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