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Organization of the lymphoid organs and tissues LYMPHOID ORGANS Primary lymphoid organs: - Bone marrow - Thymus Secondary lymphoid organs: - Spleen - Lymphatic vessels - Lymph nodes - Adenoids and tonsils - MALT (Mucosal Associated Lymphoid Tissue) GALT (Gut Associated Lymphoid Tissue) BALT (Bronchus Associated Lymphoid Tissue) SALT (Skin Associated Lymphoid Tissue) NALT (Nasal Associated Lymphoid Tissue) Primary lymphoid organs Bone marrow GENERATION OF BLOOD CELLS DURING LIFE SPAN BEFORE BIRTH AFTER BIRTH Cell number (%) Yolk sac 80 Flat bones Liver 60 40 Spleen 20 Tubular bones 0 0 1 2 3 4 5 6 7 8 9 10 20 30 40 50 60 70 years months BIRTH BONE MARROW TRANSPLANTATION Structure of the bone marrow Bone marrow CELL TYPES OF THE BONE MARROW Stem cells Osteoblasts Stromal cells BONE csont Osteoclasts B-cell precursors Progenitors Precursors Dendritic cell Central centrális sinus sinus Blood circulation Unspecialized stem cells with unlimited proliferating capacity SELF RENEWAL AND POTENCY OF DIFFERENTIATION OF STEM CELLS HSC – assymetric cell division self renewal cell differentiation Self renewal Differentiation to any precursor cell BONE MARROW HSC MYELOID PRECURSOR HEMATOPOIETIC STEM CELL LYMPHOID PRECURSOR BLOOD BLOOD DC monocyte mast neutrophil TISSUES DC THYMUS macrophage mast B-cell NK-cell T-cell LYMPHOID TISSUES B-cell T-cell Primary lymphoid organs Thymus STRUCTURE OF THE THYMUS Thymocytes from the bone marrow arrive at the thymus and mature into naive T cells Capsule Septum Blood circulation Epithelial cells Thymocytes Dendritic cell Macrophage Mature naive T- lymphocytes Hassall’s corpuscle THYMUS INVOLUTION PERIPHERAL (or SECONDARY) LYMPHOID ORGANS The innitation of adaptive immune response • Lymph nodes • Spleen • Epithelial cell – associated lymphoid tissues MALT (Mucosal Associated Lymphoid Tissue) GALT (Gut Associated Lymphoid Tissue) BALT (Bronchus Associated Lymphoid Tissue) SALT (Skin Associated Lymphoid Tissue) NALT (Nasal Associated Lymphoid Tissue) Organization (levels) of immunocytes Diffuse cells Follicle Patch organ LYMPHATIC CIRCULATION SYSTEM Lymphatic vessels Lymph circulates to the lymph node via afferent lymphatic vessels and then leaves the lymph node via the efferent lymphatic vessels towards either a more central lymph node or ultimately for drainage into a central venous subclavian blood vessel. Lymph node HOMING OF LYMPHOCYTES IN LYMPH NODES Naive lymphocytes enter lymph nodes via HEV B cells are recruited to HEV from the blood by chemokine secreted by stromal cells SPLEEN SPLEEN The spleen filters the blood and serves as a secondary lymphoid organ Spleen Lymphocyte aggregations are similar to the lymph node only that cells and pathogens enter from the blood Red pulp- filters the blood; from antigens, microorganisms and worn-out RBCs STRUCTURE OF THE SPLEEN White pulp NO LYMPHOID CIRCULATION Filtration of blood borne antigens Spleen white pulp Transverse section Marginal sinus B cell corona Red pulp Germinal centre Marginal zone Periarteriolar lymphocytic sheath (PALS) – T cell area Central arteriole PERIPHERAL LYMPHOID ORGANS Sites of lymphocyte activation and differentiation Lymph nodes Spleen Epithelial cell – associated lymphoid tissues MALT (Mucosal Associated Lymphoid Tissue) GALT (Gut Associated Lymphoid Tissue) BALT (Bronchus Associated Lymphoid Tissue) SALT (Skin Associated Lymphoid Tissue) NALT (Nasal Associated Lymphoid Tissue) Secondary lymphatic tissues MALT Lymphatic tissues that are more diffused are generally known as MALT (Mucosa associated lymphatic tissue). Similar microanatomy as the lymph nodes and spleen • Most of the pathogens get into human body through mucosa • A thin, huge surface, dinamic structure • Intense and active immune surveillance mechanisms ensure the protection • Mucus contains glycoproteins, proteoglycans, special enzymes • Anti microbial peptides provide biological defense mechanism against infection • Most of the lymphocyte reside around the mucosal surface GUT-ASSOCIATED LYMPHOID TISSUES Small intestine Large intestine GUT-ASSOCIATED LYMPHOID TISSUES Peyer’s patches 5-100 follicles forming a dome structure M-cells: microfold cells --- no glycocalyx – antigen uptake GALT • The Lamina propria contains lymphatic tissue underlying the gastrointestinal tract connective tissue • The small intestine contains lymphoid nodules; the Peyer’s patches and isolated lymphoid follicles. • Pathogens are delivered across the mucosa to APCs by specialized mucosal epithelial cells are called the M cells (microfold cells). Transport of antigens via M cells Dendritic cells of the lamina propria are able to capture antigens by sampling the gut lumen directly outside the Peyer’s patches Intra-epithelial lymphocytes