discussion anatomy

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Chapter

5 Lymphatic System ♦Overview -The lymphatic system, also known as the lymphoid system, consists of the following components (Figure 5.1, Derrickson): (i) lymphatic vessels, which contain a fluid called lymph, (ii) lymphatic organs, which include the lymph nodes, tonsils, spleen, and the thymus gland; and (iii) lymphocytes, which include B cells and T cells. ♦Functions -The lymphatic system has 2 major functions (Figure 5.2, Derrickson): 1. It drains the tissues of excess interstitial fluid. -Recall that some H2O moves from the blood into the interstitium as cells undergo gas, nutrient, and waste exchange with the capillaries. -The H2O in the interstitial fluid can diffuse into body cells if needed. -If there is too much H2O in the interstitium, the excess interstitial fluid drains into a nearby lymphatic vessel (usually a lymphatic capillary). -Note that if this excess interstitial fluid were to remain in the interstitium, the tissues would swell (edema), which causes tissue damage. -Once inside of a lymphatic capillary, the interstitial fluid is called lymph. -Thus, lymph is any excess interstitial fluid found within the lymphatic vessels of the body. -The excess interstitial fluid will eventually make it back to the blood because lymphatic vessels ultimately empty into veins. -Any pathogens (such as bacteria and viruses) that happen to be in the interstitium trying to invade body cells will also be swept into the lymphatic capillaries as a component of lymph (just like a swimmer may be swept away from the shore by a tidal wave). -Figures 5.3 and 5.4 (Derrickson) illustrate the components of a bacterial cell and a virus, respectively. 2. It participates in immunity. immunity -resistance to disease -This function is achieved by the leukocytes (white blood cells) of the body. -Because of its role in immunity, parts of the lymphatic system can also function as the immune system.

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♦Lymphatic Vessels -Lymphatic Capillaries -The lymphatic system begins with the lymphatic capillaries, which are the smallest lymphatic vessels (Figures 5.5 and 5.6, Derrickson). -Like a blood capillary, a lymphatic capillary consists of endothelial cells. –However, a lymphatic capillary differs from a blood capillary in 2 major ways: • A lymphatic capillary lacks a basement membrane. • The endothelial cells of a lymphatic capillary overlap. -This arrangement allows for unidirectional flow of fluid into the lymphatic capillary. -As excess interstitial fluid approaches a lymphatic capillary, the endothelial cells spread apart, forming large spaces between each other. -These spaces are larger than the pores in a regular blood capillary and allow small molecules (like H2O) and large substances (such as proteins, viruses, bacterial cells, cancer cells, and debris) to move from the interstitium into the lumen of the lymphatic capillary. -Thus, a lymphatic capillary is far more permeable than a blood capillary. -If the lymph tries to move out of the lymphatic capillary back into the interstitium, the endothelial cells come back together and overlap with one another, which closes off the spaces and essentially traps the lymph within the lymphatic vessel. -Larger Lymphatic Vessels -Lymphatic capillaries converge to form larger lymphatic vessels (Figure 5.7, Derrickson). -A larger lymphatic vessel resembles a vein in structure, but has a thinner wall and more valves. -Pathway of Lymph Flow Through the Lymphatic Vessels Excess interstitial fluid (and any dissolved pathogens and debris) flows from the interstitium into the lymphatic capillaries, forming lymph. The lymph then moves into larger lymphatic vessels. As these larger lymphatic vessels course through the body, they give rise to lymph nodes, where lymph is filtered of any pathogens and debris. Lymph eventually flows into the largest lymphatic vessels: the right lymphatic duct and the thoracic (left lymphatic) duct (Figures 5.8 and 5.9, Derrickson). Finally, lymph moves from the right lymphatic duct and the thoracic (left lymphatic) duct into the right and left subclavian veins, respectively.

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♦Lymphatic Organs -The lymphatic organs include the lymph nodes, the tonsils, the spleen, and the thymus gland (Figure 5.1, Derrickson). -Most lymphatic organs (namely, the lymph nodes, tonsils, and spleen) contain reticular connective tissue. reticular connective tissue -a type of connective tissue that consists of 2 main components: reticular fibers and white blood cells (Figure 5.10, Derrickson) ● reticular fibers -The reticular fibers are thin collagen fibers that interact together to form a net. ● white blood cells -The white blood cells present in reticular connective tissue include macrophages and lymphocytes (both B cells and T cells). -The purpose of reticular connective tissue is to filter foreign substances, such as pathogens and debris. As materials move through the reticular connective tissue of lymph nodes, tonsils, and the spleen, the netlike organization of the reticular fibers traps pathogens and debris, preventing these substances from moving any farther. Then the white blood cells in the reticular connective tissue interact with and destroy the pathogens and debris. -You should realize that the white blood cells that are in reticular connective tissue were initially in the bloodstream. From time to time, white blood cells leave the blood and then enter the reticular connective tissues of the lymph nodes, tonsils, and spleen and patrol these organs for foreign substances. -Afterwards, the white blood cells leave these organs and go back into the blood, and later on repeat the same cycle. -Note that the thymus gland is the only lymphatic organ that does not contain reticular connective tissue. -That’s because the thymus gland does not have a role in filtering foreign substances.

