve(PPD)fromsterile

Mycobacteriumtuberculosiscultures

Injectedintradermallyandtheresultsarecheckedvisuallyonday3-4post

administra/on

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MontouxTest

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PoisonIvyContactDerma==s

Comparison of Different Types of Hypersensi=vity

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ComparisonofDifferentTypesofHypersensi=vity

Characteris=csType-I

(anaphylac=c)

Type-II

(cytotoxic)

Type-III

(immunecomplex)

Type-IV

(delayedtype)

An=body IgE IgG,IgM IgG,IgM None

An=gen exogenous cellsurface soluble /ssues&organs

Response=me 15-30minutes minutes-hours 3-8hours 48-72hours

Appearance weal&flare lysisandnecrosiserythemaand

edema,necrosis

erythemaand

indura/on

Histologybasophilsand

eosinophil

an/bodyand

complement

complementand

neutrophils

monocytesand

lymphocytes

Transferredwith an/body an/body an/body T-cells

Examplesallergicasthma,hay

fever

erythroblastosis

fetalis,Goodpasture's

nephri/s

SLE,farmer'slung

disease

tuberculintest,

poisonivy,

granuloma