Cells of the lmmune System skin epidermis)and are very efficient at capturing and variety of immunological functions.These proteins can be processing antigens:they can ingest particulate antigens activated either by antigen-bound antibodies or by direct (phagocytosis),engulf material in the surrounding fluid nteraction with microbes.Certain of the activated up (o s (pa cantibody immune complexes which bind binding antigens to the surface of FDCs via the compl to Fe receptors.The internalized antigens are degraded ment receptors.Thus,the antigens presented by FDCsto B nd s cells are not pro MHCoieeradatioaintopeptidcs.nd ated b cells forr The dendritic cells which have captured and pro germinal centres in the lymphoid follicles.The continued antigen mature into potent APCs as a result of their nt ction wi mulation by cyto activated B ndent int on th ithi Tcell stim plator c.g. ature dendriti ells which th FD cells is due not only to their high levels of antigen pe tide have the highest affinity for the antigen (possibly as a result MHC.but also to their expression of numer us costimu somat mutation).The B cells which do not interact latory adhesion mo u and cytokine with the FDCs in this way die by apoptosis. sociated with Monocytes and Macrophages a H0 and Mo 5-10% ctively i of mononi Dendritic cells not only activate T cells specific for when they migrate into tissues.The main functions of anesoioreoatheebutkebnepoeGgTFih macrophages are to phagocytose(i.e.engulf)and destroy components and,by virtue of expressing MHO In the thym T cell pre which develop antigen receptors cific for self antigens the bone marrow Monoc ytes are larger than most are eliminated if they interact with thymic dendritic cells lymphocytes and have a kidney-shaped nucleus: they with possess rophilic lyso omal granule ntai n the ability of the ident in tiss ed ods or to discriminate between foreign and self components. where they take on various morphologies.and are known by different names,depending on their t nce n the liver,m angial Follicular Dendritic Cells binding particulate antigens such as bacteria:these include Within the B cell-rich follicles ary lymphoid eceptors tor certai for re are ce a ells (EDCs) gy known as the dendritic cells discussed above:they are receptors enabling them to bind antigens which have bee mesenchymal origin rather than bone marrow derived and coated (i.e.opsonized)with IgG antibodies and C3b they do not express MHCclass II.The function of FDCs is ent protein. respectively.In addition to the to present anuger cells (rather th s are also important i ofactivated Bcells They ess Fcre ntors which enable have r s for nh them to bind immune complexes of antibodies bound to ssed on the outer surface of apoptotic cells The binding of particulate mate ral to expre ptors on envelo evatd e souormmune with the pha ome so that their content can participate in the destruction of the ingested material. ENCYCLOPEDIA OF LIFE SCIENCES/2001Nskin epidermis) and are very efficient at capturing and processing antigens: they can ingest particulate antigens (phagocytosis), engulf material in the surrounding fluid (macropinocytosis), and take up (by receptor-mediated endocytosis) sugar-bearing antigens which bind to surface lectins or antigen–antibody immune complexes which bind to Fc receptors. The internalized antigens are degraded into peptides and some of these associate with cytoplasmic MHC molecules followed by transportation to the cell surface for presentation. The dendritic cells which have captured and processed antigen mature into potent APCs as a result of their interaction with antigen and stimulation by cytokines and certain microbial products (e.g. lipopolysaccharide). This strong T-cell stimulatory capacity of the mature dendritic cells is due not only to their high levels of antigen peptide– MHC, but also to their expression of numerous costimu￾latory adhesion molecules and cytokines. The antigen￾laden dendritic cells migrate to secondary lymphoid tissues (lymph nodes and spleen) where they form clusters with T and B cells and stimulate antigen-specific immune responses: they present antigen peptides associated with both MHC class II and MHC class I molecules, and so can induce primary activation of both CD4+ TH cells and CD8+ TC cells, respectively. Dendritic cells not only activate T cells specific for antigens of foreign pathogens, but also help to prevent T cell reactivity against the body’s own components. If the body does not have this ‘self-tolerance’, autoimmune diseases can develop. In the thymus, T cell precursors which develop antigen receptors specific for self antigens are eliminated if they interact with thymic dendritic cells expressing these antigens, and similar interactions with mature self-reactive T cells in secondary lymphoid tissues may also help to maintain the ability of the immune system to discriminate between foreign and self components. Follicular Dendritic Cells Within the B cell-rich follicles of secondary lymphoid tissues there are cells with dendritic morphology known as follicular dendritic cells (FDCs). These are not related to the dendritic cells discussed above; they are probably of mesenchymal origin rather than bone marrow derived and they do not express MHC class II. The function of FDCs is to present antigens to B cells (rather than to T cells), thereby sustaining the viability, growth and differentiation of activated B cells. They express Fc receptors which enable them to bind immune complexes of antibodies bound to antigens. This surface binding of antigens is also facilitated by the expression of complement receptors on FDCs. Complement is the collective name for a number of proteins found in the blood and in tissue fluids which are activated in the course of immune responses and have a variety of immunological functions. These proteins can be activated either by antigen-bound antibodies or by direct interaction with microbes. Certain of the activated complement proteins (particularly C3b) bind to antigens and immune complexes and can therefore be involved in binding antigens to the surface of FDCs via the comple￾ment receptors. Thus, the antigens presented by FDCs to B cells are not processed by degradation into peptides, and are not bound to MHC molecules. Following antigen recognition, activated B cells form germinal centres in the lymphoid follicles. The continued survival and maturation of these activated B cells is dependent on their interaction with antigens held on the surface of the FDCs within the germinal centres. The B cells which successfully do this are those whose receptors have the highest affinity for the antigen (possibly as a result of somatic mutation). The B cells which do not interact with the FDCs in this way die by apoptosis. Monocytes and Macrophages Monocytes, which constitute 5–10% of mononuclear leucocytes in the blood, differentiate into macrophages when they migrate into tissues. The main functions of macrophages are to phagocytose (i.e. engulf) and destroy particulate material and, by virtue of expressing MHC class II, to present antigens to TH cells (discussed above). The blood monocytes arise from myeloid progenitors in the bone marrow. Monocytes are larger than most lymphocytes and have a kidney-shaped nucleus: they possess azurophilic lysosomal granules containing lyso￾zyme, acid hydrolases and myeloperoxidase. Macrophages can be resident in tissues for prolonged periods of time where they take on various morphologies, and are known by different names, depending on their tissues of residence, e.g. Kupffer cells in the liver, mesangial cells in the kidney and microglial cells in the brain. Macrophages have a variety of surface receptors for binding particulate antigens such as bacteria; these include receptors for certain sugars (e.g. mannose) and for lipopolysaccharide (via interaction with LPS-binding protein). They also have Fc receptors and complement receptors enabling them to bind antigens which have been coated (i.e. opsonized) with IgG antibodies and C3b complement protein, respectively. In addition to the removal of microbes, macrophages are also important in the rapid clearance of tissue cells dying by apoptosis and, for example, have receptors for phosphatidylserine ex￾pressed on the outer surface of apoptotic cells. The binding of particulate material to a macrophage triggers phagocytosis: the material is enveloped in cyto￾plasm, forming an intracellular vesicle called a phagosome. Lysosomes fuse with the phagosome so that their contents can participate in the destruction of the ingested material. Cells of the Immune System ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net 5