Week 5

• Acute inflammation is rapid in onset and short in duration (minutes, hours, days)
• Chronic inflammation has a longer duration (months) and involves different cell types and tissue responses
• Causes of acute inflammation include infections (bacterial, parasitic), trauma, physical and chemical agents (e.g. burns, irradiation), tissue necrosis, foreign bodies (e.g. surgical sutures), and immune reactions
• Three major components of acute inflammation are:

  • Alterations in vascular calibre that lead to changes in blood flow
  • Structural changes in small vessels that allow plasma proteins and cells to leave circulation
  • Cellular changes including migration of leukocytes from circulation, accumulation in the area of injury, and activation to destroy injurious agents
• Vascular changes in acute inflammation include vasodilatation and increased blood flow, increased permeability allowing movement of plasma fluid and protein into tissue, and migration of leukocytes into tissue
• Increased vascular permeability in acute inflammation is caused by histamine, leukotrienes, and bradykinin, leading to formation of endothelial gaps and affecting venules
• Leukocytes are activated as part of the acute inflammatory response, releasing toxic oxygen species and killing endothelial cells
• Chemical mediators of inflammation include leukocyte extravasation, which is the process of delivering leukocytes to the site of injury to kill infectious agents or destroy dead tissue
• Cellular events in acute inflammation involve margination, rolling, adhesion to endothelium, transmigration across endothelium, migration in the tissue towards chemotactic stimulus, leukocyte activation, phagocytosis, and killing
• Phagocytosis is mainly through oxygen-dependent mechanisms, leading to the generation of Reactive Oxygen Intermediates (ROIs) and the H2O2-MPO-Halide system being the most powerful bactericidal system in Neutrophil polymorphs
• The termination of acute inflammation involves mediators of inflammation with short half-lives, such as anti-inflammatory lipoxins from arachidonic acid and anti-inflammatory TGFb from macrophages, as well as neural impulses that inhibit TNF production
• It is important to understand the control of inflammation to allow the generation of new anti-inflammatory agents