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Antibodies (Immunglobulins (Igs) A- Definition: • Immunoglobulins are a group of proteins (gamma globulins) produced by the body from B lymphocytes and plasma cells in response to presence of foreign bodies (antigens). • There are 5 basic types: G, M, A, E and D. • All of immunoglobulins have a similar basic structure. B- Basic structure of immunoglobulins: • The basic unit of all Igs molecules consists of 4 polypeptide chains linked by disulfide bonds: a) 2 polypeptide chains of low molecular weight called light chains (L) b) 2 polypeptide chains of high molecular weight called heavy chains (H) • Disulfide bonds in Ig: • 1. Inter-chain disulfide bonds - heavy(H) and light (L) chains are linked together by disulfide bond. In addition, the two heavy chains are held together by inter-chain disulfide bonds and by non-covalent interactions. • 2. Intra-chain disulfide bonds - Within each of the polypeptide chains (within H and L chains) • Enzyme called “papain” cleaves Ig into two fragments: Fab fragment and Fc fragment. Fab fragment is the part of antibody molecule which combine with antigens. Immunoglobulin classes The Igs can be divided into five different classes, based on differences in the amino acid sequences in the heavy chains. Ig G: Ig G is the most important antibodies in fighting bacteria and virus a) IgG is the major Ig in serum:70-75% of serum Ig is IgG b) IgG is composed of one basic unit (monomer), i.e of low Mol. weight c) Placental transfer: IgG is the only class of Ig that crosses the placenta. In addition, Ig G is also transferred from mother to baby in breast milk. Transplacental and breast milk-derived Ig G offer the baby a passive immunologic protection until the endogenous Ig G is produced. The half life of Ig G is about 30 days and with prolonged breast feeding the infant can get additional protection. IgA 1. Structure - IgA is a monomer in serum but found in secretions as a dimer as presented in the Figure. In diameric IgA, the molecules are joined by a small polypeptide chain called J chain linked to Fc regions. - When IgA is found in secretions:, it also has another protein associated with it called the secretory piece or T piece. The secretory piece helps IgA to be transported across mucosa and also protects it from degradation in the secretions. 2. Properties a) IgA is the 2nd most common serum Ig (10-15%). b) IgA is the major class of Ig in secretions - tears, saliva, colostrum, mucus, secretions of GIT It protects against infection of mucus membranes that lining mouth, GIT and air ways. c) can’t pass placenta IgM 1.Structure IgM normally exists as a pentamer. So it has the highest molecular weight. The five units are linked by small polypeptide chain called J chain 2. Properties a) IgM is the third most common serum Ig (5-10% of total Ig). b) IgM i Times New Roman s the first Ig be made by a virgin B cells when it is stimulated by antigen. Then other classes are synthesized. c) It can’t cross placenta IgE 1. Structure: IgE exists as a monomer. 2. Properties: a) is the least common Ig in serum b) It is largely responsible for immunity against parasites . Since serum IgE levels rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. c) It plays an important role in allergic response to allergens (antigen causes allergy or hypersensitivity such as dust or pollens). Ig E, in the presence of alleregen, binds to mast cells and basophils causing release of histamine and other substances from mast cells. These substances result in allergic manifestations. Ig D: IgD exists only as a monomer. IgD is found in low levels. in serum; its role in serum uncertain. Ig G Ig A IgM Ig D Ig E 160 160 970 184 184 % of total Ig 70-75 10-15 5-10 Less than 1 trace Cross placenta yes NO NO NO NO In breast milk yes yes NO NO NO In secretions NO yes NO NO NO Binding with mast cells NO NO NO NO yes Mass (KD)