{"id":207,"date":"2019-04-15T04:08:19","date_gmt":"2019-04-15T04:08:19","guid":{"rendered":"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/?post_type=chapter&#038;p=207"},"modified":"2019-04-15T04:35:23","modified_gmt":"2019-04-15T04:35:23","slug":"ig-classes-structure-and-function","status":"publish","type":"chapter","link":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/chapter\/ig-classes-structure-and-function\/","title":{"rendered":"Ig Classes: Structure and Function"},"content":{"raw":"&nbsp;\r\n<ol>\r\n \t<li style=\"text-align: justify\">Objectives<\/li>\r\n<\/ol>\r\n<ul style=\"text-align: justify\">\r\n \t<li>\u00a0To learn how the structure of IgG was established<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>\u00a0Different classes of Ig<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>\u00a0Their structures and functions<\/li>\r\n<\/ul>\r\n<ol style=\"text-align: justify\" start=\"2\">\r\n \t<li>Concept Map<\/li>\r\n<\/ol>\r\n<p style=\"text-align: justify\"><img class=\"aligncenter size-full wp-image-210\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127.png\" alt=\"\" width=\"540\" height=\"334\" \/><\/p>\r\n\r\n<ol start=\"3\">\r\n \t<li style=\"text-align: justify\"><strong>Description<\/strong><\/li>\r\n<\/ol>\r\n<p style=\"text-align: justify\">We referred to humoral immunity earlier. Antibodies are present in the serum and these proteins were originally detected there.<\/p>\r\n<p style=\"text-align: justify\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify\">The early electrophoretic studies of the serum revealed the presence of several proteins with their characteristic migration patterns under the influence of the electric field.<\/p>\r\n<p style=\"text-align: justify\"><img class=\"aligncenter size-full wp-image-211\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128.png\" alt=\"\" width=\"442\" height=\"460\" \/><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The terms antibodies and immunoglobulins are often used interchangeably.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">These proteins are produced by the immune system in response to the exposure to antigens.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">As all animals are invariably exposed to antigens, some antibodies are always present in the serum.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">Any intentional or accidental exposure to specific antigens produces the corresponding specific antibody population in the serum.<\/p>\r\n<p style=\"text-align: justify\"><img class=\"aligncenter size-full wp-image-212\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129.png\" alt=\"\" width=\"304\" height=\"301\" \/><\/p>\r\n<p style=\"text-align: justify\">The first break through came from looking at a homogeneous protein obtained from tumours of plasma cells<\/p>\r\n<p style=\"text-align: justify\">In 1847, Henry Bence Jones, a physician at St. George hospital in London published a paper \u201cOn a New Substance Occuring in the Urine of a Patient With Mollities Ossium, Phil. Tr. Royal Soc. London. 138:55-62\u201d<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\"><strong><em>\u201cOn the 1st of November 1845, I received from Dr. Watson the following note, with a test tube containing a thick, yellow, semi-solid substance: \u201cThe tube contains urine of very high specific gravity; when boiled it becomes highly opaque; on the addition of nitric acid it effervesces, assumes a reddish hue, becomes quite clear, but, as it cools, assumes the consistence and appearance which you see: heat reliquifies it. What is it?\u201d\u201d<\/em><\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">Thus\u00a0 A Bence Jones protein was discovered which is a monoclonal globulin protein or immunoglobulin light chain found in the urine, with a molecular weight of 22-24 kDa. Detection of Bence Jones protein may be suggestive of multiple myeloma.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">Mollitis Ossimum is now called multiple myeloma, the cancer of the plasma cells. These Bence Jones proteins (despite 700 papers!) remained a biochemical curiosity but nevertheless these were valuable diagnostic test for multiple myeloma.<\/p>\r\n<img class=\"aligncenter size-full wp-image-213\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-130.png\" alt=\"\" width=\"203\" height=\"243\" \/>\r\n<p style=\"text-align: justify\">As we have discussed, any antigen would have a number of antigenic determinants. Hence the antibodies produced in response to the exposure to an antigen is bound to produce a population of immunoglobulins.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">All immunoglobulins are specific to that particular antigen but each in fact is specific to a particular antigenic determinant.<\/p>\r\n<img class=\"aligncenter size-full wp-image-214\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131.png\" alt=\"\" width=\"432\" height=\"350\" \/>\r\n<p style=\"text-align: justify\">For much of the work in immunology, especially in the early days, the serum as such constituted the antibody preparation. When used as such, it is, for obvious reasons, often referred to as antiserum.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">In humans, there are five classes of antibodies or immunoglobulins.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The different types of immunoglobulins are of different shapes.