The Lymphatic System and Immunity

Emma Gottlieb

February 10, 2011

Anatomy 1 Extra Credit

The Lymphatic System and Immunity

Introduction

An animal must defend itself against the many potentially dangerous viruses, bacteria, and other pathogens it encounters in the air, in food, and in water. It must also contend with abnormal body cells that may develop into cancer. Two major kinds of defense have evolved to counter these threats. The first, called innate immunity, is present before any exposure to pathogens and is effective from the time of birth. Innate defenses are largely nonspecific, quickly recognizing and responding to a broad range of microbes regardless of their precise identity. Innate immunity consists of eternal barriers formed by the skin and mucous membranes, plus a set of internal cellular and chemical defenses that combat infectious agents the breach the external barriers. Key players in these internal defenses are macrophages and other phagocytic cells, which ingest and then destroy pathogens.

The second major type of immunity is adaptive immunity. It develops only after exposure to inducing agents such as microbes, abnormal body cells, toxins, or other foreign substances. Acquired defenses are highly specific – that is, they can distinguish one inducing agent from another, even though they differ only slightly. This recognition is achieved by white blood cells called lymphocytes, which produce two general types of immune responses. In the humoral response, cells derived from B lymphocytes secrete defensive proteins called antibodies that bind to microbes and mark them for elimination. In the cell-mediated response, cytotoxic lymphocytes directly destroy infected body cells, cancer cells, and foreign tissue.

Lymphatic System Structure and Functions

The lymphatic system is a subsystem of the circulatory system in the vertebrate body that consists of a complex network of vessels, tissues, and organs. The lymphatic system helps maintain fluid balance in the body by collecting excess fluid and particulate matter from tissues and depositing them in the bloodstream. It also helps defend the body against infection by supplying disease-fighting cells called lymphocytes.

Functions of the Lymphatic System

The lymphatic system works in close cooperation with other body systems to perform these important functions:

1. The lymphatic system aids the immune system in destroying pathogens and filtering waste so that the lymph can be safely returned to the circulatory system. The immune system uses two lymphocytes, T cells and B cells. Cytotoxic T cells, which are activated by various cytokines, bind to and kill infected cells and cancer cells. B lymphocytes differentiate into plasma and secrete antibodies.
2. To remove excess fluid, waste, debris, dead blood cells, pathogens, cancer cells, and toxins from these cells and the tissue spaces between them.
3. The lymphatic system also works with the circulatory system to deliver nutrients, oxygen, and hormones from the blood to the cells that make up the tissues of the body.

Lymphatic Vessels and Lymph Circulation

Lymph is conveyed from the tissues to the venous bloodstream via the lymphatic vessels. On the way, it is filtered through lymphatic organs (spleen and thymus) and lymph nodes. Pressure within the walls of the lymph vessels is lower than that in blood vessels. Lymph flows more slowly than blood. The cells walls of the lymph vessels are more permeable than those of capillary walls of blood vessels. Thus, proteins that may have been delivered to the tissues by the blood stream, but that are too big to reenter the capillaries, along with waste products and large proteins synthesized in the local tissue cells, enter the lymphatic vessels for return to the bloodstream.

The fluid and proteins within the tissues begin their journey back to the bloodstream by passing into tiny lymphatic capillaries that infuse almost every tissue of the body. Only a few regions, including the epidermis of the skin, the mucous membranes, the bone marrow, and the central nervous system, are free of lymphatic capillaries, whereas regions such as the lungs, gut, genitourinary system, and dermis of the skin are densely packed with these vessels.

Lymphatic Capillaries

The diameter of lymphatic capillaries is larger than that of blood capillaries. The endothelial cells making up the walls of the capillaries have their ends to overlap which makes the capillary able to let fluid in but not back out. Pressure outside of the lymphatic capillaries causes cells to separate and allow interstitial fluid into the capillary. Once inside the capillary, the fluid cannot get back out because the pressure is now greater in the capillary and the cells pack together. Anchoring filaments are attached to the lymphatic capillaries and their elastic fibers anchor the epithelial cells of the capillary to the surrounding tissues. These are pulled when swelling occurs and more fluid has to be allowed in.

The small intestines contain lacteals, which are specialized forms of lymphatic capillaries. They carry dietary lipids into lymphatic vessels and then continue on to the blood. Chyle is the liquid that includes these lipids because now the appearance is a milky white instead of the normal clear, pale yellow color of lymph.

