14.5: Secondary (Peripheral) Lymphoid Organs

Lymph Nodes

Lymph nodes are clusters of lymphatic tissue located alongside the major lymph vessels. Much like the thymus, these small, bean-shaped structures are encased by a connective tissue capsule and divided into compartments by extensions known as trabeculae. Apart from the support provided by the capsule and trabeculae, the lymph node's structural framework includes reticular fibers.

The primary pathways into the lymph node are through afferent lymphatic vessels, as depicted in Figure 3. Exiting the lymph node, cells and lymph typically utilize another set of vessels called efferent lymphatic vessels. Lymph enters the lymph node through the subcapsular sinus, a space populated by dendritic cells, macrophages, and reticular fibers.

Within the cortex of the lymph node are lymphoid follicles, each consisting of germinal centers where B cells undergo rapid division, surrounded by a layer of T cells and other accessory cells. As lymph continues its course through the node, it proceeds into the medulla, which houses medullary cords composed of B cells, and medullary sinuses, where lymph gathers before departing the node via the efferent lymphatic vessels. Lymph nodes are important in cleansing lymphatic fluid by removing debris and pathogens, earning them the name "lymph filters''. Whenever bacteria infiltrate the interstitial fluid, lymphatic capillaries act, capturing and conveying them to a nearby regional lymph node. Within these nodes, dendritic cells and macrophages engulf and neutralize many pathogens that traverse the lymph node, effectively eliminating them from the body. Additionally, the lymph node serves as a central place for adaptive immune responses by T cells and B cells.

Figure 3 | Structure and Histology of a Lymph Node | ⁴ A histological image shows the subcapsular sinus where the lymph first collects. Lymphocytes in the cortex and follicles interact with lymph and undergo rapid mutation and proliferation in the region of the germinal centers. Finally they exit the lymph node by efferent lymphatic vessels. 

The Spleen

The spleen, characterized by its delicate structure and rich vascularization, lacks a capsule and presents a dark red appearance due to its extensive blood supply. This organ plays a key role as a major secondary lymphoid organ (Figure 4). Measuring approximately 12 cm (5 inches) in length, it is anchored to the stomach's lateral border via the gastrosplenic ligament.

Trabeculae of connective tissue subdivide the spleen, creating distinct regions. Each splenic nodule comprises the red pulp, primarily composed of red blood cells, and the white pulp, which resembles the lymphoid follicles found in lymph nodes. The marginal zone, positioned between the red and white pulp, serves as a boundary where antigens from circulation are captured and presented to lymphocytes in the white pulp.

The red pulp encompasses reticular fibers, fixed macrophages, free macrophages, and various blood cells, including some lymphocytes. In contrast, the white pulp surrounds a central arteriole and is composed of germinal centers rich in dividing B cells. This area is enveloped by T cells and accessory cells such as macrophages and dendritic cells. As a result, the red pulp predominantly operates as a filtration system for the blood, employing elements of the relatively nonspecific immune response. In contrast, the white pulp serves as the initiation site for adaptive T and B cell responses.

The spleen is often called the "blood filter" due to its extensive vasculature and the presence of macrophages and dendritic cells that clear microbes and other substances from the blood, including aging red blood cells. The spleen contributes to the recycling of red blood cells, along with the liver and bone marrow. Its rich vascularization and slow blood circulation allow it to store a significant volume of red blood cells, which can be released in scenarios like hypovolemia. Additionally, the spleen stores platelets and facilitates the removal of aged platelets from circulation. Approximately one-fourth of the total lymphocyte population can be harbored within the spleen. Moreover, the spleen serves as a hub for immune responses against blood-borne pathogens.

While the spleen assumes a crucial role in various functions, it is not indispensable for survival, and individuals can lead healthy lives without it. In its absence, other organs in the body, particularly the liver, adapt and enhance their capabilities to combat infections and eliminate aged red blood cells.

Figure 4 | The Spleen | ⁵ (a) The spleen is organized into red pulp and white pulp based on the distribution of blood and lymphocytes. Lymphocytes enter the spleen via the splenic artery and exit by the splenic vein. (b) A micrograph of spleen tissue shows the germinal center. 

Lymphoid Nodules

Lymphoid tissues, known as lymphoid nodules, exhibit a simpler structure than the spleen and lymph nodes. These nodules consist of densely packed lymphocytes without a surrounding fibrous capsule. Typically, they are situated in the respiratory and digestive tracts, regions frequently exposed to environmental pathogens. One significant example of lymphoid nodules is the tonsils, strategically positioned along the inner lining of the pharynx (Figure 5). Tonsils play a crucial role in developing immunity against oral pathogens. Among these tonsils, the pharyngeal tonsil, located at the rear of the throat, is sometimes referred to as the adenoid when it becomes swollen—a sign of an active immune response to infection. Additionally, there are paired lingual and palatine tonsils.

Histologically, the epithelial layer extends deeply into the tonsillar tissue to form tonsillar crypts. These structures accumulate various materials introduced into the body through ingestion and inhalation. Interestingly, these crypts serve as a "welcome mat" for pathogens, encouraging them to penetrate deep into the tonsillar tissues, where they encounter numerous lymphoid follicles and are subsequently eliminated. Thus, tonsils aid in identifying, eliminating, and developing immunity against common environmental pathogens, particularly during youth, to provide protection in later years. In cases where children experience recurrent throat infections, particularly involving the palatine tonsils located on either side of the pharynx, their tonsils may be removed, especially since the enlargement of these tonsils can obstruct breathing and swallowing.

Figure 5 | Locations and Histology of the Tonsils | ⁶ (a) The pharyngeal tonsil is located on the roof of the posterior superior wall of the nasopharynx. The palatine tonsils lay on each side of the pharynx. Lingual tonsils are situated on the posterior part of the back of the tongue on either side (b) A micrograph shows the palatine tonsil tissue.

Mucosa-associated lymphoid tissue (MALT) comprises collections of lymphoid follicles directly associated with the epithelial mucous membranes. MALT forms dome-shaped structures beneath the mucosa of various body regions, including the gastrointestinal tract, breast tissue, lungs, and eyes. Peyer's patches, a specific type of MALT found in the small intestine (Figure 6), are significant in initiating immune responses against substances ingested through the digestive system.¹   

Figure 6 | Mucosa-associated Lymphoid Tissue (MALT) Nodule | ⁷  A section of the intestinal mucosa shows Peyer’s patches which are organized lymphoid aggregates that form part of MALT.