THE LYMPHATIC SYSTEM AND IMMUNITY Of what does the lymphatic system consist? The lymphatic system consists of the fluid lymph flowing within lymphatic vessels. It also consists of lymphatic tissue composed of aggregates of lymphocytes and macrophages scattered throughout the body or forming dense lymphatic nodules such as the tonsils, appendix, and peyer’s patches. The lymphatic system also consists of lymphatic organs, composed of lymphatic tissue and a connective tissue capsule. Examples include red bone marrow ( site of lymphocyte production) lymph nodes, thymus, and spleen. What is Starling’s law of the capillaries? According to Starling’s law of the capillaries, only 85% of the fluid that leaves blood (by filtration) to enter the tissue spaces is reabsorbed. The other 15% bathes the cells as interstitial fluid and is then moved into the lymphatic system for eventual return to the blood. What is lymph? Once in the lymphatic system, the interstitial fluid is called lymph (“clear water”). Interstitial fluid and lymph are essentially identical fluids. What is lymphatic tissue? Lymphatic tissue is a specialized form of reticular connective tissue that contains large amounts of lymphocytes and macrophages. List, and then briefly describe, the three essential functions of the lymphatic system. draining the interstitial fluid -- Excessive interstitial fluid and escaped plasma proteins are drained back to the blood so that they do not accumulate in the tissue spaces. transporting dietary lipids -- Lipids and lipid-soluble vitamins absorbed from the diet are carried to the blood via the lymphatic system rather than by the venous drainage of the small intestine. protection against invaders -- Lymphatic tissue, using lymphocytes and macrophages, provide immune responses. These are highly targeted to particular invaders or abnormal cells. A. LYMPHATIC VESSELS AND LYMPH CIRCULATION 1. LYMPHATIC CAPILLARIES How do lymphatic vessels begin? Lymphatic vessels begin as close-ended vessels called lymphatic capillaries. They converge to form larger tubes called, lymphatic 249 vessels or simply lymphatics. They resemble veins in structure, but are thinner and have more valves. At intervals along the lymphatics, lymph flows through lymphatic tissue structures known as lymph nodes. Where are lymphatic capillaries found in the body? Lymphatic capillaries are found throughout the body, except for the following areas: all avascular tissues (cartilage, cornea, lens, and epidermis), the central nervous system, the spleen, and bone marrow. Describe the structure and function of the lymphatic capillary. Lymphatic capillaries are similar to blood capillaries in structure, but are unique in that they allow interstitial fluid to pass into them, but not out. Instead of intercellular clefts separating adjacent endothelial cells, lymphatic capillary endothelium overlaps like shingles, forming a type of one-way valve that allows fluid to move into the capillary only. When pressure is greater inside the lymphatic capillary than in the interstitial space, the overlapping cells are pressed together, preventing the outflow of fluid. 2. FORMATION AND FLOW OF LYMPH Describe the components and volume of lymph and how flow of lymph through its vessels is maintained even though there is no “heart” in the system. Most components of blood plasma freely move through the blood capillary walls to form interstitial fluid; however, more fluid is filtered than reabsorbed back into the blood capillary. This excess fluid, about 3 liters/day, drains into lymphatic capillaries and become lymph. Ultimately, this lymph is delivered back to the blood via the lymphatic ducts. In addition, plasma proteins that may have escaped from the blood are also moved into the lymph and are returned to he blood. This is important for maintaining blood colloid osmotic pressure. The flow of lymph from the tissue spaces back to the blood, like venous return, is maintained by the “milking” action of skeletal muscles, numerous one-way valves located in lymphatic vessels, and the respiratory pump. 250 3. LYMPH TRUNKS AND DUCTS What are lymph trunks? Lymph passes from lymphatic capillaries to lymphatic vessels and then through lymph nodes. When lymphatic vessels leave the terminal-most group of lymph nodes for an area, they unite to form large lymph trunks. Describe the following: lumbar trunks -- Right and left lumbar trunks carry lymph to the lower extremities, walls and viscera of the pelvis, kidneys, adrenal glands, and abdominal wall. intestinal trunk -- The intestinal trunk carries lymph from the stomach, intestines, pancreas, and liver. bronchomediastinal trunks -- Right and left bronchomediastinal trunks carry lymph from the lungs, heart, anterior thoracic wall, and diaphragm. subclavian trunks -- Right and left subclavian trunks carry lymph from the upper extremities. jugular trunks -- Right and left jugular trunks carry lymph from the head and neck. lymphatic ducts -- These trunks eventually fuse to form the origins of the two main channels that empty into the venous blood: the left lymphatic (thoracic) duct and the right lymphatic duct. 4. 