Hypersensitivity,Guangjie Chen Dept. of Immunology and Microbiology 2015,The Big Bang Theory,Hypersensitivity （allergy） Hypersensitivity is an inappropriate immune response, which is heightened reactivity to an antigen, such response lead to tissue damage, immunopathology. The various hypersensitivity states were classified into I through IV types by Gell and Coombs. Type I, II and III reactions are mediated by antibodies, whereas type IV reactions are mediated by T cells.,I. Type I hypersensitivity（anaphylaxis）,The major components （1）allergen drug, chemical inhalant allergen ：pollens、Dust mite food allergens：nuts, seafood,Plane tree,Castor-oil plant,Dust mite,（2）Ig E antibody and IgE receptor,Levels of Ig E and atopic diseases,IgE and IgE receptors IgE-Fc RI (ITAM),Antigen indirectly cross links FcR on mast cells or basophils?,（3）Cells,Mast cell/ basophils: FcRI eosinophils：express FcRI after stimulation of IL-5，MCP-3 Cross link Degranulation Release of preformed mediators and newly produced mediators,Light photomicrograph and Electron micrograph of Mast cell activation,Abul K. abbas et al. Cellular and Molecular Immunology, 7th edition, Elsevier Saunders,2. Mechanism of Type I hypersensitivity,Sensitization phase Excitation phase Effector phase,1. Sensitization phase allergen enter the body stimulate Ag-specific B cells differentiated to plasma cells production of IgE Bind with high-affinity FcRI which expressed by mast cells and basophils,Activated mast cell or activated basophil,2. Excitation phase The same allergen enter the body againbind to IgE which was bound to mast cells and/or basophils, cross link of FcRI induction the degranuation of mast cells and basophils, release biological active mediators,Biological active mediators ： 1. preformed mediators：histamine, eosinophil chemotactic factor (ECF), kininogenase , tryptase 2. newly produced mediators: leukotrienes, prostaglandin D2, platelet activating factor, cytokines,3. Effector phase Immediate phaseseveral seconds after contact of allergen, can persist several hours, caused by histamine Late phase6-12h after contact of allergen, can persist several days,Distribution and function of histamine,type of tissue effect clinical receptor contraction relaxation manifestation H1 airway smooth muscles + asthma alimentary tract muscles + diarrhea, vomit vascular endothelial cell + edema H2 vascular smooth muscle + shock,Abul K. abbas et al. Cellular and Molecular Immunology, 7th edition, Elsevier Saunders,Biologic effects of mediators of immediate hypersenitivity,Different substances cross link FcR,image.baidu.com,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,(5) hypersensitivity reaction in skin,(4) hypersensitivity reaction in gastrointestinal tract seafood, milk,Bee sting,urticaria,Allergic reaction in response to test antigens can be divided into an immediate response and a late-phase response,Asthmatic response in the lungs with narrowing of the airways,PFER: peak expiratory flow rate,4. Principals of prevention and therapy for type I hypersensitivity,（1） Skin test,（2）Desensitization therapy Heteroserum desensitization：small dose, repeated injection, 30-50 min interval（TAT） allergic to penicillin is forbidden to use this method Specific allergen desensitization ： small dose, repeated injection, long time interval, inducing IgG production，decreasing IgE production,（3) Drug therapy,Hygiene hypothesis,The remarkable increase in asthma prevalence that has occurred over the last two decades is thought to be caused by changes in the environment due to improved hygiene and fewer childhood infection.,II. Type II hypersensitivity （cytotoxic hypersensitivity）,Mechanism of type II hypersensitivity （1）Ag cell surface Ag Ab（IgG）,（2）specific Ab, complement and effector cell ADCC、CDC、phagocytosis,2. Common diseases caused by type II hypersensitivity （1）transfusion reactions,Blood type Ag Ab/serum A A anti-B B B anti-A AB A、B none O H anti-A、anti-B,（2）Hemolytic disease of the newborn induced by Rhesus incompatibility,（3）Autoimmune hemolytic anemia infection: changed epitope drug: hapten,（4）Graves disease (special type),image.baidu.com,III. Type III hypersensitivity （soluble immune complex）,Mechanism of type III hypersensitivity large immune complexes-phagocytosis small immune complexes-kidney filtration medieum immune complexes-exist for a long time, deposit in small vessels,2. Common diseases caused by type III hypersensitivity,（1）local immune complex-mediated diseases 1903 Arthus Arthus reaction, arthus-like reaction,Inhaled antigen induced type III hypersensit