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Chapter 574585

  1. 1. The Immune System Chapter 57 Copyright © McGraw-Hill Companies Permission required for reproduction or display
  2. 2. Skin: First Line of Defense <ul><li>Three Lines Of Defense </li></ul><ul><ul><li>Skin – barrier to penetration </li></ul></ul><ul><ul><ul><li>Mucous membranes also important </li></ul></ul></ul><ul><ul><li>Cellular Counterattack – cells engulf and/or produce chemicals to kill microbes </li></ul></ul><ul><ul><li>Immune Response – immunoglobulins, B cells and T cells attack foreign antigens </li></ul></ul>
  3. 3. Skin: First Line of Defense <ul><li>Skin is largest vertebrate organ, provides first line of defense against microbe invasion </li></ul><ul><ul><li>Also barrier to dehydration </li></ul></ul><ul><li>Skin has three layers </li></ul><ul><ul><li>1) Epidermis </li></ul></ul><ul><ul><ul><li>10-30 cells thick </li></ul></ul></ul><ul><ul><ul><ul><li>Stratum corneum - Outer layer </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Continuously shed </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Basal Layer - Innermost layer </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Rapid division, replace lost cells of stratum corneum </li></ul></ul></ul></ul></ul>
  4. 4. Skin: First Line of Defense <ul><ul><li>2) Dermis </li></ul></ul><ul><ul><ul><li>15-40 times thicker than epidermis </li></ul></ul></ul><ul><ul><ul><li>Provides structural support for epidermis </li></ul></ul></ul><ul><ul><ul><li>Contains sensory receptors, blood vessels, etc. </li></ul></ul></ul><ul><ul><li>3) Subcutaneous layer </li></ul></ul><ul><ul><ul><li>Composed of fat-rich cells acting as shock absorbers and insulators </li></ul></ul></ul>
  5. 5. Other External Body Surfaces <ul><ul><li>Digestive Tract </li></ul></ul><ul><ul><ul><li>Saliva/lysozyme </li></ul></ul></ul><ul><ul><ul><li>Acidic environment of stomach </li></ul></ul></ul><ul><ul><li>Respiratory Tract </li></ul></ul><ul><ul><ul><li>Thick mucus layer traps microbes </li></ul></ul></ul><ul><ul><ul><li>Cilia “flush” microbes out to be swallowed into digestive tract </li></ul></ul></ul><ul><ul><li>Vomiting, diarrhea, coughing and sneezing also expel microbes, etc. </li></ul></ul>
  6. 6. Cellular Counterttack: Second Line of Defense <ul><li>Lymphatic System - Central location for the collection and distribution of immune system cells </li></ul><ul><ul><li>Consists of a network of lymphatic capillaries, ducts, nodes, and lymphatic organs. </li></ul></ul>
  7. 8. White Blood Cells That Kill Invading Microbes <ul><li>Macrophages </li></ul><ul><ul><li>Ingest bacteria </li></ul></ul><ul><ul><li>Fuse with lysosome </li></ul></ul><ul><li>Neutrophils </li></ul><ul><ul><li>Ingest microbes like macrophage </li></ul></ul><ul><ul><li>Also release chemicals </li></ul></ul><ul><ul><ul><li>Create “kill zone”, includes releasing cell </li></ul></ul></ul><ul><li>Natural Killer Cells – </li></ul><ul><ul><li>Attack body cells infected by invading microbes </li></ul></ul><ul><ul><li>Also kill cancer cells, before detectable tumor </li></ul></ul><ul><ul><li>Puncture plasma membrane with perforins </li></ul></ul>
  8. 11. Proteins That Kill Invading Microbes <ul><li>Complement System </li></ul><ul><ul><li>Approximately 20 different proteins circulating freely in blood plasma </li></ul></ul><ul><ul><ul><li>Some aggregate to form membrane attack complex </li></ul></ul></ul><ul><ul><ul><ul><li>Insert into cell’s plasma membrane and form pore, allowing water to rush in and burst cell </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Others attract phagocytes to infection area or make cells easier to phagocytose </li></ul></ul></ul></ul>
  9. 13. Interferons <ul><li>Alpha, beta and gamma varieties </li></ul><ul><li>Produced by viral-infected cells </li></ul><ul><li>Act on neighboring cells to prevent replication of new viruses which might infect them </li></ul><ul><li>Gamma interferon may be involved in defense against cancer </li></ul>
  10. 14. The Inflammatory Response <ul><li>Localized, nonspecific response to infection </li></ul><ul><li>Injured cells release chemical alarm signals ( histamine and prostaglandins ) that cause blood vessels to dilate </li></ul><ul><ul><li>Increased blood flow to site of injury </li></ul></ul><ul><ul><ul><li>Stretches capillary walls increasing permeability </li></ul></ul></ul><ul><ul><ul><ul><li>Redness and swelling of affected area due to increased blood flow </li></ul></ul></ul></ul><ul><ul><ul><li>Phagocyte migration into tissue </li></ul></ul></ul>
