Lymph nodes are found throughout the body, with common locations in the neck, axilla (armpit), groin, along major blood vessels, and in body cavities. These nodes consist of various immune cells like T and B lymphocytes, antigen-presenting cells (APCs), macrophages, dendritic cells, and stromal cells. They respond to antigens by initiating immune responses, including macrophages phagocytosing invading microorganisms.
Each lymph node is a small, soft structure, usually less than 3 cm in diameter, enclosed by a fibrous capsule often surrounded by fat. It has a convex surface pierced by one-way afferent lymph vessels that allow lymph to enter. The concave surface called the hilum, is where arteries, veins, and efferent lymph vessels enter and exit the node. These efferent vessels have valves to prevent lymph from flowing back into the node.
Histologically, a lymph node has three main regions: cortex, paracortex, and medulla. All three regions have sinusoids, which are enlarged spaces lined with endothelial cells, allowing lymph to flow through the node. These structural features are vital for the node’s immune function.
Cortex of Lymph Node:-
The lymph node is enclosed by a dense, irregular collagenous connective tissue capsule, which sends extensions (trabeculae) into the node’s interior, dividing the outer cortex into compartments. These compartments run along the node’s periphery, close to the hilum. The capsule thickens at the hilum, where entering vessels are surrounded by connective tissue. Within the node, there’s a three-dimensional network of reticular connective tissue forming its structural framework.
Afferent lymph vessels enter the node through the capsule on its convex surface and release lymph into the subcapsular sinus just beneath the capsule. This sinus connects to cortical sinuses, which run alongside trabeculae and ultimately lead lymph into medullary sinuses, from where it exits via efferent lymphatic vessels. These sinuses contain stellate reticular cells with processes contacting other cells and a squamous-like endothelium. Collagen fibers, coated by reticular cell processes, create a loose web within these sinuses, slowing lymph flow and enabling macrophages on reticular cells to phagocytose foreign particles.
Additional channels allow lymph to flow from the subcapsular and para-trabecular sinuses to perivenular channels surrounding high endothelial venules (HEVs) in the paracortex. These channels, called fibroblastic reticular cell conduits, are formed by fibroblastic reticular cells and fibrillin-coated collagen fibers, surrounded by dendritic cells and a packed population of naive T cells, mostly TH cells.
Lymphoid nodules come in two types: primary and secondary, with secondary nodules having germinal centers.
Primary nodules in the cortex are spherical clusters of B lymphocytes, including virgin B cells and B memory cells. They gather around follicular dendritic cells (FDCs) that form a three-dimensional network by connecting their processes. Some T cells are also present in these nodules. In certain cases, primary nodules have paler centers containing germinal centers, and they are then termed secondary lymphoid nodules. Secondary nodules only form in response to antigenic challenges and are believed to be where B memory cells and plasma cells are generated.
The outer part of the lymphoid nodule, known as the corona or mantle, contains a dense accumulation of small lymphocytes that migrate away from the germinal center.
Germinal centers within secondary nodules exhibit three zones:
Dark zone: Here, B cells, called centroblasts, rapidly proliferate without possessing surface immunoglobulins (sIgs).
Basal light zone: Centroblasts migrate here, acquire sIgs, switch their immunoglobulin class, and become centrocytes. These cells interact with antigen-bearing follicular dendritic cells, undergo hypermutation to enhance antibody production against the antigen, and those unable to produce the correct sIgs are directed into apoptosis and cleared by macrophages.
Apical light zone: Centrocytes that survive this process enter this zone, where they differentiate into either B memory cells or plasma cells before exiting the secondary follicle.
Paracortex of Lymph Nodes:-
The paracortex is the region of the lymph node located between the cortex and the medulla. It mainly contains T cells and fibroblastic reticular cells and is crucial for thymus-dependent immune responses.
In the paracortex, there’s a high concentration of T cells, and it sits between the medulla and the cortex, which is rich in follicles. Antigen-presenting cells (APCs), such as Langerhans cells from the skin or dendritic cells from mucosal tissues, migrate to the paracortex to present their antigen-antibody complexes (epitope-MHC II) to T helper cells. If T helper cells get activated, they multiply, expanding the paracortex’s width, which can even extend into the medulla. Newly formed T cells then move to the medullary sinuses, exit the lymph node, and head to areas with antigenic activity.
High endothelial venules (HEVs), which are postcapillary venules, are found in the paracortex. Lymphocytes leave the bloodstream by moving between the cuboidal cells that make up the unusual endothelium of HEVs and enter the lymph node’s tissue. B cells usually migrate to the outer cortex, while the majority of T cells remain in the paracortex.
Lymphocytes have selectins on their cell surfaces, which help them recognize the endothelial cells of HEVs and enable them to roll along the surface of these cells. When lymphocytes encounter additional signaling molecules on the endothelial cell surface, the selectins become activated, binding firmly to the endothelial cell and stopping the rolling motion. Through diapedesis, the lymphocyte then passes between the cuboidal endothelial cells, leaving the venule’s lumen and entering the lymph node’s parenchyma.
The medulla of Lymph Nodes:-
The medulla of the lymph node consists of large, winding lymph sinuses surrounded by clusters of lymphoid cells, forming structures called medullary cords.
Within the medullary cords, you’ll find a mix of lymphocytes, plasma cells, and macrophages, all interwoven with a network of reticular fibers and reticular cells. Lymphocytes migrate from the cortex and make their way into the medullary sinuses. From there, they enter the efferent lymphatic vessels, eventually leaving the lymph node.
Histological sections of the medulla also reveal the presence of trabeculae, which originate from the thickened capsule at the hilum. These trabeculae serve as conduits for blood vessels entering and exiting the lymph node.