Lymph node regions in the bodyThis drawing schematically depicts the major lymph nodes in the head and neck area that are likely to be enlarged on physical examination in patients with various local or systemic diseases. The major nodal groups are shown here in bold, with the areas draining into these nodal groups noted when appropriate. While enlargement of both the left and right supraclavicular lymph nodes may reflect disease in the thorax, left supraclavicular nodal enlargement, because of its drainage pattern, may also reflect the presence of abdominal involvement (ie, Virchow node).Normal lymph nodes are usually less than 1 cm in diameter and tend to be larger in adolescence than later in life.
A clinically useful approach is to classify lymphadenopathy as localized when it involves only one region, such as the neck or axilla, and generalized when it involves more than one region [1].
Lymph nodes are encapsulated and trabeculated organs with many afferent vessels and single/few efferents (“many ways in and only one way out!”).
The specific functions are determined by anatomic position within the node (cortex, medulla, and paracortex areas).
Exposure to antigen through a break in the skin or mucosa results in antigen being taken up by an antigen-presenting cell and carried via lymphatic channels to the nearest lymph node. Lymph channels course throughout the body except for the brain and the bones. Lymph enters the node through the afferent vessel and leaves through an efferent vessel. Because antigen-presenting cells pass through lymph nodes, they present antigen to lymphocytes residing there. Lymphocytes in a node are constantly being replaced by antigen-naïve lymphocytes from the blood. They are retained in the node via special homing receptors. B cells populate the lymphoid follicles in the cortex; T cells populate the paracortical regions. When a B cell encounters an antigen to which its surface immunoglobulin can bind, it stays in the follicle for a few days and forms a germinal center where the immunoglobulin gene is mutated in an effort to make an antibody with higher affinity for the antigen. The B cell then migrates to the medullary region, differentiates into a plasma cell, and secretes immunoglobulin into the efferent lymph.
1When a T cell in the node encounters an antigen it recognizes, it proliferates and joins the efferent lymph. The efferent lymph laden with antibodies and T cells specific for the inciting antigen passes through several nodes on its way to the thoracic duct, which drains lymph from most of the body. From the thoracic duct, lymph enters the bloodstream at the left subclavian vein. Lymph from the head and neck and the right arm drains into the right subclavian vein. From the bloodstream, the antibody and T cells localize to the site of infection.
Lymph node. Illustration showing the organization of B and T cells into specific zones.
Lymph node, normal. Normal size and appearance of germinal centers in the cortex, surrounded by a lymph node capsule and adjacent peri-lymph node adipose tissue.
++Lymph nodes are scattered in groups along lymphatic vessels in the neck, axilla, groin, thorax, and abdomen, they act as in-line filters of the lymph, removing antigens and cellular debris and adding Ig's.
Lymph nodes contain a light-staining region (germinal center) and a peripheral dark-staining region. The germinal center is key to the generation of a normal immune response.
Schematic diagram of lymph node structure. The rectangles in the center drawing are magnified in the upper and lower drawings.
A. Structure
Lymph nodes are often bean-shaped, with convex and concave surfaces (Fig. 14–2). The parenchyma consists of a peripheral cortex, adjacent to the convex surface, and a central medulla, lying near the depression (hilum) in the concave surface. The connective tissue capsule gives off trabeculae that penetrate between the cortical nodules and subdivide the cortex. Blood vessels enter and leave through the hilum.
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Cortex. The cortex stains darkly owing to the tight packing of lymphocytes. These are suspended in a reticular connective tissue network and arranged as a layer of typical secondary lymphoid nodules (containing primarily B cells) with germinal centers. The cortex also contains reticular cells, antigen-presenting follicular dendritic cells, macrophages, a few plasma cells, and some helper T cells.
Medulla. Lighter staining than the cortex, the medulla consists of cords of lymphoid tissue (medullary cords) separated by medullary sinuses. The lymphocytes are mainly small, less numerous than in the cortex, and concentrated in the cords. The cords are rich in reticular cells and fibers and contain many plasma cells that have migrated from the cortex.
Paracortical zone. This T-dependent region lies between the cortical lymphoid nodules and the medulla. It contains mainly T lymphocytes suspended in a reticular connective tissue network. B lymphocytes, plasma cells, macrophages, and antigen-presenting interdigitating dendritic cells also may be present. This zone is also characterized by many high endothelial (postcapillary) venules (HEVs). T lymphocytes bind selectively to HEVs in a two-stage process. L-selectins on the lymphocyte surface adhere loosely to receptors on the endothelial cell surface in HEVs. This association promotes tighter lymphocyte binding through integrins, initiating diapedesis. Attached T cells exit the blood to enter the paracortical zone by passing between the cuboidal endothelial cells.
