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Lymphatic System The lymphatic system carries fluid lost from capillaries. This fluid returns to the blood in the right lymphatic and thoracic ducts. Lymph also transports the products of fat digestion, and is a major component of the immune system. Lymphatic vessels transport fluid from interstitial spaces to the bloodstream. (a) The right lymphatic duct drains lymph from the upper right side of the body, and the thoracic duct (left hepatic duct) drains lymph from the rest of the body. (b) Lymphatic capillaries are microscopic, closed-ended tubes that begin in the interstitial spaces of most tissues.Lymph drainage of the right breast. Lymph Movement Lymphatic vessels recycle excess tissue fluid that accumulates in the interstitium as a result of normal capillary leakage. The walls of the lymphatic vessels act as one-way valves, only letting fluid enter. Once in the vessels, the lymph is advanced toward the systemic circulation. Along the way, the lymph is filtered through several lymph nodes where it is inspected for foreign substances. Upon reaching the thoracic duct, the lymph re-enters circulation. Lymph Nodes Lymph nodes (lymph glands) are located along the lymphatic pathways. They contain large numbers of lymphocytes and macrophages that fight invading microorganisms. Arrows indicate direction of lymph flow. As lymph moves through the sinuses, phagocytic cells remove foreign substances. The germinal centers are sites of lymphocyte production. Lymph Organs Tonsils Tonsils are large groups of lymph nodules in the oral cavity and nasopharynx. The three groups of tonsils are a pair of palatine tonsils, a pair of lingual tonsils, and a single pharyngeal tonsil. Spleen The spleen detects and responds to foreign substances in the blood, destroys worn-out erythrocytes, and acts as a blood reservoir. The parenchyma of the spleen consists of two types of tissue: red pulp and white pulp. The red pulp consists of sinuses and it is concentrated with erythrocytes. The white pulp consists primarily of lymphocytes and macrophage. Foreign substances in the blood passing through the white pulp can stimulate the lymphocytes. Thymus The thymus gland produces and matures T lymphocytes, which then move to other lymphatic tissues, where they can respond to foreign substances. The thymus secretes two hormones, thymopoietin and thymosins, which can stimulate the development and activity of T lymphocytes. Defense Mechanism Overview Pathogen A disease-causing agent such as a virus or bacterial microorganism. Bacteria A single-celled organism with a varied morphology. Bacteria can have a symbiotic relationship with their host, or under certain conditions bacteria can cause illness. Virus Viruses are one of the simplest pathogens, capable of causing disease by invading cells. Most viruses have a simple structure consisting of a small nucleic acid genome within a protein shell. Mast Cell An immune cell found in connective tissue that releases cytokines, like histamine, as part of an immune response to a local infection. Macrophage A large phagocytic cell that engulfs and destroys foreign material, damaged cells, and cellular debris. Another immunological function of the macrophage is to present foreign antigens on its surface to lymphocytes for recognition and stimulation. Antigen A foreign substance that elicits a specific immune response, such as antibody production. Cytotoxic T Lymphocyte A lymphocyte involved in cell-mediated immunity. Cytotoxic T cells monitor the cells of the body and become activated by encountering cells with abnormal surface antigens. Once activated, the cytotoxic T cell destroys the abnormal cell. T-Helper Lymphocyte A lymphocyte that amplifies the normal immune response. When stimulated by an antigen-presenting cell, such as a macrophage, T-helper cells release factors that stimulate the proliferation of B lymphocytes and attract cells key to the immune response. B Lymphocyte A type of white blood cell, or leukocyte, that is vital to antibody-mediated immunity. When stimulated by a specific antigen, it gives rise to memory cells and antibody-producing plasma cells Plasma Cell A lymphocyte that is a clone from a stimulated B lymphocyte. Plasma cells are distinguished from other lymphocytes by an abundance of rough endoplasmic reticulum, indicating active antibody production. Antibody A water-soluble globular protein produced by lymphocytes. Antibodies are involved in the immune response by specifically recognizing and binding to antigens Memory Cell A dormant lymphocyte that is cloned from the stimulation of a B lymphocyte. Once activated by a specific antigen, the memory cell undergoes clonal expansion to form more memory cells and antibody-producing plasma cells. Nonspecific Defenses Physical Barriers The body is protected from infection by the physical barrier of the skin, the acidity of the stomach, and cilia lining the respiratory tract. Should there be injury to the skin, inflammation is a complex set of responses that result in the redness, swelling, and pain familiar to all of us. Phagocytic cells are specialized to nonspecifically consume and digest antigens. The macrophage is an example of a phagocytic cell. In addition to this non-specific clean-up function, macrophages digest engulfed antigens and place small antigenic pieces on their surface for presentation to lymphocytes. Inflammation An injured blood vessel releases chemicals that result in increased permeability and dilation of blood vessels. This brings a large number of white blood cells into the area. The result is that inflammation draws phagocytic macrophages to the site of injury. They will engulf bacteria and viruses. Complement is a set of 20 or more beta globulin proteins in the blood plasma that aid the activities of the immune system by causing foreign cells to rupture. When a cell is invaded by a virus, one of the mechanisms for a nonspecific defense is to protect surrounding cells from infection. Upon viral infection, interferon may be released from the infected cell. This initiates antiviral defense mechanisms in all cells that receive the signal. Although the virus replicates and the infected cell dies from the viral attack, protection of the surrounding cells