The Lymphatic System and Immunity Chapter 15 The Lymphatic System and Immunity

Objectives Describe general functions of the lymphatic system and list the main lymphatic structures Compare nonspecific and specific, inherited and acquired, and active and passive immunity Name the major disorders associated with the lymphatic system

Objectives Discuss the major types of immune system molecules and indicate how antibodies and complement proteins function Discuss and contrast the development and functions of B and T cells Compare and contrast humoral and cell-mediated immunity

Objectives Describe the mechanisms of allergy, autoimmunity, and isoimmunity List the major types of immune deficiencies and explain their causes

The Lymphatic System Lymph—fluid in the tissue spaces that carries protein molecules and other substances back to the blood Many substances that cannot enter the capillary walls of blood vessels, such as protein molecules and excess fluid, are returned to the bloodstream as lymph. Lymph is a specialized fluid that, like blood, flows through its own elaborate set of lymphatic vessels. What is the role of lymph nodes in the spread of cancer? The lymph nodes may contain cancer cells filtered out of the lymph that drains from a cancerous area. These cells from a single tumor may spread to other areas of the body through the lymphatic system. What is lymph? How does lymph form? Lymph is a fluid formed in the tissue spaces that is transported by way of lymphatic vessels to reenter the circulatory system. Blood plasma filters out of the capillaries into the microscopic spaces between tissue cells because of the pressure generated by the pumping action of the heart (interstitial fluid).

The Lymphatic System Lymphatic vessels—permit only one-way movement of lymph Lymphatic capillaries—tiny blind-ended tubes distributed in tissue spaces Microscopic in size Sheets consisting of one cell layer of simple squamous epithelium Poor “fit” between adjacent cells results in porous walls Called lacteals in the intestinal wall (for fat transportation) Lymphatic vessels may have the appearance of a string of beads because of the presence of numerous valves that ensure one-way flow of lymph through the vessel. Ask students to compare and contrast the structure of the lymphatic vessels with those of the circulatory system. What is interstitial fluid? As lymph is formed, it is called interstitial fluid.

Principal organs of the lymphatic system.

Role of lymphatic system in fluid homeostasis Role of lymphatic system in fluid homeostasis. Fluid from blood plasma that is not reabsorbed by blood vessels drains into lymphatic vessels. Lymphatic drainage prevents accumulation of too much tissue fluid.

The Lymphatic System Lymphatic vessels Right lymphatic duct Drains lymph from the right upper extremity and right side of head, neck, and upper torso Thoracic duct Largest lymphatic vessel Has an enlarged pouch along its course, called cisterna chyli Drains lymph from about three fourths of the body Lymph flows from the small lymphatic venules to progressively larger lymphatic veins and finally to one of two ducts, depending on the position in the body. These are the only two ducts that drain lymph from the body.

Lymph drainage. The right lymphatic duct drains lymph from the upper right quarter of the body into the right subclavian vein. The thoracic duct drains lymph from the rest of the body into the left subclavian vein.

The Lymphatic System Lymphedema—swelling (edema) of tissues caused by blockage of lymphatic vessels Lymphangitis—inflammation of lymphatic vessels, may progress to septicemia (blood infection) Elephantiasis—severe lymphedema of limbs resulting from parasite infestation of lymphatic vessels Which lymphatic duct drains most of the body? Thoracic duct What is the function of the cisterna chyli? The thoracic duct has an enlarged pouchlike structure in the abdomen (cisterna chyli) that serves as a storage area for lymph moving toward its point of entry into the venous system. What are lacteals? Lymphatic capillaries in the wall of the small intestine that transport fats from digested food to the bloodstream.

Lymphedema. Notice the significant swelling in the subject’s right leg and foot. (Courtesy Walter Tunnesen, MD, The American Board of Pediatrics, Chapel Hill, NC.)

