Lecture-6 Lymphoid organs along with Thymic Schooling

Primary and Secondary lymphoid organs and their role in WBCs formation are elucidated. Thymic schooling and Clonal selection of B- cells
are shown.

1. Lecture-6 : Lymphoid Organs Prof. Sreerama Krupanidhi Email: [email protected]

2. Objectives To Review Primary Lymphoid organs To Review lymphatic fluid and lymph nodes To visualize T- Cell development 8/29/2024 Prof. Sreerama Krupanidhi 2

3. Expected Outcomes Primary and Secondary lymphoid organs and their role in WBCs formation are known . Distribution of lymphoid organs and nodes are known. Thymic schooling is acquainted. Clonal selection of B- cells is known. 8/29/2024 Prof. Sreerama Krupanidhi 3

4. PRIMARY LYMPHOID ORGANS THYMUS: The thymus is responsible for the development of T-lymphocytes. They are involved in cell mediated immune responses. This gland appears to be master Lymphoid organ important in immunogenesis in the young and in orchestrating the total lymphoid system throughout life. Thymus is bi-lobed and located dorsal to the heart and atrophied with age. 8/29/2024 4 Prof. Sreerama Krupanidhi

5. Thymic Schooling Thymic education is the process whereby thymocytes are processed to eliminate any T cells that could potentially attack our own 'self-antigens' in the body. The T-Cell-Receptor (TCR) is a receptor on T cells used for identifying foreign antigens presented by MHC molecules. Three major thymus hormones:  thymosin, thymopoietin, and thymulin , are present in the cytoplasm of the thymus epithelial cell. The positive selection of T cells results in the maturation of thymocytes into either CD4+ or CD8+ T cells wherein CD4 recognizes MH C II and CD8 recognizes MHCI. The negative selection of T cells results in the cell death of thymocytes , if the T- cell develops high affinity to self peptides thus ensuring self-tolerance. 8/29/2024 5 Prof. Sreerama Krupanidhi

6. BONE MARROW The production of blood cells in bone marrow begins roughly 4-5 months after conception. Stem cells immigrate from the liver into the bone marrow, where the "microenvironment" is decisive for the development of stem cells. This stroma promotes maturation of B lymphocytes. Macrophages also colonize the stroma . As soon as cells get matured, they proceed  from the bone marrow into the blood stream. 8/29/2024 6 Prof. Sreerama Krupanidhi

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8. Anatomy of the Lymphoid System Lymphoid system is a collection of tissues and organs designed to bring B and T cells in contact with antigens to mount appropriate response, immune cells must encounter antigen. Lymphoid system includes Lymphatic vessels Secondary lymphoid organs Primary lymphoid organs 8/29/2024 8 Prof. Sreerama Krupanidhi

9. Anatomy of the Lymphoid System 9 8/29/2024 Prof. Sreerama Krupanidhi

10. Anatomy of the Lymphoid System Lymphatic vessels Carry lymph to body tissues Lymph formed as result of body’s circulatory system Lymph travels through vessels to lymph nodes Fluid portion empties back into blood stream 8/29/2024 10 Prof. Sreerama Krupanidhi

11. Anatomy of the Lymphoid System Secondary lymphoid organs Sites where lymphocytes gather to encounter antigens; Organs include Lymph nodes Spleen Tonsils Adenoids Appendix Organs situated strategically Allows for initiation of immune response from nearly any place in body 11 8/29/2024 Prof. Sreerama Krupanidhi

12. Anatomy of the Lymphoid System Primary lymphoid organs Bone marrow and thymus are primary lymphoid organs Location where stem cells destined to become B and T cells mature B cells mature in bone marrow T cells mature in thymus Once mature, cells leave primary lymphoid organs and migrate to secondary lymphoid organs where these lymphocytes encounter antigens. 8/29/2024 12 Prof. Sreerama Krupanidhi

13. CLONAL SELECTION THEORY It is an important immunological process that determines which B and T lymphocytes (types of white blood cells) will be produced in large quantities. It is through this process that our human system recruites cells to combat antigens—substances it considers to be harmful. Niels Jerne , a Danish immunologist, provided the basis for the clonal selection theory in 1955. Prior to Jerne's theory, it was a commonly held belief that our bodies were stimulated to produce a specific antibody when a foreign substance entered. 8/29/2024 13 Prof. Sreerama Krupanidhi https://www.youtube.com/watch?v=I5bK4iZozEM

14. Thymic Schooling Differentiating T- Cells, learn to recognize Self antigens + MHC 8/29/2024 Prof. Sreerama Krupanidhi 14

15. Positive Selection: MHC It is a process in the thymus that selects immature T-cells with receptors that recognize peptide antigens presented by self-MHC molecules. Only cells that are positively selected are allowed to continue their maturation in the cortex of the thymus. 8/29/2024 Prof. Sreerama Krupanidhi 15

16. Positive selection of T-Cells Positive and negative selection of T cells: The processes of thymic selection result in mature T cells that are both self-HLA restricted and tolerant of the body’s own peptide antigens.  8/29/2024 Prof. Sreerama Krupanidhi 16

17. Positive Selection Single-positive thymocytes – double positive thymocytes mature into cells that commit and express just one or other of the two co-receptors: CD4+ CD8+ immature T cells→ CD4+ CD8-/CD4- CD8+ mature T cells 8/29/2024 Prof. Sreerama Krupanidhi 17

18. Negative Selection It is a process in the thymus whereby developing T-cells that recognize with high affinity the self-antigens with MHC are induced to die by apoptosis. 8/29/2024 Prof. Sreerama Krupanidhi 18

19. Negative selection of T cell When a TCR binds an antigen-MHC complex displayed by a sick or infected cell, the T cell can induce cell death called apoptosis (top). In order for mature, antigen-recognizing T cells to develop without being self-reactive and causing autoimmunity, T cells must go through both positive and negative selection. In positive selection, T cells in the thymus that bind moderately to MHC complexes receive survival signals (middle). However, T cells whose TCRs bind too strongly to MHC complexes, and will likely be self-reactive, are killed in the process of negative selection (bottom). 8/29/2024 Prof. Sreerama Krupanidhi 19

20. B-Cell development VCAM: Vascular cell adhesion molecule VLA: Very late antigen SCF: Serum cell factor 8/29/2024 Prof. Sreerama Krupanidhi 20

21. B-Cell development 8/29/2024 Prof. Sreerama Krupanidhi 21

22. The Clonal Selection Theory- B-cell development 22 8/29/2024 Prof. Sreerama Krupanidhi

23. Summary Primary and secondary lymphoid organs and their distribution are known. The thymic schooling wherein the mature T- cells are made to learn self-peptide coupled with MHC is known. The clonal selection of primed B-cells and their proliferation are known. 8/29/2024 23 Prof. Sreerama Krupanidhi

24. Study Questions Elaborate on Thymus. What are negative and positive selection of T cell? What are the components of Lymphoid system? Enlist lymph nodes and organs. Explain the Microenvironment of Bone marrow. What is the Clonal Selection Theory? 8/29/2024 Prof. Sreerama Krupanidhi 24

25. Acknowledgements 8/29/2024 25 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

26. Thank you 8/29/2024 Prof. Sreerama Krupanidhi 26