Macro/Microstructure of Specialized Immune Tissue PDF

15 Macro/Microstructure of specialized immune tissue I & II ILOs By the end of this lecture, students will be able to 1. Outline the different components of the lymphatic system. 2. Value the functional role of primary, secondary, and diffuse lymphoid tissue. 3. Correlate stru...

15 Macro/Microstructure of specialized immune tissue I & II ILOs By the end of this lecture, students will be able to 1. Outline the different components of the lymphatic system. 2. Value the functional role of primary, secondary, and diffuse lymphoid tissue. 3. Correlate structural adaptation of the thymus to its role in T lymphocyte maturation. 4. Correlate macro, and microscopic structure of some secondary lymphoid organs to their functional role. 5. Interpret structural changes in the lymph node in different immune responses. 6. Relate the structural changes to clinical correlations as in lymphadenopathy and lymphedema. The lymphatic System It carries excess of the extracellular fluid back to the venous system. This fluid is the result of filtration from capillaries and include large particles as pathogens, cell products (such as hormones), and cell debris. The fluid in most lymphatic vessels is clear and colorless and is known as lymph. That carried by lymphatic vessels from the small intestine is opaque and milky because of the presence of chylomicrons and is termed chyle. There are lymphatic vessels in most areas of the body EXCEPT: the brain, bone marrow, and avascular tissues such as epithelia and cartilage. Unidirectional flow of lymph is maintained by the presence of valves in the vessels. Figure 1: Lymphatic Circulation Page 1 of 7 The lymphatic system consists of: 1. Lymph nodes Figure 2: Major lymphatic vessels 2. Lymphatic vessels that drain into large veins in the 3. Lymphatic ducts neck Lymphatic vessels: They form an extensive and complex interconnected network of channels, which begin as "porous" blind-ended lymphatic capillaries in tissues of the body and converge to form a number of larger vessels, which drain into the 2 lymphatic ducts. Lymphatic Ducts: There are two lymphatic ducts thoracic duct and right lymphatic duct. a. Thoracic duct: It begins in the cisterna chili in the abdomen (in front of the lumbar vertebrae) - It ascends through the posterior abdominal and thoracic walls (deviating to the left side). - It terminates at the junction of left subclavian and left internal jugular veins. It drains lymph from all the body except the upper right quadrant. b. Right lymphatic duct: It is much smaller in size. It drains lymph from the upper right quadrant (right side of the head and neck, right upper limb, and right side of the chest) - It terminates at the junction of right subclavian and right internal jugular veins. Microstructure of specialized immune tissue Each lymphoid organ is formed of two parts: I- Stroma; it is the connective tissue supportive framework of the organ. It includes two parts; - A covering dense CT capsule and CT trabeculae that extend from the capsule for structural organization of the organ. - Fine stroma; fine reticular fibers forming a supportive network for the cells of the organ. II- Parenchyma; it is the functional cellular part. It is divided into outer cortex (denser cell population) and inner medulla. The Thymus The thymus is a primary lymphoid organ that is the site of maturation of T lymphocytes. The thymus originates early in the embryo and continues to grow until puberty, when it may weigh as much as 35 to 40 g. After the first few years of life, the thymus begins to involute (atrophy) and becomes infiltrated by adipose cells. However, it may continue to function even in older adults. Histological structure The capsule of the thymus, composed of dense, irregular collagenous connective tissue, sends septa into the lobes, subdividing them into incomplete lobules Each lobule is composed of a cortex and a medulla, although the medullae of adjacent lobules are confluent with each other. (Fig 3) Page 2 of 7  Figure 3. The thymus Function Immunological competency (functional maturation) of T cells, elimination of self-intolerant T lymphocytes, and MHC (major histocomptability) recognition occur in the thymic cortex Cells in the cortex: 1- T- lymphocytes leave the bone marrow (site of formation) to reach the cortex of thymus as immature cells. They undergo proliferation (HOW?) and maturation to become immunocompetent (immunologically active). 2- Macrophages 3- Epithelial reticular cells: These cells have interconnected branches thus forming a sort of a cellular network, the cytoreticulum that supports the developing T – cells. Note that thymus lacks reticular stroma and depends on the cytoreticulum formed by epithelial reticular cells. They are three types (I, II & III) in the cortex. Type I; shares in formation of the blood thymic barrier that prevents contact of developing T- cells in cortex with any foreign antigens circulating in blood. These cells are attached by tight junctions. The other epithelial reticular cells help in T-cell education by introduction of self -antigens. Components of the blood thymic barrier: Continuous endothelium of blood capillaries and their basal lamina. Type I Epithelial reticular cells that are attached to each other by tight junctions and their basal lamina. Functional significance of the blood thymic barrier: It prevents the contact of developing T- cells in cortex with any foreign antigens circulating in blood. It allows only contact with the self-body antigens to educate the T-cells to tolerate self-antigens. If the developing T-cells fail to recognize self-antigens i.e consider them as foreign antigen, will undergo apoptosis within the cortex. What happens if these cells continue development and maturation? Autoimmune disorders can occur. The surviving cells enter the medulla of the thymus as naïve T lymphocytes, and from there (or from the corticomedullary junction) they are distributed to secondary lymphoid organs via the vascular system. The medulla Page 3 of 7  The medulla is characterized by the presence of Hassall's corpuscles. All T-cells in medulla are immunocompetent. Epithelial reticular cells (IV, V & VI): share in the cytoreticulum and type VI share in formation of Hassall's corpuscles These large, pale-staining cells