Lesson 2: Organs and cells of the Immune System PDF

Lesson 2: Organs and cells of the Immune System 1.- Primary and secondary organs 2.- Hematopoiesis 3.- Innate (natural) IS cells 4.- Acquired (adaptive) IS cells  Organs of the IS: primary and secondary PRIMARY: Where IS cells originate and differentiate, ma...

Lesson 2: Organs and cells of the Immune System 1.- Primary and secondary organs 2.- Hematopoiesis 3.- Innate (natural) IS cells 4.- Acquired (adaptive) IS cells  Organs of the IS: primary and secondary PRIMARY: Where IS cells originate and differentiate, mature: Thymus and Bone Marrow SECONDARY: Organs where differentiated (functional) cells are placed and encounter antigens: Spleen, lymph nodes, MALT (mucosae associated lymphoid tissue)  Primary or central lymphoid organs Organs where origin and maturation of lymphocytes occur In adult life: – Thymus: maturation of T lymphocytes – Bone marrow: maturation of B lymphocytes In fetal life: – Yolk sac, spleen and liver.  Primary organs Thymus: situation and histology (I) Flat, soft, bilobed organ, placed in thorax. Thymus regress from puberty.  Primary organs Thymus: situation and hystology (II) Each lobe is divided into smaller lobes. Each one is formed by two types of tissues: Cortex: Many thymocytes Medulla: Few thymocytes Stromal thymic cells are placed among thymocytes: Epithelial cells Dendritic cells Macrophages  Primary organs Inmunidad Thymus:de mucosas: structure Sistema and MALT function Cortico-medullar differentiation gradient More than 95% of cortical lymphocytes die in a process called negative selection, which is key for SELF-TOLERANCE: potentially self-reactive T lymphocytes are eliminated during the thymic maturation process.  Bone marrow Primary organs Hematopoietic (blood) cells develop in BM. It is the source of lymphocyte precursors that migrate to thymus, where they differentiate into T cells. BM is not a particular organ, BM is formed by “islands” of haematopoietic tissue, normally surrounded by fat tissue and placed into the trabeculae of sponge bones Mostly into long bones as femur, or into big flat bones as hips. B lymphocytes maturation occurs in BM  Hematopoiesis Self-renewing Pluripotent CD = Cluster of differentiation Secondary or peripheral lymphoid organs and tissues Locations where mature lymphocytes are placed and contact antigens. Components: – Lymph vessels – Lymphoid organs Lymph nodes Spleen MALT Lymphatic Lymphatic capilars extract fluid from vessels intercellular space: lymph They converge in lymph nodes afferent vessels Efferent vessels leave the lymph node The thoracic duct drains its content in superior vena cava This system transports free or cell-bound antigens from the entrance places (skin, digestive, respiratory), to the lymph nodes Afferents  Secondary organs Lymph nodes (I) Functions: a) Antigen contact. Antigens and antigen- presenting cells reach the lymph node by afferent vessels (several). b) T-B cooperation  Secondary organs Lymph nodes (II) Cortex (B cells). Primary lymphoid follicle (virgin) Secondary lymphoid follicle (Activated) With germinal center Paracortex (T cells). Medulla: T and B activated cells and macrophages cross the medulla and leave the lymph node through the efferent vessel (only 1).  Secondary organs Spleen Functions: 1-Old red cells elimination 2-Filter: captures blood antigens. Histology: Red pulp: rich in macrophages that eliminate old erytrocytes. White pulp: similar to lymph nodes in function and structure PALS (Periarteriolar lymphoid sheath: T lymphocytes) Marginal zone: B lymphocytes organized into primary and secondary follicles  Secondary organs Mucosae Immunity: MALT system Waldeyer´s ring: – Tonsils – Adenoids – Regional lymph nodes Respiratory MALT Genitourinary MALT Gastrointestinal MALT (GALT: gut associated lymphoid tissue) – Peyer patches. – Intraepithelial lymphocytes – Lamina Propria lymphocytes  Secondary organs Waldeyer´s ring (oral cavity)  Secondary organs Gut and lung  Secondary organs Peyer patches GALT Lymphoepithelial formations placed in the submucosae of small intestine, especially ileon Capture of antigens from intestinal lumen Zone of T-B lymphocytes cooperation and IgA production Components: M cells:(epithelial) carry antigens from intestinal lumen inside the