Chronic inflammation is characterized by simultaneous active inflammation, tissue destruction, and attempts at repair over prolonged periods of weeks or months. It is caused by persistent infections, prolonged toxic exposure, or autoimmunity. Chronic inflammation features infiltration of mononuclear cells including macrophages, lymphocytes, and plasma cells. Macrophages play a key role through secretion of inflammatory mediators that can damage tissue if unchecked. Granulomatous inflammation is a type of chronic inflammation involving focal accumulations of activated macrophages that develop an epithelial-like appearance.
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Chronic inflammation is characterized by simultaneous active inflammation, tissue destruction, and attempts at repair over prolonged periods of weeks or months. It is caused by persistent infections, prolonged toxic exposure, or autoimmunity. Chronic inflammation features infiltration of mononuclear cells including macrophages, lymphocytes, and plasma cells. Macrophages play a key role through secretion of inflammatory mediators that can damage tissue if unchecked. Granulomatous inflammation is a type of chronic inflammation involving focal accumulations of activated macrophages that develop an epithelial-like appearance.
Chronic inflammation is characterized by simultaneous active inflammation, tissue destruction, and attempts at repair over prolonged periods of weeks or months. It is caused by persistent infections, prolonged toxic exposure, or autoimmunity. Chronic inflammation features infiltration of mononuclear cells including macrophages, lymphocytes, and plasma cells. Macrophages play a key role through secretion of inflammatory mediators that can damage tissue if unchecked. Granulomatous inflammation is a type of chronic inflammation involving focal accumulations of activated macrophages that develop an epithelial-like appearance.
Copyright:
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Chronic inflammation is characterized by simultaneous active inflammation, tissue destruction, and attempts at repair over prolonged periods of weeks or months. It is caused by persistent infections, prolonged toxic exposure, or autoimmunity. Chronic inflammation features infiltration of mononuclear cells including macrophages, lymphocytes, and plasma cells. Macrophages play a key role through secretion of inflammatory mediators that can damage tissue if unchecked. Granulomatous inflammation is a type of chronic inflammation involving focal accumulations of activated macrophages that develop an epithelial-like appearance.
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CHRONIC INFLAMMATION
Chronic inflammation is inflammation of prolonged
duration (weeks or months) in which active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously. Causes of chronic inflammation 1. Persistent infections by certain microorganisms, such as tubercle bacilli, Treponema pallidum (the causative organism of syphilis), and certain viruses, fungi, and parasites.
2. Prolonged exposure to toxic agents, either exogenous or
endogenous. For example, silicosis is a chronic inflammation of the lungs caused by silica when inhaled for a prolonged time. Atherosclerosis is a chronic inflammation of the arterial walls induced by endogenous toxic plasma lipid components. 3. Autoimmunity. In autoimmune diseases, autoantigens produce immune reaction that results in chronic inflammation and tissue damage.
Immune reactions play an important role in several common
chronic inflammatory diseases, such as rheumatoid arthritis and lupus erythematosus. MORPHOLOGICAL FEATURES Chronic inflammation is characterized by;
1. Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells.
2. Tissue destruction, induced by the persistent
offending agent or by the inflammatory cells.
3. Healing: Connective tissue replaces the damaged tissue,
angiogenesis and fibrosis. MONONUCLEAR CELL INFILTRATION IN CHRONIC INFLAMMATION Mononuclear Phagocyte System (MPS) Mononuclear phagocyte system, MPS (reticuloendothelial system)
Blood monocytes and tissue macrophages are the main cells of
mononuclear phagocyte system (MPS). From the blood, monocytes migrate into various tissues and differentiate into macrophages.
Macrophages are diffusely scattered in the connective tissue or
located in organs such as the liver (Kupffer cells), spleen and lymph nodes (sinus histiocytes), and lungs (alveolar macrophages). The half-life of blood monocytes is about 1 day, whereas the life span of tissue macrophages is several months or years.
The journey of a monocyte from bone marrow stem
cell to tissue macrophage is regulated by a variety of growth and differentiation factors, cytokines, adhesion molecules, and cellular interactions. Extravasation of monocytes is governed by the same factors that are involved in neutrophil emigration, that is, margination, adhesion, rolling, migration and chemical mediators with chemotactic and activating properties.
When the monocyte reaches the extravascular tissue, it
undergoes transformation into a larger phagocytic cell, the macrophage. Macrophages are activated by a variety of stimuli, including cytokines (e.g., IFN-γ) secreted by sensitized T lymphocytes.
Activation results in increased cell size, increased
levels of lysosomal enzymes, more active metabolism, and greater ability to phagocytose and kill ingested microbes. Activated macrophages secrete a wide variety of biologically active products that, if unchecked, result in the tissue injury and fibrosis characteristic of chronic inflammation. PDGF, platelet-derived growth factor; FGF, fibroblast growth factor; TGFβ, transforming growth factor β. In short-lived inflammation, if the irritant is eliminated, macrophages eventually disappear. In chronic inflammation, macrophage accumulation persists under following mechanisms; 1. Recruitment of monocytes from the circulation. It results from the expression of adhesion molecules and chemotactic factors.
Chemotactic stimuli for monocytes include;
(a). Chemokines produced by activated macrophages and lymphocytes.
