L6 ch inf - Government Medical College and Hospital,...
Transcript of L6 ch inf - Government Medical College and Hospital,...
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Chronic inflammation • Inflammation of prolonged duration in which active
inflammation, tissue destruction and repair proceed simultaneously
• May follow ac infl or begins insidiously • Causes:
- persistent infections, organisms of low toxicity & evoke delayed HS - prolonged exposure to toxic agents –exogenous (silica) or endogenous (lipid)- Atherosclerosis - autoimmunity- autoAg evoke immune reaction to cause tissue damage eg RA, SLE
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Acute
• Pathogens, injured tissues
• Neutrophils, monocytes, macrophages
• Vasoactive amines, eicosanoids
• Immediate (Few days) • Resolution, abscess formation,
chronic inflammation
Chronic
• Persistent acute inflammation -non-degradable pathogens, foreign bodies, or autoimmune
• Monocytes, macrophages, lymphocytes, plasma cells,
• IFN-γ and other cytokines, GFs, hydrolytic enzymes
• Delayed ( months or years) • Tissue destruction, fibrosis
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Systemic effects of inflammation
• Fever • Anemia • Leucocytosis • ESR • Amyloidosis
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Morphologic features of chronic inflammation
• Infiltration with mononuclear cells - by chemotactic factors & adhesion molecules, continuous infiltration - local proliferation - longer survival
• Tissue destruction macrophages release proteases, elastase, collagenase, NO, reactive oxygen radicals, cytokines (IL1,8, TNF)
• Healing by fibrosis & angiogenesis
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Types of chronic inflammation
• Chronic non-specific ch. osteomyelitis, lung abscess
• Chronic granulomatous inflammation tuberculosis, syphilis, actinomycosis
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Granulomatous Inflammation
• Distinctive pattern of chronic inflammation, in which the predominant cells are activated macrophages, which are enlarged, oval or elongated with indistinct cell boundary and called epithelioid cells.
• Granuloma – (granule + oma)- circumscribed, tiny lesion (1mm) composed predominantly of collection of epithelioid cells & rimmed at the periphery by lymphoid cells
• Diagnosis of granuloma rests on the identification of epithelioid cells.
• Epithelioid cells may coalesce to form multinucleated giant cells
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Injury (e.g. M.tb, talc)
Failure to digest agent
Weak acute inf. response
Persistence of infectious agent
T cell mediated immune response Poorly digestible agent
Activation of CD4+T cells Release of IL-1,2, growth factors-IFN, MCF
Accumulation of tissue macrophages
Macrophages activated by IFN-Y
Transformed epithelioid cells, giant cells
GRANULOMA
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a Initiation of immune re!IPOnse Anlige:nic: activation
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Mast cell NK cell yli T cell Dendritic oeU
Microci rculation
Neulroph
Monocyte f Antigen
Cherno~inas
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TNF IFN-y
) Migralion
vie lym phetics
Developing gran1.1'1omatous inlla,mma1ion b :Production ol Ag-specific T" cells in lymph node
c Formation of mature granuloma
Nec:rosis
Multi nuc:lealed glenl cell
Trafficking of Ag-specific
Th1 oe11 s
AnligerHoaded dendriliG cell
Persis!ent amigen
Pathogenesis of granuloma formation
Expert Reviews in, Molecular Medicine 2005 Published by Cambriidg.e Unrversity Press
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Granulomatous conditions • Bacterial
Tuberculosis Leprosy Syphilis Granuloma inguinale Cat scratch disease
• Fungal Actinomycosis Blastomycosis Cryptococcosis Histoplasma Coccidoides immitis
• Parasitic Schistosomiasis
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Granulomatous conditions
• Inorganic metals and dusts - Silicosis - Berylliosis - Pneumoconiosis - Asbestosis
• Misc - Sarcoidosis - Crohns disease - Foreign body granuloma
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Symptoms
TB can be related to cough, fever, and weight loss.
If untreated, fatal in over 50% of cases.
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Giant cells
• Foreign body giant cells • Langhans’ giant cells • Touton giant cells • Aschoff giant cells • Tumor giant cells • Reed-Sternberg cells
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Foreign body giant cell
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Langhans giant cell
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Tuoton giant cell
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Aschoff giant cell
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Tumor giant cell
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RS cell Osteoclastic giant cell
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Two types of granuloma
(i) Foreign body granulomas: Incited by inert foreign bodies. Example: suture materials, splinter, breast prosthesis, silica, asbestos etc.
(ii) Immune granulomas: It is Type IV hypersensitivity and mediated by T-cells, typically seen in tuberculosis.
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Mononuclear phagocyte system
• Blood monocytes • Tissue macrophages
- macrophages in inflammation - kupffer cells - alveolar macrophages - sinus histiocytes - osteoclasts - microglial cells - langerhans’ cells - Hoffbauer cells - mesangial cells