Chapter 18


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Chapter 18

  1. 1. Natural Defenses against Disease
  2. 2. Natural Defenses against Disease <ul><li>Animal Defense Systems </li></ul><ul><li>Nonspecific Defenses </li></ul><ul><li>Specific Defenses: The Immune System </li></ul><ul><li>B Cells: The Humoral Immune Response </li></ul><ul><li>T Cells: The Cellular Immune Response </li></ul><ul><li>The Genetic Basis of Antibody Diversity </li></ul><ul><li>Disorders of the Immune System </li></ul>
  3. 3. Animal Defense Systems <ul><li>Animal defense systems are based on the distinction between self and nonself. </li></ul><ul><li>There are two general types of defense mechanisms: </li></ul><ul><ul><li>Nonspecific defenses, or innate defenses, are inherited mechanisms that protect the body from many different pathogens. </li></ul></ul><ul><ul><li>Specific defenses are adaptive mechanisms that protect against specific targets. </li></ul></ul>
  4. 4. Animal Defense Systems <ul><li>Components of the defense system are distributed throughout the body. </li></ul><ul><li>Lymphoid tissues (thymus, bone marrow, spleen, lymph nodes) are essential parts of the defense system. </li></ul><ul><li>Blood plasma suspends red and white blood cells and platelets. </li></ul><ul><li>Red blood cells are found in the closed circulatory system. </li></ul><ul><li>White blood cells and platelets are found in the closed circulatory system and in the lymphatic system. </li></ul>
  5. 5. Animal Defense Systems <ul><li>Lymph consists of fluids that accumulate outside of the closed circulatory system in the lymphatic system . </li></ul><ul><li>The lymphatic system is a branching system of tiny capillaries connecting larger vessels. </li></ul><ul><li>These lymph ducts eventually lead to a large lymph duct that connects to a major vein near the heart. </li></ul><ul><li>At sites along lymph vessels are small, roundish lymph nodes . </li></ul><ul><li>Lymph nodes contain a variety of white blood cells. </li></ul>
  6. 6. Figure 18.1 The Human Lymphatic system
  7. 7. Animal Defense Systems <ul><li>White blood cells are important in defense. </li></ul><ul><li>All blood cells originate from stem cells in the bone marrow. </li></ul><ul><li>White blood cells ( leukocytes ) are clear and have a nucleus and organelles. </li></ul><ul><li>Red blood cells are smaller and lose their nuclei before they become functional. </li></ul><ul><li>White blood cells can leave the circulatory system. </li></ul><ul><li>The number of white blood cells sometimes rises in response to invading pathogens. </li></ul>
  8. 8. Animal Defense Systems <ul><li>There are two main groups of white blood cells: phagocytes and lymphocytes. </li></ul><ul><li>Phagocytes engulf and digest foreign materials. </li></ul><ul><li>Lymphocytes are most abundant. There are two types: B and T cells. </li></ul><ul><li>T cells migrate from the circulation to the thymus, where they mature. </li></ul><ul><li>B cells circulate and also collect in lymph vessels, and make antibodies. </li></ul>
  9. 9. Figure 18.2 Blood Cells (Part 1)
  10. 10. Figure 18.2 Blood Cells (Part 2)
  11. 11. Figure 18.2 Blood Cells (Part 3)
  12. 12. Animal Defense Systems <ul><li>Four groups of proteins play key roles in defending against disease: </li></ul><ul><ul><li>Antibodies , secreted by B cells, bind specifically to certain substances. </li></ul></ul><ul><ul><li>T cell receptors are cell surface receptors that bind nonself substances on the surface of other cells. </li></ul></ul><ul><ul><li>Major histocompatibility complex ( MHC ) proteins are exposed outside cells of mammals. These proteins help to distinguish self from nonself. </li></ul></ul><ul><ul><li>Cytokines are soluble signal proteins released by T cells. They bind and alter the behavior of their target cells. </li></ul></ul>
  13. 13. Nonspecific Defenses <ul><li>The skin acts as a physical barrier to pathogens. </li></ul><ul><li>Bacteria and fungi on the surface of the body ( normal flora ) compete for space and nutrients against pathogens. </li></ul><ul><li>Tears, nasal mucus, and saliva contain the enzyme lysozyme that attacks the cell walls of many bacteria. </li></ul><ul><li>Mucus and cilia in the respiratory system trap pathogens and remove them. </li></ul><ul><li>Ingested pathogens can be destroyed by the hydrochloric acid and proteases in the stomach. </li></ul><ul><li>In the small intestine, bile salts kill some pathogens. </li></ul>
  14. 14. Nonspecific Defenses <ul><li>Vertebrate blood contains about 20 antimicrobial complement proteins . </li></ul><ul><li>Complement proteins provide three types of defenses: </li></ul><ul><ul><li>They attach to microbes, helping phagocytes recognize and destroy them. </li></ul></ul><ul><ul><li>They activate the inflammation response and attract phagocytes to the site of infection. </li></ul></ul><ul><ul><li>They lyse invading cells. </li></ul></ul>
