医学免疫学英文版课件：Chapter19 Hypersensitivity

1、Chapter19 HypersensitivityDefinition: when primed host touches the same antigen for the second time, appearing a harmful immune response that is heightened reactivity to this antigen, which causes tissue injury or functional disorder. Also called allergy.Types of hypersensitivityType I: anaphylactic

2、 or immediateType II:cytotoxicType III:Immune complexType IV:cell mediated or delayedFour Types of HypersensitivityType: IgE mediatedType: Antibody mediatedType: Immune complex mediatedType: Cell mediated (delayed-type)Type hypersensitivity 1. Dominating features 2. Primary components 3. Process and

3、 mechanism 4. Common clinical disease 5. Measures of defense and therapy1. Features of Type hypersensitivity Also called anaphylaxisBe mediated by IgE antibodyLocalized or systemic changesOccur and disappear rapidlyThe major problem is functional disorder almost without tissue injury Bear an individ

4、ual difference and hereditary background2. Components of a Type hypersensitivity Antigen: Allergen IgE Antibody: IgECells: Mast cells, basophils, eosinophilsReceptor: FcRAllergenAllergen: something a person is allergic to, induce IgE production selectively. Allergens can be to drugs, plants, foods,

5、insects, and animals. IgEWhere does IgE come from?How much is present in serum?Produced by plasma cell following isotype switch.Very little present in serum (0.1-0.5g/ml).Important in combating parasitic infections. Mast cells, basophils, eosinophilsThe IgE produced by plasma cells binds to the Fc r

6、eceptors located on mast cells, basophils or activated eosinophils. When an allergen crosslinks the IgE, the cell degranulates (releases the contents of its granules). Histamine and other proteins that are released result in many of the allergic symptoms.IgE binding Fc receptors There are two kinds

7、of IgE Fc receptors:FcR: high affinityFcR (CD23): low affinityFcR -high affinity receptor (10-9) 40,000-90,000 receptors/cell crosslinking of the receptors causes degranulation Mice that are deficient in FcRI are resistant to systemic anaphylaxisFcR (CD23)low affinity receptor (10-6) soluble formcau

8、ses an increase in IgE production by B cells3. Process and mechanism Allergen-induced period Allergen-stimulated period Effect periodAllergen-induced period Allergen Production of Ig E IgE binds to FcR I on mast cells and basophils AllergenType I: IgE mediatedB cellMHC class IITCRB7CD28CD40CD40Lcyto

9、kinesIL-4Activated B cellPlasma Cell IgEPlasma CellMast cell granulesFcRI IgE IgE IgEFcRIMast cell Primed mast cellAllergen-stimulated period Antigen binding to IgE cross-links FcR molecules on the mast cellsinduces the release of mediators (degranulation) restored mediators new synthesized mediator

10、s (histamine) (leukotrienes) Sensitization against allergenspollen Rest mast cell5min after activation60mins after activationThe activators of mast cellsAllergenDegranulationHistamineProteasesHeparinChemotactic factors for neutrophils and eosinophilsImmediate responseoccurs within minutesMast cell a

11、ctivation products-Preformed mediatorsHistamine: constriction of intestinal and bronchial smooth muscle, mucus secretion, vascular permeability, vasodilatationKininogenase: kinins - constriction of smooth muscle, vascular permeability, vasodilatation, edema, attract neutrophils and eosinophilsActiva

12、ted Mast cellLeukotrienesProstaglandinCytokinesIL-4, IL-5, IL-6 and TNF-Late phase response occurs within hours.Mast cell activation products-Newly formed mediatorsLeukotriene C4 & D4: strong constriction of bronchial smooth muscle, mucus secretion, vascular permeability, vasodilatationProstaglandin

13、 D2: constriction of bronchial smooth muscle, vascular permeability, vasodilatationPAF:platelet aggregation, release histamine and 5-HTEffect periodThe effect of mediators : increase vascular permeability, vasodilatation promote bronchial and visceral smooth muscle contraction increase secretion of

14、glands early phase reaction : occurs within minutes , mainly caused by histamine，PGD constriction of smooth muscle, vascular permeability.late phase reaction : occurs within hours, caused by the induced synthesis and release of mediators including LT, PAF. 4. Common diseases caused by type I hyperse

15、nsitivitySystemic allergy: anaphylactic shock-drug, serumHypersensitivity reaction in respiratory tract allergic rhinitis， allergic asthmaHypersensitivity reaction in gastrointestinal tract food allergiesHypersensitivity reaction in skin: urticaria，eczemaMany people are allergic to the feces of dust

16、 mites.Many organ are be affected by “allergy” The skinUrticaria(hives)Many organ are be affected by “allergy” The skineczema 5.Measures of defense and therapySkin test: find allergenDesensitization: reducing the quantity of IgE present in the individualAnti-allergic drugs(hyposensitization):to bloc

17、k the production or release of mediators or to antagonize mediator actions on target cellsImmunotherapyPrinciples of immunotherapyHyposensitizationIL-13Regulation by TH1 vs TH2A TH1 response reduces allergies because IFN- production inhibits IL-4TH2 response enhances a type I response with productio

