Powerpoints Chap. 18-22


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Powerpoints Chap. 18-22

  1. 1. The Human Immune System
  2. 3. The Human Immune System <ul><li>Unlike our other organ systems, this one is composed of trillions of individual cells circulating throughout the body </li></ul><ul><li>Many of these cells are associated with the lymph nodes, thymus and spleen </li></ul>
  3. 4. Definitions: <ul><li>Immunity = Resistance to disease </li></ul><ul><ul><li>Innate Immunity – Responds to any substance that is non-self, altered-self, or missing self </li></ul></ul><ul><ul><ul><li>You are born with these defenses in place </li></ul></ul></ul><ul><ul><li>Adaptive Immunity – a highly specific response targeted against a particular foreign invader or altered-self cell </li></ul></ul><ul><ul><ul><li>Your body will synthesize or activate these defenses if required by the environment </li></ul></ul></ul><ul><li>Both systems require appropriate genes </li></ul>
  4. 5. Innate Body Defenses <ul><li>Membrane barriers – skin and mucosae </li></ul><ul><li>Antimicrobial cells </li></ul><ul><li>Inflammation </li></ul><ul><li>Antimicrobial proteins </li></ul><ul><li>Fever </li></ul>
  5. 6. Innate Body Defenses <ul><ul><li>1. Membrane Barriers - Body’s 1rst Line of Defense </li></ul></ul><ul><ul><li>Skin and Mucosae </li></ul></ul><ul><ul><ul><li>Cutaneous (Dry membranes) </li></ul></ul></ul><ul><ul><ul><ul><li>Skin – highly keratinized and acidic </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sebum – toxic to bacteria </li></ul></ul></ul></ul><ul><ul><ul><li>Mucous (Wet membranes) </li></ul></ul></ul><ul><ul><ul><ul><li>Vaginal secretions – acidic ( Lactobacillus ) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Stomach – gastric juice is pH ~2 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Saliva and lacrimal fluid - lysozyme </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sticky mucus traps – in digestive and resp. tract </li></ul></ul></ul></ul>
  6. 7. 2. Non-Specific Antimicrobial Cells <ul><li>Phagocytes </li></ul><ul><ul><li>All macrophages = “large eater”cells </li></ul></ul><ul><ul><li>Classified by tissue in which they are found </li></ul></ul><ul><ul><ul><li>Kupffer cells – liver </li></ul></ul></ul><ul><ul><ul><li>Langerhans cells – epidermis of skin </li></ul></ul></ul><ul><ul><ul><li>Microglial cells – brain </li></ul></ul></ul><ul><ul><ul><li>Monocytes – blood </li></ul></ul></ul><ul><ul><ul><li>Neutrophils - blood </li></ul></ul></ul>
  7. 8. Phagocytes in the Blood <ul><ul><li>Neutrophils </li></ul></ul><ul><ul><li>Monocytes </li></ul></ul>
  8. 9. Job Description of Neutrophils <ul><li>1rst to respond to invasion </li></ul><ul><li>React within 1 hour of invasion </li></ul><ul><li>Some granules are lysosomes </li></ul><ul><li>Some granules contain “defensins” – </li></ul><ul><ul><li>Antibiotic like proteins </li></ul></ul><ul><li>Neutrophils self-destruct when used </li></ul><ul><li>Respiratory burst  H 2 O 2 </li></ul>
  9. 10. Job Description of Monocytes <ul><li>Arrive at invasion site within 8-12 hours </li></ul><ul><li>Janitorial duty </li></ul><ul><li>Initially are small and sluggish </li></ul><ul><li>Become very active phagocytes </li></ul><ul><li>Phagosome + lysosome  </li></ul><ul><li>phagolysosome </li></ul><ul><li>Act as antigen presenting cells (APC’s) </li></ul>
  10. 11. 3. Inflammation <ul><li>Pavementing </li></ul><ul><li>Diapedesis </li></ul><ul><li>Chemotaxis </li></ul><ul><li>Pus </li></ul><ul><li>Abscess </li></ul><ul><li>Infectious granuloma </li></ul>
  11. 12. 4 Cardinal Signs of Inflammation <ul><li>Heat - histamine </li></ul><ul><li>Redness - histamine </li></ul><ul><li>Swelling - histamine </li></ul><ul><li>Pain - prostaglandins </li></ul>
