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Fachpraktikum Immunreaktionen der Haut Unterlagen zum Selbstudium vor dem Praktikum oder als Repetitorium Prof Dr. Beda M. Stadler Institut für Immunologie Text oder Illustrationen die orange umrandet sind dienen der Information und sind nicht Lernstoff. Falls Sie diese Unterlagen als PDF File und nicht als PPT haben verpassen Sie die Animationen. Das wissen Sie! Immunreaktionen der Haut 2 Working Definition HYPERSENSITIVITY adverse clinical reaction to the antigen or, “when the immune system does something bad to the host, i.e. tissue damage” Immunreaktionen der Haut 3 Coombs and Gell’s Classification of Hypersensitivity Immunreaktionen der Haut 4 Type I Hypersensitivity • Known as: – Immediate hypersensitivity – Anaphylaxis – IgE-associated immune responses Immunreaktionen der Haut 5 Type-I Hypersensitivity: Animation I Production of IgE in Response to an Allergen Immunreaktionen der Haut 6 Type-I Hypersensitivity: Animation II Allergen Interaction with IgE on the Surface of Mast Cells triggers the Release of Inflammatory Mediators Immunreaktionen der Haut 7 Sensitization Immunreaktionen der Haut 8 Triggering Phase Immunreaktionen der Haut 9 Mast cells and Basophils Immunreaktionen der Haut 10 IgE-mediated Activation Immunreaktionen der Haut 11 Biochemical Pathways of IgE-FcRI Activation of Mast Cells Immunreaktionen der Haut 12 Complement: Classical Pathway Immunreaktionen der Haut 13 Anaphylactic-type Degranulation of a Mast Cell Immunreaktionen der Haut 14 Products of Human Mast Cells Granule proteins MBP, ECP, EPO Epithelial damage / loss Muscarinic M2 dysfunction/ AHR LTC4, PAF Mucus hypersecretion, Airway narrowing Attract/activate pro-inflammatory cells Immunreaktionen der Haut Cytokines IL-3, IL-4, IL-5, GM-CSF, IL-6, IL-12, TGF-b Attract/activate eosinophils Airway remodelling, IgE, Th2 polarisation Chemokines Eotaxin, RANTES Attract/activate eosinophils 15 Skin Prick Test In this test a small needle is used to gently prick the skin through a drop of fluid containing a known allergen. It is usually done on the forearm, although with young children it may be done on the back so they don't have to see what is happening. A negative reaction means that you do not have an allergy to that particular allergen. Your clinical symptoms should correlate with the allergens to which you test positive, only then can an allergy be confidently diagnosed. Immunreaktionen der Haut 16 Die Normale Haut …in einem sensibilisierten Individuum Immunreaktionen der Haut 17 Sofort-Reaktion (Minuten) 1. 2. 3. 4. 5. 6. 7. 8. 9. Allergen überwindet Barrieren Rezeptorgebundenes IgE wird kreuzvernetzt Mediatoren verusachen arterielle Dilatation Erhöhung der venösen Permeabilität Blutstau Erythem entsteht, Extravasation von Plasma Schwellung (Quaddel); Histamin wirkt auf sensorische Nerven Neuropeptide stimulieren arterielle Dilatation Es kommt zur peripheren Rötung (flare) Immunreaktionen der Haut 18 Die Spätreaktion 1. 2. 3. Mastzellen und Th2 Zellen produzieren Zytokine, wodurch weitere Entzündungszellen aus der Peripherie angelockt werden. Dadurch entsteht eine nochmalige Schwellung und Rötung. Immunreaktionen der Haut 19 Immediate and Delayed Phases of Type I Hypersensitivity Immediate Delayed Hier ein guter Link mit Beispielen http://www.fpnotebook.com/ENT48.htm Immunreaktionen der Haut 20 Vasculature Skin Upper respiratory Lower respiratory GI Tract Immunreaktionen der Haut 21 Products of Human Eosinophils Immunreaktionen der Haut 22 Inflammation during Bronchial Asthma Immunreaktionen der Haut 23 Higher magnification of Bronchial Asthma Infiltration of eosinophils (bright red cytoplasmic granules). Immunreaktionen der Haut 24 Intervention for Type I Hypersensitivity