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1、Hypersensitivity,Guangjie Chen Dept.of Immunology and Microbiology2015,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 state
2、s 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 allerge
3、ns：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:FcRIeosinophils：express FcRI after stimulation
4、of IL-5，MCP-3Cross linkDegranulation 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,Sensitizati
5、on phaseExcitation phaseEffector phase,1.Sensitization phaseallergen 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 phaseThe
6、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),ki
7、ninogenase,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 histamineLate phase6-12h after contact of allergen,can persist several days,
8、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 Immuno
9、logy,7th edition,Elsevier Saunders,Biologic effects of mediators of immediate hypersenitivity,Different substances cross link FcR,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 react
10、ion 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
11、,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 therapyHeteroserum desensitization：small dose,repeated injection,30-50 min interval（TAT）allergic to penicil
12、lin is forbidden to use this methodSpecific 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 thoug
13、ht 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）Agcell surface Ag Ab（IgG）,（2）specific Ab,complement and effector cellADCC、CDC、phagocytosis,2.Common dis
14、eases caused by type II hypersensitivity（1）transfusion reactions,Blood typeAgAb/serumA Aanti-BB Banti-AAB A、BnoneO Hanti-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)
15、,III.Type III hypersensitivity（soluble immune complex）,Mechanism of type III hypersensitivitylarge immune complexes-phagocytosissmall immune complexes-kidney filtrationmedieum immune complexes-exist for a long time,deposit in small vessels,2.Common diseases caused by type III hypersensitivity,（1）loc
16、al immune complex-mediated diseases 1903 Arthus Arthus reaction,arthus-like reaction,Inhaled antigen induced type III hypersensitivity,Diseases,antigen,hay dust,farmers lung,fur protein,furriers lung,pigeon droppings,pigeon-fanciers disease,Penicillium casei spores,cheese washers disease,Hidden mold
17、 spores,maple bark strippers disease,（2）Systemic immune complex-mediated diseases Serum sickness Poststreptococcal glomerulonephritis Rheumatoid arthritis Systemic lupus erythematosus,Serum sickness,IV.Type IV hypersensitivity（cell mediated,delayed type）,2.Common diseases caused by type IV hypersens
18、itivity,（1）Infective hypersensitivity Leprosy,Tuberculosis,Abul K.abbas et al.Cellular and Molecular Immunology,7th edition,Elsevier Saunders,Contact dermatitis caused by ivy prison,（2）Contact dermatitis,Abul K.abbas et al.Cellular and Molecular Immunology,7th edition,Elsevier Saunders,Example：purif
19、ied protein derivative(PPD),a protein Ag of mycobacterium tuberculosis,elicits a DTH reaction,called tuberculin reaction.Positive skin test response is clinical indicator for evidence of previous or active tuberculosis infection.,Key points：Definition of hypersensitivity reactionsMechanism of hypers
20、ensitivity reaction of four typesRelated diseases,Essay Discuss ONE of the following statements,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 childhoo
21、d infection.,Allergic diseases,including rhinitis and asthma,are chronic inflammatory disorders with a prevailing Th2 immune response.The inhalation of allergens leads to hyperreactivity,recruitment of eosinophils,mast cells,and lymphocytes in the upper and lower airways triggering the inflammatory
22、cascade and generating local and systemic inflammatory responses.Th17 cells and IL-17A play a role in the development and progression of allergic diseases.Pharmacological treatment might restore the balance between Th17 and Treg promoting the resolution of inflammation in airway diseases.,Whats the role of Th17 and IL-17A in asthma and rhinitis?,
