Lymphatic System Anatomy and Physiology

The lymphatic system is why a post-mastectomy patient swells in the arm, why a splenectomy patient is immunocompromised for life, and why you palpate nodes during assessment. It drains tissue fluid, absorbs dietary fat, and houses the cells that run your patient's immune defense. Know how it moves fluid and how it mounts a response, because both show up at the bedside.

Functions of the Lymphatic System

1. Fluid balance. Lymphatic vessels return to the blood the fluid that escapes the vascular system. About 30 liters (L) of fluid pass from the blood capillaries into the interstitial spaces each day, but only 27 L return from the interstitial spaces into the blood capillaries. If the extra 3 L stayed in the tissues, the result is edema, tissue damage, and eventually death. That remaining fluid enters the lymphatic capillaries, where it is called lymph.
2. Fat absorption. The lymphatic system absorbs fats and other substances from the digestive tract. Lacteals, special lymphatic vessels in the lining of the small intestine, take up fats and carry them through the lymphatic vessels to the venous circulation.
3. Body defense. Lymphoid tissues and organs house the phagocytic cells and lymphocytes that drive defense and disease resistance.

Anatomy of the Lymphatic System

The system has two semi-independent parts: a network of lymphatic vessels, and the lymphoid tissues and organs scattered through the body.

Lymphatic Vessels

The vessels form a drainage system that picks up excess tissue fluid, now called lymph.

• Lymphatics. Also called lymphatics, they form a one-way system: lymph flows only toward the heart.
• Lymph capillaries. Microscopic, blind-ended capillaries weave between tissue cells and blood capillaries in loose connective tissue and absorb the leaked fluid.
• Mini valves. The endothelial cells of the capillary walls overlap loosely into flaplike mini-valves that act as one-way swinging doors. Anchored by fine collagen fibers, the flaps gape open when interstitial fluid pressure is higher, letting fluid in.
• Lymphatic collecting vessels. Lymph moves from the capillaries through successively larger collecting vessels until it returns to the venous system through one of two large ducts in the thoracic region.
• Right lymphatic duct. Drains lymph from the right arm and the right side of the head and thorax.
• Thoracic duct. Receives lymph from the rest of the body. Both ducts empty into the subclavian vein on their own side.

Lymph Nodes

Lymph nodes protect the body by removing foreign material like bacteria and tumor cells from the lymphatic stream and by producing lymphocytes for the immune response.

• Macrophages. Engulf and destroy bacteria, viruses, and other foreign substances in the lymph before it returns to the blood.
• Lymphocytes. Collections of lymphocytes (a type of white blood cell) sit in the nodes and respond to foreign substances in the stream.
• Size and shape. Nodes vary, but most are kidney-shaped, less than 1 inch (approximately 2.5 cm) long, and buried in surrounding connective tissue.
• Trabeculae. A fibrous capsule surrounds each node, sending strands called trabeculae inward to divide it into compartments.
• Cortex. The outer cortex holds lymphocyte collections called follicles, many with dark-staining germinal centers.
• Plasma cells. Germinal centers enlarge when B cells generate daughter cells called plasma cells, which release antibodies.
• T cells. The rest of the cortical cells are T cells "in transit," circulating continuously between blood, nodes, and lymphatic stream on surveillance.
• Medulla. Phagocytic macrophages sit in the central medulla.
• Afferent lymphatic vessels. Lymph enters the convex side of the node through afferent vessels.
• Efferent lymphatic vessels. It flows through sinuses cutting through the node and exits at the indented hilum via efferent vessels.

Other Lymphoid Organs

Beyond nodes, the lymphoid organs include the spleen, thymus gland, tonsils, and Peyer's patches of the intestine, plus bits of lymphoid tissue in epithelial and connective tissues.

Spleen

The spleen is a soft, blood-rich organ that filters blood.

• Location. Left side of the abdominal cavity, just beneath the diaphragm, curling around the anterior stomach.
• Function. It filters and cleanses blood of bacteria, viruses, and debris, provides a site for lymphocyte proliferation and immune surveillance, and most importantly destroys worn-out red blood cells, returning some breakdown products to the liver.
• Fetal spleen. In the fetus the spleen is an important hematopoietic (blood-cell-forming) site, but the adult spleen produces only lymphocytes.

Thymus Gland

The thymus functions at peak levels only during youth.

