Macrophages are resident in almost all tissues. Many tissue-resident macrophages arise during embryonic development, but some macrophages that arise in the adult animal from the bone marrow are the mature form of monocytes, which circulate in the blood and continually migrate into tissues, where they differentiate. Macrophages are relatively long-lived cells and perform several different functions throughout the innate immune response and the subsequent adaptive immune response. One is to engulf and kill invading microorganisms. This phagocytic function provides a first defense in innate immunity. Macrophages also dispose of pathogens and infected cells targeted by an adaptive immune response. Both monocytes and macrophages are phagocytic, but most infections occur in the tissues, and so it is primarily macrophages that perform this important protective function. An additional and crucial role of macrophages is to orchestrate immune responses: they help induce inflammation, which, as we shall see, is a prerequisite to a successful immune response, and they produce many inflammatory mediators that activate other immune-system cells and recruit them into an immune response.
Local inflammation and the phagocytosis of invading bacteria can also be triggered by the activation of complement. Bacterial surfaces can activate the complement system, inducing a cascade of proteolytic reactions that coat the microbes with fragments of specific proteins of the complement system.
Fig. 1.8 Myeloid cells in innate and adaptive immunity. In the rest of the book, these cells will be represented in the schematic form shown on the left. A photomicrograph of each cell type is shown on the right. macrophages and neutrophils are primarily phagocytic cells that engulf pathogens and destroy them in intracellular vesicles, a function they perform in both innate and adaptive immune responses. dendritic cells are phagocytic when they are immature and can take up pathogens; after maturing, they function as specialized cells that present pathogen antigens to t lymphocytes in a form they can recognize, thus activating t lymphocytes and initiating adaptive immune responses. macrophages can also present antigens to t lymphocytes and can activate them. the other myeloid cells are primarily secretory cells that release the contents of their prominent granules upon activation via antibody during an adaptive immune response. eosinophils are thought to be involved in attacking large antibody-coated parasites such as worms; basophils are also thought to be involved in anti-parasite immunity. mast cells are tissue cells that trigger a local inflammatory response to antigen by releasing substances that act on local blood vessels. mast cells, eosinophils, and basophils are also important in allergic responses. Photographs courtesy of n. rooney, r. Steinman, and d. Friend.
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Microbes coated in this way are recognized by specific complement receptors on macrophages and neutrophils, taken up by phagocytosis, and destroyed. In addition to their specialized role in the immune system, macrophages act as general scavenger cells in the body, clearing it of dead cells and cell debris.