10.Chronic Inflammation-definition, causes cellular cooperation, growth factors & morphology.pdf

Chronic Inflammation-definition, causes, cellular cooperation, growth factors & morphology Prof Dr Thidar Aung Learning Objectives Students will be able to 1. Define chronic inflammation. 2. List the causes of chronic inflammation. 3. Describe the macroscopic and microscopic features in chronic infl...

Chronic Inflammation-definition, causes, cellular cooperation, growth factors & morphology Prof Dr Thidar Aung Learning Objectives Students will be able to 1. Define chronic inflammation. 2. List the causes of chronic inflammation. 3. Describe the macroscopic and microscopic features in chronic inflammation. 4. Explain cellular co-operation in chronic inflammation with the help of a suitable diagram. 5. Explain the role of macrophage in chronic inflammation. 6. Explain the role of growth factors in chronic inflammation. Manipal University College Malaysia (MUCM) 2 Definition Chronic inflammation is a response of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist in varying combination. I. Begins insidiously (ab initio) or II. Preceded by acute inflammation Manipal University College Malaysia (MUCM) 3 Causes of chronic inflammation Persistent infection Mycobacterium tuberculosis Treponema pallidum Fungi, viral infections Prolonged exposure to toxic agents Exogenous: e.g., silica or asbestos Endogenous: e.g., cholesterol, lipid, uric acid crystals Autoimmune diseases e.g., Rheumatoid arthritis, SLE Diseases of unknown aetiology e.g., Inflammatory bowel disease Manipal University College Malaysia (MUCM) Progression of acute inflammation Organisation of an abscess e.g., progression of acute osteomyelitis to chronic osteomyelitis Presence of indigestible material Wood implanted into wound Surgical sutures Recurrent episodes of acute inflammation e.g., chronic cholecystitis 4 Morphologic features of chronic inflammation Macroscopic appearances Chronic ulcer e.g., chronic peptic ulcer of the stomach Chronic abscess cavity e.g., osteomyelitis, empyema thoracis. Thickening of the wall of a hollow viscus by fibrous tissue e.g., Crohn’s disease, chronic cholecystitis Granulomatous inflammation e.g., chronic fibrocaseous TB of the lung. Fibrosis e.g., chronic cholecystitis, ‘hour-glass contracture’ of the stomach, strictures that characterize Crohn’s disease Manipal University College Malaysia (MUCM) 5 The histological section taken from a gastric ulcer. Marked fibrous thickening of the wall with areas of mucosal necrosis and ulceration. Chronic cholecystitis : The histological section taken from gall bladder. Morphologic features of chronic inflammation Microscopic Appearances Characterized by Infiltration with mononuclear cells (macrophages, lymphocytes and plasma cells) Tissue destruction Repair involving angiogenesis and fibrosis (healing by connective tissue) Manipal University College Malaysia (MUCM) 8 cellular co-operation in chronic inflammation Subsets of CD4+ T cells There are three subsets of CD4+ T cells. Th1 cells produce the cytokine IFN-γ, which activates macrophages by the classical pathway. Th2 cells secrete IL-4, IL-5, and IL-13, which recruit and activate eosinophils and are responsible for the alternative pathway of macrophage activation. Th17 cells secrete IL-17 and other cytokines, which induce the secretion of chemokines responsible for recruiting neutrophils (and monocytes) into the reaction. Both Th1 and Th17 cells are involved in defense against many types of bacteria and viruses and in autoimmune diseases in which tissue injury is caused by chronic inflammation. Th2 cells are important in defense against helminthic parasites and in Manipal University College Malaysia 10 allergic inflammation. Ref Info slide IL1/TNF Th1 IL12 IL10 IL1/TNF/IL6 IL23 Th2 Th17 IFN-g IL-4, IL-5, IL-13 IL-17, IL-22 Important at mucosal sites, skin Macrophages Mononuclear Phagocyte System Circulating blood monocytes →Tissue macrophages lifespan of up to about 3 days Tissue macrophages Kupffer cells (liver) Sinus histiocytes (spleen and lymph nodes) Alveolar macrophages (lung) Micoglia (CNS) Osteoclasts (bone) Manipal University College Malaysia (MUCM) 12 Role of macrophages in chronic inflammation The main effector cells in chronic inflammation Respond to chemotactic stimuli Extravasation of monocytes Activated by cytokines (IFN-γ) and bacterial endotoxins  Transformation into larger macrophages Phagocytosis Harbour viable organisms if they are not able to kill them by the lysosomal enzymes. e.g., Mycobacterium tuberculosis and M. leprae Release of their products Tissue destruction Vascular proliferation (angiogenesis) and fibrosis Produce Interferons (IFN α and β), Interleukins (IL-1, -6 and IL-8), and TNF α Manipal University College Malaysia (MUCM) 13 Effects of Macrophage Activation Products released by macrophages Tissue destruction Proteases and other enzymes AA metabolites Toxic oxygen metabolites NO Coagulation factors Neutrophil chemotactic factors Manipal University College Malaysia (MUCM) Vascular proliferation and fibrosis GFs Cytokines Remodelling collagenase and metalloproteinase 15 Growth Factors PDGF (platelet-derived growth factor) FGF (fibroblast growth factor) TGFβ (transforming growth factor-β) Fibrosis Angiogenesis Remodeling Manipal University College Malaysia Other Cells of Chronic Inflammation Infiltration with mast cells, lymphocytes and plasma cells Lymphocytes Mobilization in both antibody – mediated and Mast Cells Widely distributed in connective tissues and participate in both acute and persistent inflammatory reactions Binds the Fc portion of the IgE antibody Plasma Cells Produce antibody directed either against persistent antigen in the inflammatory site or against altered tissue components Eosinophils parasitic infections Mediated by IgE Eotaxin – a chemokine that has the ability to prime eosinophils for chemotaxis