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Inflammation 7
The document discusses chronic inflammation and its outcomes. Chronic inflammation can result when acute inflammation fails to resolve due to persistence of the injurious agent or interference with the healing process. It is characterized by prolonged inflammation that involves tissue injury and attempted repair occurring simultaneously. Macrophages play a dominant role in chronic inflammation by attempting to eliminate injurious agents and initiate repair, but also cause much of the tissue damage through their activation. Other cells like lymphocytes, plasma cells, eosinophils and mast cells are also involved. Granulomatous inflammation is a distinctive pattern of chronic inflammation seen in certain infectious and non-infectious conditions as an attempt to contain a difficult to eradicate agent.
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Inflammation 7
- 1. Inflammation and Repair -7 Dr.CSBR.Prasad, M.D. v3-CSBRP-May-2012
- 2. Out comes ofAcute Inflammation May have one of three outcomes: 1. Complete resolution 2. Healing by fibrosis 3. Chronic inflammation v3-CSBRP-May-2012
- 3. Out comes ofAcute Inflammation May have one of three outcomes: 1. Complete resolution 2. Healing by fibrosis 3. Chronic inflammation This occurs when: • There is persistence of injurious agent • There is interference with normal healing process Eg: Peptic ulcer, Complicated pneumonia v3-CSBRP-May-2012
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- 5. Chronic Inflammation • It’sinflammation of prolonged duration (weeks or months) • Here tissue injury, and attempts at repair coexist v3-CSBRP-May-2012
- 6. Chronic Inflammation • Mayfollow an acute inflammation or • May begin insidiously v3-CSBRP-May-2012
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- 8. Chronic Inflammation CAUSES: 1. Persistentinfections Mycobacteria, viruses, fungi, & parasites 2. Immune-mediated inflammatory diseases Autoimmune diseases Allergic diseases 3. Prolonged exposure to toxic agents Silicosis (Silica) Atherosclerosis (Lipid) v3-CSBRP-May-2012
- 9. Chronic Inflammation MORPHOLOGIC FEATURES: 1. Mononuclear infiltrates 2. Tissue destruction 3. Angiogenesis & 4. Fibrosis Vvvvvvvv In acute inflammation: 1.Vascular changes 2.Edema 3.Neutrophilic infiltration v3-CSBRP-May-2012
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- 11. Chronic Inflammation ROLE OF MACROPHAGES The macrophage is the dominant cellular player in chronic inflammation Macrophages are one component of the mononuclear phagocyte system The half-life of blood monocytes is about 1 day, whereas the life span of tissue macrophages is several months or years Emigrate into extravascular tissues quite early in acute inflammation, and within 48 hours Extravasation is governed by: Adhesion molecules & chemical mediators v3-CSBRP-May-2012
- 12. Maturation of mononuclearphagocytes v3-CSBRP-May-2012
- 13. Chronic Inflammation ROLE OF MACROPHAGES Macrophages may be activated by a variety of stimuli: Microbial products binding with TLRs Cytokines (e.g., IFN-γ) and other chemical mediators v3-CSBRP-May-2012
- 14. Chronic Inflammation ROLE OF MACROPHAGES The products of activated macrophages 1. serve to ELIMINATE injurious agents & 2. to initiate the process of REPAIR 3. responsible for much of the TISSUE INJURY v3-CSBRP-May-2012
- 15. Chronic Inflammation ROLE OF MACROPHAGES Activation of macrophages results in: 1. increased levels of lysosomal enzymes 2. reactive oxygen and nitrogen species 3. production of cytokines, growth factors 4. other mediators of inflammation 5. Some of these products are toxic to microbes and host cells 6. Cytokines, chemotactic factors 7. Growth factors – PDGF, Angiogenesis v3-CSBRP-May-2012
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- 17. IFN-ɣ IL-4 v3-CSBRP-May-2012
- 18. Chronic Inflammation OTHER CELLSIN CHRONIC INFLAMMATION Lymphocytes Plasma cells Eosinophils & Mast cells v3-CSBRP-May-2012
- 19. Chronic Inflammation OTHERCELLS IN CHRONIC INFLAMMATION Lymphocytes & macrophages interact biderectionally: Lymphocytes: IFNɣ arms MØ Macrophages: IL12 acts on T-cells v3-CSBRP-May-2012
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- 21. Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION Plasma cells: • Develop from activated B lymphocytes • Produce antibodies • Abs may act against persistent foreign or self antigens v3-CSBRP-May-2012
- 22. Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION Eosinophils: • Immune reactions mediated by IgE • Parasitic infections • Chemokine that recruits EØ is eotaxin • Eosinophilic granules that contain major basic protein • MBP is toxic to parasites • EØs are of beneficial in controlling parasitic infections, but they contribute to tissue damage v3-CSBRP-May-2012
- 23. Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION Mast cells: Widely distributed in connective tissues Participate in acute and chronic inflammations Mast cell receptor (FcεRI) binds Fc portion of IgE Degranulation – releases histamine and prostaglandins Allergic reactions – sometimes fatal - anaphylactic shock Secrete a plethora of cytokines Have the ability to both promote and limit inflammatory reactions in different situations v3-CSBRP-May-2012
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- 25. GRANULOMATOUS INFLAMMATION • It’s a distinctive pattern of chronic inflammation • Seen in some infectious and noninfectious conditions • It’s an attempt to contain an offending agent that is difficult to eradicate v3-CSBRP-May-2012
- 26. GRANULOMATOUS INFLAMMATION Infective causes: Non-Infective causes: • Tuberculosis • Sarcoidosis • Leprosy • Berylliosis • Cat-scratch disease • Reactions to irritant • LGV lipids • Brucellosis • Autoimmune diseases • Syphilis • Crohn’s disease • Mycotic infections v3-CSBRP-May-2012
- 27. Granuloma Def: A granulomais a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells. v3-CSBRP-May-2012
- 28. Granuloma Components: Epithelioid cells: havea pale pink granular cytoplasm with indistinct cell boundaries, often appearing to merge into one another. The nucleus is oval or elongate, and may show folding of the nuclear membrane (boomarang) Giant cells: Epithelioid cells fuse to form giant cells in the periphery or sometimes in the center of granulomas. - Langhans-type giant cell / foreign body–type giant cell Older granulomas develop an enclosing rim of fibroblasts and connective tissue v3-CSBRP-May-2012
- 29. Granuloma Types: There are twotypes of granulomas, which differ in their pathogenesis: 1. Foreign body granulomas Eg: Silica 2. Immune granulomas Eg: TB v3-CSBRP-May-2012
- 30. Granuloma v3-CSBRP-May-2012
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- 32. Non-caseating granulomas ofsarcoidosis v3-CSBRP-May-2012
- 33. Silica granulomas –under polarized light v3-CSBRP-May-2012
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