1. Lymphoid Tissues and Organs: - Leukocytes may be distributed in the body as: 1-Single cells in tissues and circulation. 2-Lymphoid accumulations (Peyer’s patches). 3-Aggregations within Lymphoid organs; Primary and secondary lymphoid organs. -Primary Lymphoid Organs: Thymus and Bone marrow. -Secondary Lymphoid Organs: Spleen, Lymph nodes, Tonsils, and MALT.

2. Primary and Secondary Lymphoid Organs: N

3. N Primary lymphoid organs: 1- Thymus: -T Lymphocytes develop within this lymphoid organ. -Function: The clonal selection of T lymphocytes. (Lymphocyte educational Center) -It increases in size during fetal and neonatal life. -It is progressively inactivated (curved spirally) following puberty. -Two important parts: 1-Thymic Cortex. 2-Thymic Medulla.

4. Primary lymphoid organs: The Thymus and its parts. The thymus diagram : Parts and location.

5. N 2-Bone marrow: -B lymphocytes are “home schooled” within this organs. -Function: Primary differentiation of B lymphocytes. B lymphocytes begin to display IgM on their surfaces. -The primary site for cytokines-Immune cell interactions. -Bone marrow removes the B cells that show self- reactivity by apoptosis.

6. Secondary Lymphoid Organs: -Secondary lymphoid organs function as filtration devices removing foreign matter, dead cells, and microbial toxins from the circulation. -Blood vessels and lymphatic vessels richly supply these organs. -Specialized regions of the vasculature (endothelial venules) facilitate movement of immune cells between blood and the tissues of these organs. -The leukocyte-rich nature stimulate cellular interaction.

7. N Secondary Lymphoid Organs: 1-Lymph nodes: -It acts as filters to purify lymph. -Divided into the cortex and medulla. -The superficial cortex contains lymphocyte-rich nodules (follicles) (mainly B cells). -The deep cortex is the T-cell-rich area.

8. N 2-The Spleen: -The largest lymphoid organ. -Concentrates blood-borne antigens and microbes. -Contains T cells, B cells, and Large numbers of plasma cells (secreting immunoglobulins into the circulation). -Divided into: 1-Lymphocyte-rich white pulp. 2-Erythrocyte-rich red pulp (also contains macrophages).

9. N 3-Mucosa-associated lymphoid tissues(MALT): -Other sites for immune-cells interaction. -Tonsils in the nasopharynx. -Peyer’s patches in the sub-mucosal surfaces of small intestine. The Lymphatic circulatory system: -Leukocytes and their products use two circulatory systems: 1-Cardiovascular system. 2-Lymphatic circulatory system. (Textbook : Page 85-86).

10. Lymphocyte Development: -Stem cells of bone marrow (prothymocytes; negative for CD4,CD8, and TCR) migrate via the circulation to the thymic cortex. -The newly arrived thymocytes acquire CD4,8, and TCR (Positive cells) -Cortical thymocytes are selected by their interaction to cortical epithelial cells (positive selection). -Medullary thymocytes are selected (negative selection). -Mature T cells are released into the circulation.

11. Maturation of T lymphocytes in Thymus: N

12. Lymphocyte Activation: Lymphocyte activation occurs according to following consequences: 1-Antigen endocytosis and processing. 2-Antigen presentation. -Extracellular microbes and toxins are engulfed by endocytosis.(Endocytic pathway). -Intracellular microbes (viruses) are processed by cytolytic pathway.

13. N Endocytosis of extracellular microbes: 1-Phagocytosis 2-Receptor-mediated endocytosis. 3-Pinocytosis.

14. Antigen presentation by MHC Class II: -Endocytic vesicles (phagosomes; derived from phagocytosis ) fuse with lysosomes. -Phagolysosome interacts with endoplasmic reticulum vesicles. -The digested peptides carried by MHC II to cell surface.

15. Antigen presentation by MHC Class I: -Cytoplasmic protein-ubiquitin reaction. -Proteasome action on the complex. -Fusion of processed peptide with E.R vesicle which carry MHC Class I to the cell surface.

16. Activation of T Lymphocytes: -MHC II-epitope-Complex interaction with TCR. -B7(CD80/86) Co-stimulatory interaction with CD28. -IL-2 production from activated T cell. -Overexpression of IL-2R on T cell surface.

17. N -In the presence of IL-12, native CD4 lymphocyte is differentiated as a CD4 Th1. Activation of CD8 (Tc) cell by effector Th1:

18. N Activation of B Lymphocytes by effector Th2: -MHC II-epitope-Complex interaction with TCR. -CD40-CD40 Ligand interaction. -Antibody-epitope interaction.

19. Lymphocyte Effector Functions: Cell-mediated immunity: 1-Role of CD4 T cells in Delayed (- type) hypersensitivity:

20. N 2-Role of CD8 T cell: T cell Cytotoxicity : A-Target cell recognition. B-Target cell destruction: -Perforins and Granzymes effect.

21. N 3-Role of NK cells in cellular immunity:

22. N Humoral immunity: 1-Agglutination of invaders. 2-Neutralization (virus, toxins). 3-Opsonization. 4-Complement activation. 5-ADCC: NK cell and Eosinophils. 6-Immediate hypersensitivity.

23. Humoral immunity and effector lymphocyte function: N

24. The ADCC Mechanism: N