醫(yī)學(xué)免疫學(xué)課件：TypeⅠ hypersensitivity Mechanism and Treatment

1、Type hypersensitivity Mechanism and Treatment4Signal transductionTreatment目錄 | CONTENT321Brief introductionMast cell & Basophilic granulocyteHpersensitivityHypersensitivity is a set of undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions m

2、ay be damaging, uncomfortable, or occasionally fatal. ClassificationClassificationTypeAlternative namesOften mentioned disordersMediatorsIAllergy(immediate)AtopyAnaphylaxisAsthmaIgEIICytotoxic antibody-dependentAutoimmune hemolytic anemiaIgM or IgGIIIImmune complex diseaseSerum sicknessImmune comple

3、xIVDelayed-type hypersensitivityChronic transplant rejectionT cells Mechanism IgEMast cell basophilic granulocyteHistamineHeparinArachidonic acidMast cell & Basophilic granulocyteA mast cell is derived from the myeloid stem cell. It is a part of the immune and neuroimmune systems and contains many g

4、ranules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and bloodbrain barrier function.Mast cell

5、 mediatorsMast cell mediatorsHistamineProteoglycansSerotoninCytokinesHistamineH1 H2 H3 receptorVascular permabilityRecuritmentCytokines & Growth factorsIL-4 IL-5 IL-6 IL-15 IL-4 IL-5 IL-6Cytokines & Growth factorsIL-4 IL-5 IL-6 IL-15IL-4 induces B-cell class switching to IgE, and up-regulates MHC cl

6、ass II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12.IL-5 stimulates B cell growth and increases immunoglobulin secretion. It is also a key mediator in eosinophil activation.IL-6 is an important mediator of fever and of the acute phase respo

7、nse.Cytokines & Growth factorsThe primary role of TNF is in the regulation of immune cells. TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1 & IL6 producing cells.T

8、NF-alpha(Tumor necrosis factor alpha)FcRIThe high-affinity IgE receptor, also known as FcRI, or Fc epsilon RI, is the high-affinity receptor for the Fc region of immunoglobulin EFcRIFcRI - antibody binding siteFcRI- which amplifies the downstream signalFcRI - the site where the downstream signal ini

9、tiatesDirect type anaphylaxis ANTIGENTH0 cellTH2 cellB cellIgEReverse type anaphylaxis Reverse type anaphylaxis Reverse type anaphylaxis can occur through three distinct mechanisms: antibodies against the Fce portion of IgE (anti-IgE), antibodies against epitopes of the a chain of FceRI (anti-FceRIa

10、) and anti-IgG acting on IgGIgE complexes bound to FceRI.Reverse type anaphylaxisReverse type anaphylaxisReverse type anaphylaxisSignal TransductionSignal TransductionLynITAMsSykPATHWAY 1GAB2Second meassagerSignal TransductionFynPLDLATPATHWAY 2GAB2PI3KPKCPDK1AktNF-AT AP-1Into NucleusMAPKDiseasesATOP

11、YASTHMAAnaphylaxisTreatmentMeta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children and in asthma. The benefits may last for years after treatment is stopped. TreatmentCD4+ T cellTH2IL-4B cellIgEhyersensitivityTH1IL-2BcellIgG

12、normalImmune deviationTreatmentThe regulatory T cells (Tregs), formerly known as suppressor T cells, are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and abrogate autoimmune disease. IgG4 compete with IgEThe omalizumabOmalizumab is a recombinant D

13、NA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglobulin E (IgE) in the blood and interstitial fluid and to membrane-bound form of IgE (mIgE) on the surface of mIgE-expressing B lymphocytes.The omalizumabReferences1 Ishizaka K, Ishizaka T, Hornbrook MM. Phy

14、sicochemical properties of reaginic antibody. V. Correlation of reaginic activity with IgE-globulin antibody. J Immunol 1966; 97:84053.2 Scharenberg AM, Kinet J-P. Early events in mast cell signaltransduction. In: Marone G ed. Human basophils and mast cells: biological aspects. Basel: Karger 1995: 7

15、287.3 Marone G, Poto S, Celestino D, Bonini S. Human basophil releasability. III. Genetic control of human basophil releasability. J Immunol 1986; 137:358892.4 Marone G, Tamburini M, Giudizi MG, Biagiotti R, Almerigogna F, Romagnani S. Mechanism of activation of human basophils by Staphylococcus aureus Cowan 1. Infect Immun 1987; 55:8039.5 Marone G, Columbo