<\/p>\r\n&nbsp;\r\n\r\n<img class=\"aligncenter size-full wp-image-215\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132.png\" alt=\"\" width=\"356\" height=\"490\" \/>\r\n<p style=\"text-align: justify\"><strong>Immunoglobulin G (IgG)<\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">This is responsible for the major part of the immunity against blood borne infectious agents.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">It has the highest concentration of 8-16 mg\/mL in normal adult serum as compared to all other classes of the immunoglobulins.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">It has four different sub classes:<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">IgG1, IgG2, IgG3, IgG4<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">These different classes differ slightly in the amino acid sequences in a particular region called constant region in the H-chain (We will look at the different polypeptide chains of immunoglobulins shortly). These differences are reflected in their functional activities.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">Ig is the only immunoglobulin which can cross the placental barrier and thus provides passive humoral immunity to the developing foetus.<\/p>\r\n<img class=\"aligncenter size-full wp-image-216\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133.png\" alt=\"\" width=\"536\" height=\"301\" \/>\r\n<p style=\"text-align: justify\"><strong>IgG Structure<\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">All IgG immunoglobulins have a four chain structure. This 4 chain structure of IgG is in fact the basic structural unit present in all classes of the immunoglobulins<\/p>\r\n<img class=\"aligncenter size-full wp-image-217\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134.png\" alt=\"\" width=\"490\" height=\"300\" \/>\r\n<p style=\"text-align: justify\">Antibodies have 5 different kinds of heavy chains called \u00b5, \u03b4, \u03b3, \u03b5 and \u03b1 chains. These H-chains are present in IgM, IgD, IgG, IgE and IgA respectively and distinguish these different classes of antibodies\/immunoglobulins.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">In the subclases of IgG the heavy chains are different and are called \u03b31, \u03b32, \u03b33, \u03b34 and belong to the respective sub classes.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The molecular weights of the H-chain in IgG is in the range of 50-55 kDa. In any given immunoglobulin molecule, the two heavy chains and the two light chains are identical, giving an antibody molecule two identical antigen-binding sites, and thus the ability to bind simultaneously to two identical structures.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">Immunoglobulins have two different kinds of light chains. These two L-chains are called \u03ba (kappa) and \u03bb (lambda). Each has a molecular weight of 23 kDa. A given immunoglobulin either has \u03ba chains or \u03bb chains, never one of each. No functional difference has been found between antibodies having \u03bb or \u03ba light chains, and either type of light chain may be found in antibodies of any of the five major classes.<\/p>\r\n<img class=\"aligncenter size-full wp-image-218\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135.png\" alt=\"\" width=\"380\" height=\"342\" \/>\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\">The two heavy chains are linked to each other by disulfide bonds and each heavy chain is linked to a light chain by a disulfide bond.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">These intramolecular disulphide bridges create compact structural units called domains. These domains are shown in the Figure below as VH, VL, CH1, CH2, CH3. The domains are also sometimes called as regions.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The IgG molecule consists of two symmetrical units joined by one interchain disulphide bridge.<\/p>\r\n<p style=\"text-align: justify\"><img class=\"aligncenter size-full wp-image-219\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136.png\" alt=\"\" width=\"456\" height=\"393\" \/><\/p>\r\n<p style=\"text-align: justify\"><strong><em>F<\/em><\/strong><strong><em>ab<\/em><\/strong><strong><em> and F<\/em><\/strong><strong><em>c<\/em><\/strong><strong><em> fragments<\/em><\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The N-terminal half of the H-chain and all of the L-chain are also connected with an interchain disulphide bridge. This part of the molecule is called Fab fragment. The subscript ab refers to the fact that this portion has the binding site for the antigen. Thus \u201eab\u201f subscript refers to antigen binding property of the fragment F. As the immunoglobulin molecule is symmetrical, each IgG has 2 Fab fragments.<\/p>\r\n<img class=\"aligncenter size-full wp-image-220\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-137.png\" alt=\"\" width=\"343\" height=\"263\" \/>\r\n<p style=\"text-align: justify\"><strong><em>The Fc Fragment<\/em><\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The three quarter of the H-chains from the C-terminal side and the C-terminal half of the L-chains are constant. All antibodies of the same class and sub class have the same amino acid sequence. Hence these regions have been denoted as CH with C referring to constant. The C-terminal half of each H-chain constitutes Fc fragments. The subscript \u201ec\u201f refers to the fact that it was found to be easily crystallizable for X-ray diffraction studies. Thus Fc stands for fragment crystallized.