Lecture 22 - Ch. 43


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Lecture 22 - Ch. 43

  1. 1. Ch. 43 The Body’s Defenses
  2. 2. The skin and mucous membranes provide first-line barriers to infection <ul><li>The first line of nonspecific defense consists of the intact skin and mucous membranes, mucus, ciliated cells lining the upper respiratory system, lysozyme, and gastric juices. </li></ul>
  3. 3. Phagocytic cells, inflammation, and antimicrobial proteins function early in infection <ul><li>The second line of nonspecific defense depends primarily upon neutrophils and macrophages, phagocytic white cells in the blood and tissues. </li></ul><ul><li>Natural killer cells mediate lysis of virus-infected cells and tumor cells. </li></ul><ul><li>Tissue damage triggers a local inflammatory response. </li></ul><ul><li>Injured cells release histamine, a chemical signal that causes dilation and increased permeability of blood vessels, allowing fluid and large numbers of phagocytic white blood cells to enter the tissues. </li></ul><ul><li>The most important antimicrobial proteins in the blood and tissues are the proteins of the complement system, involved in both nonspecific and specific defense, and interferons. </li></ul><ul><li>Secreted by virus-infected cells, interferons inhibit virus production in neighboring cells. </li></ul>
  5. 5. Lymphocytes provide the specificity and diversity of the immune system <ul><li>A substance that elicits an immune response is called an antigen. </li></ul><ul><li>The immune system recognizes specific antigens (molecules belonging to microbes, toxins, transplanted tissue, or cancer cells) and develops an immune response that inactivates or destroys that substance. </li></ul><ul><li>B lymphocytes and T lymphocytes recognize antigens via surface antigen receptors: membrane antibodies for B cells, and T-cell receptors for T cells. </li></ul><ul><li>Lymphocytes circulate throughout the blood and lymph and are found in high numbers in lymphatic tissues. </li></ul><ul><li>The great diversity of lymphocytes, each with receptors of one particular specificity, gives the immune system the capacity to respond to virtually any antigen. </li></ul>
  6. 6. Antigens interact with specific lymphocytes, inducing immune responses and immunological memory <ul><li>Clonal selection occurs when an antigen activates a lymphocyte by binding to a specific receptor. </li></ul><ul><li>In the primary immune response (to the body's first exposure to an antigen), the lymphocyte proliferates and differentiates, forming a clone of short-lived, infection-fighting effector cells and a clone of long-lived memory cells, all specific for the antigen. </li></ul><ul><li>Secondary immune responses to that same antigen, which involve memory cells, are faster and often protective. </li></ul>
  7. 7. Lymphocyte development gives rise to an immune system that distinguishes self from nonself <ul><li>Lymphocytes develop from pluripotent stem cells in the bone marrow. </li></ul><ul><li>B cells mature in the marrow, while T cells mature in the thymus. Self-tolerance develops as lymphocytes bearing receptors specific for native molecules are destroyed or rendered nonresponsive. </li></ul><ul><li>Major histocompatibility complex (MHC) molecules are crucial to T cell function. Class I MHC molecules, located on all nucleated cells of the body, present antigen fragments to cytotoxic T cells. </li></ul><ul><li>Class II MHC molecules, found mainly on macrophages and B cells, present antigen fragments to helper T cells. </li></ul><ul><li>Developing T cells are exposed to class I and II MHC molecules on cells of the thymus. Only T cells bearing receptors with affinity for self-MHC molecules reach maturity. </li></ul>
  9. 9. Helper T lymphocytes function in both humoral and cell-mediated immunity <ul><li>Humoral, or B cell, immunity, based on circulation of antibodies in the blood and lymph, defends against free viruses, bacteria, and other extracellular threats. </li></ul><ul><li>Cell-mediated, or T cell, immunity defends against intracellular pathogens by destroying infected cells; it also defends against transplanted tissue and cancer cells. </li></ul><ul><li>A CD4-bearing helper T cell is activated when its receptor binds specifically to a class II MHC-antigen complex on the surface of an antigen-presenting cell (APC). </li></ul><ul><li>The T cell then secretes interleukin-2 and other cytokines, which help activate B cells and cytotoxic T cells. </li></ul>
