Lymphatic system

The lymphatic system is the body's network of organs, ducts, and tissues that filter harmful substances out of the fluid that surrounds body tissues. Lymphatic organs include the bone marrow, thymus, spleen, appendix, tonsils, adenoids, lymph nodes, and Peyer's patches (in the small intestine). The thymus and bone marrow are called primary lymphatic organs, because lymphocytes are produced in them. The other lymphatic organs are called secondary lymphatic organs.

Lymphocytes are a type of white blood cell (wbc), which is highly concentrated in lymphatic fluid. This clear fluid, also called lymph, travels through the lymphatic vessels, which connect the lymphatic organs. The terminal lymphatic vessels feed into the thoracic duct that returns body fluids to the heart prior to blood reoxygenation. The reincorporated fluid originates in the bloodstream, bathes organs and tissues, and is returned to the bloodstream after passing through lymphatic filters that function as part of the body's defense system against infection and cancer .

Lymph nodes, primarily clustered in the neck, armpits, and pelvic area, are the system's battle stations against infection. Lymph nodes are connected to one another by lymphatic vessels. It is in the nodes and other secondary organs where wbcs engulf and destroy debris to prevent them from reentering the bloodstream. Of the other two major secondary lymphatic organs, the spleen removes dead red blood cells (rbcs), and Peyer's patches remove intestinal antigens (foreign or harmful substances in the body).

Lymphocytes

Lymphocytes are the lymphatic system's foot soldiers. These cells identify enemy particles and attempt to destroy them. Lymphocytes fall into two general categories: T lymphocytes (T cells ) and B lymphocytes (B cells). T cells form in the thymus (in the chest), and B cells form in the bone marrow of the long, thick bones of the thigh, arm, spine, or pelvis. While T cells primarily attack viral antigens, B cells attack bacterial antigens. Both T and B cells travel in lymph, through lymphatic vessels, and into lymph nodes.

T cells are further divided into three primary classes: helper T cells (T-H cells), cytotoxic T cells (ctx T cells), and T suppressor T cells. T-H cells augment B cell responses to bacterial antigens. Cytotoxic T cells attack viral antigens and some early cancer cells. And suppressor T cells halt immune cell functions, allowing the body to rest.

B cells produce antibodies. According to their basic immunoglobulin type, antibodies are subdivided into five classes (IgM, IgD, IgG, IgE, and IgA). B cell antibodies recognize specific bacterial invaders and destroy them. Certain antibodies are more concentrated in areas of the body where they are most needed. For example, IgA-producing B cells are most concentrated in the Peyer's patches where they sample intestinal contents for potential antigens that could signal an infectious invasion of food-borne bacteria .

Lymph nodes

Lymph nodes are pockets of lymph that orchestrate the removal of foreign material (including bacteria, viruses, and cancerous cells) from the lymph. They vary in size from microscopic to about 0.16 in (0.394 cm) in diameter. Some nodes cluster at key sites where the limbs join the torso. Lymph nodes are named after their locations in the body. The nodes at the arm are called axial and brachial, those under the jaw are called subclavian, and those in the groin are called inguinal. Fibrous connective tissue covers the lymphatic tissue inside the lymph node.

Each node, also called a lymph gland, has both arterial blood supply and venous drainage. Lymphocytes drain out of the arteries into the node interior, usually through a high endothelial venule that facilitates their entry. This venule (small vein) derives its name from the higher-than-usual tightly joined endothelial cells that line it.

Before they can enter the lymph node, lymphocytes are carefully selected from other blood cells. They are recognized and distinguished by a lymphocyte-cell surface protein called E-selectin. Receptors on the endothelial cells bind the E-selectin positive lymphocytes and slowly roll them toward a gap between adjacent cells. Then the lymphocyte is fed through this area much the way film is fed into a camera. The lymphocytes emerge on the interior of the node.

The internal lymph node tissue is separated into lobes. The lobe end at the center of the node is called the medulla, whereas the wider lobe end toward the perimeter of the node is called the cortex. The lobe area just next to the cortex is called the paracortex. Surrounding the lobes is an area called the medullary sinus. T cells are concentrated in the paracortex, whereas B cells primarily are concentrated in the cortex in structures called primary follicles. Lymphocytes first travel to the medullary sinus before migrating to the cortical and paracortical regions.

