The lymphatic part of the circulatory system is a compartmentalized network of vessels, cells, and specialized accessory organs (figure 1). It begins in the farthest reaches of the tissues as tiny capillaries that transport a special fluid (lymph) through an increasingly larger system of vessels and filters (lymph nodes). It eventually connects to major vessels that drain back into the regular circulatory system. Some major functions of the lymphatic or lymphoid system relating to immune defenses are:
1. to provide an additional route for the return of extracellular fluid to the circulatory system;
2. to help drain fluid that has accumulated due to the inflammatory response; and
3. to render surveillance, recognition, and protection against foreign materials through a system of lymphocytes, phagocytes, and antibodies.
Fig1. General components of the lymphatic system, showing drainage patterns and connections with the regular circulation. (a) A general depiction of the lymphatic system, a branching network of specialized vessels that extend into most regions of the body. It includes several types of supportive tissues and organs, including the lymph nodes, MALT, spleen, GALT, thymus gland, tonsils, and bone marrow. (b) Expanded view of the right breast and axillary lymphatic circulation. The right lymphatic duct receives lymph from the right axillary and head region and drains into the regular blood circulation at the right subclavian vein. On the left side of the body, there is a similar arrangement in which the thoracic lymphatic duct returns lymph from the remainder of the body at the left subclavian vein. Through these direct connections, all lymph eventually makes its way into circulating blood.
Lymphatic Fluid Lymph is a plasmalike liquid carried by the lymphatic circulation. It is formed when certain blood components move out of the blood vessels into the extracellular spaces and diffuse or migrate into the lymphatic capillaries. Because of this, the composition of lymph parallels that of plasma in many ways. It is made up of water, dissolved salts, and 2% to 5% protein (especially antibodies and albumin). Like blood, it also transports numerous white blood cells (especially lymphocytes) and miscellaneous materials such as fats, cellular debris, and infectious agents that have gained access to the tissue spaces. Unlike blood, red blood cells are not normally found in lymph.
Lymphatic Vessels The system of vessels that transport lymph is constructed along the lines of blood vessels (process figure 2). The tiniest vessels, lymphatic capillaries, accompany the blood capillaries. The lymphatic capillaries permeate all parts of the body except the central nervous system and certain organs such as bone, placenta, and thymus. Their thin walls have a single layer of epithelial cells similar to blood capillaries, with loose junctions that allow free entry of extracellular fluid that collects from the circulatory system. Lymphatic vessels are found in particularly high numbers in the hands and feet and around the areolae of the breast.
Process Figure 2 Scheme of circulation in the lymphatic vessels and lymph nodes.
Two important differences between the bloodstream and the lymphatic system should be mentioned (figure 3). First, given that one of the main functions of the lymphatic system is returning lymph to the circulation, lymph flows only in one direction, moving from the extremities toward the heart. Eventually it will be returned to the bloodstream through the thoracic duct and the right lymphatic duct near the base of the neck (see figure 1). The second difference concerns how lymph travels through the vessels of the lymphatic system. Whereas blood is transported through the body by means of a dedicated pump (the heart), lymph is moved only through the contraction of skeletal muscles that surround the lymphatic ducts. This dependence on muscle movement helps to explain the swelling of the hands and feet that sometimes occurs during the night (when muscles are inactive) yet goes away soon after waking.
Fig3. Comparison of the circulation patterns of the regular circulatory and lymphatic systems. The movement of lymphatic flow is in one direction (green) from lymphatic capillaries to collecting vessels and ducts to large lymphatic trunks to subclavian veins to the heart. The flow of blood, on the other hand, is cyclic, with blood continuously flowing through arteries to capillaries to veins to the heart and back around. With this combined system the lymphatics can collect excess tissue fluid and return it to the bloodstream. The two systems can also participate together in surveillance of the tissues for foreign invaders. Note: The lymphatic flow (green) is shown on only one side to keep the comparison uncluttered.
The parasitic infection filariasis presents a dramatic example of what happens when the lymphatic drainage is blocked by infectious agents. Filarial worms from the infection become caught in the lymph nodes and channels of the extremities and plug them up. This prevents lymph from flowing into the accessory ducts and back to the circulation. The buildup of lymph massively distorts limbs and other body parts such as the scrotum and breasts.
