Macrophages are large phagocytic cells that detect, engulf, and destroy foreign particles, microbes, and other pathogens. When nonmotile, they are often referred to as histiocytes. They reside in every tissue of the body and play major roles in both innate (nonspecific) and adaptive (acquired or antigen-specific) immunity. Macrophages are derived from specific white blood cells termed monocytes; in fact, they are the largest type of white blood cells in the body, measuring approximately 21 micrometers (0.00083 inches) in diameter. In the event of an infection or tissue damage, or in response to the accumulation of dead (apoptotic) cells, monocytes circulating in the blood will enter the affected tissue or organ and differentiate into macrophages. At the targeted site, the macrophage surrounds the invading or unwanted particle with its cell membrane, a process called phagocytosis. With the help of opsonin molecules, phagocytosis enables the formation of a vesicle called a phagosome. Then, specialized structures known as lysosomes, which are located inside the macrophage, fuse with the phagosome (creating a phagolysosome) and release digestive enzymes that break down the pathogenic particle. Whatever then remains of the captured material is removed from the cell as waste, thereby protecting the host from infection. See also: Blood; Cell (biology); Cell biology; Endocytosis; Evolution of phagotrophy; Immunity; Immunologic cytotoxicity; Lysosome; Opsonin; Phagocytosis

A colorized scanning electron micrograph of a macrophage. (Photo courtesy of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD)

Macrophages, which routinely survive for many months, are capable of destroying numerous types of microbes. They also produce cell-signaling proteins (chemokines or cytokines) in response to inflammatory pathogens, which recruit additional macrophages to the site of infection. This capability allows macrophages to provide an innate immunity that acts nonspecifically against diverse invaders. In contrast, adaptive immunity is characterized by the ability to respond more rapidly and more intensely when encountering a pathogen for a second time, a feature known as immunological memory. In this type of defense, macrophages act as antigen-presenting cells: On their surface, they display protein fragments, or antigens, from the pathogens that they ingest. Macrophages' presentation of a foreign antigen can stimulate other cells of the immune system to produce specific antibodies or T cells (T lymphocytes) that will fight against the pathogen. The same mechanism will affect the transplant of organs from one individual to another: If the normal activities of the macrophages are not suppressed by drugs, most transplants fail. See also: Antibody; Antigen; Cellular immunology; Clinical immunology; Cytokine; Immunology; Inflammation; Transplantation biology

Although macrophages are necessary for healthy host defenses against infection, they also contribute to the pathogenesis of many inflammatory and degenerative diseases. Macrophages often create granulomas (small nodular areas or lesions of localized inflammation) in tissues. Chronic forms of granulomatous inflammation are typical of tuberculosis, leishmaniasis, leprosy, sarcoidosis, Crohn's disease, rheumatoid arthritis, and fungal infections (for example, cryptococcosis and histoplasmosis). In certain cases, such as tuberculosis and leishmaniasis, the pathogen lives inside the macrophage, avoiding destruction and continuing to replicate. Recent studies also have indicated that macrophages can promote tumor progression and growth. Therefore, investigators are targeting tumor-associated macrophages in attempts to prevent and eliminate cancers. See also: Arthritis; Cancer (medicine); Disease; Fungal infections; Immunotherapy; Leprosy; Medical parasitology; Oncology; Tuberculosis