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">Fc fragment is not involved in the antigen binding but binds to complement and some other cells of the immune system. This will be discussed in the next lecture.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">There is a hinge region around the place where Fab fragments join the Fc fragment. This is more flexible region and provides the required flexibility to the two Fab fragments to move with respect to each other (Figure 8).<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">R.R.Porter at Oxford, UK used a protease papain to break IgG into three fragments of nearly equal size.<\/p>\r\n<p style=\"text-align: justify\"><img class=\"aligncenter size-full wp-image-221\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-138.png\" alt=\"\" width=\"217\" height=\"44\" \/><\/p>\r\n<p style=\"text-align: justify\">Further work by Michael Green and Robert Valentine showed that another protease pepsin cleaved Ig differently.<\/p>\r\n<img class=\"aligncenter size-full wp-image-222\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139.png\" alt=\"\" width=\"379\" height=\"342\" \/>\r\n<p style=\"text-align: justify\"><strong><em>Hypervariable regions<\/em><\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">The following Kabat and Wu plot shows the variability of the amino acid sequences in both H-chains and L-chains among different antibodies. The different antibodies are against different antigens\/antigenic determinants. Hence the variability is the origin of the antibody specificity. Hypervariable regions constitute the antigen binding sites. Affinity labeling confirmed the existence of hypervariable regions. Reactive haptens were found to react to the antigen binding sites (the hypervariable regions). Hypervariable regions are called complementarity determining regions (CDRs).<\/p>\r\n&nbsp;\r\n\r\n<img class=\"aligncenter size-full wp-image-223\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140.png\" alt=\"\" width=\"362\" height=\"344\" \/>\r\n<p style=\"text-align: justify\">The five classes of Ig differ in the nature of their H-chain, chain structure and some other structural features. The basic structural unit is similar not only among the five classes of Ig but is also characteristic of other molecules associated with the immune system. Hence, from the evolutionary perspective, many of these arose from an ancestral gene. All these molecules, including the five classes of Ig are thus part of the super family.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">IgG is found in the vascular spaces, extravascular spaces and secretions. Major IgG is found in the serum as well as during the secondary response to many antigens. In humans, IgG is capable of moving across placenta and thus protect the growing foetus. In humans, IgG has four subclasses as mentioned before. There concentrations are different in human serum with IgG1 having the highest concentration. All can cross the placental barrier but differ in the nature of their heavy chains. All IgG subclasses except IgG4 can bind to C1q to activate the classical pathway. It can act as opsonin. Fc part plays an important role. For example, Many large granular lymphocyte have Fc receptor.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify\">FcR4 is the receptor on the placental cells that can bind to all Ig subclasses and enable their foetal circulation.<\/p>\r\n&nbsp;\r\n\r\n<strong><em>IgM<\/em><\/strong>\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\">IgM is a pentamer of the 4 chain structure. During development of the immune system, IgM is the first Ig to be produced. It is also the first Ig to be produced during the primary immune response. It is capable of complement fixation. T-independent antigens produce antibodies with IgM as the main component. It has a molecular weight of 970 kDa, making it the largest Ig. Its heavy chain is \u00b5. It has J-chain which is also synthesized by B-cells but coded by a gene different from those coding for Ig.<\/p>\r\n<img class=\"aligncenter size-full wp-image-224\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141.png\" alt=\"\" width=\"420\" height=\"549\" \/>\r\n<p style=\"text-align: justify\">IgD is present in serum in traces. It is co-expressed alongwith IgM as a cell surface receptor on differentiating B-cells. Mature B-cells (plasma cells) do not have IgD on their surfaces. During encounter of B-cells with antigens, IgD regulates B-cell function leading to internalization of the antigen which after processing is presented to Tn cells.<\/p>\r\n<img class=\"aligncenter size-full wp-image-225\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142.png\" alt=\"\" width=\"507\" height=\"237\" \/>\r\n<p style=\"text-align: justify\">It also has two subclasses IgA1 and IgA2 with identical molecular weight of 160 kDa. The subclasses have \u03b11 and \u03b12 as H-chains. The concentration of IgA1 in human serum is much higher than IgA2. IgA protects the mucous membranes and is present in all secretions as the most abundant Ig. In those specie in which IgG is not transferred across the placenta, It is IgA which protects neonates. It is present in colostrums. IgA can form dimmers and polymers. It is present in humans as monomers only and mostly as dimmers in other animals. It contains a secretory component SC and a joining chain (J-chain). SC stabilizes IgA and is involved in its transport of exocrine IgA. J-chain helps in the dimerization of secretory IgA (dimeric).