  15. 15. Nonspecific Defenses <ul><li>Interferons are produced by cells that are infected by a virus. </li></ul><ul><li>All interferons are glycoproteins consisting of about 160 amino acids. </li></ul><ul><li>They increase resistance of neighboring cells to infections by the same or other viruses. </li></ul><ul><li>Each vertebrate species produces at least three different interferons. </li></ul>
  16. 16. Nonspecific Defenses <ul><li>Phagocytes ingest pathogens. There are several types of phagocytes: </li></ul><ul><ul><li>Neutrophils attack pathogens in infected tissue. </li></ul></ul><ul><ul><li>Monocytes mature into macrophages . They live longer and consume larger numbers of pathogens than do neutrophils. Some roam and others are stationary in lymph nodes and lymphoid tissue. </li></ul></ul><ul><ul><li>Eosinophils kill parasites, such as worms, that have been coated with antibodies. </li></ul></ul><ul><ul><li>Dendritic cells have highly folded plasma membranes that can capture invading pathogens. </li></ul></ul>
  17. 17. Nonspecific Defenses <ul><li>Natural killer cells are a class of nonphagocytic white blood cells </li></ul><ul><li>They can initiate the lysis of virus-infected cells and some tumor cells. </li></ul>
  18. 18. Nonspecific Defenses <ul><li>The inflammation response is used in dealing with infection or tissue damage. </li></ul><ul><li>Mast cells and white blood cells called basophils release histamine , which triggers inflammation. </li></ul><ul><li>Histamine causes capillaries to become leaky, allowing plasma and phagocytes to escape into the tissue. </li></ul><ul><li>Complement proteins and other chemical signals attract phagocytes. Neutrophils arrive first, then monocytes (which become macrophages). </li></ul>
  19. 19. Nonspecific Defenses <ul><li>The macrophages engulf invaders and debris and are responsible for most of the healing. </li></ul><ul><li>They produce several cytokines, which may signal the brain to produce a fever. </li></ul><ul><li>Pus, composed of dead cells and leaked fluid, may accumulate. </li></ul>
  20. 20. Figure 18.4 Interactions of Cells and Chemical Signals in Inflammation (Part 1)
  21. 21. Figure 18.4 Interactions of Cells and Chemical Signals in Inflammation (Part 2)
  22. 22. Specific Defenses: The Immune System <ul><li>Four characteristics of the immune system: </li></ul><ul><ul><li>1. Specificity: Antigens are organisms or molecules that are specifically recognized by T cell receptors and antibodies. </li></ul></ul><ul><ul><ul><li>The sites on antigens that the immune system recognizes are the antigenic determinants (or epitopes ). </li></ul></ul></ul><ul><ul><ul><li>Each antigen typically has several different antigenic determinants. </li></ul></ul></ul><ul><ul><ul><li>The host creates T cells and/or antibodies that are specific to the antigenic determinants. </li></ul></ul></ul>
  23. 23. Figure 18.6 Each Antibody Matches an Antigenic Determinant
  24. 24. Specific Defenses: The Immune System <ul><ul><li>2. Diversity: </li></ul></ul><ul><ul><ul><li>It is estimated that the human immune system can distinguish and respond to 10 million different antigenic determinants. </li></ul></ul></ul><ul><ul><li>3. Distinguishing self from nonself: </li></ul></ul><ul><ul><ul><li>Each normal cell in the body bears a tremendous number of antigenic determinants. It is crucial that the immune system leave these alone. </li></ul></ul></ul><ul><ul><li>4. Immunological memory: </li></ul></ul><ul><ul><ul><li>Once exposed to a pathogen, the immune system remembers it and mounts future responses much more rapidly. </li></ul></ul></ul>
  25. 25. Specific Defenses: The Immune System <ul><li>The immune system has two responses against invaders: The humoral immune response and the cellular immune response. </li></ul><ul><li>The two responses operate in concert and share mechanisms. </li></ul>
  26. 26. Specific Defenses: The Immune System <ul><li>The humoral immune response involves antibodies that recognize antigenic determinants by shape and composition. </li></ul><ul><li>Some antibodies are soluble proteins that travel free in blood and lymph. Others are integral membrane proteins on B cells. </li></ul><ul><li>When a pathogen invades the body, it may be detected by and bound by a B cell whose membrane antibody fits one of its potential antigenic determinants. </li></ul><ul><li>This binding activates the B cell, which makes multiple soluble copies of an antibody with the same specificity as its membrane antibody. </li></ul>
  27. 27. Specific Defenses: The Immune System <ul><li>The cellular immune response is able to detect antigens that reside within cells. </li></ul><ul><li>It destroys virus-infected or mutated cells. </li></ul><ul><li>Its main component consists of T cells. </li></ul><ul><li>T cells have T cell receptors that can recognize and bind specific antigenic determinants. </li></ul>
