资料课件讲义immunology12 -e 1

1、HypersensitivityThe excessive or inappropriate reaction of immune response to an antigen is called hypersensitivity, which causes tissue injury orfunctional disorder.1Hypersensitivity reactionsn Antibody-mediatedn Type I, Immediate hypersensitivity - IgEn Type II, Cytotoxic hypersensitivity - IgG (c

2、ell-bound antigens)n Type III, Immune complex-type hypersensitivity- IgG/IgM (soluble antigens)n T Cell-mediatedn Type IV, Delayed-type hypersensitivity234Type I hypersensitivityn Allergy, anaphylaxisn Occur and disappear rapidlyn The major problem is functional disorderalmost without tissue injuryn

3、 Be mediated by Ig E antibodyn Bear an individual difference: atopic families are susceptible to allergic disease5Major Components in Type I Hypersensitivityn Allergensn IgEn Mast cells and basophil : FceR Ion cellsn Eosinophil6Some factors ofType I hypersensitivityn Allergens are antigens that indu

4、ce production ofspecific IgE.n TH2 response is initiatedn B cells produced IgEn IgE binds mast cells, basophils, eosinophils7Examples of allergens: pollens dust mite feces food cockroach antigens animal hair, animal anti-serum, insect venom8Mast cellsn Derived from hemopoietic stem cells in bone mar

5、rown Precursors develop into mast cells intissues under influence ofc-kit (CD117) and Stem Cell Factor (SCF)n Mast cells are most numerous in the skin and mucosal tissuesn Express high affinity FceRI9Contents ofmastcell granules10Contents ofmastcell granules11Basophilsn Granulocytes with very simila

6、r function to mast cellsn Express FceRIn Secrete IL-4 and IL-13n In blood stream12Eosinophilsn Granules rich in basic proteinsn Major basic protein, eosinophil cationic protein, neurotoxinn Toxic to cells and parasitesn Production in bone marrow is stimulated by IL-5, influx into tissues by chemokin

7、e, e.g., eotaxin.n Activated eosinophils express FceRIn Degranulation is induced by eotaxin, C5a, and antigens (via IgE)13Eosinophiln Th2 produce IL-5: Promotes the synthesis and secretion ofIgA from B-cells and also important in stimulating eosinophil developmentand activationn IL-4 and IL-5 produc

8、tion by Th2 cells mayaccount for the eosinophilia seen in type I hypersensitivity and parasitemia14Mediators secreted by eosinophils15Mediators secreted by eosinophils16Processesn Ag/allergen stimulate CD4+ Th2n Th2 releases IL-4, which promote B-cells specific for that Ag to differentiate into IgE

9、producing cellsn Circulating IgE binds to Fc receptors (FceR I ) on mast cells and basophilsn Elicits a transduction event to release mediators stored in granules (Degranulation)n Hypersensitivity response17Production of IgE in Response to an Allergen18Allergen Interaction with IgE on the Surface of

10、 Mast Cells triggers the Release of Inflammatory Mediators19Stages ofallergic reactionsSensitization Production of CD4 TH2 cells Th2 cells release IL-4 to facilitate the B-cell proliferation and differentiation, producing IgE specific for theallergen Binding of IgE to FceRI on mast cells and basophi

11、ls Effecter phase Acute (immediate reaction)n Mast cell/basophil degranulation Late phase reaction - chronicn Influx of eosinophils and eosinophil degranulationn Influx of TH2 CD4 T cells20Sensitization to allergens21Early IL-4 response promotes Th2 development thatdrives B cell class switching to I

12、gE22Activation ofMast Cellsn IgE from B-cells binds to FceRI on mast-cellsn FceRI on mast-cells cross-links with Ag- bounded IgE and induces degranulation of mediators23Mast cell activation by IgEcrosslinking2425resting Mast cells5 min after activation60 min after activationMediator Release from Mas

13、t Cells26Mast cell activationn Pre-formed mediators stored in granulesn Histamine, heparinn Cytokines (Tumor necrosis factor)n Enzymesn Newly synthesized mediatorsn Prostaglandins, leukotrienesn Cytokines and chemokines27Effectsn Increase vascular permeability, vasodilatationn Promote bronchial and

14、visceral smooth muscle contractionn Increase secretion of glands2829Immediate phase reaction :occurs within minutes, mainly caused by histamine.Delayed phase reaction :occurs withinhours, caused by the inducedsynthesis and release ofmediators includingleukotrienes, prostaglandins chemokines, and cyt