<\/p>\r\n&nbsp;\r\n\r\n<strong><em>IgE<\/em><\/strong>\r\n\r\n<img class=\"aligncenter size-full wp-image-226\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-143.png\" alt=\"\" width=\"222\" height=\"164\" \/>\r\n<p style=\"text-align: justify\">Its serum concentration is lowest among all the Ig under normal conditions. Its heavy chain is \u03b5 and molecular weight is 188 kDa. Apart from IgM, it is the only Ig having 5 heavy chain domains. Other Ig have 4 heavy chain domains. It is not involved in complement activation. IgE binds to mast cells and basophils which have high affinity Fc receptors. Consequently, these cells release mediators of inflammation after contact with the antigen. IgE mediates type I hypersensitivity reactions such as asthma and hay fever. It plays a very important role in protection against helminthic infections.<\/p>\r\n<img class=\"aligncenter size-full wp-image-227\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144.png\" alt=\"\" width=\"507\" height=\"258\" \/>\r\n\r\n<strong>Summary:<\/strong>\r\n\r\n&nbsp;\r\n<ul>\r\n \t<li style=\"text-align: justify\">\u00a0Bence Jones proteins (light chains) turned out to be the first step in understanding IgG structure<\/li>\r\n \t<li style=\"text-align: justify\">\u00a0IgG sequence was established first and it has two H-chains and 2 L-chains<\/li>\r\n \t<li style=\"text-align: justify\">\u00a0IgG structure is the basic structural unit for the structure of other clases of Ig<\/li>\r\n \t<li style=\"text-align: justify\">\u00a0There are five classes of Ig: IgG, IgA, IgM, IgD, IgE<\/li>\r\n \t<li style=\"text-align: justify\">\u00a0Their structures are now known and their individual functions is also now fairly well understood.<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n&nbsp;","rendered":"<p>&nbsp;<\/p>\n<ol>\n<li style=\"text-align: justify\">Objectives<\/li>\n<\/ol>\n<ul style=\"text-align: justify\">\n<li>\u00a0To learn how the structure of IgG was established<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>\u00a0Different classes of Ig<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>\u00a0Their structures and functions<\/li>\n<\/ul>\n<ol style=\"text-align: justify\" start=\"2\">\n<li>Concept Map<\/li>\n<\/ol>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-210\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127.png\" alt=\"\" width=\"540\" height=\"334\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127.png 540w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127-300x186.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127-65x40.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127-225x139.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-127-350x216.png 350w\" sizes=\"auto, (max-width: 540px) 100vw, 540px\" \/><\/p>\n<ol start=\"3\">\n<li style=\"text-align: justify\"><strong>Description<\/strong><\/li>\n<\/ol>\n<p style=\"text-align: justify\">We referred to humoral immunity earlier. Antibodies are present in the serum and these proteins were originally detected there.<\/p>\n<p style=\"text-align: justify\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify\">The early electrophoretic studies of the serum revealed the presence of several proteins with their characteristic migration patterns under the influence of the electric field.<\/p>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-211\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128.png\" alt=\"\" width=\"442\" height=\"460\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128.png 442w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128-288x300.png 288w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128-65x68.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128-225x234.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-128-350x364.png 350w\" sizes=\"auto, (max-width: 442px) 100vw, 442px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The terms antibodies and immunoglobulins are often used interchangeably.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">These proteins are produced by the immune system in response to the exposure to antigens.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">As all animals are invariably exposed to antigens, some antibodies are always present in the serum.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Any intentional or accidental exposure to specific antigens produces the corresponding specific antibody population in the serum.<\/p>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-212\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129.png\" alt=\"\" width=\"304\" height=\"301\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129.png 304w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129-150x150.png 150w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129-300x297.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129-65x64.