5. THORACIC (LEFT LYMPHATIC) DUCT RIGHT LYMPHATIC DUCT Describe the thoracic duct (left lymphatic duct) and the right lymphatic duct. The thoracic duct (left lymph duct) is 15-18 inches long, beginning as a dilation called the cisterna chyli at vertebral level L2. It is the main collection duct of the lymphatic system, receiving lymph from the left side of the head, neck, and thorax, the left upper extremity, and the entire body below the diaphragm. The intestinal trunk and the two lumbar trunks join to form the cisterna chyli. The thoracic duct then ascends along the anterior vertebral surface, posterior to the aorta and inferior vena cava. 251 Near its termination, the thoracic duct receives the left bronchomediastinal, left subclavian, and left jugular trunks. The thoracic duct terminates by joining the venous system where the left subclavian vein and the left internal jugular vein merge to form the left brachiocephalic vein. The right lymphatic duct is a very short (1/2 inch) and is formed by the union of the right jugular, subclavian, and bronchomediastinal trunks. It terminates by joining the venous system where the right subclavian vein and right internal jugular vein merge to form the right brachiocephalic vein. B. LYMPHATIC TISSUE Lymphatic (lymphoid) tissue occurs in the body in many ways. List, and then briefly describe, these tissues. diffuse lymphatic tissue -- Individual lymphocytes are dispersed in the mucosa of the GI, respiratory, and genitourinary tracts. lymphatic nodules -- Lymphatic nodules are oval shaped concentrations of lymphocytes and macrophages. They are not encapsulated (having a capsule would make them organs), but rather found as solitary discrete structures (tonsils, Peyer’s patches, in the appendix). primary lymphatic organs -- Bone marrow and the thymus gland are the sites of lymphocyte production and therefore are the primary lymphatic organs. secondary lymphatic organs -- Lymph nodes and the spleen are considered secondary lymphatic organs because lymphocytes migrate to them and reside there. In addition, these structures contain reticular tissue. 1. LYMPH NODES Describe lymph nodes as follows: gross anatomy -- Lymph nodes are bean- or oval-shaped structures ranging in size from 1-25 mm in diameter. They are located in specific groups along the lengths of lymphatic vessels prior to the formation of lymph trunks. Each group of 252 nodes receives lymph from a particular drainage area of the body. capsule -- Each lymph node is covered by a capsule of dense connective tissue that extends into the node as structures called trabeculae (singular = trabeculum). Directly beneath the capsule is the subcapsular or cortical sinus, a space that receives lymph from afferent lymphatic vessels. stroma -- Internal to the capsule is a supporting network of reticular fibers and fibroblasts that together form the stroma or framework of the lymph node. It is within this framework that the parenchymal (the essential and distinctive tissue of an organ as distinguished from its supporting framework) or functional cells (lymphocytes and macrophages) of the lymph nodes reside. cortex -- Lymph nodes are specialized into two areas: cortex and medulla. The outer cortex contains densely packed lymphocytes arranged into masses called lymphatic nodules. The outer rim of a nodule consists of T cell lymphocytes and macrophages. When an immune response is occurring, the nodule has a lighter central region called a germinal center where B cell lymphocytes are proliferating into cells that secrete antibodies (plasma cells). medulla -- The inner region of a lymph node, the medulla, is arranged into strands of packed lymphocytes called medullary cords. Describe the flow of lymph into, through, and out of a lymph node. Lymph flows into a lymph node in one direction via afferent lymphatics that penetrate the convex outer surface of the capsule at several points. Lymph dumped into the subcapsular space percolates through the node where it is monitored by the lymphocytes and macrophages for foreign or abnormal cells and antigens as they are trapped by the reticular fibers. On the concave border of the lymph node at an indented area known as the hilus, where one or two efferent lymphatics collect the lymph from the nodes and carry it away. Efferent lymphatics may pass to another lymph node (in which case they become known as afferent lymphatics again) or they may fuse with others to form lymph trunks. 