Lymphatic vessels. Lymphatic vessels associated with lymph nodes are of two types. Both contain valves to ensure unidirectional lymph flow through the node. Afferent lymphatic vessels deliver lymph by penetrating the capsule at several points on the convex surface. Efferent lymphatic vessels carry filtered lymph away from the node, exiting through the hilum on the concave surface.
Sinuses and lymph flow. Lymph node sinuses filter lymph and direct its flow. Partly lined with reticular cells and many macrophages, they are not simply open spaces but are traversed by a mesh of reticular cells and fibers, macrophages, and follicular dendritic cells. The complex sieving action slows lymph flow to facilitate antigen removal. Lymph is delivered by the afferent vessels to the cuplike subcapsular sinus between the capsule and the cortical parenchyma. From here, it flows directly into the peritrabecular sinuses surrounding the trabeculae. It subsequently flows through the anastomotic network of medullary sinuses that converge on the efferent lymphatic vessels exiting through the hilum (Fig. 14–2).
Filtration of lymph. Cellular debris and antigens carried by incoming lymph are removed by the macrophages and follicular dendritic cells of the sinuses (similar cells are found in the cortical nodules and medullary cords). Lymphocytes carried by the lymph may flow through the nodes, contacting antigen-presenting cells and macrophages in the sinuses, or leave the sinuses and enter the parenchyma. Lymph reaching the efferent lymphatic vessels has been cleared of more than 90% of antigens and cellular debris. Less than 1% of the lymph passing through a node penetrates the nodules.
Lymphocyte production (lymphopoiesis). Stimulated by antigens removed from the lymph, T lymphocytes undergo blast transformation and clonal expansion and subsequently differentiate into effector and memory cells that recognize and respond to a specific antigen. T-lymphocyte effector cells seek and destroy the antigen, entering the sinuses and leaving the node through efferent vessels. The cells reenter the blood where the lymphatic vascular system empties into the venous system (11.V.C). Stimulated B lymphocytes enter the cortical nodules’ germinal centers to undergo the blast transformation that yields memory and effector (plasma) cells. Differentiated plasma cells migrate to the medullary cords. Memory B cells either return to the nodule's peripheral mantle zone or leave the node by entering the sinuses.
Immunoglobulin production. Most plasma cells remain in the medullary cords, secreting Igs into the lymph flowing through the medullary sinuses and exiting through the efferent lymphatic vessels. These Igs reach the blood as the lymph empties into the venous system in the neck.
Flow Through a Lymph Node
Afferent lymphatic vessel → subcapsular sinus → trabecular sinus → medullary sinus (filtration by macrophages) → efferent lymphatic vessel.
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Medulla: The medulla of the node consists primarily of cords (densely packed lymphocytes) and sinuses (reticular cells and macrophages/histiocytes).
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Paracortex: The area in the deep cortex containing the high endothelial venules where both B and T cells enter from the blood. T cells are concentrated within the paracortex; hence, when a cellular adaptive immune response occurs (T cell mediated), the paracortex enlarges.
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Cortex: The area where B cells migrate and arrange in follicles . The primary follicles are densely packed and dormant, whereas the secondary follicles (after activation by antigen response) are large and have pale germinal centers.
Bite cells on peripheral blood smear, which appear as if a macrophage took a bite out of them, are formed from the splenic macrophages removing Heinz bodies in such diseases as G6PD deficiency.
Lymph Nodes
++These are the smallest but most numerous encapsulated lymphoid organs. Scattered in groups along lymphatic vessels in the neck, axilla, groin, thorax, and abdomen, they act as in-line filters of the lymph, removing antigens and cellular debris and adding Ig's.
++Lymph nodes are often bean-shaped, with convex and concave surfaces (Fig. 14–2). The parenchyma consists of a peripheral cortex, adjacent to the convex surface, and a central medulla, lying near the depression (hilum) in the concave surface. The connective tissue capsule gives off trabeculae that penetrate between the cortical nodules and subdivide the cortex. Blood vessels enter and leave through the hilum.
++
Cortex. The cortex stains darkly owing to the tight packing of lymphocytes. These are suspended in a reticular connective tissue network and arranged as a layer of typical secondary lymphoid nodules (containing primarily B cells) with germinal centers. The cortex also contains reticular cells, antigen-presenting follicular dendritic cells, macrophages, a few plasma cells, and some helper T cells.