• Location. A lymphoid mass low in the throat, overlying the heart.
• Function. Produces thymosin and other hormones that program certain lymphocytes for their protective roles.

Tonsils

The tonsils are small masses of lymphoid tissue ringing the pharynx in the mucosa.

• Function. Trap and remove bacteria and other foreign pathogens entering the throat.
• Tonsillitis. They work so efficiently that they sometimes congest with bacteria and turn red, swollen, and sore, a condition called tonsillitis.

Peyer's Patches

Peyer's patches resemble the tonsils.

• Location. In the wall of the small intestine.
• Function. Their macrophages capture and destroy the bacteria always present in the intestine, keeping them from penetrating the intestinal wall.
• MALT. Peyer's patches and the tonsils are part of the mucosa-associated lymphatic tissue (MALT), which guards the upper respiratory and digestive tracts against the constant entry of foreign matter.

Physiology of the Lymphatic System

Bacteria, viruses, and fungi land on the skin and enter the body's passageways constantly, and the patient stays healthy because of two defense systems working together.

Body Defenses

The body's defenses are the innate and the adaptive defense systems. Together they make up the immune system.

Innate Defense System

The innate (nonspecific) system responds immediately against all foreign substances. It refers to the mechanical barriers covering body surfaces plus the cells and chemicals that act on the initial battlefronts against invading pathogens.

Surface Membrane Barriers

The first line of defense is the skin and mucous membranes.

• Skin. While unbroken, the keratinized epidermis is a strong physical barrier to most microorganisms.
• Mucous membranes. Intact mucous membranes line all body cavities open to the exterior (digestive, respiratory, urinary, reproductive) and provide similar mechanical barriers.
• Protective secretions. These membranes also produce protective secretions: the acidic pH of skin secretions (pH 3-5) inhibits bacterial growth and sebum is toxic to bacteria; vaginal secretions of adult females are very acidic; the stomach mucosa secretes hydrochloric acid and protein-digesting enzymes that kill pathogens; saliva and lacrimal fluid contain lysozyme, an enzyme that destroys bacteria; and sticky mucus traps microorganisms entering the digestive and respiratory passageways.
• Structural modifications. Mucus-coated hairs in the nasal cavity trap inhaled particles, and the ciliated respiratory mucosa sweeps dust- and bacteria-laden mucus up toward the mouth, away from the lungs.
• Damage. Surface barriers get nicked by small cuts (brushing teeth, shaving), letting microorganisms into deeper tissues, where the internal innate mechanisms take over.

Internal Defenses: Cells and Chemicals

The second line of defense is a large set of cells and chemicals.

• Phagocytes. Macrophages or neutrophils engulf a foreign particle the way an amoeba ingests food: cytoplasmic extensions bind the particle, pull it inside a vacuole, fuse the vacuole with a lysosome, and digest the contents.
• Natural killer cells. A unique group of lymphocytes that police blood and lymph, lysing cancer cells and virus-infected cells before the adaptive system engages. They recognize certain sugars on the target surface and the lack of "self" markers, then attack the membrane and release a lytic chemical called perforins.
• Inflammatory response. A nonspecific response triggered whenever tissue is injured. The four cardinal signs of acute inflammation are redness, heat, swelling, and pain.
• Antimicrobial proteins. Complement is a group of plasma proteins that lyse microorganisms, enhance phagocytosis by opsonization, and intensify inflammation. Interferons are proteins released by virus-infected cells that protect uninfected cells from viral takeover and mobilize the immune system. Urine's normally acidic pH inhibits bacterial growth and flushes the lower urinary tract.
• Fever. An abnormally high body temperature, a systemic response to invading microorganisms. The body's thermostat normally sits at approximately 37 degrees Celsius but resets upward in response to pyrogens, chemicals secreted by white blood cells and macrophages exposed to foreign material.

The Inflammatory Process

• Chemical alarm. Injured cells release inflammatory chemicals, including histamine and kinins.
• Body's reaction. Histamine, kinins, and other chemicals dilate local blood vessels, make capillaries leaky, activate pain receptors, and draw phagocytes and white blood cells to the area (chemotaxis).
• Redness and heat. Vasodilation increases blood flow, producing the redness and heat.
• Edema and pain. Increased capillary permeability lets plasma leak into the tissue spaces, causing local edema (swelling) that also activates pain receptors.
• Limited joint movement. If the swollen area is a joint, function may drop temporarily, forcing the part to rest, which aids healing.

