2. AP Biology 2007-2008 Immune / Lymphatic System lymphocytes attacking cancer cell phagocytic leukocyte lymph system Fighting the Enemy Within!

3. AP Biology  Start and review with the masteringbiology.com Immunology video masteringbiology.com  Another good one from McGraw-HillMcGraw-Hill  Immune system game by NobelPrize.orgNobelPrize.org

4. AP Biology Avenues of attack  Points of entry  digestive system  respiratory system  urogenital tract  break in skin  Routes of attack  circulatory system  lymph system

5. AP Biology Why an immune system?  Attack from outside  lots of organisms want you for lunch!  animals are a tasty nutrient- & vitamin-packed meal  cells are packages of macromolecules  animals must defend themselves against invaders (pathogens)  viruses  HIV, flu, cold, measles, chicken pox  bacteria  pneumonia, meningitis, tuberculosis Lyme disease  fungi  yeast (“Athlete’s foot”…)  protists  amoeba, malaria  Attack from inside  cancers = abnormal body cells Mmmmm, What’s in your lunchbox?

6. AP Biology Lines of defense  1st line: Non-specific barriers  broad, external defense  “walls & moats”  skin & mucous membranes  2nd line: Non-specific patrols  broad, internal defense  “patrolling soldiers”  leukocytes = phagocytic WBC  3rd line: True immune system  specific, acquired immunity  “elite trained units”  lymphocytes & antibodies  B cells & T cells Bacteria & insects inherit resistance. Vertebrates acquire immunity.

7. AP Biology Pathogens (such as bacteria, fungi, and viruses) INNATE IMMUNITY (all animals) Rapid response Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Recognition of traits specific to particular pathogens, using a vast array of receptors Slower response Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic cells defend against infection in body cells. ADAPTIVE IMMUNITY (vertebrates only) Figure 43.2

8. AP Biology Development of the key players, Red & White blood cells short-lived phagocytes 60-70% WBC develop into macrophages inflammatory response fight parasites Red blood cells Lymphocytes Leukocytes

9. AP Biology Thymus Peyer’s patches (small intestine) Appendix (cecum) Adenoid Tonsils Lymphatic vessels Spleen Lymph nodes Lymph node Blood capillary Interstitial fluid Tissue cells Lymphatic vessel Masses of defensive cells Figure 43.7

10. AP Biology 1st line: Non-specific External defense  Barrier  skin  Traps  mucous membranes, cilia, hair, earwax  Elimination  coughing, sneezing, urination, diarrhea  Unfavorable pH  stomach acid, sweat, saliva, urine  Lysozyme enzyme  digests bacterial cell walls  tears, sweat Lining of trachea: ciliated cells & mucus secreting cells

11. AP Biology 2nd line: Non-specific patrolling cells  Patrolling cells & proteins  attack pathogens, but don’t “remember” for next time  leukocytes  phagocytic white blood cells  macrophages, neutrophils, natural killer cells  complement system  Free-floating proteins that destroy cells  inflammatory response  increase in body temp.  increase capillary permeability  attract macrophages yeast macrophage bacteria

12. AP Biology Leukocytes: Phagocytic WBCs  Attracted by chemical signals released by damaged cells  Neutrophils  most abundant WBC (~70%)  ~ 3 day lifespan  phagocyte  Macrophages  “big eater” phagocyte  long-lived  Natural Killer Cells  destroy virus-infected cells & cancer cells

13. AP Biology  Natural Killer Cells perforate cells  release perforin protein  insert into membrane of target cell  forms pore allowing fluid to flow in & out of cell  cell ruptures (lysis)  apoptosis Destroying cells gone bad! perforin punctures cell membrane cell membrane natural killer cell cell membrane virus-infected cell vesicle perforin

14. AP Biology Anti-microbial proteins  Complement system  ~20 proteins circulating in blood plasma  attack bacterial & fungal cells  form a membrane attack complex  perforate target cell  apoptosis  cell lysis plasma membrane of invading microbe complement proteins form cellular lesion extracellular fluid complement proteins bacterial cell

15. AP Biology Inflammatory response  Damage to tissue triggers local non-specific inflammatory response  release chemical signals  histamines & prostaglandins  capillaries dilate, become more permeable (leaky)  delivers macrophages, RBCs, platelets, clotting factors  fight pathogens  clot formation  increases temperature  decrease bacterial growth  stimulates phagocytosis  speeds up repair of tissues

16. AP Biology Figure 43.8-1 Pathogen Splinter Mast cell Macro- phage Capillary Red blood cells Neutrophil Signaling molecules

17. AP Biology Figure 43.8-2 Pathogen Splinter Mast cell Macro- phage Capillary Red blood cells Neutrophil Signaling molecules Movement of fluid

18. AP Biology Figure 43.8-3 Pathogen Splinter Mast cell Macro- phage Capillary Red blood cells Neutrophil Signaling molecules Movement of fluid Phagocytosis