Lymphoid Organs Lymphatic organs and tissues with immune functions can be classified as primary and secondary, as summarized here:
Primary organs
Thymus gland
Bone marrow
Secondary organs and tissues
Lymph nodes
Spleen
MALT—mucosal-associated lymphoid tissue
GALT—gut-associated lymphoid tissue (Peyer’s patches)
The primary lymphoid organs include the thymus and bone marrow, locations where lymphocytes are formed or reside. They are the sites of origin and maturation of lymphocytes—white blood cells with specific immune function. They subsequently release these cells to populate the secondary lymphatic sites.
Secondary lymphoid organs, such as the spleen and lymph nodes, are circulatory-based locations where encounters with microbes and immune responses often take place. Associated lymphoid tissues are collections of cells widely dispersed throughout body tissues such as the skin and mucous membranes, ready to react with any locally entering infectious agents.
The Thymus Gland The thymus originates in the embryo as two lobes in the pharyngeal region that fuse into a triangular structure. It is located in the thoracic cavity near the tip of the sternum. The size of the thymus is greatest proportionately at birth (figure3 ), and it continues to exhibit high rates of activity and growth until puberty, after which it begins to shrink gradually through adulthood.
Fig3. The thymus gland. Immediately after birth, the thymus is a large organ that nearly fills the region over the midline of the upper thoracic region. In the adult, however, it is proportionately smaller. Section shows the main anatomical regions of the thymus. Immature T cells enter through the cortex and migrate into the medulla as they mature.
BJI/Blue Jean Images/Getty Images; (Inset): Alvin Telser/McGraw Hill
Children born without a complete thymus (DiGeorge syndrome) or who have had their thymus surgically removed are severely immunodeficient and fail to thrive. Adults have developed enough mature T cells that removal of the thymus or reduction in its function has milder effects. Do not confuse the thymus with the thyroid gland, which is located in the cervical region near the larynx and has an entirely different function.
Lymph Nodes Lymph nodes are small, encapsulated, bean-shaped organs stationed, usually in clusters, along lymphatic channels and large blood vessels of the thoracic and abdominal cavities (see figure 1). Major aggregations of nodes occur in the loose connective tissue of the armpit (axillary nodes), groin (inguinal nodes), and neck (cervical nodes). Both the location and the architecture of these nodes clearly specialize them for filtering out materials that have entered the lymph and providing appropriate cells and niches for immune reactions.
Spleen The spleen is a lymphoid organ in the upper portion of the abdominal cavity nestled below the diaphragm and left of the stomach. It is somewhat similar to a lymph node except that it serves as a filter for blood instead of lymph. While the spleen’s primary function is to remove worn-out red blood cells from circulation, its most important immunologic function centers on the filtering of pathogens from the blood and their subsequent phagocytosis by resident macrophages. Adults whose spleens have been surgically removed can live a relatively normal life, but children who have failed to develop or lost their spleen are severely immunocompromised.
Associated Lymphoid Tissue Embedded throughout systems lined with mucous membranes are discrete bundles of lymphocytes and other white blood cells termed the mucosal-associated lymphoid tissue, or MALT. The positioning of this widespread system pro vides a local, rapid mechanism for responding to the constant influx of microbes entering via the gastrointestinal, respiratory, urinary, and other portals of entry. The pharynx houses a prominent source of MALT in the form of tonsils. The breasts of pregnant and lactating women also become temporary sites of lymphoid tissues that add protective antibodies to breast milk.
MALT is further divided into more than a dozen categories, based on where the specific lymphoid tissue is found. The most important example of this is the gut-associated lymphoid tissue, or GALT. GALT includes the appendix and Peyer’s patches, compact aggregations of lymphocytes in the ileum of the small intestine. GALT provides immune functions against intestinal pathogens and is a significant source of some types of antibodies. Other, less well- organized collections of secondary lymphoid tissue include skin- associated lymphoid tissue and bronchial-associated lymphoid tissue.