Lymphangitis. This condition is characterized by inflamed lymphatic vessels that appear as red streaks radiating from the source of infection. (From Zitelli BJ, Davis HW: Atlas of pediatric physical diagnosis, ed 4, Philadelphia, 2002, Mosby.) Elephantiasis. Lymphedema caused by prolonged infestation by Filaria worms produces elephant-like limbs. (From Goldstein B, editor: Practical dermatology, ed 2, St Louis, 1997, Mosby.)

The Lymphatic System Lymph nodes Filter lymph Located in clusters along the pathway of lymphatic vessels Lymphoid tissue—mass of lymphocytes and related cells inside a lymphoid organ; provides immune function and development of immune cells Lymph nodes and other lymphoid organs have functions that include defense and WBC formation Why are lymph nodes often removed during surgery for breast cancer? To ascertain whether any cancerous cells have moved beyond the original tumor site. What are the consequences of removal of regional lymph nodes in breast cancer therapy? There is a greater risk for lymphedema. Afferent = “to carry forward” from Latin. Efferent = “to carry away.” If lymph accumulates in tissues as a result of partially blocked lymph vessels, lymphangitis might occur, which can cause blood poisoning or death.

Lymph node. A, Structure of a lymph node Lymph node. A, Structure of a lymph node. B, Diagram of a skin section in which an infection surrounds a hair follicle. The yellow areas represent dead and dying cells (pus). The black dots around the yellow areas represent bacteria. Bacteria entering the lymph node via the afferent lymphatics are filtered out.

Lymphangiogram. A special dye that is opaque to x rays is injected into the tissue fluids that drain into the inguinal and pelvic lymphatic pathways. Thus the outlines of the lymphatic vessels and lymph nodes can be visualized. (Courtesy Ballinger P, Frank E: Merrill’s atlas of radiographic positions and radiologic procedures, vol 1, ed 10, St Louis, 2003, Mosby.)

Lymphatic drainage of the breast Lymphatic drainage of the breast. Note the extensive network of nodes that receive lymph from the breast.

The Lymphatic System Lymph nodes Flow of lymph: to node via several afferent lymphatic vessels and drained from node by a single efferent lymphatic vessel Lymphadenitis—swelling and tenderness of lymph nodes Cancer cells can easily move through lymphatic vessels to other parts of the body in a process called metastasis

Lymphatic metastasis. This cluster of cancer cells moving through a lymphatic vessel may eventually start another cancerous tumor in another part of the body. (From Stevens A, Lowe JS, Young B: Wheater’s basic histopathology, ed 4, Edinburgh, 2002, Churchill Livingstone.)

The Lymphatic System Lymphoma—malignant tumor of lymph nodes Thymus Two types: Hodgkin disease and non-Hodgkin lymphoma Thymus Lymphoid tissue organ located in mediastinum Total weight of about 35–40 g—a little more than an ounce

The Lymphatic System Thymus Plays a vital and central role in immunity Produces T lymphocytes or T cells Secretes hormone called thymosin Lymphoid tissue is largely replaced by fat in the process called involution Thymosins stimulate the development of what? T lymphocytes, T cells What function do T cells perform? Critical to functioning of the immune system What would you expect the course of therapy to be if a baby were born without a thymus gland? Treatment to address immunity would be essential.

The Lymphatic System Tonsils Composed of three masses of lymphoid tissue around the openings of the mouth and throat Palatine tonsils (“the tonsils”) Pharyngeal tonsils (adenoids) Lingual tonsils Subject to chronic infection Enlargement of pharyngeal tonsils may impair breathing Where is each type of tonsil located? Palatine tonsils are located on each side of the throat; pharyngeal tonsils, also known as adenoids, are near the posterior opening of the nasal cavity; lingual tonsils are near the base of the tongue. Why would you try to avoid removal of the tonsils if at all possible? Tonsils serve as the first line of defense from the exterior.

Location of the tonsils Location of the tonsils. Small segments of the roof and floor of the mouth have been removed to show the protective ring of tonsils (lymphoid tissue) around the internal opening of the nose and throat.

