Lecture-10 Immunoglobulins: Their structure and function.pptx

The detailed structure of Y-shaped Immunoglobulin as deciphered by Porter and Edelman will be familiarized.

1. Lecture -10 IMMUNOGLOBULINS : Structure and Function Prof. Sreerama Krupanidhi Email: [email protected]

2. Objectives To familiarize with the structure, complexity and nature of antibodies/immunoglobulins. To understand the functions of various regions of the assembled protein namely Igs . 8/30/2024 2 Prof. Sreerama Krupanidhi

3. Expected Outcomes The nature of Immunoglobulin will be known. The detailed structure of Immunoglobulin as deciphered by Porter and Edelman will be familiarised. The assembled Y-shaped structure of Ig will be acquainted. 8/30/2024 Prof. Sreerama Krupanidhi 3

4. What are Immunoglobulins ? Immunoglobulins are defence serum glycoproteins produced by Plasma cells upon elicitation of Immune response against the epitopes of an antigen/pathogen. Immunoglobulins are Y-shaped globular assembled serum proteins involved in host defence. . 8/30/2024 4 Prof. Sreerama Krupanidhi

5. Which cell produces Igs ? Igs are s y nth e si s ed b y the plasma cells. Constitut e s 2 -25% serum prot e ins. 5 classes of Igs – IgG, IgA, IgM, IgD & IgE based on the H-chain. They are called Isotypes. 8/30/2024 5 Prof. Sreerama Krupanidhi

6. Symmetry in Ig Two pairs of polypeptide chains: Two Light chains on either side. Each with 25,000 Daltons Two Heavy chains on either side. Each with 50,000 Daltons. Both the L and H chains are bound by disulphide bonds. 8/30/2024 6 Prof. Sreerama Krupanidhi

7. Shape & Structure of Immunoglobulin 8/30/2024 Prof. Sreerama Krupanidhi 7

8. Shape & Structure of Immunoglobulin 8/30/2024 Prof. Sreerama Krupanidhi 8

9. Shape & Structure of Immunoglobulin 8/30/2024 Prof. Sreerama Krupanidhi 9

10. Hyper variable regions 8/30/2024 10 Prof. Sreerama Krupanidhi

11. Hyper variable regions 8/30/2024 Prof. Sreerama Krupanidhi 11

12. Hyper variable regions 8/30/2024 A m ino a c id s e q u e n ce in the v a riable region of L & H c h ains are n o t u niformly v a riable C o n s ists of so m e hig h ly v a riable (hy p erv a riable) and s o me relatively in v ariable z o n e s Highly variable zo n es actu a lly ma k e co n tact wi t h the e p itope on an Ag a n d are c a lled as C o m p lem e ntarity D e termining R e gio n s (CD R s) 3 CDRs – ea c h ma d e up of 9 - 12 amino aci d s. C D R3 is the lon g e s t & m o st v a riable of the three Prof. Sreerama Krupanidhi 12

13. Amino acids L and H chains of IgG 8/30/2024 Prof. Sreerama Krupanidhi 13

14. Types of Light chains of IgG Light Chain is of two types: k a p p a (  ) & l a mb d a ( ) . Each molecule of IgG is having either (  ) or ( ) . 8/30/2024 14 Prof. Sreerama Krupanidhi

15. H-Chain : Isotypes and Subtypes of Igs Isotype (Ig Class) H-Chain Subtypes IgG  IgG1, IgG2, IgG3 and IgG4 IgM  IgA  IgA1 and IgA2 IgD  IgE  8/30/2024 Prof. Sreerama Krupanidhi 15

16. Structure of IgG 8/30/2024 Light chain contains: TWO regions Variable region (V L ) N-terminal Constant region (C L ) C-terminal Heavy Chain Contains: THREE regions CH1, CH2, and CH3 Ig contains TWO fragments Fab and FC Prof. Sreerama Krupanidhi 16

17. Y- Shaped structure Porter and Edelman 8/30/2024 17 Mercaptoethanol reduction Prof. Sreerama Krupanidhi 1929-2014 1917-1985 Nobel Prize in the year 1972 Molecular structure of Abs

18. Functions of fragments of IgG Fab Fragment – Ag b i n d i n g . Fc frag m ent - Det e rm i n e s the b i o l o g i c al p r o p e r ti e s of Ig mo l e c u l e. Receptors for Fc Fragments are expressed On: Neutrophils Eosinophils NK cells Mast cells 8/30/2024 18 Prof. Sreerama Krupanidhi

19. Functions of IgG Neutralization Direct inactivation of pathogen or toxin thereby preventing its interaction with human cells Opsonization Coating of pathogens for more efficient phagocytosis Activation of complement More efficient phagocytosis Direct killing 8/30/2024 19 Prof. Sreerama Krupanidhi

20. Various functions of Igs 8/30/2024 20 Prof. Sreerama Krupanidhi

21. Summary The structure of assembled Y-shaped Igs containing Fab and Fc regions along with L and H Chains are highlighted. The tailored hypervariable regions of Igs in the Fab region that bind to epitopes of the antigens are familiarized . The functions of immunoglobulins to eliminate pathogens are visualized. 8/30/2024 21 Prof. Sreerama Krupanidhi

22. Study Questions Draw a neat labeled diagram of IgG . Deduce imolecular weight of fragments of Igs using pepsin and papain. Indicate the number of amino acids present in each Chain of Ig. What are hypervariable regions? Indicate their functions. What are the divisions of H and L chains? What are the immune roles of Fab and Fc fragments of Ig? 8/30/2024 22 Prof. Sreerama Krupanidhi

23. Acknowledgements 8/30/2024 We acknowledge the online resources and public domains for the Preparation of the content to develop teaching material and for the dissemination of knowledge. Prof. Sreerama Krupanidhi 23

24. Thank you 8/30/2024 24 Prof. Sreerama Krupanidhi