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A major hallmark of the innate immune response is inflammation, of which two types are recognized. Acute inflammation is a short‐term inflammatory response to an insult to the body. If the cause of the inflammation is not resolved, however, it can lead to chronic inflammation, which is associated with major tissue destruction and fibrosis. Chronic inflammation is ongoing inflammation which can be caused by foreign bodies, persistent infection (e.g., tuberculosis), and autoimmune diseases (e.g., rheumatoid arthritis). In these cases, the inflammatory response continues and can be only temporarily modified by the administration of antiinflammatory agents, such as aspirin, ibuprofen, cortisone, and biopharmaceutical therapies that target cytokines involved in inflammation (e.g., tumor necrosis factor, interleukin‐17). These therapies act on several of the metabolic pathways involved in the elaboration and activation of the pharmacological mediators of inflammation. However, they do not affect the root cause of the inflammation, so when they are withdrawn, the symptoms may return.

As a physiological process, inflammation is typically initiated by tissue damage caused by endogenous factors (such as tissue necrosis or bone fracture) and by exogenous factors. The latter includes various types of damage, such as mechanical injury (e.g., cuts), physical injury (e.g., burns), chemical injury (e.g., exposure to corrosive chemicals), immunological injury (e.g., hypersensitivity reactions; see Chapters 13–15) and biological injury (e.g., infections caused by pathogenic microorganisms; see Chapter 19). Indeed, infection can be thought of as pathogen‐induced injury when considering inflammatory responses, since the innate immune cells called into play and the inflammatory responses that manifest are essentially identical, regardless of the cause of injury. While perhaps paradoxical in light of the discomfort associated with certain types of inflammatory responses (e.g., hypersensitivity to poison ivy), inflammation is a normal immunological process designed to restore immune homeostasis by bringing the injured tissue back to its normal state.

As noted above, inflammation does not have to be initiated by pathogens that cause infection, but can also be caused by tissue injuries. Such injuries cause release of damaged cellular contents at local sites even in the absence of breaks in physical barriers that would allow pathogens to enter. The inflammatory reaction triggers mobilization of phagocytic cells and other innate immune cells to the damaged area to clear cellular debris and to set the stage for wound repair, as discussed in later in this chapter Such mobilization is, in part, the result of transendothelial migration of leukocytes, as discussed below. This happens when damaged cells release their contents into the local environment which initiates release of potent inflammatory mediators from mast cells in and around the area. Inflammatory mediators include histamine, leukotrienes, and prostaglandins. Histamine increases the diameter of local blood vessels (vasodilation), causing an increase in blood flow. Histamine also increases the permeability of local capillaries, causing plasma to leak out and form interstitial fluid causing the swelling associated with inflammation.