Immunreaktionen der Haut 25 Intervention for Type I Hypersensitivity Animation: Treatment with monoclonal anti-IgE antibody Immunreaktionen der Haut 26 Type II Hypersensitivity • Directed at Cell-surface or Matrix Antigen • Mediated by IgG • Immune Processes involved: – Classical Complement Pathway – Phagocytosis via FcR and Complement receptor – ADCC via NK cells or eosinophils • Many autoimmune diseases result from type II hypersensitivity generated by autoantibodies Immunreaktionen der Haut 27 Type II Hypersensitivity Antibody-Complement Dependent Mediated Lysis Animation: IgG or IgM reacts with epitopes on the host cell membrane and activates the classical complement pathway. Membrane attack complex (MAC) then causes lysis of the cell. Immunreaktionen der Haut 28 Type II Hypersensitivity Antibody-Complement Dependent Mediated Lysis Example: Autoimmune Hemolytic Anemia Immunreaktionen der Haut 29 Complement Cascade Immunreaktionen der Haut 30 Type II Hypersensitivity Antibody Dependent Cell Mediated Cytotoxicity Animation: Antibodies react with epitopes on the host cell membrane and NK cells bind to the Fc of the antibodies. The NK cells then lyse the cell with pore-forming perforins and cytotoxic granzymes Immunreaktionen der Haut 31 Type II Hypersensitivity Antibody-Mediated Cell Disfunction Example: Myasthenia Gravis Immunreaktionen der Haut 32 Type III Hypersensitivity • “Immune complex disease” • Soluble Ag/IgG or IgM – high titers of each required • Immune processes involved: – classical complement pathway – phagocytic cells Immunreaktionen der Haut 33 Type-III Hypersensitivity: Immune Complex Animation: Large quantities of soluble antigen-antibody complexes form in the blood and are not completely removed by macrophages. These antigen-antibody complexes lodge in the capillaries between the endothelial cells and the basement membrane. The antigen-antibody complexes activate the classical complement pathway and complement proteins and antigenantibody complexes attract leukocytes to the area. The leukocytes then discharge their killing agents and promote massive inflammation. This leads to tissue death and hemorrhage Immunreaktionen der Haut 34 Arthus Reaction Immunreaktionen der Haut 35 Serum sickness Immunreaktionen der Haut 36 Sites of Complex Deposition Site Outcome glomeruli glomerulonephritis blood vessel wall arteritis synovial membrane arthritis skin rash Note: Ab responsible for immune complexes may be generate at a site distant from the point of deposition. Immunreaktionen der Haut 37 Predisposing Conditions • Repeated antigenic exposure • Chronic infection • Autoimmunity • Cancer Immunreaktionen der Haut 38 Acute Vascular Rejection Following Cardiac Transplant Note: Immune complex deposition in the vessels. Immunreaktionen der Haut 39 Examples of Type IV Hypersensitivity Immunreaktionen der Haut 40 TH1-mediated Type IV Hypersensitivity Immunreaktionen der Haut 41 TH1 Influence of Immune Response Immunreaktionen der Haut 42 Positive Tuberculin Reaction Immunreaktionen der Haut 43 Pathways of Cytotoxicity utilized by CTL’s Immunreaktionen der Haut 44 Contact Dermatitis Maybe due to either TH1 or CTL mediated hypersensitivity Immunreaktionen der Haut 45 Patch test This test is used to diagnose delayed allergic reactions such as Contact Dermatitis. It involves taping traces of various known contact allergens on the skin and keeping them there for 48 hours. It can test for allergy to Rubber, Nickel, Lanolin, dyes, cosmetics, solvents, preservatives, and medication. Immunreaktionen der Haut 46 THE END! • To understand various forms of hypersensitivity Coombs and Gell is helpful, but… • remember that many response reflect input for more than one type! Immunreaktionen der Haut 47