Antibodies emphasize that neither the omplement n thes tibody unclearvera studippor their posi linic Opsonization that vaccine tion n organ of antibodies with specific receptors on the surface of effector cells.By coating the surface of a pathogen antibodies may protect the graft from being eliminated by cellular immune effectors, antib allow the FcxR monomeric human IgGI and IgG3,the FeyRI receptor Antibody-mediated hypersensitivity reactions (CD32)preser The role of lge antibodies is reminiscent ofa double-edged n 1g( G3 sword,protecting with one edge and aggressing with the other.In the absence of antigen,basophils and mast cells antibodies trigger the effector functions carried out by ell of bi ding circula on an d monon ric antibodies with high affinit ith Engagement of thecell-bound IgE by a multivalent antigen individuals,that of subjects infested with parasites aoiaesnheamaleichrdbieeodhememgiae me laved on en a large paras FCERI the cell surface by antigen.releasing the vasoactive amines receptor.Externalization of internal sicles indu nstamine and serotonin.However,some individuals are complex tissue response to eliminate the undesirable parasite from the body. th called allergens.These inap Antibody-dependent cell-mediated cytotoxicity poneCaiseagopordieasescaledaherg or atopy Antibodies can contribute to elimination of undesirable e I and are due to so ble antig IgE antibo y recruit r cells.Follow ng antibody binding m production of 010 d h s and cytokines.These IgE-mediated alle ic rea kilerNKcells.which will initiate an antibody-mediated tions cause symptoms such as asthma.Thus,there is a correlation levels a e and bro expres the type cept h enable the the IgG or igm antibody ion forming protein which causes osmotic lysis.a cytotoxin activates complement and Fe-mediated effector reactions. that acti vates DNA-degrading enzymes within the target and the cellis attacked.This ha se ted c elass.the allergen is soluble and immune complexes of IG antibodies and allergen are formed in the tissue where they Undesirable functions cause local inflammation,such as occurs in serum sickness Rather than playing a protective role,antibodies may be nduced by injection of foreign serum responsible for undesirable functions. Antibody enhancement Further Reading This phenomenon has been described for antibodies that, Braden B and Poljak R(5) Klein J(1982)h Wiley ENCYCLOPEDIA OF LIFE SCIENCES/2001 Nature Publishing Group /www.els.net 1 emphasize that neither the complement nor phagocytes are specific for the pathogen. Instead, the antibodies involved in complement binding identify the pathogen as foreign. Opsonization Pathogens that replicate outside cells can be eliminated by a mechanism mediated by the interaction of the Fc region of antibodies with specific receptors on the surface of effector cells. By coating the surface of a pathogen, antibodies allow binding of their Fc domains to Fc receptors present on effector cells (Table 2). For example, the FcgRI receptor (CD64) exhibits appreciable affinity for monomeric human IgG1 and IgG3, the FcgRII receptor (CD32) present on phagocytic cells binds complexed IgG1 and IgG3, and the FcgRIII-b receptor (CD16) binds polymeric IgG1 and IgG3. Thus, by opsonizing pathogens via specific receptors on macrophages and neutrophils, antibodies trigger the effector functions carried out by these phagocytes (i.e. engulfment followed by internaliza￾tion and destruction). Through a similar mechanism, eosinophils interacting with IgE can attack metazoal parasites. While the serum IgE level is very low in healthy individuals, that of subjects infested with parasites increases and remains high as long as the infestation lasts. When a large parasite, such as a helminth, is coated with IgE, eosinophils attack it via the high-affinity FceRI receptor. Externalization of internal vesicles induces a complex tissue response to eliminate the undesirable parasite from the body. Antibody-dependent cell-mediated cytotoxicity Antibodies can contribute to elimination of undesirable cells by recruiting killer cells. Following antibody binding to allogeneic cells, the Fc region of the antibody may be recognized by non-T, non-B lymphoid cells, called natural killer (NK) cells, which will initiate an antibody-mediated cytotoxic process that will kill the target cells. NK cells express Fcg receptors, which enable them to recognize the IgG1 and IgG3 subclasses. Activation of NK cells triggers the release of granules containing a membrane pore￾forming protein which causes osmotic lysis, a cytotoxin that activates DNA-degrading enzymes within the target cell, and various proteolytic enzymes. This mechanism is used to clear pathogen-infected cells. Undesirable functions Rather than playing a protective role, antibodies may be responsible for undesirable functions. Antibody enhancement This phenomenon has been described for antibodies that, rather than neutralizing a virus, enhance its infectious potential, at leastin vitro.For example, serum from HIV-1- infected individuals contains antibodies that enhance infection by HIV-1 in vitro. Even though the molecular mechanisms of these antibody enhancements remain unclear, several studies support their possible clinical importance and it has been proposed that vaccine preparations against HIV-1 should exclude immunogenic epitopes for enhancing antibodies. In organ transplanta￾tion, instead of contributing to graft rejection, enhancing antibodies may protect the graft from being eliminated by cellular immune effectors. Antibody-mediated hypersensitivity reactions The role of IgE antibodies is reminiscent of a double-edged sword, protecting with one edge and aggressing with the other. In the absence of antigen, basophils and mast cells are capable of binding circulating IgE through species￾specific cell surface receptors, designated FceRI, which bind monomeric IgE antibodies with high affinity. Engagement of the cell-bound IgE by a multivalent antigen activates the mast cell, which releases chemical mediators stored in granules and capable of mediating local inflammatory reactions. Degranulation of mast cells occurs within seconds of crosslinking IgE displayed on the cell surface by antigen, releasing the vasoactive amines histamine and serotonin. However, some individuals are unable to control the mechanism of IgE recruitment and the cascade leading to the release of chemical mediators induced by antigens, called allergens. These inappropriate responses cause a group of diseases called allergy, or atopy. Most of them are of type I and are due to soluble antigens. They result from production of IgE antibodies which activate mast cells to release vasoactive amines, leuko￾trienes and cytokines. These IgE-mediated allergic reac￾tions cause symptoms such as asthma. Thus, there is a correlation between IgE levels and the prevalence and severity of bronchial asthma. In the type II class, such as occurs in some drug allergies, the allergen is cell bound and the IgG or IgM antibody against the tissue in question activates complement and Fc-mediated effector reactions, and the cell is attacked. This scenario occurs in haemolytic anaemia, seen in subjects who produce antibodies to penicillin-coated red blood cells. Finally, in the type III class, the allergen is soluble and immune complexes of IgG antibodies and allergen are formed in the tissue where they cause local inflammation, such as occurs in serum sickness induced by injection of foreign serum. Further Reading Braden B and Poljak R (1995) Structural features of the reactions between antibodies and protein antigens. FASEB Journal 9: 9–16. Klein J (1982) Immunology. The Science of Self–Nonself Discrimination. New York: John Wiley. Antibodies ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net 7