Immunoglobulin classification
- 1. Biochemistry presentation Class : Bs honors 7th Semester Roll No : 085674/ 390
- 2. Immunoglobulin and its classification • CONTENT : 1. Definition 2. Occurrence 3. General chemistry 4. General functions 5. Digestion of immunoglobulin 6. Classification a - Ig G b - Ig D
- 3. Immunoglobulin • Definition Immunoglobulin is a glycoprotein that is made in response to an antigen and can recognize and bind to the antigen that caused its production .
- 4. CONTINUE ……. The immunoglobins derive their name from the finding that they migrate in the region of globulins when antibody containing serum is placed in an electric field
- 5. Occurence: 1. Antibodies are present in serum, tissue fluids and mucosal surfaces . 2. Constitute 25-30% of total serum proteins 3. Synthesized by plasma cells in response to an antigen and which function as antibodies . 4. Immunoglobulin are gamma globulins 5. All antibodies are immunoglobulin ,but all immunoglobulin may not be antibodies
- 6. Basic structural Characteristics of Immunoglobulin A. Heavy and Light Chains • All immunoglobulin have a four chain structure as their basic unit . • They are composed of two identical light chains (23KD) and two identical heavy chains (50-70KD)
- 7. B-Disulfide Bonds • Inter-chain disulfide bonds The heavy and light chains and the two heavy chains are held together by inter-chain disulfide bonds and by non- covalent interactions . • The number of inter-chain disulfide bonds varies among different immunoglobulin molecules. • Intra-chain disulfide bonds Within each of the polypeptide chains there are also intra-chain disulfide bonds
- 8. C-Variable (V) and constant(C) Regions Both the heavy and light chain can be divided into two regions based on variability in the amino acid sequence These are the • Light chain VL(110 Amino Acid ) CL(110 amino acids) • Heavy Chain VH(110 Amino Acid ) CH (330-440 Amino Acid)
- 9. D-Hinge Region • This is the region at which the arms of the antibody molecule form a Y • It is called the hinge region because there is some flexibility in the molecule at this point E –Domains Three dimensional images of the immunoglobulin molecule show that it is not a straight molecule rather , it is folded into globular regions each of which contains an intra-chain disulfide bond .These regions are called domains 1- Light Chain Domains VL and CL 2-Heavy chain domains VH,CH1,CH2 ,CH3
- 10. F-Oligosaccharides • Carbohydrates are attached to the CH2 domain in most immunoglobulin. • However, in some cases carbohydrates may also be attached at other location.
- 12. Digestion of immunoglobulin with proteolytic enzymes Papain Enzyme • Peptide bonds in the hinge region are broken • Produces 3 fragments • 2 identical fragments called Fob fragments – antigen binding activity . • Other fragment called Fc fragment (Fraction Crystallizable) – Complement binding
- 13. Pepsin digestion • Produces a single fragment composed of two Fab like subunits F(ab)2 binds antigen • Fc fragment is not recovered digested to small numerous peptides
- 14. GENERAL FUNCTION OF IMMUNOGLOBULIN 1. Antigen Binding • Antigen binding by antibodies is the primary function of antibodies and can result in protection of the host • Each immunoglobulin binds to a specific antigenic determinant .
- 15. Complement fixation Binding to various cell types Placental transfer Opsonization 2. EFFECTOR FUNCTION
- 16. 3. Binding to various cell types • Phagocytic cells, lymphocytes, platelets , most cells and basophils have receptors that bind immunoglobulins • The binding can activate the cells to perform some function .
- 17. 4. Major Function of immunoglobulin • some immunoglobulins also bind to receptors on placental trophoblast , which result in transfer of the immunoglobulin across the placenta. • As a result ,the transferred maternal antibodies provide immunity to the fetus and newborn.
- 18. • The immunoglobulins can be divided into five different classes based on differences in the amino acid sequences in the constant region of the heavy chain. 1.IgG- Gamma heavy chains 2. IgA- Alpha heavy chains 3. IgM- Mu heavy chains 4. IgE- Epsilon heavy chains 5. IgD- Delta heavy chains Classification of Immunoglobulin
- 19. Properties of IgG • Major Ig in serum • Constitutes 80% total immunoglobin • Present in blood , plasma and tissue fluids • Produced particularly during secondary immune responses. • It has a half life of 23 days , the longest of all of the Ig isotypes • Major Ig in extra vascular spaces • The only antibody to cross the placenta • Complement fixation • Opsonization
- 20. Chemistry of IgG The molecule consists of two light chains and two heavy chains. 1. Each light chain consists of a variable (VL) and a constant (CL) region . 2. Each heavy chain consists of a variable region (VH) and a constant region that is divided into three domains (CH1,CH2 and CH3). 3. The CH2 domain contains the complement binding site 4. The CH3 domain contains a site that attaches to receptors on neutrophils and macrophages . 5. The heavy chains themselves and with light chains are linked together by disulphide bonds. 6. The antigen – binding site is formed by the hyper variable regions of both the light and heavy chains
- 21. A. Structure of IgG B.Schematic model of IgG
- 22. Subclasses of IgG • There are four IgG subclasses (IgG1,IgG2,IgG3 and IgG4) in humans ,named in order of their abundance in serum Name Percenta ge Crosses Placenta easily Comple ment Activato r Binds to Fc receptor Half life IgG1 66% Yes Second highest High Affinity 21 days IgG2 23% No Third highest Extremely low Affinity 21 days IgG3 7% Yes Highest High Affinity 7 days IgG4 4% Yes No Intermedi ate Affinity 21 days
- 23. Structure of Subclasses of IgG • Four subclasses of human IgG differ in their structure because they are encoded by different germ- line CH genes • They differ in the size of the hinge region and the number and arrangements of the interchain disulfide bonds linking heavy chains
- 24. Biological Function of IgG • Cross the placenta • Binds and neutralize microbes and toxins • Opsonize antigens for phagocytosis • Activate the complement system • protect the new born • Control infection of body tissues • involved in the regulation of Allergic reactions • play an important role in antibody dependent cell – mediated cytotoxity (ADCC) and intracellular antibody – mediated proteolysis
- 25. Properties of IgD • IgD exists only as a monomer • It is found in low levels in serum ,its role in serum is uncertain • Serum concentration 30 micrograms per ml • Constitutes 0.2% of total immunoglobulin • Half life : 3 days • IgD does not bind complement • IgD together with IgM is major membrane bound immunoglobulin on unstimulated B Lymphocytes .
- 26. Chemistry of Ig D • Secreted IgD is a glycoprotein produced as a monomeric antibody with two identical heavy chains of the Delta class , and two identical Ig light chains • The structure has two identical antigen binding areas consisting of both light and heavy chains and a valency of 2 • The light chains have two domains , one variable and one constant . • The heavy chains have four domains , one variable and three constant region domains • IgD molecule has a long hinge region between Fob and Fc
- 27. Structure of IgD
- 28. Function of IgD • act as an antigen receptor on B cells and is probably involved in regulating B cell function • Secreted IgD also exists and plays an elusive function in blood ,mucosal secretions and on the surface of innate immune effector cells such as basophils . • IgD may have some role in allergic reactions • It also able to bind to basophils and mast cells and activate these cells to produce antimicrobial factors that are functional in respiratory immune defence in humans