  28. 28. Specific Defenses: The Immune System <ul><li>Several questions arise that are fundamental to understanding the immune system. </li></ul><ul><ul><li>How does the enormous diversity of B cells and T cells arise? </li></ul></ul><ul><ul><li>How do B and T cells specific to antigens proliferate? </li></ul></ul><ul><ul><li>Why don’t antibodies and T cells attack and destroy our own bodies? </li></ul></ul><ul><ul><li>How can the memory of postexposure be explained? </li></ul></ul>
  29. 29. Specific Defenses: The Immune System <ul><li>Clonal selection explains much of this. </li></ul><ul><li>The healthy body contains a great variety of B cells and T cells, each of which is specific for only one antigen. </li></ul><ul><li>Normally, the number of any given type of B cell present is relatively low. </li></ul><ul><li>When a B cell binds an antigen, the B cell divides and differentiates into plasma cells (which produce antibodies) and memory cells. </li></ul><ul><li>Thus, the antigen “selects” and activates a particular antibody-producing cell. </li></ul>
  30. 30. Figure 18.7 Clonal Selection in B Cells
  31. 31. Specific Defenses: The Immune System <ul><li>An activated lymphocyte (B cell or T cell) produces two types of daughter cells: effector and memory cells. </li></ul><ul><li>Effector B cells , called plasma cells , produce antibodies. </li></ul><ul><li>Effector T cells release cytokines. </li></ul><ul><li>Memory cells live longer and retain the ability to divide quickly to produce more effector and more memory cells. </li></ul>
  32. 32. Specific Defenses: The Immune System <ul><li>When the body encounters an antigen for the first time, a primary immune response is activated. </li></ul><ul><li>When the antigen appears again, a secondary immune response occurs. This response is much more rapid, because of immunological memory. </li></ul>
  33. 33. Figure 18.8 Immunological Memory
  34. 34. Specific Defenses: The Immune System <ul><li>Artificial immunity is acquired by the introduction of antigenic determinants into the body. </li></ul><ul><li>Vaccination is inoculation with whole pathogens that have been modified so they cannot cause disease. </li></ul><ul><li>Immunization is inoculation with antigenic proteins, pathogen fragments, or other molecular antigens. </li></ul><ul><li>Immunization and vaccination initiate a primary immune response that generates memory cells without making the person ill. </li></ul>
  35. 35. Specific Defenses: The Immune System <ul><li>Antigens used for immunization or vaccination must be processed so that they will provoke an immune response but not cause disease. There are three principle ways to do this: </li></ul><ul><ul><li>Attenuation involves reducing the toxicity of the antigenic molecule or organism. </li></ul></ul><ul><ul><li>Biotechnology can produce antigenic fragments that activate lymphocytes but do not have the harmful part of the protein toxin. </li></ul></ul><ul><ul><li>DNA vaccines are being developed that will introduce a gene encoding an antigen into the body. </li></ul></ul>
  36. 36. Specific Defenses: The Immune System <ul><li>The body is tolerant of its own molecules, even those that would cause an immune response in other individuals of the same species. </li></ul><ul><li>Failure to do so results in autoimmune disease . </li></ul><ul><li>This self tolerance is based on two mechanisms: clonal deletion and clonal anergy. </li></ul>
  37. 37. Specific Defenses: The Immune System <ul><li>Immunological tolerance is a poorly understood but clearly observable phenomenon. </li></ul><ul><li>Exposing a fetus to an antigen before birth provides later tolerance to the antigen. </li></ul><ul><li>Continued exposure is necessary to maintain the tolerance. </li></ul><ul><li>Some individuals experience the opposite effect; they lose tolerance to themselves, which results in autoimmune disease. </li></ul>
  38. 38. Disorders of the Immune System <ul><li>HIV (human immunodeficiency virus), which leads to AIDS (acquired immune deficiency syndrome), causes a depletion of T H cells. </li></ul><ul><li>It can be transmitted through blood or by exposure of broken skin or an open wound to the body fluids of an infected person. </li></ul>
  39. 39. Figure 18.21 The Course of an HIV Infection
  40. 40. Disorders of the Immune System <ul><li>HIV uses RNA as its genetic molecule. </li></ul><ul><li>The core of the virus contains two identical molecules of RNA and the enzymes reverse transcriptase, integrase, and a protease. </li></ul><ul><li>The envelope is derived from the plasma membrane of the cell in which the virus grew. </li></ul><ul><li>The virus enters the cell via cell membrane proteins on T H cells. </li></ul>
  41. 41. Disorders of the Immune System <ul><li>Once in the cell, reverse transcriptase makes a DNA copy (cDNA) of the viral RNA, and cellular DNA polymerase makes the complementary strand. </li></ul><ul><li>Reverse transcriptase is error prone; this elevates the mutation rate and adds to the adaptability of the virus. </li></ul><ul><li>The cDNA integrates into the host DNA. </li></ul>