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-129-225x223.png 225w\" sizes=\"auto, (max-width: 304px) 100vw, 304px\" \/><\/p>\n<p style=\"text-align: justify\">The first break through came from looking at a homogeneous protein obtained from tumours of plasma cells<\/p>\n<p style=\"text-align: justify\">In 1847, Henry Bence Jones, a physician at St. George hospital in London published a paper \u201cOn a New Substance Occuring in the Urine of a Patient With Mollities Ossium, Phil. Tr. Royal Soc. London. 138:55-62\u201d<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\"><strong><em>\u201cOn the 1st of November 1845, I received from Dr. Watson the following note, with a test tube containing a thick, yellow, semi-solid substance: \u201cThe tube contains urine of very high specific gravity; when boiled it becomes highly opaque; on the addition of nitric acid it effervesces, assumes a reddish hue, becomes quite clear, but, as it cools, assumes the consistence and appearance which you see: heat reliquifies it. What is it?\u201d\u201d<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Thus\u00a0 A Bence Jones protein was discovered which is a monoclonal globulin protein or immunoglobulin light chain found in the urine, with a molecular weight of 22-24 kDa. Detection of Bence Jones protein may be suggestive of multiple myeloma.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Mollitis Ossimum is now called multiple myeloma, the cancer of the plasma cells. These Bence Jones proteins (despite 700 papers!) remained a biochemical curiosity but nevertheless these were valuable diagnostic test for multiple myeloma.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-213\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-130.png\" alt=\"\" width=\"203\" height=\"243\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-130.png 203w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-130-65x78.png 65w\" sizes=\"auto, (max-width: 203px) 100vw, 203px\" \/><\/p>\n<p style=\"text-align: justify\">As we have discussed, any antigen would have a number of antigenic determinants. Hence the antibodies produced in response to the exposure to an antigen is bound to produce a population of immunoglobulins.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">All immunoglobulins are specific to that particular antigen but each in fact is specific to a particular antigenic determinant.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-214\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131.png\" alt=\"\" width=\"432\" height=\"350\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131.png 432w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131-300x243.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131-65x53.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131-225x182.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-131-350x284.png 350w\" sizes=\"auto, (max-width: 432px) 100vw, 432px\" \/><\/p>\n<p style=\"text-align: justify\">For much of the work in immunology, especially in the early days, the serum as such constituted the antibody preparation. When used as such, it is, for obvious reasons, often referred to as antiserum.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">In humans, there are five classes of antibodies or immunoglobulins.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The different types of immunoglobulins are of different shapes.<\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-215\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132.png\" alt=\"\" width=\"356\" height=\"490\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132.png 356w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132-218x300.png 218w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132-65x89.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132-225x310.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-132-350x482.png 350w\" sizes=\"auto, (max-width: 356px) 100vw, 356px\" \/><\/p>\n<p style=\"text-align: justify\"><strong>Immunoglobulin G (IgG)<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">This is responsible for the major part of the immunity against blood borne infectious agents.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">It has the highest concentration of 8-16 mg\/mL in normal adult serum as compared to all other classes of the immunoglobulins.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">It has four different sub classes:<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">IgG1, IgG2, IgG3, IgG4<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">These different classes differ slightly in the amino acid sequences in a particular region called constant region in the H-chain (We will look at the different polypeptide chains of immunoglobulins shortly). These differences are reflected in their functional activities.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Ig is the only immunoglobulin which can cross the placental barrier and thus provides passive humoral immunity to the developing foetus.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-216\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133.png\" alt=\"\" width=\"536\" height=\"301\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133.png 536w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133-300x168.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133-65x37.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133-225x126.