Adaptive Body Defenses

The adaptive (specific) defense system, the third line of defense, recognizes foreign molecules (antigens) and acts to inactivate or destroy them.

• Three key features. It is antigen-specific (acts against particular pathogens), systemic (not limited to the initial infection site), and has memory (mounts stronger attacks on previously encountered pathogens).
• Two arms. Humoral immunity (antibody-mediated) is provided by antibodies in the body's fluids. Cellular immunity (cell-mediated) uses lymphocytes as the protective living cells.

Antigens

An antigen (Ag) is any substance that mobilizes the immune system and provokes a response.

• Foreign intruders. Almost any foreign protein, nucleic acid, many large carbohydrates, and some lipids can act as antigens. Proteins are the strongest.
• Self-antigens. Our own cells are studded with protein self-antigens that do not trigger a response in us but are strongly antigenic to other people.
• Hapten. Small molecules are usually not antigenic, but when they link to our own proteins the immune system may treat the combination as foreign and mount a harmful attack. The small molecule is then called a hapten or incomplete antigen.

Cells of the Adaptive Defense System

The crucial cells are lymphocytes and macrophages.

Lymphocytes

Lymphocytes come in two types: B lymphocytes (B cells) and T lymphocytes (T cells).

• B lymphocytes. Produce antibodies and run humoral immunity.
• T lymphocytes. Non-antibody-producing cells that form the cell-mediated arm.
• Origin. Like all blood cells, lymphocytes originate from hemocytoblasts in red bone marrow.
• Immunocompetence. Whether a lymphocyte becomes a B cell or T cell depends on where it becomes immunocompetent, meaning able to respond to a specific antigen by binding it.
• Maturation of T cells. T cells arise from lymphocytes that migrate to the thymus and mature over 2 to 3 days under thymic hormones. Only those best at identifying foreign antigens survive.
• Self-tolerance. Lymphocytes that bind strongly with self-antigens are weeded out and destroyed, so self-tolerance is an essential part of a lymphocyte's education.
• Maturation of B cells. B cells develop immunocompetence in bone marrow, though the regulating factors are less understood.
• Migration. Once immunocompetent, T cells and B cells migrate to the lymph nodes, spleen, and loose connective tissues, where they meet antigens.
• Full maturation. When they bind a recognized antigen, they complete differentiation into fully mature T cells and B cells.

Macrophages

Macrophages arise from monocytes formed in the bone marrow and distribute through the lymphoid organs and connective tissues.

• Major role. Engulf foreign particles and clear them, then present fragments of those antigens on their surface for immunocompetent T cells to recognize.
• Cytokines. Secrete cytokines, proteins important in the immune response.
• Killer macrophages. Activated T cells release chemicals that turn macrophages into insatiable phagocytes, or killer macrophages.
• Location. Macrophages tend to stay fixed in the lymphoid organs while lymphocytes, especially T cells, circulate continuously.

Humoral (Antibody-Mediated) Immune Response

• Clonal selection. An immunocompetent but immature B lymphocyte completes development into a mature B cell when antigens bind its surface receptors. The binding activates the lymphocyte to switch on and undergo clonal selection.
• Primary humoral response. The resulting family of identical cells descended from one ancestor is a clone, and clone formation is the primary humoral response to that antigen.
• Plasma cells. Most clone members become plasma cells.
• Antibody production. After an initial lag, these antibody factories produce highly specific antibodies at about 2000 antibody molecules per second.
• Life span. This activity lasts only 4 to 5 days before the plasma cells die. Antibody levels peak about 10 days after the response begins, then slowly decline.
• Memory cells. Clone members that do not become plasma cells become long-lived memory cells. They carry immunological memory, so secondary humoral responses are faster, more prolonged, and more effective than the primary response.

