Local Inflammation

Aspects of the innate and adaptive immune responses and their interactions are well illustrated by the events that occur when bacteria enter a break in the skin and produce a local inflammation (table 15.5). The inflammatory reaction is initiated by the nonspecific mechanisms of phagocytosis and complement activation. (Complement proteins are activated during humoral immunity by B lymphocytes, as described in a later section.) Activated complement further increases this nonspecific response by attracting new phagocytes to the area and by stimulating their activity.

After some time, B lymphocytes are stimulated to produce antibodies against specific antigens that are part of the invading bacteria. Attachment of these antibodies to antigens in the bacteria greatly amplifies the previously nonspecific response. This occurs because of greater activation of complement, which directly



■ Figure 15.5 The events of a local inflammation. In this inflammatory reaction, antigens on the surface of bacteria are coated with antibodies and ingested by phagocytic cells. Symptoms of inflammation are produced by the release of lysosomal enzymes and by the secretion of histamine and other chemicals from tissue mast cells.

destroys the bacteria and which also—together with the antibodies themselves—promotes the phagocytic activity of neutrophils, macrophages, and monocytes (fig. 15.5). The ability of antibodies to promote phagocytosis is called opsonization.

Leukocytes within vessels in the inflamed area stick to the endothelial cells of the vessels through interactions between adhesion molecules on the two surfaces. The leukocytes can then roll along the wall of the vessel toward particular chemicals. As mentioned earlier, this movement, called chemotaxis, is produced by molecules called chemokines. Complement proteins and bacterial products may serve as chemokines, drawing the leukocytes toward the site of infection.

The leukocytes squeeze between adjacent endothelial cells (the process of extravasation, discussed earlier) and enter the subendothelial connective tissue. There, particular molecules on the leukocyte membrane interact with surrounding molecules that guide the leukocytes to the infection. The first to arrive are the neutrophils, followed by monocytes (which can change into macrophages) and T lymphocytes (fig. 15.6). Most of the phagocytic leukocytes (neutrophils and monocytes) die in the course of the infection, but lymphocytes can travel through the lymphatic system and re-enter the circulation.

The adherence of monocytes to extracellular matrix proteins (chapter 6) promotes their conversion into macrophages. Macrophages ingest microorganisms and fragments of the extracellular matrix by phagocytosis. The macrophages also produce nitric oxide, which aids the destruction of bacteria. However, as inflammation progresses, the release of lysosomal enzymes from macrophages into the extracellular matrix causes the destruction of leukocytes and other tissue cells.

Mast cells are found in most tissues, but are especially concentrated in the skin, bronchioles (airways in the lungs), and intestinal mucosa. They are identified by their content of heparin, a molecule of clinical importance because of its

The Immune System

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■ Figure 15.6 Infiltration of an inflamed site by leukocytes.

Different types of leukocytes infiltrate the site of a local inflammation. Neutrophils arrive first, followed by monocytes and then lymphocytes.

anticoagulant ability (chapter 13). However, mast cells produce a variety of other molecules that play important roles in inflammation (and in allergy, discussed in a later section).

Mast cells release histamine which is stored in intracellu-lar granules and secreted during inflammation and allergy. Hista-mine binds to its H1 histamine receptors in the smooth muscle of bronchioles to stimulate bronchiolar constriction (as in asthma), but produces relaxation of the smooth muscles in blood vessels (causing vasodilation). Histamine also promotes increased capillary permeability, bringing more leukocytes to the infected area.

With a time delay, mast cells release inflammatory prostaglandins and leukotrienes (chapter 11; see fig. 11.34), as well as a variety of cytokines that promote inflammation. In addition, mast cells secrete tumor necrosis factora (TNFa), which acts as a chemokine to recruit neutrophils to the infected site.

These effects produce the characteristic symptoms of a local inflammation: redness and warmth (due to histamine-stimulated vasodilation); swelling (edema) and pus (the accumulation of dead leukocytes); and pain. If the infection continues, the release of endogenous pyrogen from leukocytes and macrophages may also produce a fever, as previously discussed.

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