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-133-350x197.png 350w\" sizes=\"auto, (max-width: 536px) 100vw, 536px\" \/><\/p>\n<p style=\"text-align: justify\"><strong>IgG Structure<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">All IgG immunoglobulins have a four chain structure. This 4 chain structure of IgG is in fact the basic structural unit present in all classes of the immunoglobulins<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-217\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134.png\" alt=\"\" width=\"490\" height=\"300\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134.png 490w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134-300x184.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134-65x40.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134-225x138.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-134-350x214.png 350w\" sizes=\"auto, (max-width: 490px) 100vw, 490px\" \/><\/p>\n<p style=\"text-align: justify\">Antibodies have 5 different kinds of heavy chains called \u00b5, \u03b4, \u03b3, \u03b5 and \u03b1 chains. These H-chains are present in IgM, IgD, IgG, IgE and IgA respectively and distinguish these different classes of antibodies\/immunoglobulins.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">In the subclases of IgG the heavy chains are different and are called \u03b31, \u03b32, \u03b33, \u03b34 and belong to the respective sub classes.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The molecular weights of the H-chain in IgG is in the range of 50-55 kDa. In any given immunoglobulin molecule, the two heavy chains and the two light chains are identical, giving an antibody molecule two identical antigen-binding sites, and thus the ability to bind simultaneously to two identical structures.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Immunoglobulins have two different kinds of light chains. These two L-chains are called \u03ba (kappa) and \u03bb (lambda). Each has a molecular weight of 23 kDa. A given immunoglobulin either has \u03ba chains or \u03bb chains, never one of each. No functional difference has been found between antibodies having \u03bb or \u03ba light chains, and either type of light chain may be found in antibodies of any of the five major classes.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-218\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135.png\" alt=\"\" width=\"380\" height=\"342\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135.png 380w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135-300x270.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135-65x59.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135-225x203.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-135-350x315.png 350w\" sizes=\"auto, (max-width: 380px) 100vw, 380px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The two heavy chains are linked to each other by disulfide bonds and each heavy chain is linked to a light chain by a disulfide bond.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">These intramolecular disulphide bridges create compact structural units called domains. These domains are shown in the Figure below as VH, VL, CH1, CH2, CH3. The domains are also sometimes called as regions.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The IgG molecule consists of two symmetrical units joined by one interchain disulphide bridge.<\/p>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-219\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136.png\" alt=\"\" width=\"456\" height=\"393\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136.png 456w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136-300x259.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136-65x56.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136-225x194.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-136-350x302.png 350w\" sizes=\"auto, (max-width: 456px) 100vw, 456px\" \/><\/p>\n<p style=\"text-align: justify\"><strong><em>F<\/em><\/strong><strong><em>ab<\/em><\/strong><strong><em> and F<\/em><\/strong><strong><em>c<\/em><\/strong><strong><em> fragments<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The N-terminal half of the H-chain and all of the L-chain are also connected with an interchain disulphide bridge. This part of the molecule is called Fab fragment. The subscript ab refers to the fact that this portion has the binding site for the antigen. Thus \u201eab\u201f subscript refers to antigen binding property of the fragment F. As the immunoglobulin molecule is symmetrical, each IgG has 2 Fab fragments.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-220\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-137.png\" alt=\"\" width=\"343\" height=\"263\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-137.png 343w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-137-300x230.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-137-65x50.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-137-225x173.png 225w\" sizes=\"auto, (max-width: 343px) 100vw, 343px\" \/><\/p>\n<p style=\"text-align: justify\"><strong><em>The Fc Fragment<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The three quarter of the H-chains from the C-terminal side and the C-terminal half of the L-chains are constant. All antibodies of the same class and sub class have the same amino acid sequence. Hence these regions have been denoted as CH with C referring to constant. The C-terminal half of each H-chain constitutes Fc fragments. The subscript \u201ec\u201f refers to the fact that it was found to be easily crystallizable for X-ray diffraction studies. Thus Fc stands for fragment crystallized.