253 Along with the lymph flowing from a lymph node, new lymphocytes and antibodies that were formed in the nodule during an immune response are carried our and thus ultimately back to the general blood circulation. Describe the lymphatic drainage of each of the following body regions, the lymph nodes involved and, and the trunks that ultimately receive the lymph. head and neck -- All lymph from the head and neck region moves to a chain of superficial cervical lymph nodes found in the dermis of the neck. After these nodes, lymph is passed to deep cervical lymph nodes located along the carotid sheath just lateral to the trachea. From this terminal group lymph flows into the right or left jugular lymph trunks. lower extremity/ lumbar region -- Lymph from the leg flows first to the popliteal lymph nodes located in the popliteal fossa of the posterior knee. All lymph from the lower extremity and lumbar region moves to the inguinal lymph nodes located along the inguinal ligament where the lower extremity joins the trunk. The efferent lymphatics from the distal-most nodes unite to form the right or left lumbar lymph trunks.\ viscera -- There are thousands of lymph nodes associated with the viscera of the body. These nodes are usually located where the blood supply enters the organ and along the length of the aorta. The efferent lymphatics form either the bronchomediastinal, intestinal, or a portion of the lumbar lymph trunks. upper extremity/anterior thoracic wall/ breast -- All lymph from the upper extremity and anterior thoracic wall, including the breast, moves to the axillary lymph nodes located in the adipose tissue of the axilla. There are 20 - 30 axillary nodes arranged into a series of groups. 254 The efferent lymphatics from the distal-most unite to form the right or left subclavian lymph trunks. 2. TONSILS What are tonsils? Tonsils are multiple aggregations of large lymphatic nodules embedded in mucous membrane, forming a ring of lymphoid tissue around the junction of the oral cavity, nasal cavity, and pharynx. They are strategically located to protect the body from invasion by microbes that are ingested or inhaled. What are their names and where are they located? There are the paired palatine tonsils located on either side of the fauces, the paired lingual tonsils at the base of the tongue, and a single pharyngeal tonsil (adenoid) located in the posterior wall of the nasopharynx. 3. SPLEEN Describe the spleen as follows: location -- The spleen, the largest mass of lymphoid tissue in the body, is situated in the posterolateral left hypochondriac region between the stomach and the diaphragm. structure -- The spleen is surrounded by a dense connective tissue capsule with trabeculae. Internally, reticular fibers form the stroma of the organ. (infrastructure is very much like that of a lymph node) parenchyma -- The parenchyma of the spleen consists of two types of tissue: White pulp is lymphocytes arranged around arteries passing through the organ. Red pulp consists of venous sinuses and cords of lymphocytes and macrophages. function -- The spleen has no role in lymph filtration. Its lymphocytes and macrophages are involved in phagocytosis of bacteria in blood, as well as old and damaged RBCs. It also serves as a storage depot for blood that can be used during times of high demand. With sympathetic stimulation, the capsule of the spleen contracts and forces its blood back into the circulation. 255 4. THYMUS GLAND Describe the thymus gland as follows: location -- The thymus gland is located in the superior mediastinum, posterior to the sternum, anterior to the heart, and between the lungs. structure -- It consists of two lobes held together by a connective tissue capsule. Each lobe has an outer cortex containing tightly packed lymphocytes, and an inner medulla with scattered lymphocytes and epithelial cells. function -- Immature lymphocytes leave the bone marrow and travel via the blood to the thymus gland, where they take up residence and receive immunocompetence to become T cells. atrophy -- The thymus gland grows to its maximum size in infancy, when it is most active. After puberty, it begins to involute with fat and connective tissue, so that by adulthood it is considered atrophied. C. IMMUNITY (SPECIFIC RESISTANCE TO DISEASE) What is nonspecific resistance to disease? Nonspecific resistance comprises those defense mechanisms that provide a general response against a wide variety of pathogens (a specific causative agent {as bacterium or virus} of a disease). What is immunity? The nonspecific defenses are not specifically directed against any one particular invader. The ability of the body to defend itself against specific invaders (bacteria, viruses, toxins, foreign tissue, cancer cells) in a specific manner is called immunity. What is an antigen? Substances that are recognized by the immune system and provoke immune responses are called antigens. 