Active and Passive Humoral Immunity

• Active immunity. When your B cells encounter antigens and produce antibodies, you show active immunity. It is naturally acquired during bacterial and viral infections and artificially acquired through vaccines.
• Vaccines. Vaccines spare us most signs and symptoms of the disease while their weakened antigens still stimulate antibody production and immunological memory.
• Booster shots. Boosters may intensify the response at later meetings with the same antigen.
• Passive immunity. Antibodies come from the serum of an immune human or animal donor. The B cells are never challenged, no immunological memory forms, and the borrowed protection ends as the antibodies degrade.
• Natural passive immunity. Conferred on a fetus when maternal antibodies cross the placenta, and after birth through breastfeeding.
• Artificial passive immunity. Conferred when one receives immune serum or gamma globulin.
• Monoclonal antibodies. Produced commercially from descendants of a single cell, they are pure preparations specific for one antigen only.

Antibodies

Antibodies, also called immunoglobulins (Igs), make up the gamma globulin fraction of blood proteins.

• Antibodies. Soluble proteins secreted by activated B cells or their plasma-cell offspring in response to an antigen, capable of binding that antigen specifically.
• Basic structure. Every antibody has four amino acid (polypeptide) chains linked by disulfide (sulfur-to-sulfur) bonds.
• Heavy chains. Two of the four chains are identical and contain approximately 400 amino acids each.
• Light chains. The other two chains are identical to each other and about half as long as the heavy chains.
• Antibody classes. Five major immunoglobulin classes: IgM, IgA, IgD, IgG, and IgE.
• IgD. Almost always attached to B cells, believed to be the surface receptor of immunocompetent B cells and important in B cell activation.
• IgM. Attached to B cells and free in plasma. On the membrane it serves as an antigen receptor. It is the first Ig class released to plasma during the primary response, a potent agglutinating agent, and fixes complement.
• IgG. The most abundant plasma antibody, 75% to 85% of circulating antibodies. Main antibody of both primary and secondary responses, crosses the placenta to give the fetus passive immunity, and fixes complement.
• IgA. Some in plasma; a dimer in secretions like saliva, tears, intestinal juice, and milk. Protects mucosal surfaces from pathogen attachment.
• IgE. Secreted by plasma cells in the skin, GI and respiratory mucosae, and tonsils. Binds mast cells and basophils and triggers release of histamine and other chemicals that mediate inflammation and certain allergic responses.
• Antibody function. Antibodies inactivate antigens by complement fixation, neutralization, agglutination, and precipitation.
• Complement fixation. Complement is the chief antibody weapon against cellular antigens, activated during innate defenses and very efficiently when bound to antibodies on cellular targets.
• Neutralization. Antibodies bind specific sites on bacterial exotoxins (toxic chemicals secreted by bacteria) or on viruses, blocking their harmful effects.
• Agglutination. When cross-linking involves cell-bound antigens, the foreign cells clump. This happens with mismatched blood transfusion and underlies blood-typing tests.
• Precipitation. When cross-linking involves soluble antigens, the complexes grow so large they become insoluble and settle out of solution.

Cellular (Cell-Mediated) Immune Response

Like B cells, immunocompetent T cells are activated to form a clone by binding a recognized antigen, but T cells cannot bind free antigens.

• Antigen presentation. A T cell must recognize "nonself" (the antigen fragment presented by a macrophage) and "self" (a specific glycoprotein on the macrophage surface) at the same time. Antigen binding alone does not sensitize a T cell; the macrophage must present the antigen in this "double handshake." This antigen presentation is essential for activation and clonal selection.
• Cytotoxic (killer) T cells. Specialize in killing virus-infected, cancer, and foreign graft cells, binding tightly to the target and releasing toxic perforins and granzymes from their granules.
• Helper T cells. The directors of the immune system. Once activated, they recruit other cells and release cytokines that stimulate cytotoxic T cells and B cells to grow and divide, attract protective white blood cells like neutrophils, and enhance macrophage phagocytosis.
• Regulatory T cells. Formerly called suppressor T cells, they release chemicals that suppress both T and B cell activity, winding down and stopping the response once the antigen is cleared.
• Memory cells. Most T cells in a given response die within a few days, but a few long-lived memory cells remain to provide immunological memory and a fast response to later invasions.

Lymphocyte Differentiation and Activation

• Immunocompetence. Lymphocytes destined to be T cells migrate from bone marrow to the thymus and gain immunocompetence there; B cells gain it in the bone marrow.
• Activation. After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes seed the infected connective tissues, where the antigen challenge fully activates them.
• Circulation. Activated lymphocytes circulate continuously through the bloodstream, lymph, and lymphoid organs.