Lecture-18 Types of Immunoglobulins, their isotypes and generation of diversity.pptx

The five isotypes and nine subtypes of Igs will be familiarized.
The structure and function of each of the isotypes will be known.
The diversity of Igs due to the VJ and VDJ recombination will be appreciated.

1. Lecture -18 TYPES OF IMMUNOGLOBULINS AND GENERATION OF THEIR DIVERSITY Prof. Sreerama Krupanidhi Email: [email protected]

2. Focus To understand the isotypes and subtypes of Igs . To evaluate the functions of isotypes of Igs. To appreciate the diversity among Igs. 9/6/2024 Prof. Sreerama Krupanidhi 2

3. Learning Outcomes The five isotypes and nine subtypes of Igs will be familiarized. The structure and function of each of the isotypes will be known. The diversity of Igs due to the VJ and VDJ recombination will be appreciated. 9/6/2024 Prof. Sreerama Krupanidhi 3

4. IgG Major serum Ig . Constitute 75% total Igs Four Sub-classes are found: IgG1, IgG2, IgG3, IgG4. Each having a unique gamma chain. Major Ab of Secondary Response, found both in serum and body fluids . Only maternal Ig to be transported across placenta. Participates in complement fixation, neutralization of toxins. 9/6/2024 4 Prof. Sreerama Krupanidhi

5. Ig M 5- 8 % Serum Igs. Short lived Ig. Pentameric in structure. Predominant in Primary Immune Response. Earliest Ab to be synthesized by the fetus . Not transported across placenta. Useful in the diagnosis of infections like syphilis, rubella, HIV, toxoplasmosis, COVID-19 etc 9/6/2024 5 9/6/2024 Prof. Sreerama Krupanidhi

6. Ig A Maj o r Ig in the c o lo s trum, s a liva, tears & oth e r body fluids. O c c u rs in 2 forms : IgA1 & I gA 2 . Se c retory IgA is alw a ys in dim e ric form – c o mp o s e d of 2 basic ch a in units, a J-c h ain & the se c retory c o mp o n e nt. Se c retory c o mp o n e nt h e lps to trans p ort the dim e r from t he su b mu c o s a to the mu c o s al c e ll s u rface. Se c retory co m po n ent protects IgA from proteolytic dig e stion a n d d e n a turation. IgA protects the host through mucosal immunity. 9/6/2024 6 Prof. Sreerama Krupanidhi

7. Ig D Resembles Ig G structurally Occurs along with Ig M on the surface of B cells Very Susceptible to proteolytic attack. Its specific function is not clear. IgD appears on the B-cell surface along with IgM . 9/6/2024 7 Prof. Sreerama Krupanidhi

8. Ig E Present in very low amount. Fo u nd on the surface of mast cells & bas o phils which have specific receptors for the Fc receptors of Ig E. Chiefly produced in the lung linings and intestinal tract. R e s p o n si b le for a n a p h y la c tic type of h y p ers e n s it i v i t y . D e fen c e a g ain s t p a rasitic infe c tion s . 9/6/2024 8 Prof. Sreerama Krupanidhi

9. Diversity among Igs (Susumu Tonegawa ) Mu l ti p le V - r e g i on g e n e s. V - J & V - D - J re c omb i na t io n In L and H chains . An individual produces a large number of antibodies to cope up with vast number of Antigens. Th e Ab divers i ty is due to the I g ge n es. One or only few ge n es code for C region w h ereas many ge n es code for the V reg i o n . 9/6/2024 9 Prof. Sreerama Krupanidhi

10. Chromosomes showing Ig genes of L and H chains 9/6/2024 10 Prof. Sreerama Krupanidhi

11. VJ and VDJ recombination 9/6/2024 11 Prof. Sreerama Krupanidhi

12. Mechanisms for generating antibody diversity V(D)J recombination Somatic hypermutation Class switch recombination V1-V500 D1-D12 J1-J4 constant regions 9/6/2024 12 Prof. Sreerama Krupanidhi

13. V(D)J recombination Mechanisms for generating antibody diversity V1-V500 D1-D12 J1-J4 constant regions Hozumi and Tonegawa , PNAS 1976 9/6/2024 13 Prof. Sreerama Krupanidhi

14. V(D)J recombination Mechanisms for generating antibody diversity V1-V500 D1-D12 J1-J4 constant regions 9/6/2024 14 Prof. Sreerama Krupanidhi

15. V(D)J recombination Mechanisms for generating antibody diversity V1-V500 D1-D12 J1-J4 constant regions 9/6/2024 15 Prof. Sreerama Krupanidhi

16. V(D)J recombination D to J joining Mechanisms for generating antibody diversity 9/6/2024 16 Prof. Sreerama Krupanidhi

17. V(D)J recombination D to J joining Mechanisms for generating antibody diversity 9/6/2024 17 Prof. Sreerama Krupanidhi

18. V(D)J recombination V to DJ joining Mechanisms for generating antibody diversity 9/6/2024 18 Prof. Sreerama Krupanidhi

19. V(D)J recombination Somatic hypermutation ** * Somatic mutations Mechanisms for generating antibody diversity 9/6/2024 19 Prof. Sreerama Krupanidhi

20. ** * V(D)J recombination Somatic hypermutation Class switch recombination Class switch Mechanisms for generating antibody diversity 9/6/2024 20 Prof. Sreerama Krupanidhi

21. V(D)J recombination Somatic hypermutation Class switch recombination ** * Class switch Mechanisms for generating antibody diversity 9/6/2024 21 Prof. Sreerama Krupanidhi

22. V(D)J recombination Somatic hypermutation Class switch recombination ** * V(D)J recombination and class switch recombination involve double-strand breaks Mechanisms for generating antibody diversity 9/6/2024 22 Prof. Sreerama Krupanidhi

23. 12/23 rule: R ecombination signal sequences (RSS) 9/6/2024 Prof. Sreerama Krupanidhi 23

24. Recombination signal sequence (RSS) directs V(D)J recombination

25. V(D)J recombination happens due to DNA cleavage and end-joining

26. RAG1/RAG2 genes initiates cleavage ( r ecombination a ctivating g enes) van Gent, Gellert et al. Cell 1995

27. Summary The five isotypes and their functions are elucidated. Out of the five isotypes, IgG is predominant, useful for clinical diagnostics. IgE binds to Mast cells and release histamine. Ig M is short lived and useful in the diagnosis of early infections. Mucosal immunity is mediated by IgA . Immunoglobulin diversity is introduced. 9/6/2024 27 Prof. Sreerama Krupanidhi

28. Study Questions 1. Mention your opinion on the need of diversity among Igs . Indicate the various isotypes of immunoglobulins and draw their Structures and mention their functions. What is the role of IgE ? Indicate the somatic recombination of DNA in the generation of Ig diversity in B-cell. 9/6/2024 28 Prof. Sreerama Krupanidhi

29. Acknowledgements We acknowledge online resources/public domains for the use of the content to develop teaching material and to disseminate the knowledge. . 9/6/2024 Prof.Sreeraama Krupanidhi 29

30. Thank you 9/6/2024 30 Prof. Sreerama Krupanidhi