HypersensitivityGuangjieChenDept.ofImmunologyandMicrobiology2015超敏反应英五班课件TheBigBangTheory超敏反应英五班课件 Hypersensitivity （allergy） Hypersensitivityisaninappropriateimmuneresponse,which is heightened reactivity to an antigen, suchresponse lead to tissue damage, immunopathology.ThevarioushypersensitivitystateswereclassifiedintoIthroughIVtypesbyGellandCoombs.TypeI,IIandIIIreactionsaremediatedbyantibodies,whereastypeIVreactionsaremediatedbyTcells.超敏反应英五班课件I. Type I hypersensitivity（anaphylaxis）1.The major components （1）allergen drug, chemical inhalant allergen ：pollens、Dust mite food allergens：nuts, seafood 超敏反应英五班课件Planetree超敏反应英五班课件Castor-oil plant超敏反应英五班课件Dust mite超敏反应英五班课件（2）Ig E antibody and IgE receptorTh2Igheavychainisotypeswitching超敏反应英五班课件Levels of Ig E and atopic diseases超敏反应英五班课件 IgE and IgE receptorsIgE-FcRI(ITAM)AntigenindirectlycrosslinksFcRonmastcellsorbasophils?超敏反应英五班课件（3）CellsMastcell/basophils:FcRIeosinophils：expressFcRIafterstimulationofIL-5，MCP-3CrosslinkDegranulationReleaseofpreformedmediatorsandnewlyproducedmediators超敏反应英五班课件超敏反应英五班课件LightphotomicrographandElectronmicrographofMastcellactivationAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaunders超敏反应英五班课件2. Mechanism of Type I hypersensitivitySensitization phaseExcitation phaseEffector phase超敏反应英五班课件1. Sensitization phaseallergen enter the body stimulate Ag-specific B cells differentiated to plasma cells production of IgE Bind with high-affinity Fc RI which expressed by mast cells and basophils Activatedmastcelloractivatedbasophil超敏反应英五班课件2.ExcitationphaseThe same allergen enter the body againbind to IgE which was bound to mast cells and/or basophils, cross link of Fc RI induction the degranuation of mast cells and basophils, release biological active mediators超敏反应英五班课件Biological active mediators ： 1. preformed mediators：histamine, eosinophil chemotactic factor (ECF), kininogenase , tryptase 2. newly produced mediators: leukotrienes, prostaglandin D2, platelet activating factor, cytokines超敏反应英五班课件3. Effector phase Immediate phaseseveral seconds after contact of allergen, can persist several hours, caused by histamineLate phase6-12h after contact of allergen, can persist several days超敏反应英五班课件Distribution and function of histaminetypeoftissueeffectclinicalreceptorcontractionrelaxationmanifestationH1airway smooth muscles +asthmaalimentary tract muscles +diarrhea,vomitvascular endothelial cell +edemaH2vascular smooth muscle +shock超敏反应英五班课件AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersBiologiceffectsofmediatorsofimmediatehypersenitivity超敏反应英五班课件DifferentsubstancescrosslinkFcRimage.baidu.com超敏反应英五班课件3. Ig E mediated allerigic diseases (type I hypersensitivity) (1) anaphylactic shock caused by drugs (2) anaphylactic shock caused by animal serum（TAT） (3) hypersensitivity reaction in respiratory tract allerigic rhinitis, bronchial asthma超敏反应英五班课件(5) hypersensitivity reaction in skin(4) hypersensitivity reaction in gastrointestinal tract seafood, milkBeestingurticaria超敏反应英五班课件超敏反应英五班课件Allergicreactioninresponsetotestantigenscanbedividedintoanimmediateresponseandalate-phaseresponseAsthmaticresponseinthelungswithnarrowingoftheairwaysPFER:peakexpiratoryflowrate超敏反应英五班课件4. Principals of prevention and therapy for type I hypersensitivity超敏反应英五班课件（1） Skin test超敏反应英五班课件（2）Desensitization therapyHeteroserum desensitization：small dose, repeated injection, 30-50 min interval（TAT）allergic to penicillin is forbidden to use this methodSpecific allergen desensitization ： small dose, repeated injection, long time interval, inducing IgG production，decreasing IgE production超敏反应英五班课件（3) Drug therapy超敏反应英五班课件HygienehypothesisTheremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwo decades is thought to be caused bychanges in the environment due toimproved hygiene and fewer childhoodinfection.