Tissues and organs of the ISNTTH-HCMIU-IM-2014ORIGIN OF CELLS OF THE IMMUNE SYSTEMNTTH-HCMIU-IM-2014Derived from common progenitor cell in bone marrow Pluripotent hematopoietic stem cellINNATEADAPTIVEMYELOIDLYMPHOID LINEAGEOrgans and Tissues of immune systemHow many lymphatic organs are there?Where are they?The one that you might know before this courseNTTH-HCMIU-IM-2014NTTH-HCMIU-IM-2014Primary (Central) vs. Secondary (Peripheral; Systemic+ MALT)Investigated laterSynchronized with other organsNTTH-HCMIU-IM-2014LYMPHOCYTES, LYMPHOID TISSUES AND ORGANS Lymphocytes originate in bone marrow Lymphoid tissues and organs Primary Production, development and maturation of lymphocytes Bone Marrow (B cells) and Thymus gland (T cells)NTTH-HCMIU-IM-2014 Bone Marrow (B cells) and Thymus gland (T cells) Secondary Mature lymphocytes meet pathogens and exert their effector functions Spleen, adenoids, tonsils, appendix, lymph nodes, Peyers patches, mucosa-associated lymphoid tissue (MALT)Immune SystemLymphoid systemNTTH-HCMIU-IM-2014Primary lymphoid organs In the primary lymphoid organs, lymphocytes (B, T cells): - differentiate from lymphoid stem cells- proliferate, are selected and mature in to functional cellsException: Some lymphocytes development might occur outside primary lymphoid organs.NTTH-HCMIU-IM-2014 In the primary lymphoid organs, lymphocytes (B, T cells): - acquire their repertoire of specific Ag receptor to cope with the antigenic challenges that individuals encounter during their lifetimes; - cells with receptors for autoantigens are mostly eliminated (negative selection); - T cells learn to recognize appropriate self MHC molecules in the thymus (positive selection)THYMUS Bilobed organ in the thoracic cavity overlying the heart and major blood vessels Each lobe is organized into lobules separated from each other by NTTH-HCMIU-IM-2014from each other by connective tissue trabeculae Nurse cells+ cortical TECs+ medulary TECs (thymic epithelial cells) Nurse cells= IL-17 producers; proliferationFully developed thymic lobuleT cell development in the thymusNTTH-HCMIU-IM-2014Diverse TCR (T cell RECEPTOR) are generated by recombination of gene segments encoding the TCR. CENTRAL TOLERANCEFetal liver and BM for B cellsProliferation and maturationNTTH-HCMIU-IM-2014Stromal reticular cellsNegative selectionHeavy chain rearrangementLight chain rearrangementLymphocytes (B, T) migrate to and function in secondary lymphoid organs and tissues1. Well-organized encapsulated organs/ systemic lymphoid organs: spleen: responds to blood-born pathogens/ AgsNTTH-HCMIU-IM-2014spleen: responds to blood-born pathogens/ Agslymph nodes: respond to Ags coming from skin or internal surface or lymphatic vessels2. Non-encapsulated accumulations of lymphoid tissues: MALT- mucosa- associated lymphoid tissue: protect mucosal surface: GALT, BALT, Genitourinary-ALTSPLEEN White pulp: - PALS- periarteriolar lymphoid sheaths, composed of T cell area around central arteriole; B cell area either in unstimulated follicles- virgin B cells or in stimulated follicles-Germinal Center with memory B cells- GC also contains FDC and Macrophages.NTTH-HCMIU-IM-2014Macrophages. Red pulp:- Plasma cells, macrophages,lymphocytes.