15、okines from the activated mast cells.30Immediate and Delayed Phases ofType I HypersensitivityImmediateDelayed313233Diagnosis ofallergiesn Skin testingn Antigen-specific IgEn Radio allergosorbenttest (RAST)n ELISAn Total IgE34Common diseases caused by type Ihypersensitivity1. Systemic allergy:anaphyl

16、actic shock2. Hypersensitivity reaction inrespiratory tractallergic rhinitis， allergic asthma3. Hypersensitivity reaction in gastrointestinal tractFood allergies4. hypersensitivity reaction in skin: urticaria3536Treatment ofallergicreactionsAvoidance ofallergens DrugsInhibitors ofinflammation Bronch

17、odilators1.2.AntihistaminesImmunotherapy (hyposensitization) Antibody therapy: injected monoclonal anti-IgE Ab binds free and mIgE on B cellsDesensitization3.4.Inject ofsmall amount ofallergen to reduce IgE levelShift response via subcutaneous injection37Type IIhypersensitivity38n Antibodies are dir

18、ected against Ag on particular cells/tissue or extracellular matrix, causing damage (ie RBC transfusion)n These cell- or tissue-specific Ab causediseases-Myasthenia Gravis: Ab blocks Ach-binding andcause muscle weakness and paralysis-Graves Disease: Ab stimulate TSH and causehyperthyroidism)39Featur

19、esn Ag is on surface ofcellsn Ab is IgG or IgMn Complements, macrophage, and NK cells participated inn Cell lysis or tissue injury involvedn Many autoimmune diseases result from type II hypersensitivity generated by autoantibodies40Mechanism oftype II hypersensitivityn Complement mediatedn Antibody

20、mediated cellular dysfunctionn Antibody dependent cell cytotoxicity41 Complement-dependent reactions Transfusion reactions Erythroblastosis fetal Autoimmune hemolytic anemia Certain drug reactions42Complement-dependent reactions that lead to lysis of cells or render them susceptible to phagocytosis.

21、43Slide 7.10Antibody-dependent(ADCC).May be relevant to: Graft rejectioncell-mediatedcytotoxicit The destruction oftargets too large to bephagocytosed, such as parasites or tumor cells.44IgG-coated target cells are killed by cells that bear Fc receptors for IgG (e.g., NK cells, macrophages).Slide 7.

22、1145Antibody-mediated cellular dysfunction Myasthenia gravis: muscle weakness Graves disease: hyperthyroidism46Acetylcholine receptor antibodies impair neuromuscular transmission in myasthenia gravis.47The diseases caused by Type II hypersensitivityn Transfusion reactionn Neonate hemolysis (Rh blood

23、 group antigen)n Drug reactionshemolytic anemia, thrombocytopenic purpura , granulocytopenian Autoimmune disease48Reaction Against RBCs and Plateletsn Transfusion Reactions: There are 200 genetic variant of the RBC, but the ABO is the main designationn The Rh system is also important because itscaus

24、e ofhemolytic disease in the newborn49Reaction Against RBCs and Platelets50Reaction Against RBCs and Plateletsn Hemolytic disease ofthe newborn (2nd born)-RhoGam: Its an Anti-Rh+ Antibody given to mother after the first born to prevent future complications inlater newbornsn Autoimmune Hemolytic Anem

25、ia-When provoked by allergic reactions to certain drugs, including Penicillin, quinine, and sulphonamides51Neonate hemolysis52Passive immunization against Rh preventshemolytic anemia ofthe newborn53Hemolytic anemia54Modification ofRBC by penicillin55Production ofanti-penicillin antibodies56Lysis and

26、 phagocytosis ofpenicillin-modified RBC57Antibodies are formed to red blood cell antigensOften occurs in association with other diseases such as lymphoma, or can occur in response to administration of certain drugs such as penicillinHemolysis of red blood cells results inAutoimmuneHemolytic Anemiaan

27、emia characterized by fatigue onexertion, and pallor.Diagnosis is made by the findings of decreased hematocrit (and hemoglobin), destroyed red blood cells on blood smear, and a positive Coombs antiglobulin test which detects the autoantibodies.Treatment is directed at the underlying problem or removal of the drug and may also include steroids58Type II hypersensitivity Mediated Autoimmune Diseasesn Goodpastures syndromen Graves Diseasen Insulin-resistance Diabetes59Goodpastures syndromen Anti