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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) Types of endothelium 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 csont Stromal cell Bone HSC Dendritic cell HSC – assymetric cell division self renewal cell differentiation Central sinus centrális sinus CD34+ HSC BONE MARROW MYELOID LYMPHOID CMP CLP ERYTHROID BLOOD CELLS Endothelial cells Mesenhymal Stem Cells (MSC) Other Stem Cells Fat Neuronal cells Epithelial cells of the liver, kidney, skin, myocytes of the heart and muscle, GI tract Bone Cartilage Mobilized hematopoetic stem cells (HSC) develop in close contact with osteoblasts, mesenchymal stem cells (MSC) and endothelial cells Osteoblast Nestin+MSC HSC MSC HSC HSC HSC Uccelli A et al. Nat Rev Immunol 2008 BONE MARROW HSC MYELOID PRECURSOR HEMATOPOIETIC STEM CELL LYMPHOID PRECURSOR BLOOD BLOOD DC monocyte mast neutrophil TISSUES DC THYMUS macrophage mast neutrophil 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 T cells Capsule Septum Blood circulation Epithelial cells Thymocytes Dendritic cell Macrophage Mature naive T- lymphocytes Hassall’s corpuscle STRUCTURE OF THE THYMUS THYMUS INVOLUTION 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) Organization (levels) of immunocytes Diffuse cells Follicle Patch organ Lymphatic nodes Lymphatic vessels Lymph circulates to the lymph node via afferent lymphatic vessles 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 sublcavian blood vessel. Lymph node HOMING OF B LYMPHOCYTES IN LYMPH NODES Naive B lymphocytes enter lymph nodes via HEV B cells are reqruited to HEV from the blood by CCL21 chemokine secreted by stromal cells CCL21 and CCL19 chemokines attract B lymphocytes to the lymph node . The spleen filters the blood and serves as a secondary lymphoid organ Spleen Lymphocyte aggregations 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 defence mecanism against intection • Most of the lymphocyte reside arround the mucosal surface Gut-associated lymphoid tissues 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 outside Peyer’s patches capture antigens by sampling the gut lumen directly Intra-epithelial lymphocytes GALT • The large intestine contains isolated lymphoid follicles and the appendix • Antigens arising from Peyer’s patches and Lamina Propria travel to T cell areas in the GALT or Mesenteric lymph nodes. NALT Guarding the gastrointestinal entrance Waldeyer’s ring: Pharyngeal, Tubal, Palatine and Lingual Tonsils Tonsilitis Cellular components of the cutaneous immune system