Antibody.pdf

Antibody Trefa M Abdullah Norman Master in Medical Microbiology MPhil/PhD in Medical studies/cancer immunotherapy /Medical School/ Exeter University / UK Lecturer at School of Pharmacy. Assistant Professor at American University  Antibody or immunoglobulin...

Antibody Trefa M Abdullah Norman Master in Medical Microbiology MPhil/PhD in Medical studies/cancer immunotherapy /Medical School/ Exeter University / UK Lecturer at School of Pharmacy. Assistant Professor at American University  Antibody or immunoglobulin Specialized glycoprotein, produced from activated B cells (plasma cells) in response to an antigen. Capable of combining with the antigen that triggered its production. Both the terms, immunoglobulin (Ig) and antibody are used interchangeably; representing the physiological &functional properties of same molecule respectively. Immunoglobulin (Ig) constitutes 20-25 per cent of total serum proteins. There are five classes (or isotypes) of immunoglobulins recognised-IgG, IgA, IgM, IgD and IgE. STRUCTURE OF ANTIBODY An antibody molecule is a ‘Y-shaped’ heterodimer; composed of four polypeptide chains. Two identical light (L) chains, of molecular weight 25,000 Da each Two identical heavy (H) chains each having molecular weight 50,000 Da or more.  H and L chain: All four H and L chains are bound to each other by disulfide bonds, and by noncovalent interactions such as salt linkages, hydrogen bonds, and hydrophobic bonds. All the chains have two ends- an amino terminal end (NH3) and a carboxyl terminal end (COOH). Variable and constant regions Each H and L chain comprises of two regions- variable and constant region. Variable region Represents the antigen binding site of the antibody.  FUNCTIONS OF IMMUNOGLOBULINS Effector functions (by Fc region) Fixation of complement: Antibody coating the target cell binds to complement through its Fc receptor which leads to complement mediated lysis of the target cell. Binding to various cell types Phagocytic cells, lymphocytes, platelets, mast cells, NK cell, eosinophils and basophils bear Fc receptors (FcR) that bind to Fc region of immunoglobulins. Binding can activate the cells to perform some biological functions. Some immunoglobulins (e.g. IgG) also bind to receptors on placental trophoblasts, which results in transfer of the immunoglobulin across the placenta.  Immunoglobulin G (IgG) Constitutes about 70-80% of total Igs of the body. IgG has maximum daily production. Longest half-life of 23 days. Highest serum concentration. IgG has four subclasses- IgG1, IgG2, IgG3 and IgG4; all differ from each other in the amino acid sequences of the constant region of their heavy chain. Subclasses vary in their biological functions, length of hinge region and number of disulphide bridges.  Functions of IgG IgG can cross placenta - hence provide immunity to the fetus and new born. Among subclasses, IgG2 has the poorest ability to cross placenta. Complement fixing: Complement fixing ability of subclasses varies - IgG3> IgG1> IgG2. IgG4 does not fix complements. Phagocytosis Mediates precipitation and neutralization reactions. IgG plays a major role in neutralization of toxins as it can easily diffuse into extravascular space. IgG is raised after long time following infection and represents chronic or past infection (recovery). Agglutination  Immunoglobulin M (IgM) Among all Igs, IgM has highest molecular weight, and maximum sedimentation coefficient (19S). Present only in intravascular compartment, not in body fluids or secretions. IgM exists in both monomeric and pentameric forms: When present as membrane-bound antibody on B cells, it exists in monomeric form. When present in secreted form, it is pentameric in nature Functions of IgM Acute infection Complement fixing Antigen receptor. Acts as an opsonin Mediate agglutination Immunoglobulin A (IgA) IgA is the second most abundant class of Ig next to IgG, constituting about 10-15% of total serum Ig. Exists in both monomeric and dimeric forms. Serum IgA IgA in serum is predominantly in monomeric form. Dimeric in nature; two IgA monomeric units joined by a J chain. Secretory component Location-Predominant antibody found in body secretions like milk, saliva, tears, intestinal & respiratory tract mucosal secretions. Function of secretory IgA Local or mucosal immunity Effective against bacteria like Salmonella, Vibrio, Neisseria, and viruses like polio and influenza. Breast milk is rich in secretory IgA and provides good protection to the immunologically immature infant gut. Formation of secretory IgA Dimeric secretory IgA is synthesised by plasma cells situated near mucosal epithelium. J chain is also produced in the same cell.  Subclasses of IgA Depending upon the amino acid sequences in the constant region of heavy chain, IgA exists in two isotypes: IgA1 IgA2 Immunoglobulin E (IgE) Lowest serum concentration. Shortest half life. Minimum daily production. Only heat labile antibody (inactivated at 56º C in one hour). Has affinity for the surface of tissue cells (mainly mast cells) of the same species (homocytotropism). Extravascular in distribution. Functions of IgE Mediator of type I hypersensitivity reactions IgE is elevated in helminthic infections.  Immunoglobulin D (IgD) IgD is found as membrane Ig on the surface of B cells and acts as a B cell receptor along with IgM. Has the highest carbohydrate content among all the Igs. No other function is known for IgD so far. Isotypes The five classes of Igs and their subclasses are called as isotypes. Vary from each other in the amino acid sequences of the constant region of their heavy chains. Such variation is called as isotypic variation. THANK You!