The Lymphatic System Spleen Largest lymphoid organ in body Located in upper left quadrant of abdomen Often injured by trauma to abdomen Surgical removal called splenectomy Functions include phagocytosis of bacteria and old RBCs; acts as a blood reservoir Splenomegaly—enlargement of the spleen How much blood can the spleen contain? About 500 mL of blood What does the spleen salvage from RBC hemoglobin and store for future use? Iron What are the consequences of splenectomy? If the spleen has been damaged, removal will help stop the loss of blood.

The Immune System Protects body from pathological bacteria, foreign tissue cells, and cancerous cells Made up of defensive cells and molecules Nonspecific immunity Skin—mechanical barrier to bacteria and other harmful agents How does the immune system differ from most other systems of the body? It’s made up of cells and molecules rather than organs. What is an example of a nonspecific form of immunity? Phagocytosis of bacteria by WBCs.

The Immune System Nonspecific immunity Tears and mucus—wash eyes and trap and kill bacteria Inflammation attracts immune cells to site of injury, increases local blood flow, increases vascular permeability; promotes movement of WBCs to site of injury or infection What can you do to prevent the spread of infection that involves the body’s first line of defense? Wash your hands!

The Immune System Specific immunity—ability of body to recognize, respond to, and remember harmful substances or bacteria Inherited or inborn immunity—inherited immunity to certain diseases from time of birth Describe what happens when a cut gets infected. An inflammatory response produces heat and redness (from increased blood flow to the area) and pain and swelling (from the increased vascular permeability). What causes the swelling? What causes the redness? Increased blood flow What causes the discomfort? Increased capillary permeability Specific immunity involves memory—the second time a person is exposed to the offending organism, no symptoms occur because the organism is quickly recognized and destroyed.

Inflammatory response Inflammatory response. In this example, bacterial infection triggers a set of responses that tend to inhibit or destroy the bacteria.

The Immune System Acquired immunity Natural immunity—exposure to causative agent is not deliberate Active—active disease produces immunity Passive—immunity passes from mother to fetus through placenta or from mother to child through mother’s milk Ask the students for examples of active immunity. Active immunity develops as a result of contracting childhood diseases such as measles. How long is passive immunity effective after birth? Approximately 3-6 months Which immunity lasts longer—active immunity or passive immunity? Active

The Immune System Acquired immunity Artificial immunity—exposure to causative agent is deliberate Active—vaccination results in immunity Passive—protective material developed in another individual’s immune system and given to previously nonimmune individual What is an example of artificial immunity? Immunization What are the pros and cons of passive artificial immunity, and in what situations is it likely to be used? See Table 15-1.

Immune System Molecules Antibodies Protein compounds with specific combining sites Combining sites attach antibodies to specific antigens (foreign proteins), forming antigen-antibody complex—called humoral or antibody-mediated immunity Antigen-antibody complexes may: Neutralize toxins Clump or agglutinate enemy cells Promote phagocytosis

Antibody function. Antibodies produce humoral immunity by binding to specific antigens to form antigen-antibody complexes. These complexes produce a variety of changes that inactivate or kill threatening cells.

Immune System Molecules Complement proteins Group of proteins normally present in blood in inactive state Complement cascade Important mechanism of action for antibodies Complement-binding sites on antibody are exposed after attaching to antigen Complement triggers a series (cascade) of reactions that produce tiny protein rings that create holes in the surface of a foreign cell Complement cascade: Shape of antibody may be slightly altered when it binds to an antigen or foreign cell. This exposes two hidden regions on the antibody called complement-binding sites. A doughnut-shaped assemblage is formed by the combination of antibody, antigen, plasma membrane, and complement molecules. This initiates a series of events that kill the invading cell. Annihilation of the invader is accomplished by drilling holes in the plasma membrane allowing sodium to diffuse into the cell. Water follows by osmosis and the cell literally bursts.

