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The second major function associated with complement activation is the action of anaphylatoxins (see Figure 4.6B). C5a is the most potent, followed by C3a; C4a is much less potent. The name “anaphylatoxin” derives from the earliest recognition of their function: the ability to induce the shock‐like characteristics of the systemic allergic or anaphylactic response (see Chapter 13). We now recognize that these small peptides play key roles in inducing inflammatory responses, which form part of the body’s defenses in removing an infectious agent that has penetrated the tissues.

The anaphylatoxins interact with receptors expressed on many different cell types (see Table 4.2 and Figure 4.6B). They activate vascular endothelial cells (lining the walls of blood vessels), increasing the vascular permeability and leading to local accumulation of fluid (edema) in the tissue. The influx into the tissue of fluid containing phagocytic cells (macrophages and neutrophils), antibodies, and complement components enhances the response to the pathogen. The anaphylatoxins are also chemotactic for neutrophils; that is, the cells migrate from an area of lesser concentration to an area of higher concentration. As a result, neutrophils circulating in the blood are activated, leave the circulation at the site of inflammation, and destroy the foreign material. The anaphylatoxins also induce smooth muscle contraction. Interaction of the anaphylatoxins with basophils or mast cells in tissues results in the release of many inflammatory mediators, including histamine. The effects of histamine (discussed in Chapter 13) and the anaphylatoxins on vascular permeability and smooth muscle contraction are similar.