1. Lymphoid System T and B Cell Development Prof. Dr. Zahid Shakoor MBBS, Dip. Med. Immunology (UK), Ph D (London) King Saud University

2. Blood Cells Blood cell precursors originate in yolk sac and liver In postnatal life the stem cells reside in the bone marrow Stem cells differentiate into cells of erythroid, myeloid or lymphoid series

3. Blood Cells Precursors … Yolk Sac Migrate Liver Thymus T- lymphocyte Bone Marrow B- lymphocyte B Cells T Cells

4. Primary Lymphoid Organs

5. Primary Lymphoid Organs … Primary Lymphoid Organs Either : Disapear Lose Their Function After Birth Primary Lymphoid Organs Are : Thymus – Liver – Bone Marrow - Yolk Sac

6. Secondary Lymphoid Organs

7. T Cells First, Immature T cells Aggregate in the cortex of the thymus. Then it goes to the Medulla To become Maturet. From there it leaves the medulla to blood stream. So, in short.. CortexMedulla (mature)Blood stream

8. T-Lymphocyte Differentiation Stem cells lack antigen receptors and CD3, CD4, CD8 surface markers All T cells should have CD3 ! During their passage through thymus they differentiate into T cells expressing these markers, In other words … Initially, the stem cell will have CD3 – which is the marker for T cells – as well as the 2 receptors ( CD4 & CD8 ) and that is Called Double Positive. -Then it will lose one of the cell receptors and become either : CD4 Positive OR CD8 Positive cell. All T cells should have CD3 ! Stem cells initially do not express CD4 and CD8 (Double Negative)

9. T-Lymphocyte Differentiation ( cont) CD8 +ve cell ( Cytotoxic cell ) if the double +ve contacts with MHC I and loses its CD4 receptor. MHC I is present in All Cells having Nucleus. CD4 +ve ( T helper cells ) if the double +ve contacts with MHC II and loses CD8 receptor. MHC II present in Macrophages, Monocytes, Dyndrit cells …. Etc T Cells could be …

10. T-Lymphocyte Differentiation Thymic Education – teaching the cell to recognize the body cells from foreign, invading and abnormal cells. Involves two processes CD4 and CD8 positive bearing receptors for “self” proteins are killed (clonal deletion). This type of removal is called “negative selection”- tolerance to self proteins CD4 and CD8 positive cells bearing antigen receptors that do not react with self MHC proteins are also killed this process is called “positive selection” In Other Words

11. Thymic Education In the thymus, MHC is going to teach the T cells to : 1. Recognize the body cells from foregin bodies. 2. Kill The body cells if they look abnormal. Cont

12. Thymic Education Negative Selection – Killing of T cells That recognize the body cells as foreign bodies and attack it ( so, they have the capacity to kill your own cells ) Positive Selection – Killing of T cells that doesn’t have the ability to recognize the body cells.

13. Mature Lymphocyte

14. T-Lymphocytes Effector Functions CD8+ve cells ( cytotoxic ) will kill virus- infected cell, tumor cells and allografts (tissue transplant from one human to another ) T cell precursors differentiate under the influence of thymic hormones (thymocins and thymopoetins) into T cell subpopulations ie, CD3, CD4 and CD8.

15. T-Lymphocytes All T cells have CD3 proteins on their cell surface in association with T cell receptor(CD4 – CD8 ), that transmits information - that T cell receptor is occupied – to the inside of the cell. Mature T cells have either CD4 or CD8 proteins but not both

16. Functions of Helper Lymphocytes CD4 Lymphocytes (T Helper ) Functions Help B cells to develop into antibody producing plasma cells Help CD8 cells to become activated cytotoxic T cells Help macrophages in delayed ( Chronic ) type of hypersensitivity

17. CD4 Positive Lymphocytes Functions Mediated By Chemicals Produced From T Helper Cells : Main FunctionsCytokine Mediating That Function Activates the antigen specific helper T cell to produce a clone of these cells IL-2 Activates cytotoxic T cellsIL-2 Activates B cellsIL-4 and IL-5 Activates MacrophagesInterferon Gamma

18. CD8 positive cells About 35% of peripheral blood T cells Perform cytotoxic functions They kill virus-infected cell, tumor and allograft cells Perforins ( a chemical that makes wholes in the attacked cell ) Programmed cell death (apoptosis)

19. B cells Origin During embryogenesis – fetal liver Migrate to bone marrow – final destination They do not require thymus for maturation Maturation of B cells involves two phases: Antigen independent phase consists of stem cells, pre-B cells and B cells Antigen dependent phase consists of activated B cells and plasma cells The difference Between B cells – the antibody that it produces is present on its surface Plasma Cells – it will send its antibody to the circulation

20. B cells B cells display surface IgM which serves as antigen receptor Surface IgD on some B cells also serves as and antigen receptor Pre B cells are found in bone marrow and mature B cells are found circulating in bloodstream

21. Important Point ! Once the B lymphocyte recognizes the Special Pathogen, or foreign body and became activated, it will be special for that pathogen only for the rest of Its Life. So, if the lymphocyte come across a Myobacterium TB and became activated to kill it, it will never fight another pathogen Except This Myo.TB for the rest of its life.

22. B cells B cells constitute about 30% of circulating small lymphocyte Their life span is short ie, days or weeks Location: lymph nodes – germinal centers, spleen – white pulp and Peyer ’ s patches

23. B cells Clonal selection Antigen reacts with surface IgM and IgD on the best fit basis After antigen binds to B cell it will be stimulated to proliferate to form a clone of cells These selected B cells later differentiate into antibody producing plasma cells that secrete antibody specific to that antigen

24. /B cell is located in the lymph node in: a)cortex. b)paracotex. c)medulla d)trabeculae. /T lymphocytes"school" is: a)thymus. b)bone marrow. c)fetal liver. d)tonsill. e)thyroid.

25. Thank you