Antibodies PDF - Immunoglobulin Structure and Function

## Immunoglobulins (Igs, Antibodies) **Definition:** They are the y-fraction of the plasma globulin proteins. They are glycoproteins secreted by B-lymphocytes after their differentiation into plasma cells following the exposure to a variety of antigens. **Basic structure of the immunoglobulin:**...

## Immunoglobulins (Igs, Antibodies) **Definition:** They are the y-fraction of the plasma globulin proteins. They are glycoproteins secreted by B-lymphocytes after their differentiation into plasma cells following the exposure to a variety of antigens. **Basic structure of the immunoglobulin:** * The basic unit of any type of immunoglobulin is called monomer. * Each monomer is formed of 4 polypeptide chains linked together by interchain disulfide bonds and arranged in a Y-shaped structure, two heavy chains & two light chains (Heavy and light chain in regards to the M.W.). **Both heavy and light chains have C-terminal regions and N-terminal regions.** * **Light chains** have molecular weight 25,000 & are of two types: * "Lambda" * "Kappa" * **Heavy chains** have molecular weight 50,000-75,000 & are of five types: * "gamma": presents in IgG * "alpha": presents in IgA * "mu": presents in IgM * "epsilon": presents in IgE * "delta": presents in IgD **III- Papain:** * It is a proteolytic enzyme that cleaves the antibody molecule at the hinge region into three fragments. * **Two identical fragments "Fab" (Fragment antigen binding): ** The amino terminal end of each Fab fragment contains antigen binding site due to presence of variable regions of both heavy & light chains, so two antigen binding sites in both fragments are present. * **Fc (fragment crystalline) fragment: ** it contains the constant regions of the heavy chains & it determines the biological activities of the antibody molecule depending on the presence of Fc receptors for the Fc portion on various cells upon which the antibody acts. **IV- Domains:** * Each light & heavy chain formed of domains, each domain is held by intra-chain disulfide bond: * **Amino terminal domains:** They are variable from one antibody to another & called variable region, VL & VH, with three amino acid sequence that show marked degree of variation & it is the antigen recognition & binding site and called hypervariable region. * **Other domains are constant and called:** CL, CH1, CH2 & CH3. | Protein Chemistry | Description | | --------------------------------------------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Amino terminal | The functional group that is always at the end of a polypeptide chain | | Antigen binding site | The part of the antibody that binds to the antigen. | | Light chain | A type of polypeptide chain that makes up an antibody. | | Heavy chain | A type of polypeptide chain that is longer than a light chain. | | **Domain** | A distinct structural and functional unit of a protein | | Inter-chain disulfide bond | A covalent bond between two cysteine residues on different polypeptide chains. | | Intra-chain disulfide bond | A covalent bond between two cysteine residues on the same polypeptide chain. | | **Hinge region (site of action of papain)** | The flexible region of an antibody that allows the Fab fragments to move independently of the Fc fragment. | | **Fab fragment** | The fragment of an antibody that binds to the antigen. | | **Fc fragment** | The fragment of an antibody that interacts with the immune system, such as complement proteins and immune cells. | | **Carbohydrate residues** | The sugar molecules that are attached to the polypeptide chains in the antibody. | | **Carboxyl terminal** | The functional group that is always at the end of a polypeptide chain | ### **Immunoglobulin monomer** * There are 5 types of immunoglobulins which are: * **Immunoglobulin G (IgG):** * Site: It represents 80% of serum immunoglobulins. * Molecular weight: Relatively small, 160,000 dalton. * Half life: Relatively long, 23 days. * Structure: Monomer with two antigen binding sites & four classes which are IgG1, 2, 3, 4. * Carbohydrate residue: 2-4%. * Biological activities: * It is major antibody in the secondary immune response. * It is the antibody that crosses the placenta due to presence of Fc receptor for its Fc portion on the trophoblasts (placental cells). * It fixes & activates the complement. * **Immunoglobulin A (IgA):** * Site: Serum & body secretions. * Carbohydrate residue: 5-10%. * **Structure:** * Serum IgA: is formed of monomer with two antigen binding sites. * Secretory IgA: is dimmer with four antigen binding sites & two classes IgA1 &2, the two monomer are joined by J-chain & acquire secretory piece which : * Facilitates the transport of the IgA in the secretions. * Protects it from being digested by the proteolytic enzymes. | | Description | | ---------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | **J-Chain** | A small polypeptide chain that links together antibody monomers in the form of dimers, trimers, pentamers, and hexamers. | | Serum IgA | The form of IgA found in the blood serum. | | Dimeric IgA | A form of IgA that consists of two antibody monomers linked together by a J-chain. | | Secretory IgA | A form of IgA that is found in the secretions, such as saliva, tears, breast milk, and mucus. It is made of two antibody monomers linked together by a J-chain, as well as a secretory component that helps it to be secreted. | * Biological activities: * It presents in the secretions of the respiratory, genitourinary, G.I.T, milk, colostrum, tears, sweat & saliva to provide local immunity against invasion by microorganisms. * It doesn't cross the placenta. * It doesn't fix the complement. * **Immunoglobulin M (IgM):** * Site: Serum. * Molecular weight: Relatively large, 900,000 dalton. * Half life: Relatively short. * Carbohydrate residue: 10 %. * Structure: Pentamer (5 monomers) with 10 antigen binding sites joined together by J-chain forming stare like structure. * **Biological activities:** * It is major antibody in the primary immune response, so its presence indicates recent infection. * It fixes & activates the complement * It doesn't cross the placenta. * **Immunoglobulin E (IgE):** * Site: It presents in a very low concentration in the serum. * Structure: It is formed of monomer with two antigen binding sites. * Biological activities: * It plays an important role in type-l hypersensitivity reaction as it cause degranulation of the mast cells & basophils with release of histamine & other inflammatory mediators. * It plays an important role in immunity against parasitic infestation. * It doesn't cross placenta or fix the complement. * **Immunoglobulin D (IgD):** * Site: It presents in a very low concentration in the serum. * Structure: Monomer with two antigen binding sites. * Biological activities: It is expressed on the surface of B-lymphocytes acting as antigen receptors