256 Two properties distinguish immunity from nonspecific resistance. List and briefly describe them. specificity -- The cells of immunity show specificity for particular foreign molecules (antigens). This also involves the ability to distinguish “self” from “nonself” molecules. memory -- The cells of immunity have “memory” for most previously encountered antigens so that a second encounter prompts an even more vigorous and faster response. 1. FORMATION OF T CELLS AND B CELLS What are T cells and B cells? Where do they become immunocompetent? What does immunocompetence mean? The cells that carry out immune responses are lymphocytes (T and B cells) and macrophages antigen-presenting cells). Both types of lymphocytes, T and B cells, develop from stem cells in the bone marrow and must then receive immunocompetence in order to become functional. B cells become immunocompetent in bone marrow, and then pass into the blood for distribution throughout the lymphoid tissues. Immature T cells pass from bone marrow to the blood, enter the thymus gland, and after a few days emerge as immunocompetent T cells for distribution throughout the lymphoid tissues. With immunocompetence, T and B cells acquire several distinctive proteins on their cell surface that function as antigen receptors. Each cell is now capable of recognizing a specific antigen and has therefore gained antigen specificity. 2. TYPES OF IMMUNE RESPONSES Describe cell-mediated immunity. What is it effective against? Immunity consists of two kinds of closely allied immune responses, both of which are triggered by the presence and recognition of antigens. In cell-mediated (cellular) immune responses, T cells proliferate into several subpopulations (subclones) that are involved in directly attacking the invading antigen. 257 Cytotoxic (killer) T Cells (CD8) directly destroy antigens by secreting cytotoxins on to the antigen. Helper T Cells (CD4) aid both T and B cell responses. Suppressor T cells suppress the response so that it is controlled. Memory T cells remain in the lymphoid tissues, allowing a secondary or anamnestic response that occurs quickly, destroying the pathogen before signs and symptoms of the disease appear. Cellular immunity is particularly effective against slowly developing bacterial infections (tuberculosis, brucellosis), intracellular viruses, fungi, cancer cells, and transplanted cells and tissues. Three Phases a. Recognition -antigen presentation - T Cell Activation (costimulation and clonal selection) b. Attack -role of Helper T cells - role of Cytotoxic T cells c. Memory -memory T cells -anamnestic response 258 259 Describe antibody-mediated immunity. What is it effective against? In antibody-mediated (humoral) immune responses, B cells proliferate to form two subclone populations, plasma cells and memory B cells. Plasma cells secrete antibodies specific for the particular antigen that stimulated the response. Antibodies bind to the antigen and deactivate it, thus marking it for destruction. Memory B cells remain in the lymphoid tissues and initiate an anamnestic (secondary) response so that the pathogens are destroyed before signs and symptoms of the disease appear. Humoral immunity is particularly effective against antigens dissolved in bodily fluids (viruses), and bacteria that multiply in extracellular fluids but do not invade body cells. Three Phases a. Recognition -antigen binds to B cell receptors -B cell activation -clonal selection -plasma cells -memory B cells b. Attack -plasma cell secrete antibodies -antibodies mark antigen for destruction c. Memory -memory B cells -anamnestic response 260 D. FOUR CLASSES OF IMMUNITY -Natural active immunity- production of one’s own antibodies after exposure naturally -Artificial active immunity-production of one’s own antibodies as of a result of vaccination -Natural passive immunity- naturally acquiring antibodies by another person (temporary) -Artificial passive immunity- acquires antibodies from injection from human or antimal (temporary) 261