patch Macrophages T Lymphocytes B lymphocytes IS cells Neutrophil 90% of granulocytes Short life (2-3 days) 100 x106 per day Nucleus with several lobes They increase in bacterial infections (leukocytosis) Function: phagocytosis Specific granules: lysozyme, collagenase, elastase Azurophilic granules: lysosomes containing enzymes and other microbicidal substances, including defensins and cathelicidins Eosinophil 1-3% of leukocytes Bilobulated nucleus Granules with protein content that bind acidic dyes and is toxic for parasites Defense against helmints https://www.youtube.com/watch? v=fw_I21RnBWg Basophil < 1% of leukocytes Bilobulated nucleus Express FcRI Blue granules with content that binds basic dyes: Histamine Heparine Serin proteases Function: parasites defense and allergy reactions Mast cell Bone marrow-derived cells that are present in the skin and mucosal epithelium and contain abundant cytoplasmic granules filled with cytokines, histamine, and other mediators. Mast cells provide defense against helmints but are also responsible for symptoms of allergic diseases Platelets Megakaryocyte fragments without nucleus No role in immunity: Coagulation Role in chemotaxis Monocyte Horseshoe nucleus Azurophilic granules (lysosomes) Peroxidase and acid hydrolase Lysozyme and lactoferrin They only remain 8 hours in blood and after that they migrate to tissues and become macrophages or dendritic cells. Macrophage Half life: years/months Horseshoe nucleus and prominent nucleoli Many mitochondria and lysosomes. Membrane with pseudopodia Functions: Innate Inm: Phagocytosis Adaptive Inm: APC Macrophage cells in tissues: Liver: Cel. Kupffer. Lung: alveolar macrophages Bone: Osteoclasts Conective tissue: Histiocyte Brain: microglia  PRODUCTION OF CYTOKINES BY ACTIVATED MACROPHAGES IL-1,IL-6,TNF- α IL-12 and IL-18: Promote T CD4+ lymphocytes differentiation, induce Induction of local the production of γ-interferons by NK and systemic cells and possibly by macrophages inflammatory and dendritic cells. response. Growing factors that CHEMOKINES. They promote the production mediate recruiting of of different cellular different leukocyte lineages populations in the infection focus. IL-10 and TGF-β: Mediate anti- inflammatory and tolerogeneic activity Dendritic cells Together with macrophages, they are the major antigen presenting cells (APC) in the body. They have phagocityc activity. Types: Classic DC: Myeloid origin Express class I and class II HLA Present antigens to T lymphocytes Follicular DC: They do not derive from BM. ¿fibroblasts? They are not phagocytic. Only have class I HLA They show antigens to B lymphocytes T, B and NK Lymphocytes 20-40% total leukocytes Small cells with very few cytoplasm (when naïve). When they contact the antigen they duplicate the size and proliferate. They become effector cells and memory cells. They are produced in primary lymphoid organs and migrate to secondary organs. B Lymphocytes They differentiate in bone marrow 5-15 % of total lymphocytes They recognize antigen in soluble form (isolated) thanks to a membrane immunoglobulin (IgM and IgD), also called BcR. Once they contact the antigen they divide actively into memory B lymphocytes and plasma cells which segregate big amount of Igs of specificity identical to that of the membrane (Primary IR:IgM, secondary IR: IgG/IgA/IgE) To be activated they need the cooperation of cytokines from Th lymphocytes (T-B cooperation). Characteristic markers: BcR, CD19, CD20 and CD21. Plasma cells They differentiate from B lymphocytes. They lack membrane Ig CD38 + Big protein production organella: Golgi and ER They are placed in the effector response locations They live several days and die by apoptosis. However, B memory cells live for long years. T Lymphocytes Around 75% of lymphocytes They recognize especific antigens thanks to a membrane receptor similar to an antibody: TCR They do not recognize soluble or isolated antigens, they only recognize antigens bound to special proteins called MHC (HLA). T lymphocyte types: – > 90 % T cells CD3+ TCR  CD4 +: T helper, their main function is to manage the immune response. CD8 +: T cytotoxic, their main function is to lyse infected cells – < 5% T cells CD3+ TcR . Unclear function https://www.youtube.com/watch?v=RPIzIznmAO0 The end