proteins (the antigens) are broken down into peptides inside dendritic cells and macrophages. these peptides are then bound to the cell's major histocompatibility complex (mhc) glycoproteins, which carry the peptides back to the phagocyte's surface where they can be "presented" to lymphocytes. mature macrophages do not travel far from the site of infection, but dendritic cells can reach the body's lymph nodes, where there are millions of lymphocytes. this enhances immunity because the lymphocytes respond to the antigens presented by the dendritic cells just as they would at the site of the original infection. but dendritic cells can also destroy or pacify lymphocytes if they recognize components of the host body; this is necessary to prevent autoimmune reactions. this process is called tolerance. immunological tolerance main article: immunological tolerance dendritic cells also promote immunological tolerance, which stops the body from attacking itself. the first type of tolerance is central tolerance, that occurs in the thymus. t cells that bind (via their t cell receptor) to self antigen (presented by dendritic cells on mhc molecules) too strongly are induced to die. the second type of immunological tolerance is peripheral tolerance. some self reactive t cells escape the thymus for a number of reasons, mainly due to the lack of expression of some self antigens in the thymus. another type of t cell; t regulatory cells can down regulate self reactive t cells in the periphery. when immunological tolerance fails, autoimmune diseases can follow. professional phagocytes phagocytes derive from stem cells in the bone marrow phagocytes of humans and other jawed vertebrates are divided into "professional" and "non-professional" groups based on the efficiency with which they participate in phagocytosis. the professional phagocytes are the monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells. one litre of human blood contains about six billion phagocytes. activation all phagocytes, and especially macrophages, exist in degrees of readiness. macrophages are usually relatively dormant in the tissues and proliferate slowly. in this semi-resting state, they clear away dead host cells and other non-infectious debris and rarely take part in antigen presentation. but, during an infection, they receive chemical signals—usually interferon gamma—which increases their production of mhc ii molecules and which prepares them for presenting antigens. in this state, macrophages are good antigen presenters and killers. if they receive a signal directly from an invader, they become "hyperactivated", stop proliferating, and concentrate on killing. their size and rate of phagocytosis increases—some become large enough to engulf invading protozoa. in the blood, neutrophils are inactive but are swept along at high speed. when they receive signals from macrophages at the sites of inflammation, they slow down and leave the blood. in the tissues, they are activated by cytokines and arrive at the battle scene ready to kill. migration neutrophils move from the blood to the site of infection when an infection occurs, a chemical "sos" signal is given off to attract phagocytes to the site. these chemical signals may include proteins from invading bacteria, clotting system peptides, complement products, and cytokines that have been given off by macrophages located in the tissue near the infection site. another group of chemical attractants are cytokines that recruit neutrophils and monocytes from the blood. to reach the site of infection, phagocytes leave the bloodstream and enter the affected tissues. signals from the infection cause the endothelial cells that line the blood vessels to make a protein called selectin, which neutrophils stick to on passing by. other signals called vasodilators loosen the junctions connecting endothelial cells, allowing the phagocytes to pass through the wall. chemotaxis is the process by which phagocytes follow the cytokine "scent" to the infected spot. neutrophils travel across epithelial cell-lined organs to sites of infection, and although this is an important component of fighting infection, the migration itself can result in disease-like symptoms. during an infection, millions of neutrophils are recruited from the blood, but they die after a few days. monocytes main article: monocytes monocytes in blood (giemsa stain) monocytes develop in the bone marrow and reach maturity in the blood. mature monocytes have large, smooth, lobed nuclei and abundant cytoplasm that contains granules. monocytes ingest foreign or dangerous substances and present antigens to other cells of the immune system. monocytes form two groups: a circulating group and a marginal group that remain in other tissues (approximately 70% are in the marginal group). most monocytes leave the blood stream after 20–40 hours to travel to tissues and organs and in doing so transform into macrophages or dendritic cells depending on the signals they receive. there are about 500 million monocytes in one litre of human blood. macrophages main article: macrophages mature macrophages do not travel far but stand guard over those areas of the body that are exposed to the outside world. there they act as garbage collectors, antigen presenting cells, or ferocious killers, depending on the signals they receive. they derive from monocytes, granulocyte stem cells, or the cell division of pre-existing macrophages. human macrophages are about 21 micrometers in diameter. pus oozing from an abscess caused by bacteria—pus contains millions of phagocytes this type of phagocyte does not have granules but contains many lysosomes. macrophages are found throughout the body in almost all tissues and organs (e.g., microglial cells in the brain and alveolar macrophages in the lungs), where they silently lie in wait. a macrophage's location can determine its size and appearance. macrophages cause inflammation through the production of interleukin-1, interleukin-6, and tnf-alpha. macrophages are usually only found in tissue and are rarely seen in blood circulation. the life-span of tissue macrophages has been estimated to range from four to fifteen days. macrophages can be activated to perform functions that a resting monocyte cannot. t helper cells (also known as effector t cells or th cells), a sub-group of lymphocytes, are responsible for the activation of macrophages. th1 cells activate macrophages by signaling with ifn-gamma and displaying the protein cd40 ligand. other signals include tnf-alpha and lipopolysaccharides from bacteria. th1 cells can recruit other phagocytes to the site of the infection in several ways. they secrete cytokines that act on the bone marrow to stimulate the production of monocytes and neutrophils, and they secrete some of the cytokines that are responsible for