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-Now that you know some basic information about the lymphatic organs, you are ready to learn about each of these organs in more detail. 1. lymph nodes -small, bean-shaped masses that are located between lymphatic vessels -Locations - Single lymph nodes are found throughout the body. - Lymph nodes can also exist in groups; this is especially the case with the lymph nodes in the neck, armpit, and groin (Figure 5.11, Derrickson). -These lymph nodes are called cervical nodes, axillary nodes, and inguinal nodes, respectively. -Structure -A lymph node contains reticular connective tissue and germinal centers (Figure 5.11, Derrickson). -The reticular connective tissue gives the interior of the lymph node a netlike organization. -The germinal centers are sites where white blood cells divide during immune responses. -Connections to Lymphatic Vessels -More than one lymphatic vessel goes to and from a given lymph node. -The lymphatic vessels that carry lymph to a lymph node are called afferent lymphatic vessels. -The lymphatic vessels that carry lymph away from a lymph node are called efferent lymphatic vessels. -Function Lymph nodes filter lymph of foreign substances (such as pathogens and debris). Afferent lymphatic vessels bring lymph to lymph nodes. As lymph travels through each lymph node, foreign substances in the lymph are trapped by the netlike reticular fibers, which then allows the white blood cells (macrophages and lymphocytes) within the lymph node to destroy them. The efferent lymphatic vessels carry the filtered lymph away from the lymph node.

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2. tonsils - located in the pharynx (throat) and the oral cavity -3 types (Figure 5.12, Derrickson): a. pharyngeal tonsil -unpaired -also called the adenoid -located in wall of the nasopharynx b. palatine tonsils -paired -located in the posterior end of the oral cavity -The palatine tonsils are most susceptible to infection and may have to be removed (tonsillectomy). c. lingual tonsils -paired -located at the base of the tongue -Structure -The tonsils are isolated masses that consist of reticular connective tissue. -In addition, the tonsils have invaginations that form valleys called tonsillar crypts. -Function -The tonsils filter air, food, and beverages of pathogens, debris, and other foreign substances. -The location of the tonsils in the oral cavity and pharynx allows the tonsils to achieve this function: As pathogens in air, food, or a beverage interact with the tonsils, the pathogens become trapped in the tonsillar crypts. By chance, the pathogens then move deeper into the reticular connective tissue within the tonsils, where they get caught in the reticular fibers and then the macrophages and lymphocytes destroy them.

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3. spleen -the largest lymphatic organ -located on the left side of the body between the diaphragm and the stomach -Structure -The spleen consists of reticular connective tissue that is organized into regions called white pulp and red pulp (Figure 5.13, Derrickson). -The white pulp and red pulp are named as such because the white pulp is lighter in color than the red pulp. -However, both white pulp and red pulp are regions of reticular connective tissue within the spleen. -In addition, the spleen is heavily vascularized: the splenic artery provides blood to the spleen, while the splenic vein drains it. -Since the spleen is so heavily vascularized, trauma to the spleen can cause severe bleeding and even death. -If this happens, the spleen must be removed (splenectomy) to stop the bleeding. -Functions -The spleen is involved in 2 major functions: a. It filters the blood of foreign substances. The splenic artery brings blood to the spleen. From the splenic artery, blood eventually moves into the reticular connective tissue that forms the white pulp and the red pulp. As blood moves through the white pulp and red pulp, lymphocytes and macrophages remove and destroy any pathogens that get caught in the reticular fibers. The blood then moves from the white pulp and red pulp into the splenic vein, which takes the filtered blood away from the spleen. b. It destroys worn out red blood cells. -As blood is filtered in the spleen, the macrophages can remove and destroy any worn out red blood cells via phagocytosis.