超敏反应英五班课件II. Type II hypersensitivity （cytotoxic hypersensitivity） 超敏反应英五班课件1.Mechanism of type II hypersensitivity（1）Agcell surface Ag Ab（IgG）超敏反应英五班课件（2）specific Ab, complement and effector cellADCC、CDC、phagocytosis超敏反应英五班课件超敏反应英五班课件2. Common diseases caused by type II hypersensitivity（1）transfusion reactions Blood typeAgAb/serumA Aanti-BB Banti-AAB A、BnoneO Hanti-A、anti-B超敏反应英五班课件（2）Hemolytic disease of the newborn induced by Rhesus incompatibility超敏反应英五班课件（3）Autoimmune hemolytic anemia infection: changed epitope drug: hapten 超敏反应英五班课件（4）Graves disease (special type) Thyroid epithelial cellTSH-RTSHT3、T4Anti-TSH-R Ab超敏反应英五班课件image.baidu.com超敏反应英五班课件超敏反应英五班课件III. Type III hypersensitivity （soluble immune complex） 1.Mechanism of type III hypersensitivitylargeimmunecomplexes-phagocytosissmallimmunecomplexes-kidneyfiltrationmedieumimmunecomplexes-existforalongtime,depositinsmallvessels超敏反应英五班课件超敏反应英五班课件2. Common diseases caused by type III hypersensitivity （1）local immune complex-mediated diseases1903ArthusArthusreaction,arthus-likereaction 超敏反应英五班课件Inhaled antigen induced type III hypersensitivityDiseasesantigenhaydustfarmerslungfurproteinfurrierslung pigeondroppingspigeon-fanciersdiseasePenicilliumcaseisporescheesewashersdiseaseHiddenmoldsporesmaplebarkstrippersdisease超敏反应英五班课件（2）Systemic immune complex-mediated diseasesSerumsicknessPoststreptococcalglomerulonephritisRheumatoidarthritisSystemiclupuserythematosus超敏反应英五班课件Serumsickness超敏反应英五班课件超敏反应英五班课件超敏反应英五班课件IV. Type IV hypersensitivity（cell mediated, delayed type） 1.Mechanism of type IV hypersensitivityAg effector cellInflammation and cytotoxicityTh1Tc超敏反应英五班课件超敏反应英五班课件2. Common diseases caused by type IV hypersensitivity （1）Infective hypersensitivityLeprosy超敏反应英五班课件TuberculosisAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaunders超敏反应英五班课件Contactdermatitiscausedbyivyprison（2）Contact dermatitis 超敏反应英五班课件AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersExample：purified protein derivative (PPD), a protein Ag ofmycobacterium tuberculosis, elicits a DTH reaction,calledtuberculinreaction.Positive skin test response is clinical indicator forevidenceofpreviousoractivetuberculosisinfection.超敏反应英五班课件超敏反应英五班课件Key points：DefinitionofhypersensitivityreactionsMechanismofhypersensitivityreactionoffourtypesRelateddiseases超敏反应英五班课件Essay DiscussONE ofthefollowingstatements1.Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.超敏反应英五班课件2.Allergicdiseases,includingrhinitisandasthma,arechronicinflammatory disorders with a prevailing Th2 immuneresponse.Theinhalationofallergensleadstohyperreactivity,recruitmentofeosinophils,mastcells,andlymphocytesintheupperandlowerairwaystriggeringtheinflammatorycascadeand generating local and systemic inflammatory responses.Th17cellsandIL-17Aplayaroleinthedevelopmentandprogression of allergic diseases. Pharmacological treatmentmightrestorethebalancebetweenTh17andTregpromotingtheresolutionofinflammationinairwaydiseases.WhatstheroleofTh17andIL-17Ainasthmaandrhinitis?超敏反应英五班课件超敏反应英五班课件