  11. 15. Local Inflammation Copyright © McGraw-Hill Companies Permission required for reproduction or display
  12. 16. The Inflammatory Response <ul><li>Temperature Response </li></ul><ul><ul><li>When macrophages initiate counterattack, they send a message to brain to raise body temperature </li></ul></ul><ul><ul><ul><li>Fever inhibits microbial growth </li></ul></ul></ul><ul><ul><ul><li>But body temperature over 103 F dangerous and over 105 often fatal </li></ul></ul></ul>
  13. 17. The Immune Response: Third Line of Defense <ul><li>Key Concepts </li></ul><ul><ul><li>Antigen - molecule that provokes a specific immune response </li></ul></ul><ul><ul><ul><li>Antigenic Determinant Sites - Different portions/shapes of a large antigen, each stimulating a different immune response </li></ul></ul></ul><ul><ul><li>Lymphocytes called B cells respond to antigens by producing antibodies </li></ul></ul><ul><ul><ul><li>Antibody proteins are secreted into the blood and other body fluids and thus provide humoral immunity </li></ul></ul></ul>
  14. 18. The Immune Response: Third Line of Defense <ul><li>T cells directly attack cells carrying specific antigens </li></ul><ul><ul><li>Cell-mediated immunity </li></ul></ul><ul><li>Active or Acquired Immunity – use antibodies readily produced as a result of this or a previous exposure </li></ul><ul><li>Passive Immunity - immunity gained by transference of antibodies via placenta, breast feeding or injection </li></ul>
  15. 19. Immune System <ul><li>Involve actions of leukocytes </li></ul><ul><ul><li>T and B Cells are lymphocytes </li></ul></ul><ul><ul><ul><li>T Cells originate in bone marrow and migrate to thymus </li></ul></ul></ul><ul><ul><ul><ul><li>Develop ability to identify foreign particles by antigens exposed on their surfaces </li></ul></ul></ul></ul>
  16. 20. Cells of the Immune System <ul><li>T Cell types </li></ul><ul><ul><li>Inducer - Oversee T cell development </li></ul></ul><ul><ul><li>Helper - Initiate immune response </li></ul></ul><ul><ul><li>Cytotoxic - Lyse infected cells </li></ul></ul><ul><ul><li>Supressor - Terminate immune response </li></ul></ul>
  17. 21. Cells of the Immune System <ul><li>B Cells </li></ul><ul><ul><li>Are produced and complete maturation in bone marrow </li></ul></ul><ul><ul><ul><li>Circulate in blood and lymph </li></ul></ul></ul><ul><ul><ul><ul><li>When bind antigen can convert to plasma cells and produce large quantities of antibodies </li></ul></ul></ul></ul>
  18. 22. Initiating the Immune Response <ul><li>Macrophages inspect surfaces of cells encountered for MHC (major histocompatability complex) proteins </li></ul><ul><ul><li>Self versus nonself recognition </li></ul></ul><ul><ul><li>MHC genes highly polymorphic (170+ alleles) </li></ul></ul><ul><ul><li>T cells only bind to antigens presented to them on surface of cells </li></ul></ul><ul><ul><ul><li>Foreign particles are taken in and partially digested </li></ul></ul></ul><ul><ul><ul><ul><li>Antigens are processed and moved to the surface of plasma membrane </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Antigen Presenting Cells </li></ul></ul></ul></ul></ul>
  19. 27. Initiating the Immune Response <ul><li>Macrophages that encounter pathogens lacking proper MHC proteins, or a virus-infected cell with viral proteins stuck to surface, secrete alarm signal </li></ul><ul><ul><li>Interleukin-1 </li></ul></ul><ul><ul><ul><li>Stimulates helper T cells to initiate: </li></ul></ul></ul><ul><ul><ul><ul><li>Cellular response of T cells </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Humoral response of B cells </li></ul></ul></ul></ul>
  20. 28. T Cells: Cell-Mediated Immune Response <ul><li>Helper T cells become activated when they bind to complex of MHC proteins and antigens presented by macrophages. </li></ul><ul><ul><li>Helper T cells secrete interleukin-2. </li></ul></ul><ul><ul><ul><li>Stimulates production of cytotoxic T cells </li></ul></ul></ul><ul><ul><ul><ul><li>Any cytotoxic T cell whose receptor fits the particular antigen-MHC protein complex begins to multiply rapidly </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Any cells bearing traces of viral infection are destroyed </li></ul></ul></ul></ul></ul>