Immune System Molecules Complement proteins Complement cascade Ultimately causes cell lysis by permitting entry of water through a defect created in the plasma membrane of the foreign cell Complement proteins play many other roles in immunity, including the inflammatory response

Effect of the complement cascade Effect of the complement cascade. A, Complement molecules activated by antibodies form doughnut-shaped complexes in a bacterium’s plasma membrane. B, Holes in the complement complex allow sodium (Na+) and then water (H2O) to diff use into the bacterium. C, After enough water has entered, the swollen bacterium bursts.

Immune System Cells Phagocytes Types Neutrophils—short-lived phagocytic cells Monocytes—develop into phagocytic macrophages and migrate to tissues (Figure 15-15) Dendritic cells (DCs)—often found at or near external surfaces Where do phagocytes and lymphocytes originate? From bone marrow cells When do phagocytes wander out of the blood and into the tissue? In response to infection What do monocytes develop into once they enter tissues? Macrophages

Phagocytosis. This series of scanning electron micrographs shows the progressive steps in phagocytosis of damaged red blood cells (RBCs) by a macrophage. A, RBCs (R) attach to the macrophage (M). B, Plasma membrane of the macrophage begins to enclose the RBC. C, The RBCs are almost totally ingested by the macrophage. (Courtesy Emma Shelton.)

Immune System Cells Phagocytes Ingest and destroy foreign cells or other harmful substances via phagocytosis Macrophages and DCs act as antigen-presenting cells (APCs) by displaying ingested antigens on their outer surface to trigger specific immune cells

Immune System Cells Lymphocytes Most numerous of immune system cells Development of B cells—primitive stem cells migrate from bone marrow and go through two stages of development

B-cell development. B-cell development takes place in two stages B-cell development. B-cell development takes place in two stages. First stage: shortly before and after birth, stem cells development into immature B cells, which then mature into inactive B cells that migrate to lymphoid organs. Second stage (occurs only if inactive B cell contacts its specific antigen): inactiveB cell develops into activated B cell, which divides rapidly and repeatedly to form a clone of plasma cells and a clone of memory cells. Plasma cells secrete antibodies capable of combining with specific antigen that caused inactive B cell to develop into active B cell. Stem cells maintain a constant population of newly differentiating inactive B cells.

Immune System Cells Lymphocytes Development of B cells First stage—stem cells develop into immature B cells Takes place in the liver and bone marrow before birth and in the bone marrow only in adults B cells are small lymphocytes with antibody molecules (which they have synthesized) in their plasma membranes After they mature, inactive B cells migrate chiefly to lymph nodes How many lymphocytes are in the body? Several million Where are dense populations of lymphocytes found? In the lymph nodes, spleen, thymus, and liver, but also found in all body fluids. What are lymphocytes responsible for? Antibody production What is an important source of stem cells? Bone marrow What is the role of a bone marrow transplant in cancer treatments? To try to replace stem cells

Immune System Cells Development of B cells Second stage—inactive B cell develops into activated B cell Initiated by inactive B cell’s contact with antigens, which bind to its surface antibodies, plus signal chemicals from T cells Activated B cell, by dividing repeatedly, forms two clones of cells—plasma (effector) cells and memory cells Plasma cells secrete antibodies into blood; memory cells are stored in lymph nodes If subsequent exposure to antigen that activated B cell occurs, memory cells become plasma cells and secrete antibodies What is the function of plasma cells? Secrete antibodies into blood What is the function of memory cells? They can become plasma cells and secrete antibodies

Immune System Cells Function of B cells—indirectly, B cells produce humoral immunity Activated B cells develop into plasma cells Plasma cells secrete antibodies into the blood Circulating antibodies produce humoral immunity

Immune System Cells Development of T cells—stem cells from bone marrow migrate to thymus gland First stage—stem cells develop into T cells Occurs in thymus during few months before and after birth T cells migrate chiefly to lymph nodes Second stage—T cells develop into activated T cells Occurs when, and if, antigen binds to T cell’s surface proteins and chemical signal received from another T cell As with B cells, clones made up of effector cells and memory cells are formed Discuss the significance of the development of monoclonal antibody techniques. What is the principle on which the early pregnancy test kit is based? Detection of chorionic gonadotropin in the urine

T-cell development. The first stage takes place in the thymus gland shortly before and after birth. Stem cells maintain a constant population of newly differentiating cells as they are needed. The second stage occurs only if a T cell contacts antigen, which combines with certain proteins on the T cell’s surface.

