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Immune / Lymphatic System

phagocytic leukocyte. Fighting the Enemy Within !. Immune / Lymphatic System. lymphocytes attacking cancer cell. lymph system. What attacks us?. Viruses Bacteria Fungus Protozoa Parasites Prions. Why an immune system?. Attack from outside lots of organisms want you for lunch!

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Immune / Lymphatic System

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  1. phagocytic leukocyte Fighting theEnemy Within! Immune / LymphaticSystem lymphocytes attacking cancer cell lymph system

  2. What attacks us? • Viruses • Bacteria • Fungus • Protozoa • Parasites • Prions

  3. 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 • no cell wall • traded mobility for susceptibility Mmmmm, What’s in your lunchbox?

  4. Why an immune system? • animals must defend themselves against invaders • viruses • HIV, flu, cold, measles, chicken pox, SARS • bacteria • pneumonia, meningitis, tuberculosis • fungi • yeast (“Athlete’s foot”…) • protists • amoeba, Lyme disease, malaria Mmmmm, What’s in your lunchbox?

  5. Why an immune system? • Attack from inside • defend against abnormal body cells = cancers Mmmmm, What’s in your lunchbox?

  6. Avenues of attack • Points of entry • digestive system • respiratory system • urogenital tract • break in skin • eyes

  7. Avenues of attack • Routes of attack • circulatory system • lymph system

  8. Production & transport of leukocytes Traps foreign invaders Lymph system lymph vessels (intertwined amongst blood vessels) lymph node

  9. Development of Red & White blood cells inflammatory response Red blood cells fightparasites short-lived phagocytes 60-70% WBC develop into macrophages

  10. Lines of defense • 1st line: Barriers • broad, external defense • “walls & moats” • skin & mucus membranes • Lysozyme in tears Bacteria & insectsinheritresistance. Vertebratesacquireimmunity!

  11. Lines of defense • 2nd line: Non-specific Immunity • Innate Immunity • broad, internal defense • “patrolling soldiers” • leukocytes = phagocytic WBC • macrophages Bacteria & insectsinheritresistance. Vertebratesacquireimmunity!

  12. Lines of defense • 3rd line: Acquired Immunity • Specific Immunity • “elite trained units” • lymphocytes & antibodies • B cells & T cells Bacteria & insectsinheritresistance. Vertebratesacquireimmunity!

  13. 1st line: External defense • Physical & chemical defenses • non-specific defense • external barrier • epithelial cells & mucus membranes • skin • respiratory system • digestive system • uro-genital tract Lining of trachea: ciliated cells & mucus secreting cells

  14. Skin • The dead, outer layer of skin, known as the epidermis, forms a shield against invaders and secretes chemicals that kill potential invaders • You shed between 40 – 50 thousand skin cells every day!

  15. ~Mucus and Cilia~ • As you breathe in, foreign particles and bacteria bump into mucus throughout your respiratory system and become stuck • Hair-like structures called cilia sweep this mucus into the throat for coughing or swallowing Don’t swallowed bacteria have a good chance of infecting you?

  16. Chemical Protection • Saliva contains many chemicals that break down bacteria. • Swallowed bacteria are broken down by incredibly strong acids in the stomach that break down your food. • Lysozyme is a digestive enzyme that is abundant in a number of secretions, such as tears, saliva, human milk, and mucus.

  17. 2nd line: Internal, broad range patrol leukocytes • Innate, general defense • rapid response

  18. 2nd line: Internal, broad range patrol leukocytes • Patrolling cells & proteins • attack invaders that penetrate body’s outer barriers • Leukocytes - WBC • Complement System • anti-microbial proteins • Inflammatory Response

  19. Leukocytes: Phagocytic WBCs • Attracted by chemical signals released by damaged cells • enter infected tissue, engulf & ingest microbes • lysosomes • Neutrophils • most abundant WBC (~70%) • ~ 3 day lifespan • Macrophages • “big eater”, long-lived , • comes from monocytes

  20. Phagocytes macrophage yeast

  21. Leukocytes: Phagocytic WBCs • Natural Killer Cells • Cytotoxic cell • Destroy virus-infected cells & cancer cells by releasing chemicals that cause these cells to pop.