Lymph Trunks and Ducts

Once within the lymphatic system, the extracellular fluid, which is now called lymph, drains into larger vessels called the lymphatics. These vessels converge to form one of two large vessels called lymphatic trunks, which are connected to veins at the base of the neck. One of these trunks, the right lymphatic duct, drains the upper right portion of the body, returning lymph to the bloodstream via the right subclavian vein. The other trunk, the thoracic duct, drains the rest of the body into the left subclavian vein. Lymph is transported along the system of vessels by muscle contractions, and valves prevent lymph from flowing backward. The lymphatic vessels are punctuated at intervals by small masses of lymph tissue, called lymph nodes, that remove foreign materials such as infectious microorganisms from the lymph filtering through them.

There are five main lymphatic trunks in the body – the lumbar, intestinal, bronchomediastinal, subclavian, and jugular trunks. The lumbar trunks drain lymph from free lower limbs, the wall and viscera of the pelvis, the kidneys, the adrenal glands, and the abdominal wall. The intestinal trunk drains lymph from the stomach, intestines, pancreas, spleen, and part of the liver. The bronchiomediastinal trunks drain lymph from the thoracic wall, lung and heart. The subclavian trunks drain the free upper limbs.

After going through the lymph trunks, lymph travels to two main ducts, the thoracic duct and the right lymphatic duct. The thoracic duct is a vascular structure which recirculates lymph into the blood stream. It begins in the abdomen and tracks alongside the aorta and esophagus to eventually join with the left brachiocephalic vein. The thoracic duct begins as a dilation known as the cisterna chyli. This is the primary duct that returns lymph to blood. The thoracic duct collects lymph from the left side of the head, neck, and chest, the left free upper limb, and the entire body below the ribs. The right lymphatic duct is a vessel that conveys lymph from the right upper quadrant of the body into the bloodstream in the neck at the junction of the right internal jugular and the right subclavian veins. About 1.25 cm long, the duct courses over the medial border of the scalenus anterior. At its orifice are two semilunar valves that prevent venous blood from flowing backward into the duct. Lymph drains into the right lymphatic duct from numerous capillaries and vessels and from three lymphatic trunks in the right quadrant.

Formation and Flow of Lymph

Interstitial fluid that enters the lymphatic system through lymph capillaries in the interstitial spaces is called lymph. This substance is filtered through lymph nodes rich in white blood cells and then returned to the blood circulatory system through large lymph ducts. Lymph maintains the fluid level in the body, fights infection, and by filtering through the gastrointestinal tract, absorbs and transports fats.

In upright humans, up to 70% of the circulating blood volume is below the heart, with the vast majority of this blood being stored in the venous capacitance vessels. As the thin-walled veins readily distend with relatively small increases in transmural pressure, compensatory mechanisms must be present to prevent the blood from pooling in the extremities and aid in the return of blood to the heart. Two of the most widely accepted of these mechanisms are the respiratory muscle pump and the skeletal muscle pump. The respiratory muscle pump is the process by which pressure is changed during inhalation and exhalation. This system drives lymph from the abdominal region to the thoracic region during inhalation and the opposite way during exhalation. The skeletal muscle pump is the process by which skeletal muscle contractions apply pressure to lymphatic vessels and forces lymph toward the junction of the internal jugular and subclavian veins.

Lymphatic Organs and Tissues

The lymphatic system is commonly divided into the primary lymphoid organs, which are the sites of B and T cell maturation, and the secondary lymphoid organs, in which further differentiation of lymphocytes occurs. Primary lymphoid organs include the thymus, bone marrow, fetal liver, and, in birds, a structure called the bursa of Fabricius. In humans the thymus and bone marrow are the key players in immune function. All lymphocytes derive from stem cells in the bone marrow. Stem cells destined to become B lymphocytes remain in the bone marrow as they mature, while prospective T cells migrate to the thymus to undergo further growth. Mature B and T lymphocytes exit the primary lymphoid organs and are transported via the bloodstream to the secondary lymphoid organs, where they become activated by contact with foreign materials, such as particulate matter and infectious agents, called antigens in this context.

Thymus

The thymus is a pyramid-shaped lymphoid organ that, in humans, is immediately beneath the breastbone at the level of the heart. This organ is called thymus because its shape resembles that of a thyme leaf.

The thymus is divided into two lobes, lying on either side of the midline of the body, and into smaller divisions called lobules. It is covered by a dense connective tissue capsule, which sends fibers into the body of the thymus for support. The thymus tissue is distinguishable into an outer zone, the cortex, and an inner zone, the medulla.