  12. 13. Inflammation - Body’s 2 nd line of defense <ul><ul><li>Prevents spread of damaging agents </li></ul></ul><ul><ul><li>Disposes of cell debris and pathogens </li></ul></ul><ul><ul><li>Sets the stage for the healing process </li></ul></ul><ul><ul><li>Brings in large quantities of </li></ul></ul><ul><ul><ul><li>O 2 </li></ul></ul></ul><ul><ul><ul><li>Nutrients </li></ul></ul></ul><ul><ul><ul><li>Fighter cells & </li></ul></ul></ul><ul><ul><ul><li>proteins </li></ul></ul></ul>
  13. 14. Non-Specific Antimicrobial Cells , cont.: Natural Killer Cell <ul><li>Not a phagocyte </li></ul><ul><li>Release chemicals onto surface of non-self or altered-self cell </li></ul><ul><ul><li>Synthesize and release perforin </li></ul></ul><ul><ul><li>Cause holes to form in cell membrane </li></ul></ul><ul><ul><li>May be used in future to fight cancers </li></ul></ul>
  14. 15. 4. Antimicrobial Proteins <ul><li>Complement System </li></ul><ul><ul><li>A collection of proteins dissolved in the blood until activated </li></ul></ul><ul><ul><li>Enhances effects of the inflammatory process </li></ul></ul><ul><ul><li>2 pathways: </li></ul></ul><ul><ul><ul><li>Classical </li></ul></ul></ul><ul><ul><ul><li>Alternate </li></ul></ul></ul><ul><ul><ul><li>Both pathways have a common terminal pathway </li></ul></ul></ul><ul><ul><ul><li>Make Membrane Attack Complex (MAC) </li></ul></ul></ul>
  15. 16. Complement/ Formation of MAC
  16. 17. MAC = M embrane A ttack C omplex <ul><li>Causes </li></ul><ul><ul><li>Cell lysis </li></ul></ul><ul><ul><li>Promotes phagocytosis </li></ul></ul><ul><ul><li>Enhances inflammation </li></ul></ul><ul><ul><li>Causes opsonization of target cell </li></ul></ul>
  17. 18. Interferons <ul><li>When cells are infected by viruses, they release small proteins called interferons before they die </li></ul><ul><li>Interferons’ job is to inhibit viral replication in neighboring cells </li></ul><ul><li>Inhibit synthesis of mRNA and DNA, thereby preventing synthesis of viral particles </li></ul><ul><li>Are not target specific, but are host specific </li></ul><ul><li>Also activate macrophages and NK cells </li></ul>
  18. 19. Interferons, cont. <ul><li>Have been used clinically to treat viral infections and viral induced cancers </li></ul><ul><ul><li>Resistant herpes infections </li></ul></ul><ul><ul><li>Viral induced cancers such as </li></ul></ul><ul><ul><ul><li>Kaposi’s sarcoma </li></ul></ul></ul><ul><ul><ul><li>Hepatitis C </li></ul></ul></ul><ul><ul><ul><li>Hairy cell leukemia </li></ul></ul></ul><ul><ul><li>Other viral infections such as AIDS </li></ul></ul><ul><li>Currently made using genetic engineering </li></ul>
  19. 20. 5. Fever <ul><li>Normal T B = 98.6 o F ( ? o C?) </li></ul><ul><li>Regulated by __________? </li></ul><ul><li>Pyrogens – secreted by macrophages </li></ul><ul><li>Raise T B </li></ul><ul><li>Fever metabolic rate </li></ul><ul><ul><li>Causes liver & spleen to sequester Fe & Zn </li></ul></ul>
  20. 21. Adaptive Body Defenses <ul><li>The Adaptive Immune System = </li></ul><ul><li>Body’s 3 rd line of defense </li></ul><ul><li>Major difference between Innate and Adaptive immune systems – </li></ul><ul><ul><li>Adaptive Immune System is: </li></ul></ul><ul><ul><ul><li>Target specific </li></ul></ul></ul><ul><ul><ul><li>Systemic </li></ul></ul></ul><ul><ul><ul><li>Challenge sensitive </li></ul></ul></ul><ul><ul><ul><li>It has memory </li></ul></ul></ul>
  21. 22. 2 Divisions in Adaptive Immune System <ul><li>Humoral mediated immunity </li></ul><ul><li>Cell mediated immunity </li></ul>
