Antibodies ovided 0 that the ar he evidence that interactions are noncova supstance.called the adiuvant.that enhances immuno od that the antibodya genicity.Other factors that influence tions fron an lomain he dos the rout ids fr provide the specificity of the interaction.The shape and or particulate,native or denatured). size of the combining site can vary,depending on the complex analysed Pathogen neutralization 0 Antibodies recognize antigens outside the cells,where most pacteria and b erial toxins are for hey can bind to a over large sterically and electrostatically complementarity ock its Hydrophobic determinants of the antigen interac 地and bl nts anti an block the adhe of hact to hos cells by binding to cell-surface proteins used by the and r nd ac bacterium to adhere to the cell. rial adheren and prevent i hich ith Antibodies as a first line of defence IgM antibodies are generally encoded by germline Function ncoded variable region genes and are of low affinity However,be r pentameric stru n in th an bind tom resent on the ides Th xistence of 10antigen-binding sites on an IgM molec and enhances the strength of its effective binding. IgM and mp ow) also enective in comp he main i activation presented by MHC class U molecules to antigen cific T type i the ood and the helper cells.In tur,T lymphocytes provide signals for the tion and complement activation (see below).IgG anti differentia B cells. For the bodies can diffuse into tissues and bind toxins rapidly and m by with high aftinity a critical role in destruction of extracellular pathog gA he principal isotype in tions.particularly in prevention against the spread of intracellular infections and protection against toxins I he tw structural portions from infectious agents (Fc) ab constant against pathogen ted by the mot es col co Fab-mediated functions onferring nrote ection from infections to the newborn.The protective role of IgA is also indicated b Antigen recognition hat individuals deficient in A produce high The immune system is able to g nerate a large repertoire of titres of anti antibody-combining sites capable of recognizing virtually all possib presen pathogens and the nate in certain locations.For example.cholera toxins trigger few,if any,circulating antibodies but induce the production of IgA in the faeces of the infected individual carbohydrates,nucleic acids and phospholipids,but their Interaction with superantigens induction gener ation of the antigen a carner ENCYCLOPEDIA OF LIFE SCIENCES/e 2001 Nature Publishing Group /www.els.net combining site, and have confirmed the domain-type organization of the immunoglobulin initially deduced from amino acid sequence analysis. They have provided evidence that antigen–antibody interactions are noncova￾lent and that the antibody-binding site requires contribu￾tions from the H- and L-chain variable domains of the Fab fragment. Amino acids from the CDRs, also called loops, between strands of the b sheets in the variable domains provide the specificity of the interaction. The shape and size of the combining site can vary, depending on the particular antigen–antibody complex analysed, from a shallow groove of 15
6 A˚ in size to a conical pocket of approximately 10 A˚ in diameter. The interactions occur over large sterically and electrostatically complementarity areas. Hydrophobic determinants of the antigen interact with hydrophobic determinants of the antibody-binding site, charged side-chains interact with side-chains of opposite charge, and proton donors and acceptors are involved in hydrogen bonding. Thus, electrostatic forces between charged amino acid side-chains (salt bridges), hydrogen bonds, van der Waals forces and hydrophobic forces, together with surface complementarity, impart antibody-specific recognition. Function For the immune system, immunoglobulins present on the B-lymphocyte surface play an essential role in transducing signals to the cytoplasmic and nuclear effectors, and in delivering the antigen to the cell compartment where it is degraded, processed and returned to the cell surface to be presented by MHCclass II molecules to antigen-specific T helper cells. In turn, T lymphocytes provide signals for the proliferation and differentiation of B cells. For the organism, antibodies secreted by B lymphocytes are responsible for the humoral immune response, which plays a critical role in destruction of extracellular pathogens, prevention against the spread of intracellular infections, and protection against toxins. The two structural portions of the antibody, i.e. the variable (Fab) and the constant (Fc) fragments, impart distinct biological functions. Fab-mediated functions Antigen recognition The immune system is able to generate a large repertoire of antibody-combining sites capable of recognizing virtually all possible antigens present in pathogens and their products (bacteria, viruses, and protozoal and metazoal parasites), and in environmental antigens. Antibodies can be raised against a variety of molecules, including carbohydrates, nucleic acids and phospholipids, but their induction generally requires the association of the antigen to a protein, called a carrier. Remarkably, even epitopes that do not exist in nature, such as synthetic haptens, can be exquisitely recognized and bound. A strong antibody response requires that the antigen be injected with a substance, called the adjuvant, that enhances immuno￾genicity. Other factors that influence immunogenicity include the dose injected, the route of immunization (subcutaneous injections are more immunogenic than intravenous injections) and the form of the antigen (soluble or particulate, native or denatured). Pathogen neutralization Antibodies recognize antigens outside the cells, where most bacteria and bacterial toxins are found. They can bind to a pathogen and block its access to cells, thereby preventing infection or destruction of host cells. In addition, antibodies can block the adherence of bacteria to host cells by binding to cell-surface proteins used by the bacterium to adhere to the cell. This binding will inhibit bacterial adherence and prevent infection. Antibodies may also be important for protection against viruses, which will not be able to infect cells and replicate. Antibodies as a first line of defence IgM antibodies are generally encoded by germline￾encoded variable region genes and are of low affinity. However, because of their pentameric structure and their rapid generation in the blood, they can bind to multivalent antigens, such as bacterial cell wall polysaccharides. The existence of 10 antigen-binding sites on an IgM molecule enhances the strength of its effective binding. IgM antibodies are also effective in complement activation (see below). IgG is the main isotype in the blood and the extracellular fluid. It plays an important role in opsoniza￾tion and complement activation (see below). IgG anti￾bodies can diffuse into tissues and bind toxins rapidly and with high affinity. IgA is the principal isotype in secretions, particularly in the intestinal and respiratory tracts. Its main property is to neutralize foreign antigens and to protect epithelial cells from infectious agents, providing a first line of defence against pathogens. This is illustrated by the crucial role of sIgA present in the mother’s colostrum, which contains approximately the same level of sIgA as other external secretions, conferring protection from infections to the newborn. The protective role of IgA is also indicated by observations that individuals deficient in IgA produce high titres of antibodies against various milk antigens. In response to certain pathogens, IgA antibodies predomi￾nate in certain locations. For example, cholera toxins trigger few, if any, circulating antibodies but induce the production of IgA in the faeces of the infected individual. Interaction with superantigens Recently, a new type of lymphocyte ligand, referred to as a superantigen, has been discovered. Initially described for T Antibodies ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net 5