ImmuneS I System t Disorders: Di d Hypersensitivity ype se s t ty&Autoimmunity uto u ty dr.

DickyKurniawan Tontowiputro,SH,SpPD

ImmuneSystemDisorders
Hypersensitivity(Allergy):Anabnormal responsetoantigens. FourTypesofHypersensitivityReactions:
TypeI(Anaphylactic)Reactions TypeII(Cytotoxic)Reactions TypeIII(ImmuneComplex)Reactions TypeIV(CellMediated)Reactions

TypeI(Anaphylactic)Reactions
Occurwithinminutesofexposuretoantigen AntigenscombinewithIgEantibodies IgE g bindstomastcellsandbasophils, p ,causing g

themtoundergodegranulation andrelease severalmediators:

Histamine:Dilatesandincreasespermeabilityof bloodvessels(swellingandredness),increases mucussecretion(runnynose),smoothmuscle contraction(bronchi). Prostaglandins:Contractionofsmoothmuscleof respiratory i systemand di increased dmucussecretion. i Leukotrienes:Bronchialspasms.
Anaphylacticshock:Massivedropinblood

pressure.Canbefatalinminutes.

MastCellsandtheAllergic Response

MastCellsandtheAllergic Response

TypeII(Cytotoxic)Reactions
Involveactivationofcomplement byIgGorIgM

bindingtoanantigeniccell. Antigeniccellislysed. Transfusionreactions:

ABOBloodgroupsystem:TypeOisuniversaldonor. Incompatibledonorcellsarelysedastheyenter bloodstream. RhBloodGroupSystem:85%ofpopulationisRh positive.ThosewhoareRhnegativecanbe sensitizedtodestroyRhpositivebloodcells.
Hemolyticdiseaseofnewborn:Fetalcellsare destroyedbymaternalantiRhantibodiesthatcross theplacenta.

TypeIII(ImmuneComplex)Reactions
Involvereactionsagainstsoluble antigenscirculatingin

serum. UsuallyinvolveIgG antibodies,s0metimesinvolve otherIg suchasIgM. AntibodyAntigenimmunecomplexesaredepositedin organs,activate i complement, l and dcauseinflammatory i fl damage.
Glomerulonephritis:Inflammatorykidneydamage. damage
Occurswithslightlyhighantigenantibodyratiois

p present.

ImmuneComplexMediated Hypersensitivity

TypeIV(CellMediated)Reactions
InvolvereactionsbyTD memorycells. Firstcontactsensitizesperson. Subsequentcontactselicitareaction. Reactionsaredelayed byoneormoredays(delayed

typehypersensitivity).
DelayisduetomigrationofmacrophagesandTcellsto siteofforeignantigens.
Reactionsarefrequentlydisplayedontheskin:

itching,redness,swelling,pain.
Tuberculosisskintest Poisonivy Metals L Latex i ingloves l and dcondoms d ( (3% %of fh health l hcareworkers) k )

Anaphylacticshockmayoccur.

AllergicContactDermatitis ResponsetoPoisonIvyHapten

AutoimmuneDiseases
Loss L of fself lftolerance t l leads l d to t production d ti

ofantibodiesorTcellsthatreactagainst ones ownantigens. ti Immunesystemresponsetoselfantigens causesdamagetoorgans. Threetypesofautoimmunedisorders:

Cytotoxic(TypeIIreactions) Immunecomplex(TypeIIIreactions) Cellmediated(TypeIVreactions)

AutoimmuneDiseases
A.TypeII(Cytotoxic)AutoimmuneReactions Involveantibody reactionstocellsurface molecules,without cytotoxicdestructionof cells.
GravesDisease: Antibodiesattachtoreceptorsonthyroidglandand stimulateproductionofthyroidhormone. Symptoms:Goiter(enlargedthyroid)andbulging eyes. eyes Myastheniagravis: Progressivemuscleweakness.Antibodiesblock acet lcholinereceptorsatneuromuscular acetylcholine ne rom sc larsynapse. s napse Affects25,000Americans(mainlywomen). Todaymostpatientssurvivewhentreatedwithdrugs orimmunosuppressants. i

AutoimmuneDiseases
B.TypeIII(ImmuneComplex)Autoimmune B Reactions
SystemicLupusErythematosus: Affectsabout200,000Americans(90%women). Namederivedfromredskinrashonface. AutoantibodiesreactagainstDNA,bloodcells, neurons,andothertissues. Whencellsdie,immunecomplexes formanddeposit underskin,joints,inkidneys,bloodvessels,and centralnervoussystem. Inflammationinterfereswithnormalfunctionof thesesites(arthritis,rash,kidneydamage). Mostpatientsdiefromkidneydamage. Nocure.Symptomstreatedwithantiinflammatory andimmunosuppressivedrugs.

AutoimmuneDiseases
B.TypeIII(ImmuneComplex)Autoimmune B Reactions(Continued)
RheumatoidArthritis: Affectsabout2millionAmericans(70%+women). Causeunknown,butmicrobialmimicry maybe i involved. l d IgMautoantibodies(rheumatoidfactors)againstIgG p injoint, j ,leading gtoinflammationand formcomplexes cartilagedamage. Oftencausesfingerandjointdeformities. Nocure. cure Symptomstreatedwithantiinflammatory (aspirin)andimmunosuppressivedrugs.Physical therapykeepsjointsmovable.Surgicalreplacement ofjointsmaybenecessary. necessary

AutoimmuneDiseases
C.TypeIV(CellMediated)Autoimmune C Reactions(Continued)
Insulindependent(TypeIorJuvenile)Diabetes

Mellitus: Diabetesaffectsupto5%ofAmericans. IntheU.S.,35,000peopledieeveryyearfromall typesofdiabetesmellitusandcomplications (gangrene,kidneyandcardiovasculardisease, dehydration,andnervedamage).

InsulinDependent(TypeIorJuvenile)Diabetes: Makesup10%ofdiabetescases. cases Characterizedby insufficientinsulinproductionduetoimmunological destructionofinsulinsecretingcellsofthepancreas byTcells. cells Usuallydevelopsbeforetheageof15. 15 Treatedwithinsulininjections.