  22. 23. 2 Divisions in Adaptive Immune System <ul><li>Humoral Mediated Immunity </li></ul><ul><li>Proteins that circulate in body fluids </li></ul><ul><ul><li>Blood </li></ul></ul><ul><ul><li>Lymph </li></ul></ul><ul><ul><li>Sweat, tears, saliva, breast milk </li></ul></ul><ul><li>Proteins selectively bind to specific target molecules </li></ul><ul><li>Cell Mediated Immunity </li></ul><ul><li>Cells attacking other, specific cells </li></ul><ul><li>Can act directly by lysing cells, or </li></ul><ul><li>Act indirectly </li></ul><ul><ul><li>by releasing chemicals that increase inflammatory response or activate other macrophages/ lymphocytes </li></ul></ul>
  23. 24. Definitions: <ul><li>Antibody </li></ul><ul><li>Immunoglobulins (proteins) secreted by B- lymphocytes that have matured into plasma cells </li></ul><ul><li>These two molecules form an antigen/ antibody complex </li></ul><ul><li>Antigen </li></ul><ul><li>Usually a protein </li></ul><ul><li>Very large (M.W. >10,000 AMU’s) </li></ul><ul><li>Very complex </li></ul><ul><li>Foreign to blood & other body proteins </li></ul>
  24. 25. Why plastics are not good antigens <ul><li>Are large molecules, BUT </li></ul><ul><li>Are composed of simple, highly repeating hydrocarbon units </li></ul><ul><li>Can be used in body </li></ul><ul><ul><li>Prostheses </li></ul></ul><ul><ul><li>Stints </li></ul></ul><ul><ul><li>Wraps </li></ul></ul><ul><li>Teflon </li></ul>
  25. 26. Haptens <ul><li>Small organic molecules that can become antigenic if they bind to carrier proteins in the body </li></ul><ul><li>Example: penicillin, urushiol (poison ivy toxin) </li></ul>
  26. 27. Humoral Mediated Immunity <ul><li>Draw blood </li></ul><ul><ul><li>Serum </li></ul></ul><ul><ul><li>Buffy coat </li></ul></ul><ul><ul><li>Packed red cells </li></ul></ul><ul><li>Electrophoresis of serum </li></ul><ul><ul><li> and  globulins </li></ul></ul>
  27. 28. B-Lymphocytes Regulate Humoral Mediated Immunity <ul><li> Plasma cell </li></ul><ul><li>Lymphocytes </li></ul>
  28. 29.  Globulins = Immunoglobulins = Antibodies
  29. 30. Antibodies Are Immunoglobulins <ul><li>2 light chains </li></ul><ul><li>2 heavy chains </li></ul><ul><li>Constant Regions – Fc </li></ul><ul><ul><li>Crystallizable fragment </li></ul></ul><ul><li>Variable Regions - Fab </li></ul><ul><ul><li>Antigen binding site </li></ul></ul><ul><ul><li>Binds with antigen determinant site on antigen </li></ul></ul>
  30. 31. The 5 Classes of Immunoglobulins <ul><li>IgG – most plentiful in body fluids; protects fetuses </li></ul><ul><li>IgE – causes allergic reactions; hypersensitivity reactions; used against parasites </li></ul><ul><li>IgA – found in body secretions such as sweat and breast milk </li></ul><ul><li>IgM , IgD – are secreted during first stage of initial infection by a pathogen </li></ul>
  31. 32. 5 Ways That Antibodies Render Antigens Harmless
  32. 33. B-Lymphocytes Regulate Humoral Mediated Immunity <ul><li>“ B” stands for Bursa of Fabricius - or Bone Marrow </li></ul><ul><li>Mature into plasma cells that secrete </li></ul><ul><li>antibodies </li></ul>
  33. 34. B-Lymphocytes Regulate Humoral Mediated Immunity <ul><li> Plasma cell </li></ul><ul><li>Lymphocytes </li></ul>
  34. 35. B-Lymphocyte Clonal Selection <ul><li>Note only 1 kind of B-lymph is activated by a particular antigen </li></ul><ul><ul><li>Called “ Clonal Selection ” </li></ul></ul><ul><li>Most B lymphs mature into plasma cells, which secrete antibodies </li></ul><ul><li>Note that Memory cells are also made </li></ul><ul><li>Memory cells impart immunity </li></ul>
  35. 36. Primary and Secondary Response to Infection <ul><li>Memory Cells Impart Immunity </li></ul>
  36. 38. Primary Response <ul><li>Primary Response = </li></ul><ul><ul><li>The first time you are infected by a microbe </li></ul></ul><ul><ul><li>The first time you are vaccinated </li></ul></ul><ul><ul><li>Initial high concentrations of IgM/ IgD </li></ul></ul><ul><ul><li>Followed by in IgG </li></ul></ul>
