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