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4. thymus gland -bilobed gland that partially covers the superior portion of the heart (Figure 5.14, Derrickson) -The size of the thymus gland changes with age: it is largest during infancy and childhood and gradually gets smaller as we age. -Structure -Unlike the other lymphatic organs, the thymus gland does not contain reticular connective tissue. -Instead, the thymus gland contains T lymphocytes (T cells). -Function The thymus gland promotes the maturation of T cells. Immature T cells are initially produced in red bone marrow. Afterwards, these immature T cells are released into the blood and then migrate to the thymus gland. The thymus gland produces hormones called thymosins that mature the T cells. The mature T cells then migrate back into the blood. Some T cells patrol the blood for pathogens, while others move into lymphatic organs (like the lymph nodes) to fight pathogens there. -Note that B cells are produced and matured in red bone marrow and, therefore, do not migrate to the thymus gland.

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♦Immunity: An Overview -Immunity -resistance to disease -2 major types (Figure 5.15, Derrickson): 1. nonspecific immunity -the ability to protect the body from any foreign substance in a general, nonspecific way -Recall that there are several types of white blood cells that are involved in nonspecific immunity (neutrophils, monocytes/macrophages, eosinophils, and basophils). 2. specific immunity -the ability to protect the body from any foreign substance in a way that involves specificity and memory -Recall that specific immunity is achieved through the activities of B lymphocytes and T lymphocytes (also called B cells and T cells, respectively). -Note that the difference between nonspecific immunity and specific immunity is based on specificity and memory. • specificity -Specific immunity targets a specific pathogen (example: E. coli vs. the influenza virus). -The more specific the immune response is, the easier it is to kill the invading pathogen. -Nonspecific immunity is more general and, therefore, can target any type of pathogen (any type of bacterium or virus, etc.) -A major disadvantage to this generalized approach is that it is harder to kill a pathogen without being able to specifically target it. • memory -Specific immune responses involve memory, while there is no memory associated with nonspecific immunity. -A person often becomes ill upon the first exposure to a particular pathogen. -This is because it usually takes time for nonspecific immunity and for specific immunity to become effective. -Because specific immunity involves memory, the person does not get sick due to a subsequent exposure to the same pathogen because the specific immunity response acts quicker this time around. -Since there is no memory associated with nonspecific immunity, the nonspecific immunity response will still occur at the same slow pace as before and the person runs the risk of still becoming sick until the nonspecific immunity response can become effective.

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-Specific Immunity: A Closer Look -In order to describe specific immunity in more detail, one must first understand the concept of an antigen. antigen -Definition -An antigen is any substance that the body recognizes as being foreign (nonself) and is therefore immunogenic (promotes a specific immune response). -Examples Antigens are usually foreign proteins or carbohydrates that have strange shapes (Figure 5.16, Derrickson): 1. different components of pathogens a. the capsid (protein coat) or glycoproteins of a virus b. the proteins in the cell wall and flagellum of a bacterial cell 2. pollen -During their reproductive cycles, many plants release pollen, which is a multicellular male structure that gives rise to sperm. -The cell membranes of the cells in pollen contain proteins that are immunogenic in many people. 3. certain foods - For some people, certain foods such as shellfish and peanuts can be antigens. -That’s because shellfish and peanuts contain proteins and carbohydrates that the body of these individuals cannot tolerate, resulting in an immune response. 4. foreign human cells -Cells from other people contain proteins or carbohydrates that are immunogenic: a. the A or B antigens (which are glycolipids) in the cell membranes of the blood cells of a person who has a blood type different than yours. b. the MHC antigens found in nucleated cells of the tissues and organs of other people -This concept will be discussed shortly. c. strange proteins found in the cell membranes of cells that become cancerous in your body -As a normal cell turns into a cancer cell, it produces strange proteins that the body will recognize as foreign. -Once antigens are introduced into the body, B cells and T cells will find them and destroy them. -Note that most plastics are not immunogenic; consequently, they can be used to replace damaged heart valves or damaged areas of the hip or knee without fear of rejection from the body.

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-MHC Proteins: the Self-Antigens -Our cells contain a variety of macromolecules. -The majority of lipids, nucleic acids, carbohydrates, and proteins are the same from person to person and, consequently, are not immunogenic to other people. -However, there is a group of proteins called the major histocompatibility complex (MHC) that is unique from individual to individual and, consequently, causes an immune response when introduced into another person (Figure 5.17, Derrickson). major histocompatibility complex -a special group of proteins found in the plasma membrane of nucleated cells -unique from individual to individual -Exception: identical twins -serve as cellular “identity tags” or self-antigens -Self-antigens are proteins that belong in one person and nobody else. -The MHC complex is the basis of tissue rejections during tissue or organ transplantations. -However, the MHC antigens in the cells of one of your close relatives are very similar to your own MHC antigens; therefore, a close relative can donate an organ to you without there being a severe immunogenic response in your body. -not found in RBCs -RBCs are non-nucleated cells; consequently, they lack MHC proteins. -Nevertheless, RBCs do contain their own self-antigens: the antigens of the ABO blood group and those of the Rh blood group. -Production and Maturation of B cells and T cells -B cells and T cells are produced and undergo maturation in the following way (Figure 5.18, Derrickson): B cells and T cells are produced in red bone marrow from hemocytoblasts via via the process of hematopoiesis. Once they are produced, the B cells remain in the red bone marrow for a while to undergo maturation. T cells, however, do not mature in red bone marrow. Once they are produced, T cells migrate via the blood to the thymus gland to undergo