  37. 39. Secondary Response <ul><li>Requires prior exposure to specific antigens – a very rapid release of high antibody concentration </li></ul><ul><ul><li>Active Immunity – Requires presence of memory cells </li></ul></ul><ul><ul><ul><li>Naturally acquired and artificially acquired </li></ul></ul></ul><ul><ul><ul><ul><li>Must have had disease or been vaccinated </li></ul></ul></ul></ul><ul><ul><li>Passive Immunity – Based only on the presence of antibodies </li></ul></ul><ul><ul><ul><li>Naturally acquired and artificially acquired </li></ul></ul></ul><ul><ul><ul><ul><li>Breast fed baby or administration of  globulins </li></ul></ul></ul></ul><ul><ul><ul><li>A short-term response </li></ul></ul></ul>
  38. 40. Phases of Sickness <ul><li>Incubation </li></ul><ul><li>Prodromium </li></ul><ul><li>Acute phase </li></ul><ul><li>Convalescence </li></ul>
  39. 41. Vaccines <ul><li>Clinical immunization programs </li></ul><ul><li>All vaccines work by eliciting the production of memory cells </li></ul><ul><li>Vaccination from Latin word for “cow” (“vacca”) </li></ul><ul><li>Vaccines are made from dead or weakened organisms (or viruses) or purified products from them </li></ul>
  40. 42. Cell Mediated Immunity <ul><li>The Development of </li></ul><ul><li>T-Lymphocytes </li></ul>
  41. 43. 2 Basic Kinds of T-Lymphocytes <ul><li>T 4 Lymphocytes </li></ul><ul><ul><li>AKA T helper lymphs </li></ul></ul><ul><ul><li>T suppressor lymphs (?) </li></ul></ul><ul><li>T 8 Lymphocytes </li></ul><ul><ul><li>T cytotoxic killer lymphs </li></ul></ul><ul><ul><li>T supressor lymphs (?) </li></ul></ul>
  42. 44. <ul><li>MHC Class II Markers T 4 lymphs </li></ul><ul><ul><li>MHC II markers are found on: </li></ul></ul><ul><ul><ul><li>Macrophages (APC’S) </li></ul></ul></ul><ul><ul><ul><li>B lymphocytes </li></ul></ul></ul><ul><li>MHC Class I Markers T 8 lymphs </li></ul><ul><ul><li>MHC I markers are found on: </li></ul></ul><ul><ul><ul><li>All nucleated cells in the body </li></ul></ul></ul><ul><li>System depends upon bonding by coreceptor proteins and antigen specific Tcell receptors </li></ul>
  43. 45. <ul><li>CD8 coreceptor bonds T8 cells to all nucleated cells of body via MHC class I markers </li></ul><ul><li>CD4 coreceptor bonds T4 cells to all cells bearing MHC class II markers (macrophages, B lymphs) </li></ul>
  44. 46. <ul><li>The Role of T helper Lymphocytes in the Cell-Mediated Immune Response </li></ul>
  45. 47. T4 Cells Secrete IL1 and IL2 Activate Other Components of the Immune System
  46. 49. The Molecular Structure of HIV
  47. 52. Symptoms of AIDS – Opportunistic Infections/ rare cancers <ul><li>Kaposi’s sarcoma </li></ul><ul><li>Candidiasis </li></ul>
  48. 53. Cachexia = body wasting
  49. 54. <ul><li>The Face </li></ul><ul><li>of </li></ul><ul><li>AIDS </li></ul>
  50. 55. AIDS is a Pandemic
  51. 57. Treatment of AIDS
  52. 58. <ul><li>It pays to start therapy early </li></ul><ul><li>HAART= H ighly A ggressive A nti R etroviral T herapy </li></ul><ul><li>The use of HAART has reduced the AIDS mortality rate in the U.S. </li></ul><ul><li>Medication holidays </li></ul>
  53. 59. Designing HIV vaccines
  54. 60. Autoimmunity <ul><li>Definition </li></ul><ul><ul><li>Autoimmune Diseases: Examples </li></ul></ul><ul><ul><ul><li>Systemic Lupus Erythematosis (SLE) </li></ul></ul></ul><ul><ul><ul><li>Type I Diabetes (Juvenile Onset) </li></ul></ul></ul><ul><ul><ul><li>Grave’s Disease </li></ul></ul></ul><ul><ul><ul><li>Multiple Sclerosis </li></ul></ul></ul><ul><li>Why we are not autoimmune </li></ul><ul><ul><li>Clonal Deletion </li></ul></ul><ul><ul><ul><li>(Supported by tissue and organ transplants to embryos) </li></ul></ul></ul><ul><ul><li>Clonal Anergy </li></ul></ul><ul><ul><ul><li>(Supported by sudden development of autoimmunity) </li></ul></ul></ul>
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