In addition to lymphocytes, several other kinds of antigen-fighting wbcs are contained within the nodes. Macrophages destroy and devour foreign antigens under direction from lymphocytes. Within the cortex, a large wbc called an interdigitating dendritic cell actually gathers the foreign antigen and presents it to the T cells that, in turn, trigger the antigen's destruction. This system is carefully controlled to avoid destroying host cells. Within the paracortex, follicular dendritic cells present antigens to B cells in a region of the follicles called the germinal centers. Within germinal centers, memory B cells are formed that are specifically primed to launch an attack against an antigen if it is encountered again. Like seasoned soldiers who know how to fight a particular enemy, memory B cells are molecularly armed to combat a known antigen.

Foreign antigens are constantly being destroyed; however, when a particularly strong infection occurs, the lymph nodes will sometimes swell with the influx of backup troops (more wbcs) sent in to help fight a particular molecular attacker. Eventually, the lymphocytes leave the node through the efferent lymphatic vessel.

Lymphatic vessels

Lymphatic vessels infiltrate tissues that are bathed in fluid released from blood into those tissues. Pockets of fluid collect in the tissues, and increased pressure allows the fluid to seep into the lymphatic vessels. Whereas blood vessels return deoxygenated blood to the heart to be pumped to the lungs for oxygen , lymphatic vessels return fluid that has leaked out of the capillaries into various tissues. However, before this lymphatic fluid is rejoined with venous fluid at the thoracic duct, it is filtered through the lymph nodes to remove infectious agents.

Lymphatic vessels are made up of single-cell epithelial layers that drain fluid away from tissue. Smooth muscles controlled by the autonomic nervous system direct the fluid away from tissues toward the lymph nodes and, eventually, the heart. The vessels contain one-way valves that close behind fluid traveling back to the heart so that lymphatic fluid cannot go backward. Lymphatic fluid is usually returned to the circulation within 24 hours. When the lymphatic vessels become clogged, stopped up, or blocked, severe edema (bloating due to water retention) can result in a condition known as lymphedema.

Other lymphatic organs

Of the remaining lymphatic system components, the thymus, bone marrow, spleen, and Peyer's patches have fairly unique roles. Both the bone marrow and thymus introduce "virgin" lymphocyte to the lymphatic system. The spleen filters old rbcs from the blood and fights infections with lymphocytes and monocytes (cells that engulf and devour antigens). And the Peyer's patches are lymph tissue pockets under raised intestinal projections that examine intestinal contents for foreign antigens. Although the spleen's role is important, the human body is capable of functioning without it if it becomes injured or diseased.

Although the thymus is critical for T cell development in children, it begins to shrink as they progress toward adulthood and thereafter plays an increasingly reduced role. T cells are "educated" in the thymus to recognize "self" versus "nonself" (foreign) antigens. Without the ability to recognize self-antigens, T cells would target a person's own tissues in a very destructive manner. The thymus is also responsible for fostering maturation of T cells into their various subclasses. T cells function in a cell-mediated way such that they only recognize antigens presented to them by other cells; hence, T cell immunity is called cell-mediated immunity.

Both T cells (before branching off to develop in the thymus) and B cells originate in the pluripotential stem cells of the bone marrow or the fetal liver. Pluripotential stem cells are the body's cellular sculpting clay. They can be shaped into any cell-including lymphocytes, rbcs, macrophages, and numerous other blood constituentsand become increasingly specialized as they reach maturity. The B cells can generate an infinite number of antibodies in response to a multitude of foreign antigens. This amazing diversity arises from the many combinations of antibody components that can be rearranged to recognize individual antigens. Once a B cell identifies a particular enemy, it undergoes a process called clonal expansion. During this process, it makes many clones (copies) of itself in order to fight several invaders of a single type. This highly sophisticated molecular process destroys infections wherever they arise in the body.