(b). Product of complement system, C5a. (c). Growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-α (TGF-α). (d). Fragments from the breakdown of collagen and fibronectin; and fibrinopeptides.
Most of the macrophages present at the site of chronic inflammation are
recruited from circulating monocytes. 2. Local proliferation (division) of macrophages occurs at the focus of chronic inflammation. Macrophage proliferation occurs prominently in some chronic inflammatory lesions, such as atheromatous plaques.
3. Immobilization of macrophages occurs within the site of inflammation.
Certain cytokines and oxidized lipids can cause such immobilization. Tissue injury in chronic inflammation Tissue destruction is hallmark of chronic inflammation.
(A). Macrophage based tissue injury in chronic inflammation
Activated macrophages eliminate injurious agents such as
microbes and initiate the process of repair. The products produced by macrophages are also responsible for much of the tissue injury in chronic inflammation. Some macrophage products causing tissue injury are,
1. Toxic to host cells: Reactive oxygen and nitrogen intermediates and
extracellular matrix proteases.
2. Increase influx of other cells: Some chemical mediators of
macrophages origin , such as cytokines.
3. Growth factors: Such as fibroblast growth factor (FGF), platelet derived
growth factor (PDGF) and transforming growth factor (TGF), causing fibroblast proliferation, collagen deposition, and angiogenesis. (B). Other substances causing tissue injury in chronic inflammation
Necrotic tissue itself can activate complement, kinin, coagulation, and
fibrinolytic systems, the release of mediators from leukocytes, and liberation of substances like uric acid from dying cells.
T lymphocytes may directly kill cells.
OTHER CELLS IN CHRONIC INFLAMMATION
1. Lymphocytes and macrophages interact in a bidirectional way, and
these reactions play an important role in chronic inflammation. Macrophages display antigens to T cells, and produce membrane molecules (costimulators) and cytokines (IL-12) that stimulate T-cell. Activated T lymphocytes produce cytokines, and one of these IFN-γ, is a major activator of macrophages. OTHER CELLS IN CHRONIC INFLAMMATION
2. Eosinophils are abundant in immune reactions mediated by IgE and in
parasitic infections. The recruitment of eosinophils involves extravasation from the blood and their migration into tissue by processes similar to those for other leukocytes. One of the chemokines that is especially important for eosinophil recruitment is eotaxin.
Eosinophils have granules that contain major basic protein, that is toxic to parasites but also causes lysis of mammalian epithelial cells. OTHER CELLS IN CHRONIC INFLAMMATION
3.Mast cells are widely distributed in connective tissues and
participate in both acute and chronic inflammatory reactions.
In acute inflammation mast cells are major source of histamine.
In chronic inflammatory reactions mast cells produce cytokines that contribute to fibrosis. Figure: Macrophage- lymphocyte interactions in chronic inflammation. Activated lymphocytes and macrophages influence each other and also release inflammatory mediators that affect other cells OTHER CELLS IN CHRONIC INFLAMMATION
4. Neutrophils are characteristic of acute inflammation but
many forms of chronic inflammation continue to show large numbers of neutrophils, induced either by persistent microbes or by mediators produced by macrophages and T lymphocytes.
In chronic bacterial infection of bone (osteomyelitis), a
neutrophilic exudate can persist for many months. Neutrophils are also important in the chronic damage induced in lungs by smoking and other irritant stimuli. GRANULOMATOUS INFLAMMATION Granulomatous inflammation is a type of chronic inflammation characterized by focal accumulations of activated macrophages, which often develop an epithelial- like (epithelioid) appearance.
It is encountered in a number of infectious and some
noninfectious conditions. Examples of granulomatous inflammation are tuberculosis, sarcoidosis, cat-scratch disease, lymphogranuloma inguinale, leprosy, brucellosis, syphilis, some mycotic infections, berylliosis.
Recognition of the granulomatous pattern in a biopsy
specimen is important because of the limited number of possible conditions that cause it and the significance of the diagnoses associated with the lesions. Granuloma
A granuloma is 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.
In the usual hematoxylin and eosin stains, the epithelioid cells
have a pale pink granular cytoplasm with indistinct cell boundaries. Older granulomas develop an enclosing rim of fibroblasts and connective tissue.
Frequently, epithelioid cells fuse to form giant cells in the
periphery or sometimes in the center of granulomas. These giant cells may attain diameters of 40 to 50 µm. They have a large mass of cytoplasm containing 20 or more small nuclei arranged either peripherally (Langhans- type giant cell) or haphazardly (foreign body-type giant cell). Types of granulomas
There are two types of granulomas.
1. Foreign body granulomas are incited by relatively inert
foreign bodies. These granulomas are formed when material such as talc, sutures, or other fibers are in the focus Epithelioid cells and giant cells formed and are apposed to the surface and surround the foreign body. The foreign material can usually be identified in the center of the granuloma. 2. Immune granulomas are caused by insoluble particles, such as microbes which are poorly degradable. In these responses, macrophages engulf the foreign material and present some of it to T lymphocytes, causing them to become activated. The responding T cells produce cytokines, such as IL-2, which activates other T cells, and IFN-γ, which activates macrophages and transforming them into epithelioid cells and multinucleate giant cells. The prototype of the immune granuloma is that caused by the mycobacterium tuberculosis. In this disease, the granuloma is called a tubercle and is classically characterized by the presence of central caseous necrosis.