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IMMUNOLOGICALDISEASES
ANINTRODUCTIONTOHYPERSENSITIVITY
Allergy&hypersensi?vity
HYPERSENSITIVITY=harmfulimmuneresponses
autoimmunity(selfan1gen)
allergy(foreignan1gen)
Classifica?onofHypersensi?vity
Type
Mechanism
Example
I
IgEmediated
SystemicanaphylaxisegpeanutallergyAsthmaII
An?bodymediated
Haemoly?cdiseaseofthenewbornIII
Immunecomplexmediated
Arthusreac?onGlomerularnephri?sIV
Cellmediated(delayed)
Contactderma??s
Anaphylac1chypersensi1vity
Cytotoxichypersensi1vity
Immunecomplexhypersensi1vity
Cell-mediatedhypersensi1vity
TypeIhypersensi?vity(Immediatereac?on)
• DependantonIgEandMastcells.
• Requirespriorsensi1sa1ontoan1gen.
ResponseoftypeIhypersensi?vity
Mastcelldegranula?on
KeyEvent.Mastcellac?va?on(elicita?onphase)
HistamineProstaglandinD2LeukotrieneC4Cytokines(TNF-α)
YYYYYIgE
an1gen
Effectormechanisms
• Mastcellac1va1on:– preformedmediators
• histamine• enzymes(e.g.tryptase)• TNF-α
– synthesis• leukotrienesC4,D4• IL-4,IL-5
• Results:– vasodila1onandincreasedpermeability– increasedmucussecre1on– bronchoconstric1on– Cough– chemotaxisofotherinflammatorycells
TypeIIhypersensi?vity
• CausedbyIgMorIgGan1bodiestocellsurfaceandextracellularmatrixproteins.
• Absinteractwithcomplementcomponentsandeffectorcellssuchasmacrophagesandneutrophils.
• Thisresultsin1ssuedamageviamechanismsnormallyac1veagainstforeignan1gens.
EXAMPLES
1. Reac1onsagainstincompa1blebloodtransfusions.2. Autoimmunehaemoly1canaemia.Sensi1sedto
pa1ents’ownRBCs.O\endruginduced.3. GoodpasturesSyndrome.Abagainstbasement
membraneproteinsproducenephri1s.4. MyastheniaGravis.Muscularweaknessassociated
withAbstoacetylcholinereceptors.5. Haemoly1cdiseaseofthenewborn.Pregnant
womanissensi1sedtothefetalerythrocytes.
Autoimmunehemoly1canemia
HAEMOLYTICDISEASEOFTHENEWBORN(HDNB)
• Occurswhenmotherhasbecomesensi1sedtoAgontheinfant’serythrocytes.RhesusDcommonly.
• O\enRh–vemothercarryingasecondorsubsequentrhesus+veinfant.
• Sensi1sa1onofthemotherduringthebirthofthefirstRh+vebaby.
• Subsequentchildrenhaveanincreasedriskofbeingaffected.
HAEMOLYTICDISEASEOFTHENEWBORN
Firstbirth Postpartum Subsequentpregnancy
RhD+foetus
RhD-mother
Exposure sensi1sa1on disease
Exposure nosensi1sa1on nodisease
RhD+foetus
Agremovedpreventssensi1sa1on
An?DAbsgivenimmediatelyaVerbirth
Firstbirth Postpartum Subsequentpregnancy
Musclefibres
Acetylcholinefromnerveimpulse
Acetylcholinereceptors
Normalnervesignal
MYASTHENIAGRAVIS
Abagainstthereceptorisonlypartofthediseaseprocess
Muscleweaknessfromreducedsignaltransmission
An1bodiestothereceptorblockacetylcholinebinding
ANAPHYLAXISAnimmediate,severe,systemichypersensi1vityorallergicreac1on,some1mesfatal,usuallycharacterisedbyatleastone
orotherofthefollowingsymptoms,respiratorydifficulty,hypotensionorcirculatoryfailure.Generalisedur1cariaand1ssueswellingalsocommon.
MediatedbyIgEan1bodiesandMastcellsImmunologically
disease.‘TypeOnehypersensi1vity’
Commoncausesofanaphylaxis
• Foods• Serum/vaccines• Beeandwasps1ngs• Drugs• Latexrubber-gloves
Foodscommonlycausinganaphylaxis
• Peanuts• Treenuts(eg.brazilnut,almond,hazlenut)• Fish• Shellfish• Egg• Milk• Sesame
Drugscausinganaphylaxis
• An1bio1cs(especiallypenicillin)• Intravenousanaesthe1cdrugs• Aspirin• Non-steroidalan1-inflammatorydrugs
Ur1cariaRaised,erythematousintenselyitchyskinerup1oncausedbyIgE-mediatedhistaminereleasefrommastcells.
Causes: Drugs Foodallergens penicillin Environmentalallergens cephalosporins Insectbites latex
TheEnd