3. Chronic Inflammation.pdf

Chronic Inflammation Dr. B. Mulenga Chronic Inflammation Chronic inflammation is a response of prolonged duration (weeks or months) in which inflammation, tissue injury and attempts at repair coexist, in varying combinations Causes: 1. Persistent injurious agent/infection 2. Ina...

Chronic Inflammation Dr. B. Mulenga Chronic Inflammation Chronic inflammation is a response of prolonged duration (weeks or months) in which inflammation, tissue injury and attempts at repair coexist, in varying combinations Causes: 1. Persistent injurious agent/infection 2. Inability of the host to overcome the injurious agent 3. Hypersensitivity diseases 4. Prolonged exposure to potentially toxic agents, either exogenous or endogenous Morphological Characteristics 1. Chronic inflammatory cell infiltrate a) Lymphocytes b) Plasma cells c) Macrophages 2. Tissue destruction 3. Repair a) Neovascularization b) Fibrosis Morphology: Chronic and Acute Inflammation Image A: There is fibrosis (arrow), macrophages and lymphocytes (asterisk) and tissue destruction (arrow head). Under what circumstances, does it develop? 1. Progression from acute inflammation (Tonsillitis, osteomyelitis, etc.) 2. Repeated exposure to toxic agent (Silicosis, asbestosis, hyperlipidemia, etc.) 3. Viral infections (Hepatitis C, HIV, CMV, HSV, etc.) 4. Persistent microbial infections (Mycobacteria, Treponema, Fungi, etc.) 5. Autoimmune disorders (Rheumatoid arthritis, SLE, systemic lupus, etc.) Macrophages Macrophages: Derived from circulating monocytes or resident tissue cells (yolk sac derived) Scattered in tissues (resident tissue cells): a) Kupffer cells (liver) b) Sinus histiocytes (spleen & LN) c) Alveolar macrophages (lung) d) Microglia (CNS) Activated mainly by IFN-g secreted from T lymphocytes 1. Increased cell size 2. Increased lysosomal enzymes 3. More active metabolism, i.e. greater ability to kill ingested organisms 4. Epithelioid appearance Sources of Macrophages How do Macrophages Accumulate at Sites of Chronic Inflammation? 1. Recruitment of monocytes from circulation by chemotactic factors: Chemokines, C5a, PDGF, TGFa, fibrinopeptides, fibronectin, collagen breakdown fragments. 2. Proliferation of macrophages at foci of inflammation 3. Immobilization of macrophages at sites of inflammation From Circulating blood to site of injury Other cells of chronic inflammation Lymphocytes B and T lymphocytes (Th1, Th2, Th17) Eosinophils Mast cells Neutrophils Lymphocytes Two types: B and T lymphocytes Activated by Microbes and other environmental antigens to amplify and propagate chronic inflammation Leads to generation of long lived memory CD4+ T lymphocytes promote inflammation and influence the nature of the inflammatory reaction by virtual of secreting cytokines Th1 (secrete IFN-γ that activates macrophages) Th2 ( secrete IL- 4, IL-5, and IL-13 recruit and activates eosinophils) Th 17 ( secrete cytokines and chemokines) Lymphocytes Activated B lymphocytes differentiate into antibody producing cells called plasma cells Some differentiates into memory B cells (principle for vaccine formulation) These plasma cells secrete different types of antibodies depending on the type of stimuli: IgA (Found in mucosal membranes like mouth, GI, conjunctiva) IgE ( In allergic inflammatory conditions) IgM IgD IgG Granulomatous Inflammation A distinctive form of chronic inflammation characterized by collections of activated macrophages (Epithelioid) Granuloma, in addition to Epithelioid macrophages, may have one or more of the following: 1. A surrounding rim lymphocytes & plasma cells 2. A surrounding rim of fibroblasts & fibrosis 3. Giant cells 4. Central necrosis e.g. caseation granulomas in TB Examples of Granulomatous Inflammation Bacterial a) Mycobacterium tuberculosis Fungal a) Histoplasma capsulatum (TB) b) Blastomycosis b) Mycobacterium Leprae c) Cryptococcus neoformans (Leprosy) d) Coccidioides immitis c) Treponema pallidum (Syphilis) Foreign body d) Bartonella henslae (cat Suture, other prosthesis, keratin scratch) Parasitic Unknown a) Schistosomiasis (Bilharzia) Sarcoidosis Inorganic metals a) Silicosis, Berylliosis Epithelioid macrophages Granuloma with giant cells Systemic Effects of Inflammation Systemic Effects of Inflammation Inflammation, even if it is localized, is associated with cytokine-induced systemic reactions that are collectively called the acute-phase response The cytokines TNF, IL-1, and IL-6 are important mediators of the acute-phase reaction The acute-phase response consists of several clinical and pathologic changes: 1. Fever 2. Acute phase proteins (CRP, SAA, Complement proteins, Fibrinogen) 3. Leucocytosis Consequences of Defective Inflammation 1. Susceptibility to infections Defective innate immunity 2. Delayed repair a) Delayed clearance of debris and necrotic tissue b) Lack of stimuli for repair Consequences of Excessive Inflammation 1. Allergic reactions ( e.g Asthma, Eczema etc.) 2. Autoimmune disorders (e.g Type 1 diabetes Mellitus) 3. Atherosclerosis 4. Ischemic heart disease