- Erythrocytes, platelets, granulocytes Marginal zone:-vascular organization- B, DC and MacrophagesNotes on THE SPLEEN Spleen Lymphoid organ in upper left abdomen Functions Remove damaged or old erythrocytes Activation of lymphocytes from blood borne pathogensNTTH-HCMIU-IM-2014 Architecture of Spleen Red pulp Erythrocytes removed White pulp Lymphocytes stimulatedLymph NodesKidney- shaped organs at intervals along lymphatic vesselsSize: 2- 10 mm in diameterCortexAPCsCentral MedullaNTTH-HCMIU-IM-2014Filter Ags from the interstitial tissue fluid and lymphParacortexCentral MedullaGerminal Center (spleen, lymph nodes, MALT)NTTH-HCMIU-IM-2014SECONDARY LYMPHOID TISSUES ASSOCIATED WITH MUCOUS MEMBRANES- MALT Primary portals of entry for pathogens Respiratory tract Gastrointestinal tract Secondary lymphoid tissues Bronchial-associated lymphoid tissue (BALT)NTTH-HCMIU-IM-2014 Bronchial-associated lymphoid tissue (BALT) Gut-associated lymphoid tissues (GALT) Tonsils, adenoids, appendix, Peyers patches Pathogens are directly transferred across mucosa by M cells-numerous microfoldsGALTNTTH-HCMIU-IM-2014Exist as either solitary nodules or aggregated nodules such as appendixNTTH-HCMIU-IM-2014Peyers patches as well as tonsils and other lymphoid areas of MALT are sites of lymphocytes priming by Ags, which are internalized by M cells in the Follicle-Associated Epithelium-FAETHE LYMPHATIC SYSTEMand LYMPHATIC CIRCULATIONNTTH-HCMIU-IM-2014LYMPHATIC CIRCULATIONLymphatic circulation is the process by which the lymphatic system circulates the fluid lymph throughout the bodyTHE LYMPHATIC SYSTEM: terminologya subsystem of the circulatory system in the vertebrate body that consists of a complex network of vessels, tissues, and organs.The lymphatic system helps maintain fluid balance in the body by collecting excess fluid and particulate matter from tissues and depositing them in the bloodstream. NTTH-HCMIU-IM-2014It also helps defend the body against infection by supplying disease-fighting cells called lymphocytes. BRITANICA ENCYCLOPEDIATHE LYMPHATIC SYSTEM: terminology Lymph Fluid and cells in lymphatic vessels Lymphatic vessels Collect and return interstitial fluid to blood Transport immune cells throughout body Transport lipid from intestine to bloodNTTH-HCMIU-IM-2014 Transport lipid from intestine to blood Lymph nodes Kidney shaped organs at intervals along lymphatic vessels Other secondary lymphatic tissues and organsShort summary Nave lymphocytes circulate between blood, lymph and secondary lymph nodes Pathogens from infected tissue sites are picked up by lymphatic vessels and arrive at closest lymph nodeNTTH-HCMIU-IM-2014 T and B cells congregate at specific regions of nodes Architecture and size of nodes change in response to activation of lymphocytesNTTH-HCMIU-IM-20143. Circulation: cardiac and lymphaticWheres the oxygen-rich blood?Thoracic/ right lymphatic ductNTTH-HCMIU-IM-2014Color Atlas of Immunology- 2003NTTH-HCMIU-IM-2014NTTH-HCMIU-IM-2014SUMMARYNTTH-HCMIU-IM-2014TISSUES & ORGANS OF ISHemopoiesisLymphopoiesisMyeolopoiesis+/- SelectionThe ARMYs CAMPsNTTH-HCMIU-IM-2014GALT- M cells-2.52; BALT; NALT; CALT; O-MALT; D-MALT+/- SelectionFig 2.26: Major organs- tissuesFig 2.28; 2.292.32 for TFig 2.35 for BInteresting info to exploreReviews on T- cells and TCR http://www.lsic.ucla.edu/classes/mimg/spring_05/mimgm261/miceli_5_21_reading.pdf http://www.nature.com/nri/journal/v5/n7/full/nri1636.htmlIntestinal M cell: the fallible sentinel http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1876659/NTTH-HCMIU-IM-2014Lymphatic Drainage Therapy:http://www.tropos.us/Lymphatic%20Drainage.htm1.2.3.4.5.6.NTTH-HCMIU-IM-2014