Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download 1. dia - immunology.unideb.hu
Document related concepts
Transcript
HYPERSENSITIVITY REACTIONS Innocous materials can cause hypersensitivity in certain individuals unwanted inflammation damaged cells and tissues Non-proper reaction of the immune system to foreign substances Mainly harmless substances – after second or multiple times The effector mechanisms and tissue destruction in hypersensitivity reactions are identical to those seen in autoimmune diseases. ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS HYPERSENSITIVITY REACTIONS TYPE I ALLERGY TYPE II TYPE III Soluble antigen Cell surface or matrix antigen Soluble antigen IgE Mast cell Hay fever Asthma Systemic anaphylaxis 1-2 min IgG – immune complex FcγR+ cells NK, macrophage Certain drug allergies (penicillin) 4-8 h IgG – immune complex FcγR+ cells Complement Serum sickness Arthus reaction 2-8 h Type II hypersensitivity IgG type antibodies bound to the cell surface or to tissue antigens • cells expressing the antigen become sensitive to complement mediated lysis or to opsonized phagocytosis • frustrated phagocytosiss tissue demage • the antibody inhibits or stimulates target cell function – no tissue damage (e.g. M. gravis – receptor blocker antibodies) MECHANISMS OF TYPE II HYPERSENSITIVITY REACTIONS Hemolytic anemia of newborns Erythroblastosis fetalis NK Mf Killing of target cell by effectormacrophage or NK-cell IgG ADCC IgG C' complement activation Killing of target cell by complementmediated lysis Receptor-specific autoantibody interferes with signal transduction Drug induced Hemolytic anemia Trombocytopenia Penicillin-based antibiotics Anti-arythmic drug quinidin Myastenia gravis Penicillin-induced hypersensitivity FRUSTRATED PHAGOCYTOSIS MEDIATED BY IgG TYPE ANTIBODIES Binding Opsonization Internalization C3b C3b C3b C3b Enzyme release C3b C3R FcR The tissue, which can not be phagocytosed, is damaged Absorbed antigen (drug) C3b Opsonized surface Binding Frustrated Enzyme release phagocytosis TYPE III HYPERSENSITIVITY Antibodies binding to soluble antigens Small circulating immune complexes Depends on: Size of immune complexes Antigen-antibody ratio Affinity of antibody Isotype of antibody Size of immune complexes formed during immune responses The pathology is determined by the site of immune complex deposition Arthus reaction hard swelling, erythema THE PROCESS OF TISSUE DAMAGE CAUSED BY IMMUNE COMPLEXES Antigen C' Immune complex Antibody Complementa ctivation (C3a , C5a ) PMN Chemotaxis C' Endothelium Ba sophil Ba sa l membra ne gra nulocyte Vessel wa ll Thrombocytes Deposition Blood vessel wall permeability Frustrated phagocytosis Vasoactive a mines Immune complexes activate the complement system, neutrophils, bazophil granulocytes and thrombocytes Serum sickness • Mechanisms of tissue demage is independent on the site of deposition • Steps of tissue demage – Formation immune complexes in the blood – Deposition depends on the size, composition and cytophylic properties of the antibody (IgM, IgG, IgA) – FcγRIII has a pivotal role – Permeability of endothelium – Tissue demage • Increased permeability of blood vessels • Reqruitment of neutrophils – enzymes, chemoattractans, dilatators, prostaglandins • fibrosis • Consequences of tissue demage depends on the site of deposition – Acute serum disease – 7 – 10 days • • • • • Polyclonal antibodies against snake venom produced in horses Immune suppresszive anti-lymphocyte globulin Bacterial trombolytic streptokinase – treatment of miocardial infarction Subacute bacterial endocarditis – pathogens are not eliminated Chronic viral hepatitis Skin symptoms of serum sickness Serum sickness TYPE IV HYPERSENSITIVITY REACTION T CELL MEDIATED PROCESS Type IV hypersensitivity reaction Chemokines, cytokines, cytotoxins Tuberculin skin test Ag = antigen Mycobacterium protein (PPD) Introduction of Ag Delayed-type hypersensitivity (DTH) (e.g., tuberculin skin test) TH1 from a previous immunization (memory) Contact Dermatitis *a contact-sensitizing agent is usually a small molecule that penetrates the skin then binds to self-proteins, making them “look” foreign Delayed-type hypersensitivity is mediated by T cells