Medulla. Lighter staining than the cortex, the medulla consists of cords of lymphoid tissue (medullary cords) separated by medullary sinuses. The lymphocytes are mainly small, less numerous than in the cortex, and concentrated in the cords. The cords are rich in reticular cells and fibers and contain many plasma cells that have migrated from the cortex.
Paracortical zone. This T-dependent region lies between the cortical lymphoid nodules and the medulla. It contains mainly T lymphocytes suspended in a reticular connective tissue network. B lymphocytes, plasma cells, macrophages, and antigen-presenting interdigitating dendritic cells also may be present. This zone is also characterized by many high endothelial (postcapillary) venules (HEVs). T lymphocytes bind selectively to HEVs in a two-stage process. L-selectins on the lymphocyte surface adhere loosely to receptors on the endothelial cell surface in HEVs. This association promotes tighter lymphocyte binding through integrins, initiating diapedesis. Attached T cells exit the blood to enter the paracortical zone by passing between the cuboidal endothelial cells.
Lymphatic vessels. Lymphatic vessels associated with lymph nodes are of two types. Both contain valves to ensure unidirectional lymph flow through the node. Afferent lymphatic vessels deliver lymph by penetrating the capsule at several points on the convex surface. Efferent lymphatic vessels carry filtered lymph away from the node, exiting through the hilum on the concave surface.
Sinuses and lymph flow. Lymph node sinuses filter lymph and direct its flow. Partly lined with reticular cells and many macrophages, they are not simply open spaces but are traversed by a mesh of reticular cells and fibers, macrophages, and follicular dendritic cells. The complex sieving action slows lymph flow to facilitate antigen removal. Lymph is delivered by the afferent vessels to the cuplike subcapsular sinus between the capsule and the cortical parenchyma. From here, it flows directly into the peritrabecular sinuses surrounding the trabeculae. It subsequently flows through the anastomotic network of medullary sinuses that converge on the efferent lymphatic vessels exiting through the hilum (Fig. 14–2).
Filtration of lymph. Cellular debris and antigens carried by incoming lymph are removed by the macrophages and follicular dendritic cells of the sinuses (similar cells are found in the cortical nodules and medullary cords). Lymphocytes carried by the lymph may flow through the nodes, contacting antigen-presenting cells and macrophages in the sinuses, or leave the sinuses and enter the parenchyma. Lymph reaching the efferent lymphatic vessels has been cleared of more than 90% of antigens and cellular debris. Less than 1% of the lymph passing through a node penetrates the nodules.
Lymphocyte production (lymphopoiesis). Stimulated by antigens removed from the lymph, T lymphocytes undergo blast transformation and clonal expansion and subsequently differentiate into effector and memory cells that recognize and respond to a specific antigen. T-lymphocyte effector cells seek and destroy the antigen, entering the sinuses and leaving the node through efferent vessels. The cells reenter the blood where the lymphatic vascular system empties into the venous system (11.V.C). Stimulated B lymphocytes enter the cortical nodules’ germinal centers to undergo the blast transformation that yields memory and effector (plasma) cells. Differentiated plasma cells migrate to the medullary cords. Memory B cells either return to the nodule's peripheral mantle zone or leave the node by entering the sinuses.
Immunoglobulin production. Most plasma cells remain in the medullary cords, secreting Igs into the lymph flowing through the medullary sinuses and exiting through the efferent lymphatic vessels. These Igs reach the blood as the lymph empties into the venous system in the neck.
Lymph node, normal. Biopsy section. Normal size and appearance of germinal centers in the cortex, surrounded by a lymph node capsule and adjacent peri-lymph node adipose tissue.
Lymph node, normal. Biopsy section. High magnification. The border of a germinal center (variation in lymphocyte size) and the surrounding mantle zone (mostly small lymphocytes).
Lymph nodes act as a filter for the lymphatic fluid. With the exception of the central nervous system, all tissues contain lymphatic vessels that collect interstitial fluid (lymph). This low-pressure system delivers lymph to lymph nodes positioned along the lymphatic drainage system. Resting lymph nodes are small (<1.5 cm), encapsulated structures that contain highly organized collections of B lymphocytes, T lymphocytes, antigen-presenting dendritic cells, phagocytic macrophages, and antibody-producing plasma cells (Fig. 1-10). Lymph suffuses slowly through the lymph nodes, enabling its contents to be examined thoroughly by resident immune cells. As anyone who has had a sore throat and tender lymph nodes realizes, lymphadenopathy is common in many different types of acute and chronic immune reactions. Much less often lymphadenopathy is a presenting symptom of lymphoma, a malignancy of lymph node–homing B or T cells.