19. AP Biology Fever  When a local response is not enough  system-wide response to infection  activated macrophages release interleukin-1  triggers hypothalamus in brain to readjust body thermostat to raise body temperature  higher temperature helps defense  inhibits bacterial growth  stimulates phagocytosis  speeds up repair of tissues  causes liver & spleen to store iron, reducing blood iron levels  bacteria need large amounts of iron to grow

20. AP Biology  Specific defense with memory  lymphocytes  B cells  antibodies (a.k.a. immunoglobulins)  T cells  Responds to…  antigens  cellular name tags  specific pathogens  specific toxins  abnormal body cells (cancer) 3rd line: Acquired (active) Immunity B cell

21. AP Biology “self”“foreign” How are invaders recognized?  Antigens  cellular name tag proteins  “self” antigens  no response from WBCs  “foreign” antigens  response from WBCs  pathogens: viruses, bacteria, protozoa, parasitic worms, fungi, toxins  non-pathogens: cancer cells, transplanted tissue, pollen

22. AP Biology Lymphocytes  B cells  mature in bone marrow  humoral response system  “humors” = body fluids  attack pathogens still circulating in blood & lymph  produce antibodies  T cells  mature in thymus  cellular response system  attack invaded cells  “Maturation”  learn to distinguish “self” from “non-self” antigens  if react to “self” antigens, cells are destroyed during maturation bone marrow

23. AP Biology Humoral (antibody-mediated) immune response Cell-mediated immune response Antigen (1st exposure) Engulfed by Antigen- presenting cell Helper T cell Memory helper T cells Antigen (2nd exposure) B cell Plasma cells Secreted antibodies Defend against extracellular pathogens Memory B cells Memory cytotoxic T cells Active cytotoxic T cells Defend against intracellular pathogens and cancer Cytotoxic T cell Key Stimulates Gives rise to           Figure 43.20

24. AP Biology B cells  Attack, learn & remember pathogens circulating in blood & lymph  Produce specific antibodies against specific antigen  Types of B cells  plasma cells  immediate production of antibodies  rapid response, short term release  memory cells  continued circulation in body  long term immunity

25. AP Biology macrophage plasma cells release antibodies Y Y Y Y Y Y Y Y Y Y Y Y Y B cell immune response tested by B cells (in blood & lymph) 10 to 17 days for full response invader (foreign antigen) B cells + antibodies Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y recognition Y Y Y Y Y Y Y Y clones 1000s of clone cells Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y memory cells “reserves” Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y YY Y Y captured invaders

26. AP Biology Antibodies  Proteins that bind to a specific antigen  multi-chain proteins  binding region matches molecular shape of antigens  each antibody is unique & specific  millions of antibodies respond to millions of foreign antigens  tagging “handcuffs”  “this is foreign…gotcha!” each B cell has ~50,000 antibodies Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y antigen antigen- binding site on antibody variable binding region

27. AP Biology s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s Structure of antibodies light chains antigen-binding site heavy chains antigen-binding site light chain B cell membrane heavy chains light chain variable region antigen-binding site Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y

28. AP Biology What do antibodies do to invaders? macrophage eating tagged invaders invading pathogens tagged with antibodies Y Y Y Y Y Y neutralizecaptureprecipitateapoptosis

29. AP Biology  Immunoglobulins  IgM  1st immune response  activate complement proteins  IgG  2nd response, major antibody circulating in plasma  promote phagocytosis by macrophages  IgA  in external secretions, sweat & mother’s milk  IgE  promote release of histamine & lots of bodily fluids  evolved as reaction to parasites  triggers allergic reaction  IgD  receptors of B cells??? macrophage eating tagged invaders invading pathogens tagged with antibodies Y Y Y Y Y Y Classes of antibodies Weeks 0246 IgMIgG Exposure to antigen Antibody levels

30. AP Biology Stem cell Cell division and gene rearrangement Elimination of self-reactive B cells Clonal selection Antigen Antibody Formation of activated cell populations Memory B cells Plasma cells Pathogen Receptors bind to antigens Figure 43.UN02

31. AP Biology Vaccinations  Immune system exposed to harmless version of pathogen  stimulates B cell system to produce antibodies to pathogen  “active immunity”  rapid response on future exposure  creates immunity without getting disease!  Most successful against viruses

32. AP Biology Jonas Salk  Developed first vaccine  against polio  attacks motor neurons 1914 – 1995 April 12, 1955 Albert Sabin 1962 oral vaccine

33. AP Biology  Obtaining antibodies from another individual  maternal immunity  antibodies pass from mother to baby across placenta or in mother’s milk  critical role of breastfeeding in infant health  mother is creating antibodies against pathogens baby is being exposed to  Injection  injection of antibodies  short-term immunity Passive immunity

34. AP Biology 2007-2008 What if the attacker gets past the B cells in the blood & actually infects (hides in) some of your cells? You need trained assassins to recognize & kill off these infected cells! T Attack of the Killer T cells! But how do T cells know someone is hiding in there?