coalesce around each other, forming whorl-shaped thymic corpuscles (Hassall's corpuscles), whose numbers increase with a person's age. Type VI cells may become highly cornified and even calcified. (Fig 4) Figure 4. Thymus cortex and medulla (A) and Hassal’s corpuscles (B). A B The Lymph nodes They are small oval encapsulated structures along the course of lymphatic vessels. It has convex outer surface and concave one which contain hilum. Figure 5. Structure of LN and lymphatic circulation Regions associated with clusters or a particular abundance of lymph nodes Page 4 of 7  Each lymph node is divided into an outer cortex, paracortex and inner medulla. All three regions have a rich supply of lymphatic sinusoids, which are wide endothelium-lined spaces through which lymph flows. Stroma: Dense CT capsule that is thickened at the hilum (portal of entry or exit of blood vessels). Incomplete trabeculae arise from the capsule into the cortex and medulla subdividing them into small compartments. The Cortex The cortex of the lymph node is subdivided into compartments that house aggregated B cells in the form of rounded or oval structures, which are the primary and secondary lymphoid nodules. There are two types of lymphoid nodules: primary and secondary. a. Primary lymphoid nodules: composed of small B-lymphocytes, macrophages and follicular dendritic cells (antigen presenting cells). b. Secondary lymphoid nodules: have a central germinal center formed of large lymphoblasts that represent proliferating B-cells in response to exposure to a foreign antigen (Ag). Fate of lymphoblasts: These lymphoblasts differentiate into plasma cells (secrete specific antibodies to the antigen) and memory B-cells that can rapidly identify the foreign antigens on re exposure). Fate of Plasma & B-memory cells: The newly formed cells differentiate into B memory and plasma cells. Plasma cells leave the cortex and form the medullary cords of the medulla. About 10% of the newly formed plasma cells stay in the medulla and release antibodies into the medullary sinuses. The remainder of the plasma cells enters the lymphatic sinuses and reaches the bone marrow, where they continue to manufacture antibodies until they die. Some B memory cells stay in the primary lymphoid nodules of the cortex, but most leave the lymph node to reside in other secondary lymphatic organs of the body. Therefore, if there is a second exposure to the same antigen, a large number of memory cells are available to induce a rapid and potent secondary response. (How is this related to concept of vaccination?) The Paracortex It houses mostly T cells and is the thymus-dependent zone of the lymph node. High endothelial venules (HEVs) are located in the paracortex and represent the main route of entry of lymphocytes into the lymph node. Both B & T Lymphocytes leave the vascular supply by migrating between the cuboidal cells of this unusual endothelium and enter the substance of the lymph node. B cells migrate to the outer cortex, whereas most T cells remain in the paracortex. The Medulla The medulla is composed of large, tortuous lymph sinuses surrounded by lymphoid cells that are organized in clusters known as medullary cords. The cells of the medullary cords (lymphocytes, plasma cells, and macrophages) are enmeshed in a network of reticular fibers and reticular cells. Page 5 of 7  Histological sections of the medulla also display the presence of trabeculae arising from the thickened capsule of the hilum, conveying blood vessels into and out of the lymph node. Figure 6: Types of lymphatic nodules Secondary lymphatic nodule Capsule 1ry Germinal center Route of exit of lymphocytes from the lymph node: The lymphocytes migrate from the cortex to enter the medullary sinuses, from which they enter the efferent lymphatic vessels to leave the lymph node. Functions of the lymph node a. Filtration of the lymph as it flows within the lymphatic sinusues between the cortex and medulla and act as sites for antigen recognition. b. Recognition of foreign antigens in the lymph; as lymph enters the lymph node, the flow rate is reduced, which gives the macrophages that reside in (or have their processes that extend into) the sinuses more time to phagocytose foreign particulate matter. In this fashion, 99% of the impurities found in lymph are removed. c. Humoral immune response (productions of antibodies): If a foreign antigen is recognized and a B cell becomes activated, that B cells proliferate, forming a germinal center and the primary lymphoid nodule becomes known as a secondary lymphoid nodule. This is followed by formation of plasma cells and B-memeory cells with subsequent production of antigen specific antibodies. d. Cell mediated immune response: It is mediated by T-cells in the paracortex, for example; malignant cells and virus infected cells. CLINICAL CORRELATIONS Lymphangitis, Lymphadenitis, and Lymphedema (Fig.7) Lymph nodes are located along the paths of lymph vessels and form a chain of lymph nodes so that lymph flows from one node to the next, thus infection and malignant cells can spread. Lymphangitis and lymphadenitis are secondary inflammations of lymphatic vessels and lymph nodes, respectively. These conditions may occur when the lymphoid system is involved in chemical or bacterial transport after severe injury or infection. Page 6 of 7  The lymphatic vessels, not normally evident, may become apparent as red streaks in the skin, and the nodes become painfully enlarged. This condition is potentially dangerous because the uncontained infection may lead to septicemia (What is septicemia?). Lymphedema, a localized type of edema, occurs when lymph does not drain from an area of the body. For instance, if cancerous lymph nodes are surgically removed from the axilla (armpit), lymphedema of the limb may occur. Solid cell growths may permeate lymphatic vessels and form minute cellular emboli (plugs), which may break free and pass to regional lymph nodes. In this way, further lymphogenous spread to other tissues and organs may occur. (What do we call this condition?) Figure 7. Lymphadenitis Lymphangitis Lymphedema Young girl with inflamed, swollen, Granzow, Jay & soft cervical lymph node leading to Forearm lymphangitis due to cellulitis of the hand Soderberg, Julie; 2014 abscess formation Prasanta Raghab Mohapatra; 2009 ⮚ Page 7 of 7