Cells of the Immune System This destructio s(.g pat s the oo large to be DS)E macrophages to mediate enabling them t s a ing,and nugen pre 0n,1s ontents (In ding majo stobrimgPleat age to the tar matory mediators like prostaglandins and leucotrienes. Eosinophils also produce cytokines.prostaglandins and They are also an important source of some complement leucotrienes,and enzymes which can inhibit the inflam- proteins. Neutrophils Basophils and Mast Cells named The main products of basophilks and mast phonuclear leucocytes because of their multilobed nuclei ed be re found in the circulation where they constitute less than 1%of white blood cells.Mast cells occur in tissues in two are short-lived (2-3 days).They migrate into tissues -connective tissue mast cells and r ucosal mast cells. particularly to sites of infection where they are involved in me most similar to b for%of granulcy durine the course of immune respor nses,e.g.at a site of in infection.Mast cells have high-affinity Fc receptors for IgE th somal granules which.in addition to mveloperoxidase and are coated with gEant odies which they adsorb Irom lysozyme and acid hydrolases,contain other antimicrobia ErsrToun hat the proteins (e.g. defensin and serprocid surface triggers activation.Mast cells can also be duced dur ggers their rel their tare (20-fold m activation (e.g.histamine,heparin and factors s which attract eosinophils) wh macrophages)specific for IgG or IgA,and complement eas others are more receptors for binding opsonized mat erial.They also bring tor).Mast cells can also produce various cytokines.The sin the cumulative effect of all these inflammatory mediators h prominent role in the acute phase of the response to (togethe Irom other cells)pro uced at a site of bacterial infection. .They alsc ce some cytokines well a prostaglandin ucotriene In contra antibodies and complement proteins)out of the ent antigens to ertgaRadmothendaiagsnsntheeh时ya Eosinophils Other Cells which Contribute to the The granulocytes whose granules stain with acidic dyes are Immune System called eosinophils.They comprise 2-5%of white blood digestion normally displayed 6 ENCYCLOPEDIA OF LIFE SCIENCES/2001 Nature Publishing Group /www.els.net This destruction is mediated partly by reactive oxygen species (e.g. hydroxyl radicals and nitric oxide) generated by enzyme activity known as the oxidative or respiratory burst, and also by the digestive lysosomal enzymes. The maximal activation of macrophages to mediate phagocytosis and killing, and also antigen presentation, is stimulated by cytokines, particularly interferon g. Macro￾phages are themselves producers of cytokines and inflam￾matory mediators like prostaglandins and leucotrienes. They are also an important source of some complement proteins. Neutrophils Granulocytes, so named because of their prominent cytoplasmic granules, comprise the majority of white blood cells (60–70%). They are also known as polymor￾phonuclear leucocytes because of their multilobed nuclei and are larger than most mononuclear blood cells. Derived from myeloid progenitors in the bone marrow, granulo￾cytes are released at a rate of seven million per minute, but are short-lived (2–3 days). They migrate into tissues, particularly to sites of infection where they are involved in the acute response. Neutrophils account for 95% of granulocytes in the blood. Like macrophages, they contain azurophilic lyso￾somal granules which, in addition to myeloperoxidase, lysozyme and acid hydrolases, contain other antimicrobial proteins (e.g. defensins and serprocidins). They also possess secondary specific granules which contain the iron-binding protein lactoferrin as well as lytic enzymes. The main function of neutrophils is the phagocytosis and intracellular digestion of particulate antigens (e.g. bacteria) essentially as described for macrophages. Thus, neutrophils express a similar range of receptors for binding their targets, including Fc receptors (20-fold more than macrophages) specific for IgG or IgA, and complement receptors for binding opsonized material. They also bring about destruction with reactive oxygen species and the antimicrobial enzymes and proteins. The vast number of neutrophils in the circulation means that they have a prominent role in the acute phase of the response to bacterial infection. They also produce some cytokines as well as prostaglandins and leucotrienes. In contrast to macrophages, neutrophils do not normally express MHC class II and so do not present antigens to TH cells. Eosinophils The granulocytes whose granules stain with acidic dyes are called eosinophils. They comprise 2–5% of white blood cells and have bilobed nuclei. In contrast to the phagocy￾tosis and intracellular digestion normally displayed by neutrophils, eosinophils secrete their granule contents for extracellular digestion of infectious pathogens which are too large to be engulfed (e.g. parasitic worms). Eosinophils have Fc receptors for IgG and IgE antibodies and for C3b, enabling them to bind to opsonized targets. They then secrete their antibiotic granule contents (including major basic protein and eosinophil cationic protein) and reactive oxygen species to bring about damage to the target. Eosinophils also produce cytokines, prostaglandins and leucotrienes, and enzymes which can inhibit the inflam￾matory products of mast cells (e.g. histaminase and aryl sulfatase). Basophils and Mast Cells The main products of basophils and mast cells are mediators which promote inflammatory responses. Baso￾phils (so called because their granules stain with basic dyes) are found in the circulation where they constitute less than 1% of white blood cells. Mast cells occur in tissues in two forms – connective tissue mast cells and mucosal mast cells. The latter are the most similar to basophils. There are two main mechanisms for mast cell activation during the course of immune responses, e.g. at a site of infection. Mast cells have high-affinity Fc receptors for IgE and are coated with IgE antibodies which they adsorb from their surroundings. Specific binding of antigen to multiple IgE molecules so that they are crosslinked on the mast cell surface triggers activation. Mast cells can also be stimulated by small peptides called anaphylatoxins (C3a and C5a) produced during complement activation. The activation of mast cells triggers their release of a wide range of inflammatory mediators; some are stored in cytoplasmic granules and released immediately upon activation (e.g. histamine, heparin and factors which attract neutrophils or eosinophils), whereas others are synthesized de novo and are released more slowly (leucotrienes, prostaglandins and platelet-activating fac￾tor). Mast cells can also produce various cytokines. The cumulative effect of all these inflammatory mediators (together with those from other cells) produced at a site of infection is to facilitate and encourage the movement of lymphocytes, monocytes, granulocytes and their products (e.g. antibodies and complement proteins) out of the bloodstream and into the underlying tissues where they can fight the infection. Other Cells which Contribute to the Immune System The appropriate regulation and functioning of cells of the immune system requires not only that they interact with Cells of the Immune System 6 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net