Immune System Cells Functions of T cells—produce cell-mediated immunity Cytotoxic T cells—kill infected or tumor cells by releasing a substance that poisons infected or tumor cells Helper T cells—release chemicals that attract and activate macrophages to kill cells by phagocytosis; produce chemicals that help activate B cells Regulatory T cells—release chemicals to suppress immune responses What happens when T-cell function is impaired? Cell-mediated immunity is affected Describe the effect of AIDS on T cells. The HIV virus contains RNA that undergoes reverse transcription inside affected cells to form its own DNA. The viral DNA becomes part of the cell’s DNA and steals raw materials from the cell. The cell is destroyed and immunity is impaired. As the T cell dies, it releases new retroviruses that can spread the HIV infection. What is interferon? What is its clinical significance?

T cells. The blue spheres seen in this scanning electron microscope view are T cells attacking a much larger cancer cell. The cells are a significant part of our defense against cancer and other types of foreign cells. (Courtesy James T Barrett.)

T-cell function. Activated T cells produce cell-mediated immunity by releasing various compounds in the vicinity of infected or tumor cells. Some compounds act directly, and some act indirectly, on these cells.

Hypersensitivity of the Immune System Inappropriate or excessive immune response Allergy—hypersensitivity to harmless environmental antigens (allergens) Immediate allergic responses usually involve humoral immunity Delayed allergic responses usually involve cell-mediated immunity What is antibody-mediated immunity? Resistance to disease organisms as a result of circulating antibodies What is cell-mediated immunity? Resistance to disease organisms as a result of actions of cells Hypersensitivity is an inappropriate or excessive immune response. What are some common allergies?

Contact dermatitis. Dermatitis, or skin inflammation, can result from contact with allergens—substances that trigger allergic responses in hypersensitive individuals. (Courtesy Cerio R, Jackson WF: Colour atlas of allergic skin disorders, London, 1992, Mosby-Wolfe.)

Hypersensitivity of the Immune System Autoimmunity—inappropriate, excessive response to self-antigens Causes autoimmune diseases Systemic lupus erythematosus (SLE)—chronic inflammatory disease caused by numerous antibodies attacking a variety of tissues

Lupus erythematosus. A red “butterfly” rash on the face is sometimes seen in cases of systemic lupus erythematosus (SLE). (From Habif TP: Clinical dermatology: a color guide to diagnosis and therapy, ed 3, St Louis, 1996, Mosby.)

Hypersensitivity of the Immune System Isoimmunity—excessive reaction to antigens from another human May occur between mother and fetus during pregnancy May occur in tissue transplants (causing rejection syndrome) Tissue typing helps to prevent rejection syndrome by identifying the recipients and donors and human lymphocyte antigens (HLAs) and other antigens and matching them so that tissue rejection is less likely to occur. To what classification of drugs do cyclosporine and prednisone belong? Immunosuppressive

Immune System Deficiency Congenital immune deficiency or immunodeficiency (rare) Results from improper lymphocyte development before birth Severe combined immune deficiency (SCID)—caused by disruption of stem cell development Although SCID is rare, it is a serious concern when diagnosed. What are some treatment options? Gamma globulin, bone marrow transplants, and gene therapy

Immune System Deficiency Acquired immune deficiency Develops after birth Acquired immunodeficiency syndrome (AIDS)—caused by HIV infection of T cells What are some factors that can contribute to an acquired immune deficiency? What are some strategies used to control the spread of AIDS? What are some of the common drugs used to slow the progression of AIDS? AZT and Norvir