Lymphatic System

The lymphatic system is an important part of our immune system and plays a major role in returning excess tissue fluid back into cardiovascular circulation. There are several organs in the lymphatic or lymphoid system that house immune cells (lymphocytes). The thymus, spleen, tonsils, and lymph nodes all provide sites for proliferation of B- and T-lymphocytes. When pathogens are identified by the immune system, B- and T- lymphocytes proliferate (make more cell copies). Lymph nodes in our axillary (armpit) and cervical (neck) region are close to the skin, so we can feel them more easily. It is common to feel a swollen lymph node when you are fighting an infection. This makes sense because we are asking the cells in these structures to rapidly make tons of immune system cells!

In this chapter we will focus on the histology of the lymph node. The lymph node serves as a filter for the fluid (lymph) being collected by our lymphatic vessels and returned to cardiovascular circulation. Multiple afferent (incoming) lymphatic vessels transport lymph into a lymph node, where it is filtered and cleansed. The entire lymph node is surrounded by a dense connective tissue covering called the capsule (Figure 1, pink fibers). The outer region of the lymph node is called the cortex, and the inner region is called the medulla.

Let’s first look at the structure of the cortex. Trabeculae of connective tissue divide the lymph node into smaller compartments called nodules (Figure 1, pink fibers). Each nodule has a similar structure. The vey center of the nodule contains a pale-staining circular shaped area called the germinal center (Figure 1, teal with pink dots). The germinal center is the side of B-lymphocyte proliferation. Surrounding the germinal center of the lymphoid follicle, is the site of T-lymphocyte proliferation (Figure 1, dark blue). Surrounding the lymphoid follicle is the subcapsular (“under the capsule”) sinus, which is full of resident macrophages. Lymph flows from the subcapsular sinus into the lymphoid nodule, allowing for contact  between the lymph and resident immune cells.

Figure 1: The lymph node with and without illustration overlay

The medulla is made up of reticular connective tissue. Reticular fibers create an elaborate fibrous meshwork, called medullary cords, that serve as a scaffold for immune cells which can be exposed to pathogens as lymph flows through the medullary sinus. Attached to the reticular fibers are lymphocytes and numerous macrophages, which can activate the immune system upon exposure to a pathogen. This elaborate meshwork is the reason why the lymph nodes are common sites of cancer metastasis. If a cancer cell breaks off from the tumor, it can travel through the lymphatic vessels and become stuck in a lymph node. The cancer cell continues dividing and the lymph node becomes a secondary tumor site.

Filtered and cleansed lymph (fluid) exits the lymph node through one or two efferent (outgoing) lymphatic vessels and continues its journey to rejoin the blood supply.

Review of reticular connective tissue

Reticular connective tissue is found in our lymphoid organs, including lymph nodes, spleen, and bone marrow. Reticular connective tissue is a specialized type of tissue found in locations that act as filters to trap cellular debris or pathogens (lymph nodes and spleen). The main fibers in reticular connective tissue are reticular fibers, which are a specialized type of collagen that forms branching networks (branches on a tree) instead of long, linear strands like we see in other types of connective tissue. These fibers, produced by reticulocytes (special type of fibroblasts), don’t stain very well with typical microscope stains (H&E, which stains pink and purple). Instead, silver stain is typically used, which gives reticular fibers a dark brown color. Reticular connective tissue contains two other types of immune cells: macrophages are found in loosely arranged areas, and lymphocytes are found in tightly packed areas. The cells in reticular connective tissue stain yellow/light orange.

Figure 2 shows reticular connective tissue with and without an illustration overlay. In the microscope image, reticular fibers appear brown and lymphocytes appear yellow/orange. In the illustration overlay, reticular fibers are drawn in purple and lymphocytes are drawn in pink.

Figure 2: Reticular connective tissue with and without illustration overlay

Chapter Illustrations By:

Juan Manuel Ramiro Diaz, Ph.D.