One specialized form of antibody, IgA, detects antigens in the gastrointestinal tract at Peyer's patches. IgA contained within small projections, called lamina propriae, that extend into the small intestine test the intestinal lining for pathogens . The IgA binds to the foreign antigen, returns to exit the patch at its efferent lymphatic vessel, and travels to a mesenteric lymph node that gears up to fight the invader. IgA antibodies are also passed to nursing babies in their mothers' milk, because newborns do not synthesize IgAs until later.

Lymphatic diseases

Although lymph nodes commonly enlarge to fight infection, an overwhelming infection can leave a lymph node and travel through the lymphatic system to other nodes and even to other body tissues. Cancer can spread very easily through the lymph system, but different cancers vary in how soon they attack the nodes. Lymphedema, fluid accumulation, can occur when the movement of fluid in a lymphatic region is blocked. Although lymphedema is rare, limbs are the most commonly affected areas.

The unregulated growth of cells and tissues of the lymphatic system can lead to lymphoma, or lymph cancer. Lymphomas are classified into two types, Hodgkin's or non-Hodgkin's, both of which can be malignant. Hodgkin's disease is marked by enlargement of lymph nodes, usually those in the neck. Symptoms of Hodgkin's include chronic fatigue, depressed immune function, weight loss, night sweats, and pain after drinking alcohol . Hodgkin's is diagnosed by lymph node biopsy, with identification confirmed by the presence of Reed-Sternberg cells, large multinucleated cells. Hodgkin's is further categorized as lymphocyte predominant, nodular sclerosis, mixed cellularity, or lymphocyte-depleted on the basis of the cell populations present in the biopsy sample. Hodgkin's can be successfully treated and cured with radiation or chemotherapy if it is caught in its early stages. Although the cause of Hodgkin's is unknown, males, Caucasians, people of higher socioeconomic status, the well-educated, and people with certain blood types are more prone to develop it. Hodgkin's most often affects people in their 20s or 70s for unknown reasons. People who work with certain chemicals, such as benzene and rubber products, also seem to be more prone to develop the disease .

Non-Hodgkin's lymphoma is also diagnosed through lymph tissue biopsy. Several lymphomas have been identified, but have little in common. Burkitt's lymphoma, prevalent among Central African children, is characterized by enlargement of the lymph nodes under the jaw. In contrast with most lymphomas whose causes are unclear, Burkitt's lymphoma has been linked to infection with the Epstein-Barr virus . Mycosis fungoides is a rare T cell lymphoma that affects the skin.

Non-Hodgkin's lymphomas are further classified as lymphocytic or histiocytic. Lymphocytic lymphomas may be poorly differentiated (according to the extent to which they have evolved from the pluri potential stem cell); they may also be nodular (concentrated) or diffuse.

Symptoms for most lymphomas are similar. Many patients experience enlargement of the liver and spleen as well as the lymph nodes. Some patients have bloody stools or vomit blood. Tiredness, itching, weight loss, fever, and general immunosuppression may also be present. The symptoms may abate and intensify over several months before a diagnosis is made. Sometimes, a bone marrow biopsy is also performed. Treatment includes radiation or chemotherapy with effectiveness varying according to severity of the lymphoma at the time of diagnosis. Bone marrow transplants have been effective against some advanced-stage lymphomas. The "cure" rate for non-Hodgkin's lymphomas is generally poorer than for Hodgkin's lymphomas.

See also Antibody and antigen; Immune system.

Resources

books

Alberts, B., D. Bray, J. Lewis, M. Raff, K. Roberts, and J. Watson, eds. Molecular Biology of the Cell. 3d ed. New York: Garland Publishing, 1994.

Marieb, Elaine Nicpon. Human Anatomy & Physiology. 5th ed. San Francisco: Benjamin/Cummings, 2000.

Louise Dickerson

KEY TERMS

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Lymph

—Lymphatic fluid, rich in white blood cells, that runs through the lymphatic vessels, lymph nodes, and other lymphatic organs.

Lymph node

—Region of lymphoid tissue along lymph vessels that filters harmful antigens from the blood and some tissues.

Lymphocyte

—A cell that functions as part of the lymphatic and immune systems by attacking specific invading substances.