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Fc fragment is not involved in the antigen binding but binds to complement and some other cells of the immune system. This will be discussed in the next lecture.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">There is a hinge region around the place where Fab fragments join the Fc fragment. This is more flexible region and provides the required flexibility to the two Fab fragments to move with respect to each other (Figure 8).<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">R.R.Porter at Oxford, UK used a protease papain to break IgG into three fragments of nearly equal size.<\/p>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-221\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-138.png\" alt=\"\" width=\"217\" height=\"44\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-138.png 217w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-138-65x13.png 65w\" sizes=\"auto, (max-width: 217px) 100vw, 217px\" \/><\/p>\n<p style=\"text-align: justify\">Further work by Michael Green and Robert Valentine showed that another protease pepsin cleaved Ig differently.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-222\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139.png\" alt=\"\" width=\"379\" height=\"342\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139.png 379w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139-300x271.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139-65x59.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139-225x203.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-139-350x316.png 350w\" sizes=\"auto, (max-width: 379px) 100vw, 379px\" \/><\/p>\n<p style=\"text-align: justify\"><strong><em>Hypervariable regions<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">The following Kabat and Wu plot shows the variability of the amino acid sequences in both H-chains and L-chains among different antibodies. The different antibodies are against different antigens\/antigenic determinants. Hence the variability is the origin of the antibody specificity. Hypervariable regions constitute the antigen binding sites. Affinity labeling confirmed the existence of hypervariable regions. Reactive haptens were found to react to the antigen binding sites (the hypervariable regions). Hypervariable regions are called complementarity determining regions (CDRs).<\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-223\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140.png\" alt=\"\" width=\"362\" height=\"344\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140.png 362w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140-300x285.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140-65x62.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140-225x214.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-140-350x333.png 350w\" sizes=\"auto, (max-width: 362px) 100vw, 362px\" \/><\/p>\n<p style=\"text-align: justify\">The five classes of Ig differ in the nature of their H-chain, chain structure and some other structural features. The basic structural unit is similar not only among the five classes of Ig but is also characteristic of other molecules associated with the immune system. Hence, from the evolutionary perspective, many of these arose from an ancestral gene. All these molecules, including the five classes of Ig are thus part of the super family.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">IgG is found in the vascular spaces, extravascular spaces and secretions. Major IgG is found in the serum as well as during the secondary response to many antigens. In humans, IgG is capable of moving across placenta and thus protect the growing foetus. In humans, IgG has four subclasses as mentioned before. There concentrations are different in human serum with IgG1 having the highest concentration. All can cross the placental barrier but differ in the nature of their heavy chains. All IgG subclasses except IgG4 can bind to C1q to activate the classical pathway. It can act as opsonin. Fc part plays an important role. For example, Many large granular lymphocyte have Fc receptor.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">FcR4 is the receptor on the placental cells that can bind to all Ig subclasses and enable their foetal circulation.<\/p>\n<p>&nbsp;<\/p>\n<p><strong><em>IgM<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">IgM is a pentamer of the 4 chain structure. During development of the immune system, IgM is the first Ig to be produced. It is also the first Ig to be produced during the primary immune response. It is capable of complement fixation. T-independent antigens produce antibodies with IgM as the main component. It has a molecular weight of 970 kDa, making it the largest Ig. Its heavy chain is \u00b5. It has J-chain which is also synthesized by B-cells but coded by a gene different from those coding for Ig.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-224\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141.png\" alt=\"\" width=\"420\" height=\"549\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141.png 420w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141-230x300.png 230w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141-65x85.