  21. 31. B Cells: Humoral Immune Response <ul><li>B cells recognize invading microbes and use proteins (antibodies) to mark pathogen for destruction </li></ul><ul><ul><li>Can bind to free, unprocessed antigens </li></ul></ul><ul><ul><li>Antigen particles enter B cells by endocytosis and get processed </li></ul></ul><ul><ul><ul><li>Helper T cells that recognize the specific antigen bind to the complex and stimulate B cells to divide </li></ul></ul></ul>
  22. 32. B Cells: Humoral Immune Response <ul><li>Antibodies are proteins in class immunoglobulins (Ig), which is subdivided into subclasses based on structure and function of the specific proteins </li></ul><ul><ul><li>IgM - Secreted during primary response </li></ul></ul><ul><ul><li>IgG - Secreted during secondary response </li></ul></ul><ul><ul><li>IgD - Receptors for antigens on B cells </li></ul></ul><ul><ul><li>IgA - Found in external secretions </li></ul></ul><ul><ul><li>IgF - Promote histamine release </li></ul></ul>
  23. 36. Antibodies <ul><li>Structure of Antibodies </li></ul><ul><ul><li>Each antibody consists of two short polypeptides, light chains , and two identical long chains, heavy chains . </li></ul></ul><ul><ul><ul><li>Antibodies with the same variable segments have identical clefts and therefore recognize the same antigen. </li></ul></ul></ul>
  24. 39. Antibodies <ul><li>Antibody Diversity </li></ul><ul><ul><li>Estimated human B cells can make between 10 6 and 10 9 different antibody molecules. </li></ul></ul><ul><ul><li>Immune receptor genes are assembled by stitching together three or four DNA segments that code for different parts of the receptor molecule. </li></ul></ul><ul><ul><ul><li>Somatic Rearrangement </li></ul></ul></ul><ul><ul><ul><li>And a lot more… </li></ul></ul></ul>
  25. 41. Immunological Tolerance <ul><li>Immune response does not respond to the animal’s own tissue </li></ul><ul><ul><li>Immune system of an embryo is able to respond to both foreign and self molecules </li></ul></ul><ul><ul><ul><li>Loses ability to respond to self molecules as development proceeds </li></ul></ul></ul><ul><ul><ul><li>If regained as adult result is autoimmune disease </li></ul></ul></ul>
  26. 42. Active Immunity Through Clonal Selection <ul><li>Binding of antigen to its receptor on the lymphocyte surface stimulates cell division and produces a clone ( clonal selection ) of memory cells </li></ul><ul><ul><li>Primary Immune Response carried out by “original cells from this proliferation </li></ul></ul><ul><ul><li>Secondary Immune Response occurs when body is again invaded by same pathogen/antigen and this time body starts with a large clone of lymphocytes that recognize the pathogen </li></ul></ul>
  27. 46. Antibodies in Medical Diagnosis <ul><li>Blood Typing </li></ul><ul><li>(ABO System) </li></ul><ul><ul><li>The immune system is tolerant to its own red blood cell antigens. </li></ul></ul><ul><ul><ul><li>People with type A blood make antibodies against the B antigen and vise-versa. </li></ul></ul></ul><ul><ul><ul><li>People who are type AB do not produce anti-A or anti-B antibodies. </li></ul></ul></ul><ul><ul><ul><li>People who are type O have both anti-A and anti-B antibodies. </li></ul></ul></ul>
  28. 48. Antibodies in Medical Diagnosis <ul><li>Rh Factor </li></ul><ul><ul><li>People who have Rh antigen are Rh-Positive and people who do not have the antigen are Rh-Negative </li></ul></ul><ul><ul><ul><li>If a mother produces antibodies against the Rh factor and her second child is Rh-positive, the antibodies can cause hemolysis of the Rh-Positive red blood cells of the fetus </li></ul></ul></ul><ul><ul><ul><ul><li>Erythroblastosis fetalis </li></ul></ul></ul></ul>
  29. 49. Antibodies in Medical Diagnosis <ul><li>Monoclonal Antibodies </li></ul><ul><ul><li>Monoclonal antibodies exhibit specificity for one antigenic determinant </li></ul></ul><ul><ul><li>Animal is injected with an antigen, and subsequently killed </li></ul></ul><ul><ul><ul><li>B lymphocytes are then obtained from the animal’s spleen and placed in incubation vessels </li></ul></ul></ul><ul><ul><ul><ul><li>Hybridized with cancerous multiple myeloma cells </li></ul></ul></ul></ul>
