أسئلة الثامنة باثو PPPM (قبل التعديل)

• Chronic inflammation involves prolonged inflammation (weeks to months) where inflammation, tissue injury, and attempts at repair coexist in varying degrees.
• Chronic inflammation can follow acute inflammation or begin as chronic specific inflammation, like a granuloma.

Causes of Chronic Inflammation

• Persistent infections from hard-to-eradicate microorganisms, such as mycobacteria, viruses, fungi, and parasites, can cause chronic inflammation.
• These organisms often cause a delayed-type hypersensitivity immune reaction.
• Immune-mediated inflammatory diseases occur when immune reactions develop against an individual's own tissues.
• Auto-antigens produce a self-perpetuating immune reaction, resulting in chronic tissue damage and inflammation; examples include rheumatoid arthritis and multiple sclerosis.
• Prolonged exposure to exogenous or endogenous toxic agents can cause chronic inflammation.
• Particulate silica is an example of an exogenous agent that, when inhaled for prolonged periods, leads to silicosis (an inflammatory lung disease).
• Unregulated immune responses can be against microbes, as in inflammatory bowel disease, or common environmental substances, as in bronchial asthma.

Morphologic Features of Chronic Inflammation

• Infiltration of mononuclear cells, including macrophages, lymphocytes, and plasma cells occur.
• Tissue destruction is induced by the persistent offending agent or by the inflammatory cells themselves.
• Attempts at healing by connective tissue occur through proliferation of small blood vessels (angiogenesis) and fibrosis.

Pathogenesis of Chronic Inflammation: Macrophages

• Macrophages are derived from blood monocytes.
• Macrophages function in phagocytosis and destruction of debris and bacteria.
• Macrophages function in processing and presentation of antigens to the immune system.
• Macrophages function in controlling other cells by cytokine release and synthesis.
• Macrophages synthesize cytokines, complement components, blood clotting factors, and proteases.

Lymphocytes and Plasma Cells

• T-cells regulate macrophage activation and recruitment by secreting specific mediators (lymphokines).
• T-cells modulate antibody production and mediate cell-mediated cytotoxicity.
• T-cells maintain immunologic memory.
• NK cells help defend against viral and bacterial infections.

Functions of Lymphocytes

• Lymphocytes functions are complex and mainly immunological.
• B lymphocytes differentiate to produce antibodies.
• T lymphocytes are involved in control and cytotoxic functions.
• Lymphocytes and macrophages interact bidirectionally, playing an important role in chronic inflammation.

Dendritic Cells

• Dendritic cells are professional antigen-presenting cells that trigger immune responses to antigens.
• Dendritic cells phagocytose antigens, migrate to lymph nodes, and present those antigens.
• T cell recognition of antigen and co-stimulatory molecules leads to recruitment of specific cell subsets to regulate the inflammatory process.

Acute Inflammatory Cells

• Neutrophils are the primary cells in acute inflammation.
• Neutrophils may still be present during chronic inflammation if there is ongoing infection and tissue damage.
• Eosinophils are prominent in allergic-type reactions and parasitic infestations.

Fibroblasts

• Fibroblasts' key function is the production of components of the ECM.
• Fibroblasts rebuild the scaffolding of the ECM within tissues.
• Activated fibroblasts produce cytokines and chemokines, creating a tissue microenvironment that regulates the behavior of inflammatory cells.

Effects of Chronic Inflammation

• Fibrosis e.g. can occur in the Gall bladder resulting in chronic cholecystitis, and in chronic ulcers.
• Impaired function can occur e.g. in Chronic inflammatory bowel disease.
• Increased function, although rare, can occur e.g. Mucus secretion, thyrotoxicosis.
• Atrophy can occur e.g. in Gastric mucosa, adrenal glands.
• Chronic inflammation effects Stimulation of the immune response (Macrophage - lymphocyte interactions)

Granuloma

• A granuloma is a distinct pattern of chronic inflammation where the main reactive cell is an activated macrophage.
• Macrophages aggregate together forming nodular collections, which fuse to form large tumor-like masses.
• Granulomas are a Type 4 hypersensitivity reaction resulting in macrophage activation.

Pathogenesis of Granulomas

• Antigen presentation to inflammatory cells is present.
• Lymphocyte-macrophage interactions occur, with activated lymphocytes and macrophages influencing each other by releasing mediators.
• Macrophage activation occurs via cytokines from immune-activated T-cells and non-immunologic stimuli, such as endotoxin, fibronectin, and other mediators.
• Macrophage accumulation occurs.

Microscopic Picture of a Granuloma

• Granulomas feature a characteristic appearance depending on the irritant.
• Irritants may be observed inside or outside of phagocytic cells.
• Granulomas consist of macrophages, epithelioid cells, giant cells, lymphocytes, and fibroblasts.

Giant Cells

• Multinucleated giant cells originate from the fusion of macrophages.
• Giant cells exhibit an even greater phagocytic capacity than macrophages.

Types of Giant Cells

• Langhans giant cells feature 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 feature nuclei dispersed throughout the cytoplasm.

Types of Granulomas

• Infective Granulomas can be caused by bacteria, viruses, parasites, and fungi.
• Non-Infective Granulomas include:
  • Allergic granuloma: as seen in Rheumatic fever.
  • Foreign body granuloma: resulting from foreign bodies, such as beryllium.
  • Granulomas of unknown cause, e.g., sarcoidosis.

Chronic inflammation involves prolonged inflammation where inflammation, tissue injury, and repair coexist. Persistent infections by microorganisms can cause chronic inflammation. Autoimmune reactions and prolonged exposure to toxic agents can also be causes.