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141-225x294.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-141-350x458.png 350w\" sizes=\"auto, (max-width: 420px) 100vw, 420px\" \/><\/p>\n<p style=\"text-align: justify\">IgD is present in serum in traces. It is co-expressed alongwith IgM as a cell surface receptor on differentiating B-cells. Mature B-cells (plasma cells) do not have IgD on their surfaces. During encounter of B-cells with antigens, IgD regulates B-cell function leading to internalization of the antigen which after processing is presented to Tn cells.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-225\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142.png\" alt=\"\" width=\"507\" height=\"237\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142.png 507w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142-300x140.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142-65x30.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142-225x105.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-142-350x164.png 350w\" sizes=\"auto, (max-width: 507px) 100vw, 507px\" \/><\/p>\n<p style=\"text-align: justify\">It also has two subclasses IgA1 and IgA2 with identical molecular weight of 160 kDa. The subclasses have \u03b11 and \u03b12 as H-chains. The concentration of IgA1 in human serum is much higher than IgA2. IgA protects the mucous membranes and is present in all secretions as the most abundant Ig. In those specie in which IgG is not transferred across the placenta, It is IgA which protects neonates. It is present in colostrums. IgA can form dimmers and polymers. It is present in humans as monomers only and mostly as dimmers in other animals. It contains a secretory component SC and a joining chain (J-chain). SC stabilizes IgA and is involved in its transport of exocrine IgA. J-chain helps in the dimerization of secretory IgA (dimeric).<\/p>\n<p>&nbsp;<\/p>\n<p><strong><em>IgE<\/em><\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-226\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-143.png\" alt=\"\" width=\"222\" height=\"164\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-143.png 222w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-143-65x48.png 65w\" sizes=\"auto, (max-width: 222px) 100vw, 222px\" \/><\/p>\n<p style=\"text-align: justify\">Its serum concentration is lowest among all the Ig under normal conditions. Its heavy chain is \u03b5 and molecular weight is 188 kDa. Apart from IgM, it is the only Ig having 5 heavy chain domains. Other Ig have 4 heavy chain domains. It is not involved in complement activation. IgE binds to mast cells and basophils which have high affinity Fc receptors. Consequently, these cells release mediators of inflammation after contact with the antigen. IgE mediates type I hypersensitivity reactions such as asthma and hay fever. It plays a very important role in protection against helminthic infections.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-227\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144.png\" alt=\"\" width=\"507\" height=\"258\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144.png 507w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144-300x153.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144-65x33.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144-225x114.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-144-350x178.png 350w\" sizes=\"auto, (max-width: 507px) 100vw, 507px\" \/><\/p>\n<p><strong>Summary:<\/strong><\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li style=\"text-align: justify\">\u00a0Bence Jones proteins (light chains) turned out to be the first step in understanding IgG structure<\/li>\n<li style=\"text-align: justify\">\u00a0IgG sequence was established first and it has two H-chains and 2 L-chains<\/li>\n<li style=\"text-align: justify\">\u00a0IgG structure is the basic structural unit for the structure of other clases of Ig<\/li>\n<li style=\"text-align: justify\">\u00a0There are five classes of Ig: IgG, IgA, IgM, IgD, IgE<\/li>\n<li style=\"text-align: justify\">\u00a0Their structures are now known and their individual functions is also now fairly well understood.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"author":3,"menu_order":10,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["dr-m-n-gupta"],"pb_section_license":""},"chapter-type":[],"contributor":[58],"license":[],"class_list":["post-207","chapter","type-chapter","status-publish","hentry","contributor-dr-m-n-gupta"],"part":3,"_links":{"self":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/207","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/users\/3"}],"version-history":[{"count":6,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/207\/revisions"}],"predecessor-version":[{"id":231,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/207\/revisions\/231"}],"part":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/207\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/media?parent=207"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapter-type?post=207"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/contributor?post=207"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/license?post=207"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}