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Lymphatic System

Part I: Lymphatic System

1. The lymphatic system consists of the lymphatic vessels, lymph nodes, and certain other lymphoid organs in the body (Figure 12.1).

2. Extremely porous blind-ended lymphatic capillaries pick up excess tissue fluid leaked from the blood capillaries (Figure 12.2). The fluid (lymph) flows into the larger lymphatics and finally into the blood vascular system through the right lymphatic duct and the left thoracic duct.

3. Lymph transport is aided by the muscular and respiratory pumps and by contraction of smooth muscle in the walls of the lymphatic vessels.

4. Lymph nodes are clustered along lymphatic vessels, and the lymphatic stream flows through them. Lymph nodes form agranular WBCs (lymphocytes), and phagocytic cells within them remove bacteria, viruses, and the like from the lymph stream before it is returned to the blood.

5. Other lymphoid organs include the tonsils (in the throat), which remove bacteria trying to enter the digestive or respiratory tracts: the thymus, a programming region for some lymphocytes of the body; Peyer's patches, which prevent bacteria in the intestine from penetrating deeper into the body; and the spleen, a RBC graveyard and blood reservoir.

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Part 11: Body Defenses

Nonspecific Body Defenses

1. The first line of defense against pathogens are the surface membranes (skin and mucous membranes). They provide mechanical barriers to pathogens. Some produce secretions and/or have structural modifications that enhance their defensive effects: The skin's acidity, lysozyme, mucus, keratin, and ciliated cells are examples.

2. Phagocytes (macrophages and neutrophils) engulf and destroy pathogens that penetrate epithelial barriers. This process is enhanced when the pathogen's surface is altered by attachment of antibodies and/or complement.

3. Natural killer cells are nonimmune cells that act non-specifically to lyse vims-infected and malignant cells.

4. The inflammatory response prevents spread of harmful agents, disposes of pathogens and dead tissue cells, and promotes healing (Figure 12.3). Protective leukocytes enter the area; the area is walled off by fibrin and tissue repair occurs. The signs and symptoms of the inflammatory response are: pain, redness, swelling, and heat.

5. When complement (a group of plasma proteins) becomes fixed on the membrane of a foreign cell, lysis of the target cell occurs. Complement also enhances phagocytosis and tlie inflammatory and immune responses.

6. Interferon is a group of proteins synthesized by virus-infected cells and certain immune cells. It prevents viruses from multiplying in other body cells.

7. Fever enhances the fight against infectious microorganisms by increasing metabolism, which speeds up repair processes; and by causing the liver and spleen to store iron and zinc, which are needed for bacterial multiplication,

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Specific Body Defenses: The Immune System

1. The immune system recognizes something as foreign and acts to inactivate or remove it. Immune response is antigen-specific, is systemic, and has memory. The two arms of immune response are humoral immunity, mediated by antibodies, and cellular immunity. mediated by living cells (lymphocytes).

2. Antigens

   1. Antigens are large, complex molecules (or parts of them) recognized as foreign by the body. Foreign proteins are the strongest antigens.

   2. Complete antigens provoke an immune response and bind with products of that response (antibodies or sensitized lymphocytes).

   3. Incomplete antigens, or haptens, are small molecules that are unable to cause an immune response by themselves but do so when they bind to body proteins and the complex is recognized as foreign.

3. Cells of the immune system: An overview

   1. Two main cell populations, lymphocytes and macrophages, provide for immunity.

   2. Lymphocytes arise from hemocytoblasts of bone marrow. T cells develop immunocompetence in the thymus and oversee cell-mediated immunity. B cells develop immunocompetence in bone marrow and provide humoral immunity. Immunocompetent lymphocytes seed lymphoid organs, where antigen challenge occurs, and circulate through blood, lymph, and lymphoid organs.