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maturation there with the help of thymosins (thymic hormones). During the maturation process, the B cells and the T cells become immunocompetent, which is the process by which B cells and T cells develop specific antigen-binding receptors in their plasma membranes. Once the maturation process has been completed, the immunocompetent B cells and T cells leave the red bone marrow and thymus gland, respectively, and migrate into the blood and into the reticular connective tissue of lymphatic organs. These lymphocytes continuously travel between the blood and lymphatic organs as they patrol these areas for antigens. - Diversity of Antigen Receptors -There are millions of different antigens in the environment that could potentially cause a person to become sick. -Fortunately, the body already contains a specific B cell or T cell that can destroy each one of these antigens before you even encounter them!!!!!! -Hence, there are millions of different types of B cells and millions of different types of T cells in the body; each of these cells contains a specific antigen-binding receptor in its plasma membrane (Figure 5.19, Derrickson). -Clonal Selection -Again, there are millions of different types of B cells and millions of different types of T cells in the body. -However, there are only a few copies of each of these different types of B cells and T cells before the initial exposure to antigens. -Such a small army consisting of only a few copies of each of these lymphocytes is not enough to fight a massive invasion of pathogens. -As a solution to this problem, when a B cell or T cell binds to an antigen, it undergoes clonal selection (Figure 5.20, Derrickson). clonal selection -the process by which a B cell or T cell divides into a clone of cells that can bind to the same antigen -results in the production of more B cells or T cells (often thousands of them) that can be used to destroy an antigen -In addition, the cells of the clone become differentiated. -Although the differentiated cells of the clone bind to the same antigen, they function differently in the specific immune response that is about to occur.

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• Formation of B Cell Clones (Figure 5.21, Derrickson) An antigen invades the body. The receptor on the appropriate B cell binds to the antigen. The B cell is then activated by cytokines released from a helper T cell. The B cell subsequently undergoes clonal selection, resulting in the production of many plasma cells and memory B cells. Both of these cell types bind to the same antigen as the original B cell. ● plasma cells -secrete antibodies into the blood or other body fluids antibody -also called an immunoglobulin (Ig) -a protein that binds to and subsequently destroys an antigen -The antibodies secreted by the plasma cell are specific for the antigen that was recognized by the original B cell. -In fact, the antibody has the same shape as the antigen receptor that is in the plasma membrane of the B cell. -Antibodies are found in many types of body fluids (blood, saliva, lymph, tears, mucus, breast milk, etc.) ● memory B cells -cells that remember the antigen that caused the original B cell to undergo clonal selection -Should the same antigen invade the body again, the memory B cells immediately produce more plasma cells and more memory B cells that possess the same antigen specificity. -Consequently, there is a rapid production of antibodies produced by the plasma cells, which results in the quick destruction of the the pathogen. -This response is so fast that the person typically does not exhibit any signs of being ill. - Memory B cells stay around in the body for decades.

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• Formation of T cell clones (Figure 5.22, Derrickson) An antigen invades the body. The receptor on the appropriate T cell binds to the antigen. The T cell is then activated by cytokines released from a helper T cell. The T cell subsequently undergoes clonal selection, resulting in the production of many cytotoxic T cells, helper T cells, suppressor T cells, and memory T cells. All of these cell types bind to the same antigen as the original T cell. ● cytotoxic T cells -also called killer T cells -Cytotoxic T cells function by poking holes in the cell membranes of their target antigens, resulting in cell lysis and cell death (Figure 5.23, Derrickson). ● helper T cells -activate both B cells and T cells, resulting in clonal selection -Consequently, a specific immune response cannot be achieved without the helper T cells. -Helper T cells activate B cells and T cells via the secretion of chemicals called cytokines (example: interleukin). -HIV (the virus that causes AIDS) kills helper T cells; when the helper T count becomes very low, the immune system ceases to function. ● suppressor T cells -reduce the activity of B cells and T cells once the pathogen has been destroyed -Hence, these cells only become active once the battle is over and victory has been declared. ● memory T cells -cells that remember the antigen that caused the original T cell to undergo clonal selection -Should the same antigen invade the body again, the memory T cells immediately produce more cytotoxic T cells, helper T cells, suppressor T cells, and memory T cells that possess the same antigen specificity. -Consequently, the pathogen is quickly killed by the huge numbers of cytotoxic T cells. -This response is so rapid that the person typically does not exhibit any signs of being ill. -Like memory B cells, memory T cells also stay around in the body for decades.

