Immune System and Lymphatics Anatomy-Histology Correlate By: Michael Lu, Class of ‘07
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Immune System and Lymphatics Anatomy-Histology Correlate By: Michael Lu, Class of ‘07 - The immune system, which is designed to protect us from foreign particles and organisms, is not localized to any part of the body. In fact, it is dispersed in bone marrow, lymph nodes, lymphatic duct and vessels, the gut, tonsils, thymus gland, and the spleen. Here we will focus on 4 of them – the lymph node, spleen, thymus, and tonsils. - Lymph nodes vary in size, shape, and location. The typical description is that they are kidney-bean shaped organs enclosed by a connective tissue capsule that forms trabecula within the lymph node. It is further subdivided into cortex and medulla. Note the germinal centers, sinuses, and postcapillary high endothelial venules, all which will be discussed later. - Lymph nodes receive both blood and lymph via different routes. The circulation through a lymph node is detailed in the bottom right. - Circulating lymphocytes play an important role in the immune defense. They can enter a lymph node via two routes – 1) 85 – 90% of lymphocytes, mostly undifferentiated, enter the lymph node from the blood via postcapillary high endothelial venules; and 2) 10 – 15% of lymphocytes, mostly memory cells, enter via the afferent lymphatic vessels. - A histological slide of a lymph node is shown on the top left. Note the capsule and trabecula. The vertical line marks the border between the cortex and medulla. Note at the hilum of the lymph node the efferent lymphatics and the blood vessels. - Lymphatic vessels may be difficult to identify. They are generally very thin-walled and dilated and contain lymphocytes instead of red blood cells. Shown in the bottom left is an afferent lymphatic vessel entering the lymph node through the capsule. - The afferent lymphatics empty their contents into the subcapsular sinus (bottom right) lined by endothelial cells and crossed by reticular cells. The sinus is readily permeable to both lymph and cells – lymphocytes, plasma cells, and macrophages. - In the cortex of the lymph node, there are multiple follicles. In the middle of a follicle may be a paler staining germinal center (magnified in bottom left) that indicates an antibody response to an antigen is occurring. The left nodule is a primary follicle, while the one on the right is a secondary follicle. - The follicles or nodules are B-cell rich. When an antigen is presented to the B-cells by dendritic cells, they undergo clonal expansion and differentiate into antibody secreting plasma cells and memory cells. - Outside the germinal center (bottom right) is the diffuse or deep cortical zone which is T-cell rich. IMPORTANT: The follicles (black bracket) contain germinal centers (white bracket), which are B-cell rich. The remainder of the cortex is T-cell rich. -Within the lymph node cortex, indicated by the blue arrows here (and the white arrows in the bottom right panel in the previous slide), are postcapillary high endothelial venules. They are composed of high cuboidal cells, which may be difficult to individually identify because of the extravasation of lymphocytes. This is one way that lymphocytes in the body enter lymph nodes, exiting the postcapillary high endothelial venules and entering the deep cortex. - The lymph node medulla in shown in the bottom right. It is filled with medullary sinuses separated by medullary cords. The medulla then empties into the efferent lymphatic vessels which exit at the hilum. There are variable amounts of macrophages, lymphocytes, and plasma cells. - Next we will look at the spleen. It is located in the left upper quadrant of the abdomen, tucked away behind the stomach and tail of the pancreas. It is connected to the stomach by the gastrosplenic ligament and to the left kidney by the splenorenal ligament. - The spleen is supplied by the splenic artery, which is a main branch off the celiac trunk from the abdominal aorta. - Functionally, the spleen can be divided into red pulp and white pulp. Note the functions stated below on the bottom right. - The red and white pulp are shown here histologically. The white pulp is lymphocyte rich, and therefore is more basophilic and stains more darkly (black arrows in bottom left). The red pulp contains a series of cords and sinuses reflecting the large number of red blood cells. - Similar to a lymph node, the spleen also contains a connective tissue capsule that extends into the parenchyma and forms trabecula. - Within the splenic tissue, we can also find larger vessels known as trabecular arteries and veins. Note the circulation of blood within the spleen detailed in the bottom right. - Arterial branches arising from the trabecular arteries are surrounded by mostly T lymphocytes. This region of white pulp, also the site of T-cell help, is known as the periarterial lymphatic sheath (PALS), as shown by the bracket in the top panel below. The artery in the middle of PALS is called the central artery (CA). - The spleen also contains lymphatic nodules that are rich in B lymphocytes. They are randomly distributed along the side of the PALS (bottom panel) and may also have germinal centers (GC). Surrounding the follicle and separating it from the red pulp (RP) is the marginal zone (MZ), which will be discussed next. - The marginal zone (bracket in top left) contains many reticular fibers, reticular cells, and macrophages (major antigen-presenting cells). Functionally, the marginal zone is very important because blood is emptied into this space by arterioles and capillaries, known as open splenic circulation. - Outside the marginal zone are the typical splenic cords and sinuses within the red pulp. Blood is emptied directly into the splenic cords via open circulation (unique to the spleen), flows across the walls of the splenic sinuses, and enters the venous drainage system of the spleen. Note the walls of the splenic sinuses formed by the rod cells. - The thymus gland can be found in the superior mediastinum of the thoracic chest cavity. It is located superior to the heart and anterior to the roots of the great vessels. - Shown on the bottom left is a low power view of the thymus gland. Note the abundance of thymic lobules (L) separated by septa (Se). The dark and light staining areas are the thymic cortex (C) and medulla (M), respectively. The light staining of the medulla reflects the fact that it contains less lymphocytes. Note also within the medulla the presence of Hassell’s corpuscles (HC). They are aberrantly keratinized epithelial cells that serve no functional purpose, but help in the identification of thymic tissue. - As shown in the top left, antigen-independent differentiation of T-lymphocytes takes place in the thymic cortex. Note the lack of germinal centers. The most newly formed cells are near the capsule, while the immunocompetent T cells exit the thymus by entering venules in the medulla. A Hassell corpuscle is also labeled. - Within the cortex, the capillaries exhibit a bloodthymus barrier. Functionally, this barrier is very important to ensure the proper differentiation of T cells and avoid reacting against any possible self antigens. The epithelial reticular cells that make up the barrier play an important role in the positive selection of Tcells. - The thymic tissue is slowly replaced by fat with increasing age via a process called thymic involution. Immunocompetent T cells exit the thymus during childhood and enter other lymphatic organs in the body. At older ages, the thymus is no longer necessary for T-cell related immune functions. - Finally, we will look at the palatine tonsils. Note the location of the tonsils at the posterior of the oral cavity. - The palatine tonsil is a dense accumulation of lymphatic tissue that lies within the connective tissue underneath the oral epithelium. It is poorly encapsulated and sits adjacent to mucous glands, skeletal muscle, and large vessels and nerves. - Stratified squamous epithelium lines the crypts of the oral cavity. - Note the germinal centers of the tonsils. There are both diffuse and nodular lymphatic tissue. - The lightly staining spots within the germinal center are macrophages, which are the major antigenpresenting cells of the palatine tonsil. They give the tonsil its distinct “starry sky” appearance, which helps in the identification of the tissue. - The macrophages in the bottom right panel are indicated by the big black arrows. Note the large vesicular nucleus with a conspicuous nucleolus.