  30. 51. Antibodies in Medical Diagnosis <ul><li>Development of much more sensitive clinical laboratory tests </li></ul><ul><ul><li>Monoclonal antibodies react against one specific antigen </li></ul></ul><ul><ul><ul><li>Modern pregnancy tests </li></ul></ul></ul>
  31. 52. (hCG)
  32. 53. Evolution of the Immune System <ul><li>Bacteria </li></ul><ul><ul><li>Defend against viral invasion through restriction endonucleases that degrade foreign DNA lacking specific DNA pattern </li></ul></ul><ul><li>Invertebrates </li></ul><ul><ul><li>Mark cell surfaces with self labels </li></ul></ul><ul><ul><ul><li>Employ negative test </li></ul></ul></ul><ul><ul><ul><ul><li>May not recognize cells that resemble self marker as foreign </li></ul></ul></ul></ul>
  33. 54. Evolution of the Immune System <ul><li>Shared Elements of Invertebrate and Vertebrate Immune Responses </li></ul><ul><ul><li>Phagocytes </li></ul></ul><ul><ul><li>Distinguishing Self from Non-Self </li></ul></ul><ul><ul><li>Lymphocytes </li></ul></ul><ul><ul><li>Immunoglobulins </li></ul></ul><ul><ul><ul><li>Antibodies in vertebrates </li></ul></ul></ul><ul><ul><ul><li>Lectins in invertebrates </li></ul></ul></ul>
  34. 55. Evolution of the Immune System <ul><li>Vertebrates </li></ul><ul><ul><li>Modern vertebrate immune system first arose in fish with jaws </li></ul></ul><ul><ul><ul><li>Sharks are oldest surviving group </li></ul></ul></ul><ul><ul><ul><ul><li>Have immune response much like that in mammals </li></ul></ul></ul></ul>
  35. 57. T Cell Destruction: AIDS <ul><li>The AIDS retrovirus (HIV) mounts a direct attack on CD4 + T cells </li></ul><ul><li>HIV’s attack on CD4 + T cells cripples the immune system in at least three ways: </li></ul><ul><ul><li>HIV-infected cells die only after releasing replicated viruses </li></ul></ul><ul><ul><li>HIV causes infected cells to secrete a soluble suppressing factor that blocks other T cells from responding </li></ul></ul><ul><ul><li>May block transcription of MHC genes </li></ul></ul>
  36. 60. T Cell Destruction: AIDS <ul><li>Treatment was limited to drugs that inhibit reverse transcriptase (AZT) </li></ul><ul><ul><li>Recently, protease inhibitors have become available </li></ul></ul><ul><ul><ul><li>Inhibit enzyme necessary for viral assembly </li></ul></ul></ul><ul><ul><li>Like the influenza virus, HIV engages in some form of antigen shifting, making it difficult to develop an effective vaccine. </li></ul></ul>
  37. 62. Antigen Shifting <ul><li>Pathogen may defeat the immune system by mutating frequently so that it varies the nature of its surface antigens. </li></ul><ul><ul><li>By the time a significant number of antibodies have been generated against one form of a protein, another form is already present in the population. </li></ul></ul><ul><ul><ul><li>Survives immunological attack and reproduces </li></ul></ul></ul><ul><ul><ul><li>Trypanosomes/sleeping sickness </li></ul></ul></ul>
  38. 63. Autoimmunity and Allergy <ul><li>Autoimmune diseases are produced by a failure of the immune system to recognize and tolerate self antigens </li></ul><ul><ul><li>Results in the activation of autoreactive T cells and production on of autoantibodies by B cells </li></ul></ul><ul><ul><li>More than 40 known human autoimmune diseases </li></ul></ul><ul><ul><li>Treated by suppressing immune system and/or antiinflammatory drugs (e.g. aspirin) </li></ul></ul>
  39. 64. Autoimmunity and Allergy <ul><li>Allergy refers to particular types of abnormal immune responses to antigens - allergens </li></ul><ul><ul><li>Immediate Hypersensitivity - Due to an abnormal B cell response to an allergen that produces symptoms within seconds or minutes, IgE involved </li></ul></ul><ul><ul><li>Delayed Hypersensitivity - Abnormal T cell response that produces symptoms within about 48 hours after allergen exposure </li></ul></ul>
  40. 65. Autoimmunity and Allergy <ul><li>Mast cells initiate inflammatory response </li></ul><ul><ul><li>Release histamine causing capillaries to swell </li></ul></ul><ul><ul><ul><li>Widespread and excessive release of histamine may cause Anaphylactic Shock (an uncontrolled fall in blood pressure) </li></ul></ul></ul>
  41. 67. Copyright © McGraw-Hill Companies Permission required for reproduction or display