18、n of IL-3, IL-4, IL-5 and IL-10IL-4 stimulates the switch to IgEIL-3, -4, -10 enhance mast cell productionIL-3, -5 stimulate eosinophil maturation and proliferationType I: IgE mediatedType II: Antibody mediatedType III: Immune complex mediatedType IV: Cell mediated (delayed-type)Four Types of Hypers

19、ensitivityType hypersensitivity 1. Dominating features 2. Primary components 3. Process and mechanism 4. Common clinical disease1. Dominating features Also called cytotoxic hypersensitivity Ag is on surface of cell Ab is IgG or IgM Complements, macrophage, NK cells participated in Cell lysis or tiss

20、ue injury2. Components of a Type hypersensitivity Antigen: on the surface of target cellAntibody: IgM, IgGCells: macrophage, neutrophil, NKReceptor: FcRComplements 3.Mechanism of type II hypersensitivity Ab is induced by the Ag Binding of the antigen on cells by the corresponding antibody can cause

21、activation of complements-MAC, C3a/5a recruit neutrophils Opsonization of phagocytosis (C3b, Ab) ADCCType II hypersensitivity mechanism4. The diseases caused by Type II hypersensitivityTransfusion ReactionsNeonate hemolysis(Rh blood group antigen)Drug reactions- hemolytic anemia hemolytic anemia, th

22、rombocytopenic purpura, granulocytopeniaGoodpastures syndromeGraves diseaseTransfusion ReactionsABO blood group antigens stimulate a type II response.Usually the antibody produced is IgM.Typing the blood before a transfusion prevents this reactionHemolytic Disease of the NewbornMaternal IgG specific

23、 for the fetal blood groups crosses the placenta and destroys the fetal red blood cellsHemolytic anemia of the newborn can be prevented by treating the mom with an anti-Rh antibody (Rhogam) 72 hours after the first Rh+ child is born.Rhogam binds to the fetal cells and helps them be eliminated before

24、 B cell activation occurs.Drug-Induced hemolytic anemiaSome antibiotics (penicillin, cephalosporin and streptomycin) stick nonspecifically to proteins on red blood cells.An antibody response can develop to the drug/protein complex.Lysis of the red blood cells causes anemia.Drug reaction-hemolytic an

25、emiaType I: IgE mediatedType II: Antibody mediatedType III: Immune complex mediatedType IV: Cell mediated (delayed-type)Four Types of HypersensitivityType hypersensitivity 1. Dominating features 2. Primary components 3. Process and mechanism 4. Common clinical disease1. Dominating featuresAlso calle

26、d Immune complex mediated hypersensitivityAntigen is soluble Antibody is Ig G or IgMImmune complex disease 2. Components of a Type hypersensitivity Antigen: solubleAntibody: IgM, IgG, IgAComplementsCells: basophil, mast cell, neutrophil, plateletsAg+AbImmune complex,ICLarge ICPhagocytosis by phagocy

27、tesSmall ICDischarged from circulationMedium ICExist in circulation, and deposit3.Mechanism of type III hypersensitivityFormation of medium immune complexDeposition of the medium IC on basement membraneThe complements are activated by the IC, producing C3a and C5a, which mediate an local inflammatio

28、n by activating mast cells and basophils and recruiting neutrophils C3a,C5a: active mast cells and basophils-edema Neutrophils: release enzymes-tissue injury Platelets: ischemia, necrosisType III hypersensitivity mechanism4. Diseases caused by type III hypersensitivityLocalized diseases: Arthus reac

29、tionSysmetic diseases: serum sickness poststreptococcal glomerulonephritis rheumatoid arthritis systemic lupus erythematosusArthus reactionArthus reactionType-IIWeal & flare reactionType-IBefore antibiotics were available patients were treated with antiserum produced in horses.Serum sickness occurre

30、d in some of these patients.Serum sickness is caused when the foreign (horse)proteins in the serum are bound by antibodies and form immune complexes.Clemens Pirquet 1874-1929The symptoms of serum sickness are:fever, chills, rash, arthritis and sometimes glomerulonephritis. These occur 7-10 days afte

31、r anti-serum injection.Today serum sickness can occur followingtreatment with antivenin (serum from horsesimmunized with snake venoms).Serum sicknessSystemic lupus erythematosusType I: IgE mediatedType II: Antibody mediatedType III: Immune complex mediatedType IV: Cell mediated (delayed-type)Four Ty

32、pes of HypersensitivityTypehypersensitivity 1. Dominating features 2. Primary components 3. Process and mechanism 4. Common clinical disease1. Dominating featuresA hypersensitivity reaction mediated by specific T cells (Th1)Delayed reaction: arises more than a day after encounter with the same antig

33、en and reaches top reaction in 48-72 hrPathological change is an inflammation characterized by infiltration of macrophage and lymphocyteNo antibody and complement attend2. Components of a Type hypersensitivity AntigenAntibody: noComplements: noCells: T cells, macrophages3.Mechanism of type IV hypersensitivity Formation of sensitized Th1 The same antigen is presented by DC to elicite the secondary response, in which the effector Th1 activates the macrophage to induce an inflammation characterized by infiltration of macrophages and lymphocytes CTL induced cytotoxicity4. Diseases c