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-Acquired Immunity -There are four ways to acquire specific immunity (Figure 5.24, Derrickson): 1. active natural immunity -specific immunity (i.e. proliferation of B cells/antibodies or T cells) that a person develops due to natural exposure to an antigen (i.e. by chance) -The person will typically develop signs of illness since there has not been a previous encounter with the antigen. 2. active artificial immunity -specific immunity that a person develops due to deliberate exposure to an antigen by a process called vaccination - In this process, a person receives a vaccine, which typically consists of an attenuated (weakened) pathogen. -Since the pathogen is attenuated, it does not cause harm to the body but it is still immunogenic and will result in the production of either B cells/antibodies or T cells. -Years after the vaccine has been administered, the person may need a booster shot to stimulate the number of memory cells in that person’s body just in case some of the previous memory cells that developed after the first vaccination have dwindled in number. 3. passive natural immunity -specific immunity that develops when antibodies are passed from mother to fetus through the placenta or from mother to infant via breast milk -Neither a fetus nor an infant has a well-developed immune system and, therefore, both are susceptible to frequent pathogenic invasions. -Passive natural immunity assures that the fetus and the infant are not totally helpless. -These antibodies do not last forever; they are eventually broken down and the infant will have to rely on his or her own developing immune system to provide protection. 4. passive artificial immunity -specific immunity that a person develops by receiving serum -often involves the following steps: Vaccinate an animal (such as a horse or rabbit) The animal’s immune system will respond to the vaccination by making antibodies in its blood.

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Remove the blood from the animal and then extract the serum, which contains the antibodies. Inject the antibodies into the person that needs immunity to provide immediate protection. -Passive artificial immunity is the preferred type of acquired immunity when there is an epidemic and, consequently, there is not enough time for a person to develop his or her own specific immune response. ♦ Clinical Applications and Disorders -Look up the following clinical applications and disorders in Tortora: 1. breast cancer metastasis through the lymphatic system p. 854 2. ruptured spleen p. 857 3. tonsillitis p. 858 4. abscesses and ulcers p. 863 5. graft rejection and tissue typing p. 873 6. monoclonal antibodies p. 876 7. immunotherapy and cancer p. 880 8. AIDS p. 882, 884-885 and Figure 5.25 (Derrickson) 9. Allergens, type I (anaphylactic) reactions, and anaphylactic shock p. 885 10. autoimmune diseases p. 885-886

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11. infectious mononucleosis p. 886 12. lymphomas p. 886 13. systemic lupus erythematosus p. 886-887 14. allograft p. 887 15. autograft p. 887 16. lymphedema p. 887 17. splenomegaly p. 887 18. xenograft p. 887

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Figure 5.1 Components of the Lymphatic System

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Figure 5.2 Lymphatic System Functions

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Figure 5.3 Components of a Bacterial Cell

DNA

plasma membrane

ribosomes

flagellum

cell wall capsule

pilus

Bacterial shapes

bacillus (rod)

cytosol

coccus (sphere)

spirochete (spiral)

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Figure 5.4 Components of a Virus

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Figure 5.5 Lymphatic Capillaries: the Initial Vessels of the Lymphatic

System

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Figure 5.6 Organization of Lymphatic Capillaries

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Figure 5.7 Examples of Larger Lymphatic Vessels

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Figure 5.8 The Largest Lymphatic Vessels

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Figure 5.9 The Largest Lymphatic Vessels: An Enlarged View

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Figure 5.10 Reticular Connective Tissue

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Figure 5.11 Lymph Nodes

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Figure 5.12 Tonsils

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Figure 5.13 Spleen

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Figure 5.14 Thymus Gland

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Figure 5.15 Types of Immunity

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Figure 5.16 Antigens

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Figure 5.17 MHC Proteins

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Figure 5.18 Production and Maturation of B Cells and T Cells

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Figure 5.19 Diversity of B Cells and T Cells

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Figure 5.20 Clonal Selection: An Overview

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Figure 5.21 B Cell Clonal Selection

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Figure 5.22 T Cell Clonal Selection

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Figure 5.23 Cytotoxic T Cell Function

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Figure 5.24 Acquired Immunity

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Figure 5.25 HIV Life Cycle