the migration of monocytes and neutrophils out of the bloodstream. th1 cells come from the differentiation of cd4+ t cells once they have responded to antigen in the secondary lymphoid tissues. activated macrophages play a potent role in tumor destruction by producing tnf-alpha, ifn-gamma, nitric oxide, reactive oxygen compounds, cationic proteins, and hydrolytic enzymes. neutrophils main article: neutrophils neutrophils with a segmented nuclei surrounded by erythrocytes, the intra-cellular granules are visible in the cytoplasm (giemsa stained) neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells. one litre of human blood contains about five billion neutrophils, which are about 10 micrometers in diameter and live for only about five days. once they have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection. they are ferocious eaters and rapidly engulf invaders coated with antibodies and complement, and damaged cells or cellular debris. neutrophils do not return to the blood; they turn into pus cells and die. mature neutrophils are smaller than monocytes and have a segmented nucleus with several sections; each section is connected by chromatin filaments—neutrophils can have 2–5 segments. neutrophils do not normally exit the bone marrow until maturity but during an infection neutrophil precursors called metamyelocytes, myelocytes and promyelocytes are released. the intra-cellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties. neutrophils can secrete products that stimulate monocytes and macrophages. neutrophil secretions increase phagocytosis and the formation of reactive oxygen compounds involved in intracellular killing. secretions from the primary granules of neutrophils stimulate the phagocytosis of igg-antibody-coated bacteria. when encountering bacteria, fungi or activated platelets they produce web-like chromatin structures known as neutrophil extracellular traps (nets). composed mainly of dna, nets cause death by a process called netosis – after the pathogens are trapped in nets they are killed by oxidative and non-oxidative mechanisms. dendritic cells main article: dendritic cell a dendritic cell dendritic cells are specialized antigen-presenting cells that have long outgrowths called dendrites, that help to engulf microbes and other invaders. dendritic cells are present in the tissues that are in contact with the external environment, mainly the skin, the inner lining of the nose, the lungs, the stomach, and the intestines. once activated, they mature and migrate to the lymphoid tissues where they interact with t cells and b cells to initiate and orchestrate the adaptive immune response. mature dendritic cells activate t helper cells and cytotoxic t cells. the activated helper t cells interact with macrophages and b cells to activate them in turn. in addition, dendritic cells can influence the type of immune response produced; when they travel to the lymphoid areas where t cells are held they can activate t cells, which then differentiate into cytotoxic t cells or helper t cells. mast cells main article: mast cell mast cells have toll-like receptors and interact with dendritic cells, b cells, and t cells to help mediate adaptive immune functions. mast cells express mhc class ii molecules and can participate in antigen presentation; however, the mast cell's role in antigen presentation is not very well understood. mast cells can consume and kill gram-negative bacteria (e.g., salmonella), and process their antigens. they specialize in processing the fimbrial proteins on the surface of bacteria, which are involved in adhesion to tissues. in addition to these functions, mast cells produce cytokines that induce an inflammatory response. this is a vital part of the destruction of microbes because the cytokines attract more phagocytes to the site of infection. professional phagocytes main location variety of phenotypes blood neutrophils, monocytes bone marrow macrophages, monocytes, sinusoidal cells, lining cells bone tissue osteoclasts gut and intestinal peyer's patches macrophages connective tissue histiocytes, macrophages, monocytes, dendritic cells liver kupffer cells, monocytes lung self-replicating macrophages, monocytes, mast cells, dendritic cells lymphoid tissue free and fixed macrophages and monocytes, dendritic cells nervous tissue microglial cells (cd4+) spleen free and fixed macrophages, monocytes, sinusoidal cells thymus free and fixed macrophages and monocytes skin resident langerhans cells, other dendritic cells, conventional macrophages, mast cells non-professional phagocytes dying cells and foreign organisms are consumed by cells other than the "professional" phagocytes. these cells include epithelial cells, endothelial cells, fibroblasts, and mesenchymal cells. they are called non-professional phagocytes, to emphasize that, in contrast to professional phagocytes, phagocytosis is not their principal function. fibroblasts, for example, which can phagocytose collagen in the process of remolding scars, will also make some attempt to ingest foreign particles. non-professional phagocytes are more limited than professional phagocytes in the type of particles they can take up. this is due to their lack of efficient phagocytic receptors, in particular opsonins—which are antibodies and complement attached to invaders by the immune system. additionally, most non-professional phagocytes do not produce reactive oxygen-containing molecules in response to phagocytosis. non-professional phagocytes main location variety of phenotypes blood, lymph and lymph nodes lymphocytes blood, lymph and lymph nodes nk and lgl cells (large granular lymphocytes) blood eosinophils and basophils skin epithelial cells liver hepatocytes blood vessels endothelial cells connective tissue fibroblasts pathogen evasion and resistance cells of staphylococcus aureus bacteria: the large, stringy capsules protect the organisms from attack by phagocytes. a pathogen is only successful in infecting an organism if it can get past its defenses. pathogenic bacteria and protozoa have developed a variety of methods to resist attacks by phagocytes, and many actually survive and replicate within phagocytic cells. avoiding contact there are several ways bacteria avoid contact with phagocytes. first, they can grow in sites that phagocytes are not capable of traveling to (e.g., the surface of unbroken skin). second, bacteria can suppress the inflammatory response; without this response to infection phagocytes cannot respond adequately. third, some species of bacteria can inhibit the ability of phagocytes to travel to the site of infection by interfering with chemotaxis. fourth, some bacteria can avoid contact with phagocytes by tricking the immune system into "thinking" that the bacteria are "self". treponema pallidum—the bacterium that causes