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Transcript
L.4/2016-2017 Immunology Asst.Prof.Dr. IFAD KERIM ALSHIBLY Lymphoid organs (Organs of the Immune System) The lymphoid system is the part of the immune system comprising a network of ducts called lymphatic vessels that carry a clear fluid called lymph (from Latin lympha "water") unidirectionally toward the heart. The lymphoid system is composed of the organs that produce lymphocytes (bone marrow and thymus), and organs largely composed of lymphoid tissue (lymph nodes, spleen, and the tonsils of the pharyngeal lymphoid ring). Mature lymphocytes are naive when they leave the primary lymphoid organs (bone marrow and thymus). Immunological reactions are initiated by the presentation of antigens to lymphocytes by antigen-presenting cells within secondary lymphoid organs or mucosaassociated lymphoid tissues. Lymphoid tissue associated with the lymphatic system is concerned with immune functions in defending the body against the infections and spread of tumors. The lymphoid system has multiple interrelated functions; it is responsible for the removal of interstitial fluid from tissues. It transports white blood cells to and from the lymph nodes into the bones. The lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune response is stimulated. Lymphoid tissues: The lymphoid tissue may be primary or secondary, depending upon the stage of lymphocyte development and maturation it is involved in: A. Primary lymphoid organs The central (generative) or primary lymphoid organs generate lymphocytes from immature progenitor cells, and where lymphocytes first express 1 L.4/2016-2017 Immunology Asst.Prof.Dr. IFAD KERIM ALSHIBLY antigen receptors and achieve phenotypic and functional maturity. The thymus and the bone marrow constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. B. Secondary lymphoid organs Secondary or peripheral lymphoid organs maintain mature naive lymphocytes and initiate an adaptive immune response. The peripheral lymphoid organs are the sites of lymphocyte activation by antigen. Activation leads to clonal expansion and affinity maturation. Mature lymphocytes recirculate between the blood and the peripheral lymphoid organs until they encounter their specific antigen. Secondary lymphoid tissue provides the environment for the foreign or altered self-antigens to interact with the lymphocytes. It is exemplified by the lymph nodes, and the lymphoid follicles in tonsils, Peyer's patches, spleen, adenoids, skin, etc., that are associated with the mucosa-associated lymphoid tissue (MALT). 1. Thymus: The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just "T cells," mature in the thymus. It is the site of T cell maturation and education (learn to discriminate between self and non-self-antigens). The lymphocytes (thymocytes) are T cells at various stages of maturation. The most immature T cells enter the thymic cortex through the blood vessels. Maturation begins in the cortex, then thymocytes migrate toward the medulla, so that the medulla contains mostly mature T cells. After puberty, thymus atrophies. Before birth, the thymus receives stem cells from the marrow that proliferate and 2 L.4/2016-2017 Immunology Asst.Prof.Dr. IFAD KERIM ALSHIBLY undergo selection and maturation (by interacting with epithelial-reticular cells and APC reticular cells), before seeding out via the blood to populate the secondary organs with T or thymus-dependent immunologically competent lymphocytes. Self-reactive lymphocytes are selected against, die, and are phagocytosed, while the surviving T lymphocytes migrate from subcapsular cortex towards the medulla. At puberty the thymus starts a slow involution and replacement by adipose tissue, accelerated by severe stresses. Despite the involution, the adult thymus maintains a low level of T-cell development from immature precursors that have not yet rearranged their TCR genes. 2. Bone Marrow: Bone marrow, the soft tissue in the hollow center of bones, is the ultimate source of all blood cells, including white blood cells designed to become immune cells. Bone marrow is the site for B cell maturation and education. 3. Lymph nodes: Lymph node is an organized collection of lymphoid tissue, through which the lymph passes on its way to returning to the blood. They are small, bean-shaped lymph nodes located along the lymphatic vessels, with clusters in the neck, armpits, abdomen, and groin. Each lymph node contains specialized compartments where immune cells congregate, and where they can encounter antigens. Lymph nodes are located at intervals along the lymphatic system. Several afferent lymph vessels bring-in lymph, which infiltrates through the substance of the lymph node, and is drained out by an efferent lymph vessel. Lymph nodes are the organs 3 L.4/2016-2017 Immunology Asst.Prof.Dr. IFAD KERIM ALSHIBLY in which adaptive immune response to lymph-borne antigens are initiated, act as filters that clear the lymph at different sites before it reaches the blood. A lymph node consists of an outer cortex and an inner medulla. The aggregates of cells (follicles) are present in the cortex ,and there are two types of follicles :1-primary follicles without germinal center enriched with mature but naïve B cells, 2-secondary follicles with germinal center and mature proliferative B cells with high affinity to produce Ab and memory cells. APCs are located in the areas around the follicles. 4. Spleen: The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and work, and serves as a meeting ground where immune defenses meet antigens. The spleen is an important filter for blood. To the naked eye, most of the freshly cut organ is red pulp with white spots - white pulp. Red pulp consists of a loose reticular tissue infiltrated with blood cells; White pulp is a dense lymphoid tissue ensheathing branches of the arteries. Until birth, the spleen takes part in myelopoiesis, as do lymph nodes. White pulp serves for (a) recirculation of lymphocytes. (b) Formation of new lymphocytes and plasma cells for immune responses to blood-borne antigens, met first at the marginal zone. Red pulp provides: (a) blood cleansing by the sequestration and phagocytic destruction by macrophages of unfit blood cells and platelets, and bacteria. (b) Metabolic breakdown of RBCs so that their iron can be reused. (c) Sites by the marginal zone for plasma cells after antigenic stimulation, analogous to the cortex and medulla of the active lymph node. Macrophages of red pulp clear the blood from microbes and other foreign particles, and the spleen is the major site for the phagocytosis of 4 L.4/2016-2017 Immunology Asst.Prof.Dr. IFAD KERIM ALSHIBLY Ab-coated (opsonized) microbes. Individuals lacking a spleen (splenoctomized) are extremely susceptible to encapsulated infections such as pneumococci and meningococci because such microbes are normally cleared by opsonization and phagocytosis. This function is defective in the absence of the spleen. 5. MALT (mucosa-associated lymphoid tissue): MALT (mucosa-associated lymphoid tissue), are aggregates of nodules occur in the tonsils, appendix and ileal Peyer's patches of the GI tract; whereas solitary nodules may exist anywhere in the mucosa of all tubular systems open to the outside. Wherever nodules may be found, close by are lymphoid cells dispersed more diffusely. The gut- and bronchus-associated diffuse lymphoid tissues (GALT, BALT) are notable. Having an epithelium between the microorganisms and the connective tissue, where most of the lymphoid cells reside. Over the nodules, special low columnar epithelial cells - M cells - develop in order to pass antigens to the underlying antigen-presenting cells in the lamina propria. The APC and lymphocytes sometimes lie in a pocket in the M cell. ('M' for microfolds on the M cell surfaces.). The antibodies subsequently made by the plasma cells are immunoglobulins of a kind that the typical epithelial cells can take up basally, and secrete apically into the lumen needing protection(SIgA). The immune response mediated by MALT is characterized by the production of high level of S-IgA. So the main function of MALT is the local defense against foreign substances at mucosal surfaces. 5