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Antibody Classes and Biological Activities
In this lecture the educator explains about Antibodies – II. The section one consists of and Immunoglobulin E and D. The various immunoglobulin isotypes and classes have been mentioned briefly already. Each class is distinguished by unique amino acid sequences in the heavy-chain constant region that confer class-specific structural and functional properties. In this section, the structure and effector functions of each class are described in more detail. The molecular properties and biological activities of the immunoglobulin classes are summarized. The structures of the five major classes are diagrammed. Immunoglobulin G (IgG) IgG, the most abundant class in serum, constitutes about 80% of the total serum immunoglobulin. The IgG molecule consists of two heavy chains and two or two light chains. There are four human IgG subclasses, distinguished by differences in chain sequence and numbered according to their decreasing average serum concentrations: IgG1, IgG2, IgG3, and IgG4. The amino acid sequences that distinguish the four IgG subclasses are encoded by different germ-line CH genes, whose DNA sequences are 90%–95% homologous. The structural characteristics that distinguish these subclasses from one another are the size of the hinge region and the number and position of the interchain disulphide bonds between the heavy chains.
In section two the educator explains about Antigenic Determinants. Since antibodies are glycoproteins, they can themselves function as potent immunogens to induce an antibody response. Such anti-Ig antibodies are powerful tools for the study of B-cell development and humoral immune responses. The antigenic determinants, or epitopes, on immunoglobulin molecules fall into three major categories: isotypic, allotypic, and idiotypic determinants, which are in characteristic portions of the molecule. Isotypic determinants are constant-region determinants that collectively define each heavy-chain class and subclass and antibody is routinely used for research purposes to determine the class or subclass of serum antibody produced during an immune response or to characterize the class of membrane-bound antibody present on B cells.
Although all members of a species inherit the same set of isotype genes, multiple alleles exist for some of the genes. These alleles encode subtle amino acid differences, called allotypic determinants, that occur in some, but not all, members of a species. The unique amino acid sequence of the VH and VL domains of a given antibody can function not only as an antigen-binding site but also as a set of antigenic determinants. The idiotypic determinants arise from the sequence of the heavy- and light-chain variable regions. Each individual antigenic determinant of the variable region is referred to as an idiotope. In some cases, an idiotope may be the actual antigen-binding site, and in some cases an idiotope may comprise variable-region sequences outside of the antigen binding site.
The B-Cell Receptor
The B-Cell Receptor (BCR), Fc Receptors Bind to Fc Regions of Antibodies and Types of Fc Receptors are explained insection three. Immunologists have long been puzzled about how mIg mediates an activating signal after contact with an antigen. The dilemma is that all isotypes of mIg have very short cytoplasmic tails: the mIgM and mIgD cytoplasmic tails contain only 3 amino acids; the mIgA tail, 14 amino acids; and the mIgG and mIgE tails,28 amino acids. In each case, the cytoplasmic tail is too short to be able to associate with intracellular signalling molecules (e.g., tyrosine kinases and G proteins). General structure of the B-cell receptor (BCR). This antigen-binding receptor is composed of membrane-bound immunoglobulin (mIg). Each heterodimer contains the immunoglobulin-fold structure and cytoplasmic tails much longer than those of mIg. Many cells feature membrane glycoproteins called Fc receptors (FcR)that have an affinity for the Fc portion of the antibody molecule. These receptors are essential for many of the biological functions of antibodies. Fc receptors are responsible for the movement of antibodies across cell membranes and the transfer of IgG from mother to fetus across the placenta. These receptors also allow passive acquisition of antibody by many cell types, including B and T lymphocytes, neutrophils, mast cells, eosinophils, macrophages, and natural killer cells.
The Immunoglobulin Superfamily
In section four the educator briefs about The Immunoglobulin Superfamily and Members of IgSF. The structures of the various immunoglobulin heavy and light chains described earlier share several features, suggesting that they have a common evolutionary ancestry. All heavy- and light-chain classes have the immunoglobulin-fold domain structure. The presence of this characteristic structure in all immunoglobulin heavy and light chains suggests that the genes encoding them arose from a common primordial gene encoding a polypeptide of about 110 amino acids. Gene duplication and later divergence could then have generated the various heavy- and light-chain genes. Large numbers of membrane proteins have been shown to possess one or more regions homologous to an immunoglobulin domain. Each of these membrane proteins is classified as a member of the immunoglobulin superfamily. The term super family is used to denote proteins whose corresponding genes derived from a common primordial gene encoding the basic domain structure. These genes have evolved independently and do not share genetic linkage or function. The following proteins, in addition to the immunoglobulins themselves, are representative members of the immunoglobulin superfamily.
Polyclonal vs Monoclonal Antibodies, Clinical Uses of Monoclonal Antibodies and Abzymes - Catalytic Monoclonal Antibodies are discussed in section five. The resulting serum antibodies are heterogeneous, comprising a mixture of antibodies, each specific for one epitope. Such a polyclonal antibody response facilitates the localization, phagocytosis, and complement-mediated lysis of antigen; it thus has clear advantages for the organism in vivo. Unfortunately, the antibody heterogeneity that increases immune protection in vivo often reduces the efficacy of an antiserum for various in vitro uses. For most research, diagnostic, and therapeutic purposes, monoclonal antibodies, derived from a single clone and thus specific for a single epitope, are preferable. Monoclonal antibodies are proving to be very useful as diagnostic, imaging, and therapeutic reagents in clinical medicine. Initially, monoclonal antibodies were used primarily as in vitro diagnostic reagents. Among the many monoclonal antibody diagnostic reagents now available are products for detecting pregnancy, diagnosing numerous pathogenic microorganisms, measuring the blood levels of various drugs, matching histocompatibility antigens, and detecting antigens shed by certain tumors.