helps avoid a widespread infection. Complement The complement system is a group of inactive plasma proteins that become activated when certain proteins bind to an antigen-antibody complex (the classical pathway) or when other complement proteins bind to the polysaccharides of microbes (the alternate pathway). Once activated, complement proteins enhance the inflammatory response, form a membrane attack complex (MAC), which destroys microbial membranes, or bind to microbial membranes to enhance phagocytosis, a process called opsonization. Part of nonspecific immunity is a set of about 20 proteins called complement. One mode of action of complement proteins is to form a membrane attack complex when triggered by foreign cells or body cells infected by virus. Clusters of complement protein perforate the cell, whose contents leak out. Complement also stimulates phagocytic white blood cells to engulf these foreign or infected cells. Fever is a nonspecific immune response to infection. Bacteria entering the body through a cut may cause an infection. Upon recognition of the bacterial invasion, lymphocytes release pyrogens that signal the brain to raise body temperature. An elevated body temperature creates an unfavorable environment for microbial growth. A fever also enhances the normal immune response. Lymphocytes All lymphocytes originate in the bone marrow. T cells mature in the thymus. Cytotoxic T cells directly attack foreign cells. Helper T cells stimulate B cells. B cells convert into plasma cells, which release antibodies into the bloodstream. Some B cells differentiate into memory cells that will respond to future invasions. Humoral Immunity Once released, antibodies use several mechanisms to render antigens harmless: 1. 2. 3. 4. Agglutination: When an antibody binds to multiple cells simultaneously and the cells stick together. Precipitation: Occurs when the resulting antigen-antibody complex is too large to remain in solution. Complement fixation: Occurs when an antigen-antibody complex involving IgG or IgM binds and activates complement, thus stimulating inflammation, promoting opsonization of bacteria, and the formation of a membrane attack complex. Neutralization: When an antibody binds to an antigen, such as a toxin, and renders in ineffective. Clonal Selection and Ensuing Events of the Humoral Immune Response 1. 2. 3. 4. 5. Immunocompetent B cells exposed to antigen. Antigen binds only to B cells with complementary receptors. B cell displays processed antigen fragments. Helper T cell binds to B cell and secretes helper factor. Helper factor stimulates B cell to divide repeatedly and form a clone. Some cells of the clone become memory B cells. Most differentiate into plasma cells. Plasma cells synthesize and secrete antibody. Antibodies are proteins that play an integral role in the complex system of specific immunity. They bind to and inactivate foreign proteins called antigens. Each type of antibody binds to one kind of antigen molecule. B cells are one of the two types of white blood cells that make antibodies. When a bacterial cell enters the bloodstream, proteins on its surface act as antigens and trigger response by the immune system. These antigens will bind to the unique B cells that have the corresponding antibodies on their surfaces. These B cells now divide. Some continue to divide, producing many plasma cells. Plasma cells secrete large quantities of antibodies into the bloodstream. This division of only the appropriate B cells is called clonal selection. Cell Mediated Immunity T-lymphocytes are not able to recognize free antigen molecules. In order for an immune response to be initiated in T cells, the T cell must first be presented with the foreign antigen along with a self antigen known as a major histocompatibilty protein. This is the function of an antigenpresenting cell or an APC. The APC recognizes the foreign antigen and moves towards it. The APC surrounds the antigen and internalizes it by endocytosis. Once the antigen has been ingested, lysosomes containing digestive enzymes fuse with the phagosome containing the antigen. The antigen is degraded into molecular fragments. Molecular fragments of the anitgen are combined with MHC class two proteins. This complex is sent to the cell membrane. The T cell can now recognize the antigen. The T cell antigen receptor binds to the MHC class 2 protein and antigen fragment complex. An immune response will be initiated. There are a number of types of T cells involved in specific immunity. T cells recognize their specific foreign protein or antigen only when it is presented on the surface of a body cell. One type of T cell is the cytotoxic or killer T cell. Its role is to destroy infected or cancerous body cells. In this case a pathogen enters the cell on the left and that cell moves foreign protein to its surface. A patrolling killer T cell recognizes and binds to that protein and releases perforin, a protein that ruptures the membrane of the infected cell. A second type of T cell is the helper T cell. One of the roles of a helper T cell is to activate B cells. At the top of the screen a phagocytic white blood cell is presenting antigen from a pathogen it has engulfed. The B cell that responds has antibodies for the same antigen that activates the helper T cell. The T cell sends out chemical signals that affect various immune cells. These chemicals stimulate the B cell to divide and produce a clone of antibody-releasing cells. Cytokines are polypeptides produced by virus-infected cells. They stimulate many parts of the immune system including specific immunity. Vaccination is the process of exposing an individual to an antigen to stimulate an immune response and produce antibodies to that antigen. Vaccines employ the benefits of "priming" the immune system for exposure to a pathogen. Many vaccines are "attenuated" or disabled forms of a pathogen. These attenuated pathogens are recognized by lymphocytes resulting in clonal expansion and production of plasma cells and memory cells. The memory cells lie dormant until later exposure to the virulent pathogen, at which point they become activated. This secondary response will involve contact with more immunospecific memory cells initially, which results in a faster, more robust immune response.