   3. Immunocompetence is signaled by the appearance of antigen-specific receptors on surfaces of lymphocytes.

   4. Macrophages arise from monocytes produced in bone marrow. They phagocytize pathogens and present parts of the antigens on their surfaces for recognition by T cells.

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4. Humoral (antibody-mediated) immune response

   1. Clonal selection of B cells occurs when antigens bind to their receptors, causing them to proliferate. Most clone members become plasma cells, which secrete antibodies (Figure 12.4). This is called the primary immune response.

   2. Other clone members become memory B cells, capable of mounting a rapid attack against the same antigen in subsequent meetings (secondary immune responses). These memory cells provide immunological "memory."

   3. Active humoral immunity is acquired during an infection or via vaccination and provides im-munoiogical memory. Passive immunity is conferred when a donor's antibodies are injected into the bloodstream, or when the mother's antibodies cross the placenta. It does not provide immunological memory.
   4. Basic antibody structure. Antibodies are proteins produced by sensitized B cells or plasma cells in response to an antigen, and they are capable of binding with that antigen.

   1. An antibody is composed of four polypeptide chains (two heavy and two light) that form a Y-shaped molecule (Figure 12.5).

   2. Each polypeptide chain has a variable and a constant region. Variable regions form antigen-binding sites, one on each arm of the Y. Constant regions determine antibody function and class.

   3. Five classes of antibodies exist: IgA, IgG. IgM, IgD, IgE, They differ structurally and functionally.

   4. Antibody functions include complement fixation, neutralization, precipitation, and agglutination.

   5. Monoclonal antibodies are pure preparations of a single antibody type useful in diagnosis of various infectious disorders and cancer, and in treatment of certain cancers.

5. Cellular (cell-mediated) immune response

   1. T cells are sensitized by binding simultaneously to an antigen and a self-protein displayed on the surface of a macrophage. Clonal selection occurs, and clone members differentiate into effector T cells or memory T cells.

   2. There are several different classes of effector T cells. Cytotoxic (killer) T cells directly attack and lyse infected and cancerous cells. Helper T cells interact directly with B cells bound to antigens. They also liberate lymphokines, chemicals that enhance the killing activity of macrophages, attract other leukocytes, or act as helper factors that stimulate activity of B cells and cytotoxic T cells. Delayed hypersensitivity T cells release chemicals that enhance inflammation and promote a delayed allergic reaction. Suppressor T ceils terminate the normal immune response by releasing suppressor chemicals (Figure 12.6).

6. Disorders of immunity

   1. In allergy or hypersensitivity the immune system overreacts to an otherwise harmless antigen, and tissue destruction occurs. Immediate (acute) hypersensitivity, as seen in hayfever, hives, and anaphylaxis, is due to IgE antibodies. Delayed hypersensitivity (for example, contact dermatitis) reflects activity of T cells and lymphokines, and nonspecific killing by activated macrophages.

   2. Immunodeficiencies result from abnormalities in any immune element. Most serious is severe combined immunodeficiency disease (a congenital disease) and AIDS, an acquired immunodeficiency disease caused by a virus that attacks and cripples the helper T cells,

   3. Autoimmune disease occurs when the body's self-tolerance breaks down, and antibodies and/or T cells attack the body's own tissues. Most forms of autoimmune disease result from inefficient lymphocyte programming in the fetus, changes in structure of self-antigens or appearance of formerly hidden self-antigens in blood, and cross-reactions with self-antigens and antibodies formed against foreign antigens.

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Developmental Aspects of the Lymphatic System and Body Defenses

1. Lymphatic vessels form by budding off veins. The thymus gland is the first lymphoid organ to appear in the embryo. Other lymphoid organs remain relatively undeveloped until after birth.

2. Development of immune response occurs around the time of birth.

3. The ability of immunocompetent cells to recognize foreign antigens is genetically determined. Stress appears to interfere with normal immune response.

4. Efficiency of immune response wanes in old age, and infections, cancer, immunodeficiencies, and autoimmune diseases become more prevalent.