35. AP Biology How is any cell tagged with antigens?  Major histocompatibility (MHC) proteins  proteins which constantly carry bits of cellular material from the cytosol to the cell surface  “snapshot” of what is going on inside cell  give the surface of cells a unique label or “fingerprint” T or B cell MHC protein MHC proteins displaying self-antigens Who goes there? self or foreign?

36. AP Biology T cell antigen receptor T cell Cytoplasm of T cell Plasma membrane  chain  chain Disulfide bridge Antigen- binding site Variable regions Constant regions Transmembrane region V V C C Figure 43.11

37. AP Biology How do T cells know a cell is infected?  Infected cells digest some pathogens  MHC proteins carry pieces to cell surface  foreign antigens now on cell membrane  called Antigen Presenting Cell (APC)  macrophages can also serve as APC  tested by Helper T cells MHC proteins displaying foreign antigens infected cell T cell with antigen receptors T H cell WANTED

38. AP Biology T cells  Attack, learn & remember pathogens hiding in infected cells  recognize antigen fragments  also defend against “non-self” body cells  cancer & transplant cells  Types of T cells  helper T cells  alerts rest of immune system  killer (cytotoxic) T cells  attack infected body cells  memory T cells  long term immunity T cell attacking cancer cell

39. AP Biology Figure 43.12 Displayed antigen fragment MHC molecule Antigen fragment Pathogen Host cell T cell T cell antigen receptor (a) Antigen recognition by a T cell (b) A closer look at antigen presentation Antigen fragment MHC molecule Host cell Top view

40. AP Biology © 2011 Pearson Education, Inc. Animation: Role of B Cells Right-click slide / select “Play”

41. AP Biology Attack of the Killer T cells Killer T cell binds to infected cell  Destroys infected body cells  binds to target cell  secretes perforin protein  punctures cell membrane of infected cell  apoptosis infected cell destroyed cell membrane Killer T cell cell membrane target cell vesicle perforin punctures cell membrane

42. AP Biology Immune system & Blood type blood type antigen on RBC antibodies in blood donation status A type A antigens on surface of RBC anti-B antibodies __ B type B antigens on surface of RBC anti-A antibodies __ AB both type A & type B antigens on surface of RBC no antibodies universal recipient O no antigens on surface of RBC anti-A & anti-B antibodies universal donor Matching compatible blood groups is critical for blood transfusions A person produces antibodies against foreign blood antigens

43. © 2011 Pearson Education, Inc. Animation: Helper T Cells Right-click slide / select “Play”

44. AP Biology © 2011 Pearson Education, Inc. Animation: Cytotoxic T Cells Right-click slide / select “Play”

45. AP Biology Figure 43.16 Antigen- presenting cell Pathogen Antigen fragment Class II MHC molecule Accessory protein Antigen receptor Helper T cell Cytokines Humoral immunity Cell- mediated immunity B cell Cytotoxic T cell 321    

46. AP Biology Figure 43.17-1 Cytotoxic T cell 1 Accessory protein Class I MHC molecule Infected cell Antigen receptor Antigen fragment

47. AP Biology Figure 43.17-2 Cytotoxic T cell 12 Accessory protein Class I MHC molecule Infected cell Antigen receptor Antigen fragment Perforin Pore Gran- zymes

48. AP Biology Figure 43.17-3 Cytotoxic T cell 312 Accessory protein Class I MHC molecule Infected cell Antigen receptor Antigen fragment Perforin Pore Gran- zymes Released cytotoxic T cell Dying infected cell

49. AP Biology Immune system malfunctions  Auto-immune diseases  immune system attacks own molecules & cells  lupus  antibodies against many molecules released by normal breakdown of cells  rheumatoid arthritis  antibodies causing damage to cartilage & bone  HIV  Helper T cells attacked by virus  multiple sclerosis  T cells attack myelin sheath of brain & spinal cord nerves  Allergies  over-reaction to environmental antigens  allergens = proteins on pollen, dust mites, in animal saliva  stimulates release of histamine

50. AP Biology Figure 43.22 IgE Allergen Histamine Granule Mast cell

51. AP Biology Figure 43.23

52. AP Biology  Human Immunodeficiency Virus  virus infects helper T cells  helper T cells don’t activate rest of immune system: killer T cells & B cells  also destroys helper T cells  AIDS: Acquired ImmunoDeficiency Syndrome  infections by opportunistic diseases  death usually from  “opportunistic” infections  pneumonia, cancers HIV & AIDS HIV infected T cell

53. AP Biology © 2011 Pearson Education, Inc. Animation: HIV Reproductive Cycle Right-click slide / select “Play”

54. AP Biology Latency AIDS Helper T cell concentration Years after untreated infection Helper T cell concentration (in blood (cells/mm 3 ) Relative anti-HIV antibody concentration Relative HIV concentration 800 600 400 200 0 0 12 3 456 78 9 10 Figure 43.25

55. AP Biology Review Videos  Bioflix: Immune responseImmune response  Bozeman Biology: Plant and Animal Defense video Bozeman Biology: Plant and Animal Defense