Inflammation Revisited Inflammatory Mediators (2024-25) PDF

Mediators of inflammati on and the inflammat ory process Alexander.strach [email protected] Session aims To prepare students for the study of inflammatory immunopathologies, and pharmacological modulators of inflammation. To build from consideration of inflammation in year 1 with a...

Mediators of inflammati on and the inflammat ory process Alexander.strach [email protected] Session aims To prepare students for the study of inflammatory immunopathologies, and pharmacological modulators of inflammation. To build from consideration of inflammation in year 1 with a deeper consideration of selected cellular mediators of inflammation (e.g. vasoactive amines and kinins) Learning objectives Students should be able to: List examples of inflammatory mediators and their key functions overview the role of inflammatory mediators as key regulators of the chronic inflammatory process Discriminate between mechanisms in acute and chronic inflammation The inflammatory process; an overview How does this happen? The inflammatory process; The inflammatory process; a overview The inflammatory process; Extravasation Key process in inflammatio n Recruits immune cells to site of injury Rapid action The inflammatory process;  The inflammatory process; an overview Cellular components of the inflammatory response are supported by soluble mediators of inflammation The components of acute and chronic inflammation and their principal functions The inflammatory process; What are the mediators of inflammation? Plasma derived Cell derived Clotting system Auxiliary cells Kinin system Basophils, mast cells, Fibrinolytic system platelets (plasmins) Lymphocytes Complement system Monocytes (covered already) Kinins A series of enzymatic proteins which result in the production of bradykinin and lysyl-bradykinin. Powerful vasoactive peptide: Venous dilation (NO) Increased vascular permeability Activated by: Hageman factor (XIIa) in clotting cascade Plasmin system Enzymes from damaged tissues Mediators of Plasmins Originally identified as breaking down fibrin Activated by soluble or tissue derived plasminogen activators Converts plasminogen to plasmin In turn, plasmin activates MMPs (tissue remodelling) Promote angiogenesis via cytokine release Mediators of  Anti-histamines Cell-derived mediators Mast cells, basophils and platelets Activated by C3a and C5a (innate) and IgE (adaptive) Rapid release of pre-formed histamine and serotonin (degranulation) Result in vasodilation and increased permeability Mediators of Cell-derived mediators Mast cells, basophils and platelets Slow release (hours) of leukotrienes and prostaglandins Cell-derived mediators Mast cells, basophils and platelets Activated by immune complexes (antibodies) Platelet activating factor (PAF) from neutrophils, basophils and macrophages Involved in type 1 and 2 hypersensitivity (later case) Mediators of Cell-derived mediators Mast cells, basophils and platelets Recruitment and activation of other immune cells CCL3 (MIP1-a) and leukotriene B4 (chemotactic for monocytes) Chemokines and cytokines to modulate local immune responses Mediators of Pain Mast cell and basophil derived mediators: PAF, histamine, serotonin, prostaglandins, and leukotrienes Act on C fibres Poorly localised, dull, aching pain (inflammatory pain)  Arachidonic acid pathway Arachidonic acid is an important factor in generation of key inflammatory mediators prostaglandins and leukotrienes. Kumar, V., Abbas, A.K. and Aster, J.C. (2015) Robbins & Cotran Pathologic Basis of Disease. 9th Edition, Mediators of chronic inflammatio n If antigens or insult persists: Immune cells accumulate Response becomes uncontrolled / dysregulated Repair response inhibited Q: where might we see this type of reaction in the oral tissues? Key point: mechanisms of chronic inflammation are often major causes of tissue damage and incapacity Mediators of inflammation summary Mediators of Activity On your tables, discuss: why a knowledge of inflammatory mediators is important for clinical practice how the effects of inflammatory mediators may be modulated (E.g. by pharmaceuticals) possible outcomes of the acute inflammatory process key features of the chronic inflammatory state and contrast these with acute inflammation Any questions? [email protected]