The organ is composed principally of two types of cells, called, respectively, lymphocytes and reticular cells. The reticular cells form a loose meshwork, as in a lymph node, while the spaces between them are packed with lymphocytes. The cortex, characterized by its heavy lymphocyte concentration, is the site of much lymphocytic proliferation. Proliferation of lymphocytes in the thymus is distributed evenly throughout the cortex, instead of germinal centers, as occurs in other lymphoid tissue. Some of the daughter cells – called T (thymus derived) cells – that are produced in the cortex migrate to the medulla, where they enter the bloodstream through the medullary veins, adding to the lymphocytes seen in the peripheral blood and the lymphoid organs. Very few of these T cells actually survive in the cortex because they are screened for possible autoimmune functions and ultimately destroyed. The medulla also has thymic (Hassalls’s) corpuscles which are concentric layers of five or six epithelial cells. Their role is currently unknown.

During the involution, or shrinking, of the thymus after puberty, the cortex becomes thin. Lymphocytes disappear and are replaced by fat tissue from the partitions of the lobules. The process of involution is never complete, and the bits of thymus tissue that remain are probably sufficient to maintain its function.

The thymus differs structurally from other lymphoid organs in that is does not have lymphatic vessels draining into it. It is not a filter like the lymph nodes, which are situated so that microorganisms and other antigens are exposed to their cells. The thymic lymphocytes are sealed from the rest of the body by a continuous layer of epithelial cells that entirely surround the organ. While thus sequestered, the lymphocytes differentiate, or acquire the capabilities to perform specialized tasks.

Lymph Nodes

Lymph nodes are any of the small, bean-shaped masses of lymphoid tissue enclosed by a capsule of connective tissue that occur in association with the lymphatic vessels. As part of the lymphatic system, lymph nodes serve as filters for the blood, providing specialized tissues where foreign antigens can be trapped and exposed to cells of the immune system for destruction. They are typically found concentrated near junctions of the major lymphatic vessels, most prominently in the neck, groin, and armpits.

Each lymph node is divided into two general regions, the capsule and the cortex. The capsule is an outer layer of connective tissue. Underlying the capsule is the cortex, a region containing mostly inactivated B and T lymphocytes plus numerous accessory cells such as dendritic cells and macrophages. The cortex is further divided into two functional areas: the outer cortex and inner cortex, or paracortex. These regions surround an inner medulla, which consists primarily of activated antibody-secreting plasma cells.

Cells enter the lymph node through two primary routes. Lymph and its associated cells enter through the afferent lymphatic vessels, which drain into each node through its convex surface. These vessels may drain directly from th elymphatic capillaries, or they may be connected to a previous node. Lymphocytes generally enter through specialized blood vessels called high endothelial venules (HEVs). HEVs contain a single layer of large endothelial cells that possess surface receptors specific for B and T lymphocytes. As these cells pass through the HEVs, they bind to the receptors and are carried into the paracortex of the lymph node.

The structural divisions within a lymph node serve different purposes. Most of the lymphocytes within a node are “naive”—i.e., they have yet to encounter antigen—and therefore must migrate to regions where they will be most effective in recognizing foreign agents. B cells enter the paracortex through the HEVs and then migrate into the outer cortex and join specialized dendritic cells and macrophages to form follicles. Primary follicles consist of a resting B cellsurrounded by a loose network of dendritic cells. After encountering a foreign antigen, the B cell becomes activated and is surrounded by a more tightly packed association of dendritic cells and macrophages, forming a germinal center. The germinal center in turn is enclosed by a mantle zone—a ring of resting B cells and dendritic cells. The germinal center and mantle together compose a secondary follicle, which is the site of antigen-dependent B-cell maturation. The activated B cells then migrate through the paracortex to the medulla, where they proliferate as antibody-secreting plasma cells. T cells enter the lymph node through the HEVs and remain in the paracortex, where the cortical macrophages and dendritic cells present antigenic peptides to the naive T cells, stimulating them to become activated helper T cells or cytotoxic T lymphocytes. All activated lymphocytes migrate through the medulla and enter the lymphatic circulation through the efferent lymphatic vessel, which drains either into adjacent lymph nodes or ultimately into the thoracic duct, a major vessel of the lymphatic system.

The central role played by lymph nodes in filtering microorganisms and other undesired substances from the blood is critical to the functioning of the immune system but also makes lymph nodes vulnerable to cancer. As cancerous cells spread by metastasis, they can become trapped and concentrated in lymph nodes, where they proliferate. Virtually all cancers have the potential of spreading to lymph nodes, a condition that greatly complicates treatment. In most cases surgery alone will not remove the cancer from the nodes, and therefore postoperative radiation or chemotherapy is required.

Spleen

The spleen is an organ of the lymphatic system located in the left side of the abdominal cavity under the diaphragm, the muscular partition between the abdomen and the chest. In humans it is about the size of a fist and is well supplied with blood. As the lymph nodes are filters for the lymphatic circulation, the spleen is the primary filtering element for the blood. The organ also plays an important role in storing and releasing certain types of immune cells that mediate tissue inflammation.