  10. 10. In the cell-mediated response, cytotoxic T cells counter intracellular pathogens <ul><li>Most cytotoxic T cells are activated by cytokines and specific binding to class I MHC-antigen complexes on a target (infected, transplanted, or cancerous) cell. </li></ul><ul><li>The T cell then secretes perforins, which form pores in the target cell membrane, causing the cell to lyse. </li></ul>
  11. 11. In the humoral response, B cells make antibodies against extracellular pathogens <ul><li>B cells are activated by cytokines and specific binding of their membrane antibodies to extracellular antigens. </li></ul><ul><li>Most of these antigens are proteins or large polysaccharides, each with multiple epitopes. </li></ul><ul><li>Antibodies, also called immunoglobulin (Ig) molecules, are serum proteins. </li></ul><ul><li>The variable regions of an Ig molecule bind to a specific epitope; the constant regions determine the antibody's class. </li></ul><ul><li>The five major immunoglobulin classes are IgG, IgM, IgA, IgD, and IgE. </li></ul><ul><li>An antibody does not destroy an antigen directly but neutralizes it or targets it for elimination by opsonization, agglutination, precipitation, or complement fixation. </li></ul><ul><li>Opsonization, agglutination, and precipitation enhance phagocytosis of the antigen-antibody complex; complement fixation leads to lysis of a complement protein-bound bacterium or virus. </li></ul>
  12. 12. Invertebrates have a rudimentary immune system <ul><li>Invertebrates have the ability to distinguish between self and nonself. </li></ul><ul><li>In many invertebrates, amoeboid cells called coelomocytes can identify and destroy foreign substances. </li></ul><ul><li>Experiments with earthworms show that their defense systems form memory against tissue grafts. </li></ul>
  13. 13. <ul><li>Immune Responses video </li></ul>
  15. 15. Immunity can be achieved naturally or artificially <ul><li>Active immunity occurs when the immune system responds to a foreign antigen acquired either by natural infection or artificially, as by immunization. </li></ul><ul><li>In immunization, a nonpathogenic form of a microbe or part of a microbe generates an immune response to and immunological memory for that microbe. </li></ul><ul><li>Passive immunity occurs when antibodies are transferred from one individual to another. </li></ul><ul><li>t occurs naturally, when IgG passes from mother to fetus or when IgA passes from mother to infant in breast milk, or artificially, when antibodies from an animal immune to a disease are injected into another animal, conferring short-term protection. </li></ul>
  16. 16. The immune system's capacity to distinguish self from nonself limits blood transfusion and tissue transplantation <ul><li>Certain antigens on red blood cells determine whether a person has type A, B, AB, or O blood. Antibodies to nonself blood types (generally IgM) already exist in the body. </li></ul><ul><li>If incompatible blood is transfused, the transfused cells are killed by antibody- and complement-mediated lysis. </li></ul><ul><li>The Rh factor, another red blood cell antigen, creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses. </li></ul><ul><li>During delivery of the first Rh-positive infant, the mother's immune system develops anti-Rh IgG, which can cross the placenta and may attack the red blood cells of a subsequent Rh-positive fetus. </li></ul><ul><li>The chances of success in organ or tissue transplantation are improved if the donor and recipient MHC tissue types are well matched. </li></ul><ul><li>In addition, immunosuppressive drugs help prevent rejection. In bone marrow transplantation, there is danger of a graft versus host reaction. </li></ul>
  17. 17. Abnormal immune function can lead to disease <ul><li>In allergies such as hay fever, an allergen, such as pollen, triggers histamine release from mast cells, inducing vascular changes and typical symptoms. </li></ul><ul><li>Sometimes the immune system loses tolerance for self, leading to autoimmune diseases such as rheumatoid arthritis and insulin-dependent diabetes. </li></ul><ul><li>Some people are naturally deficient in humoral or cell-mediated immune defenses, or both. </li></ul>
  18. 18. AIDS is an immunodeficiency disease caused by a virus <ul><li>Acquired immunodeficiency syndrome (AIDS) is caused by the direct and indirect destruction of CD4-bearing T cells by HIV, the human immunodeficiency virus, over a period of years. </li></ul><ul><li>AIDS, the final stage of this process, is marked by low helper T cell levels and opportunistic diseases characteristic of a deficient cell-mediated immune response. </li></ul>
  19. 19. <ul><li>HIV Reproductive Cycle video </li></ul><ul><li>What Causes Infections in AIDS Patients? video </li></ul><ul><li>Why Do AIDS Rates Differ Across the U.S.? video </li></ul>