L6: Chronic Inlammation Flashcards
What is the definition of chronic inflammation?
- inflammation of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations.
- It may follow acute inflammation or start as chronic specific inflammation (Granuloma).
What are the causes of chronic inflammation?
1- Persistent infections by microorganisms
2- Immune-mediated inflammatory diseases
3- Prolonged exposure to potentially toxic agents
4- unregulated immune responses
What are the microorganisms that cause persistent infection? And what type of reaction do they cause?
-such as mycobacteria, and certain viruses, fungi,
and parasites, they difficult to eradicate
-These organisms often evoke an immune reaction called delayed-type hypersensitivity. (DTH)
Immune-mediated inflammatory diseases (IMID) (Auto-immune diseases)
- Under certain conditions immune reactions develop against the individual’s own tissues.
- auto-antigens produce a self-perpetuating immune reaction that results in chronic tissue damage and inflammation
examples: rheumatoid arthritis and multiple sclerosis.
What are the potentially toxic agents that cause chronic inflammation?
- either exogenous or endogenous.
- example of an exogenous agent: is particulate silica, a non-degradable inanimate material that, when inhaled for prolonged periods, results in an inflammatory lung disease called silicosis
What are examples of unregulated immune responses?
- against microbes, as in inflammatory bowel disease.
- Immune responses against common environmental substances are the cause of allergic diseases, such as bronchial asthma.
What are the morphological features of chronic inflammation?
- Infiltration with mononuclear cells, which include macrophages, lymphocytes, and plasma cells.
- Tissue destruction induced by the persistent offending agent or by the inflammatory cells.
- Attempts at healing by connective tissue are accomplished by the proliferation of small blood vessels (angiogenesis) (for blood supply needed for repair) and fibrosis.
What are the cells that become active in chronic inflammation?
1- Macrophages 2- Lymphocytes and plasma cells 3- dendritic cells 4- acute inflammatory cells 5- fibroblasts
What are macrophages derived from?
They are derived from blood monocytes. Various levels of ‘activation’.
What are the functions of macrophage?
- Phagocytosis and destruction of debris & bacteria.
- Processing and presentation of antigen to immune system.
- Control of other cells by cytokine release
- Synthesis; Cytokines, complement components, blood clotting factors, proteases.
T-cells
T-cells regulate macrophage activation and recruitment by secreting specific mediators (lymphokines)
T-cells modulate antibody production and cell-mediated cytotoxicity and maintain immunologic memory
NK cells
NK cells, as well as other lymphocyte subtypes, help defend against viral and bacterial infections
What are the functions of lymphocytes and plasma cells?
a. Complex, mainly immunological.
b. B lymphocytes differentiate to produce antibodies.
c. T lymphocytes involved in control & cytotoxic functions.
What are dendritic cells?
professional antigen-presenting cells that trigger immune responses to antigens.
What is the function of dendritic cells?
- They phagocytose antigens and migrate to lymph nodes, where they present those antigens.
- Recognition of antigen and other co-stimulatory molecules by T cells —->recruitment of specific cell subsets to the inflammatory process.
Acute Inflammatory cells in chronic inflammation
What are fibroblasts?
- Fibroblasts are cells whose chief function is to produce components of the ECM.
- They are the construction workers of the tissue, rebuilding the scaffolding of ECM upon which tissue is re-established.
What do activated fibroblasts produce?
Activated fibroblasts produce cytokines and chemokines creating a tissue microenvironment that further regulates the behavior of inflammatory cells.
What are the effects of chronic inflammation?
- Fibrosis e.g. gall bladder (chronic cholecystitis), chronic ulcers.
- Impaired function e.g. chronic inflammatory bowel disease
- Rarely, increased; e.g. mucus secretion, thyrotoxicosis
- Atrophy e.g. gastric mucosa, adrenal glands
- Stimulation of immune response (Macrophage - lymphocyte interactions)
- Chronic inflammation can be complicated by fibrosis
What is the definition of granuloma?
A distinct pattern of chronic inflammation in which the chief reactive cell is activated macrophage —>aggregates together forming nodular collections — >fuse to form tumor-like mass grossly.
What is the pathogenesis of granuloma?
This type of reaction is Type 4 hypersensitivity reaction with the end result in macrophage activation:
1- Antigen presentation to inflammatory cells.
2- Lymphocyte-macrophage interactions
3- Macrophage activation occurs
4- Macrophage accumulation.
Lymphocyte-macrophage interactions
- Activated lymphocytes and macrophages influence each other.
- Release mediators that affect other cells Lymphocyte- macrophage interactions
Macrophage activation occurs by?
- Cytokines from immune-activated T-cells.
- Non-immunologic stimuli: endotoxin, fibronectin, mediators.
What is the microscopic picture of granuloma?
- It is characteristic with each irritant.
- The irritant may be seen inside or outside the phagocytic cells.
- The granuloma is formed of : Macrophages, Epithelioid Cells, Giant Cells, Lymphocytes Fibroblasts
What are giant cells?
- Multinucleated giant cells originate by the fusion of macrophages.
- They have stronger phagocytic power than macrophages.
What are the types of giant cells?
Langhans giant cells
- have nuclei arranged in a horseshoe-shaped pattern around the periphery of the cell.
- This type is characteristic (but not specific) for tuberculosis
Foreign body giant cells
- have the nuclei dispersed in the cytoplasm
What are the types of granuloma?
1- Infective granuloma: Bacteria, Virus, Parasite, Fungi
2- Non infective granuloma:
Allergic granuloma: as Rheumatic fever
Foreign body granuloma: foreign bodies as beryllium
Granulomas of unknown cause: as sarcoidosis