  22. Destroying cells gone bad! • Natural Killer Cells perforate cells • release perforin protein • insert into membrane of target cell • forms pore allowing fluid to flow into cell • cell ruptures (lysis) • apoptosis vesicle natural killer cell perforin cell membrane perforinpuncturescell membrane cell membrane virus-infected cell

  23. Inflammatory response 2nd line: Internal, broad range patrol • Damage to tissue triggers local non-specific inflammatory response

  24. Inflammatory response • capillaries dilate, more permeable (leaky) • increase blood supply • delivers WBC, RBC, platelets, clotting factors • fight pathogens • clot formation • accounts for swelling, redness & heat of inflammation & infection

  25. Inflammatory response • release histamines & prostaglandins • “smoke signals” to call in other WBC

  26. Inflammatory response • Reaction to tissue damage Pin or splinter Blood clot swelling Bacteria Chemical alarm signals Phagocytes Blood vessel

  27. Anti-microbial proteins 2nd line: Internal, broad range patrol • Complement system • ~20 proteins circulating in blood plasma

  28. Anti-microbial proteins • attack bacterial & fungal cells • form a membrane attack complex • perforate target cell • Cause apoptosis • cell lysis extracellular fluid complement proteinsform cellular lesion plasma membrane of invading microbe complement proteins bacterial cell

  29. Fever • When a local response is not enough • systemic response to infection • activated macrophages release interleukin-1 • triggers hypothalamus in brain to readjust body thermostat to raise body temperature

  30. Fever • 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

  31. 3rd line: Acquired (active) Immunity • Specific defense • lymphocytes • B lymphocytes (B cells) • T lymphocytes (T cells) • antibodies • immunoglobulins

  32. 3rd line: Acquired (active) Immunity • Responds to… • antigens • specific pathogens • specific toxins • abnormal body cells (cancer)

  33. How are invaders recognized: antigens • Antigens • proteins that serve as cellular name tags • foreign antigens cause response from WBCs • viruses, bacteria, protozoa, parasitic worms, fungi, toxins • non-pathogens: pollen & transplanted tissue “self” “foreign”

  34. How are invaders recognized: antigens • B cells & T cells respond to different antigens • B cells recognize intact antigens • pathogens in blood & lymph • T cells recognize antigen fragments • pathogens which have already infected cells “self” “foreign”

  35. bone marrow Lymphocytes • B cells • mature in bone marrow • humoral response system • “humors” = body fluids • produce antibodies

  36. bone marrow Lymphocytes • T cells • mature in thymus • cellular response system • Learn to distinguish “self” from “non-self” antigens during maturation • if they react to “self” antigens, they are destroyed during maturation

  37. B cells • Humoral response = “in fluid” • defense against attackers circulating freely in blood & lymph • Specific response • produce specific antibodiesagainst specific antigen

  38. B cells • Types of B cells • plasma cells • immediate production of antibodies • rapid response, short term release • memory cells • long term immunity

  39. 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 Antibodies Y Y • Proteins that bind to a specific antigen • multi-chain proteins produced by B cells • 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!” Y Y Y antigen-binding site on antibody Y antigen Y Y Y variable binding region Y Y each B cell has ~100,000 antigen receptors

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

  41. Y Y Y Y Y Y invading pathogens tagged with antibodies macrophageeating tagged invaders How antibodies work

  42. Exposure to antigen IgM IgG Antibody levels 0 2 4 6 Weeks Y Y Y Y Y Y invading pathogens tagged with antibodies Classes of antibodies macrophageeating tagged invaders • 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???

  43. 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 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 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 invader(foreign antigen) B cells + antibodies memory cells “reserves” recognition Y capturedinvaders 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 clone 1000s of clone cells plasma cells release antibodies 10 to 17 days for full response B cell immune response tested by B cells (in blood & lymph)

  44. 1° vs 2° response to disease • Memory B cells allow a rapid, amplified response with future exposure to pathogen

  45. How do vertebrates produce millions of antibody proteins, if they only have a few hundred genes coding for those proteins? antibody By DNA rearrangement & somatic mutation vertebrates can produce millions of B & T cells Translation of mRNA rearrangement of DNA mRNA V Transcription of gene D DNA of differentiated B cell J C C B cell chromosome of undifferentiated B cell

  46. Vaccinations • Immune system exposed to harmless version of pathogen • triggers active immunity • stimulates immune system to produce antibodies to invader • rapid response if future exposure • Most successful against viral diseases

  47. Albert Sabin 1962 oral vaccine 1914 – 1995 Jonas Salk April 12, 1955 • Developed first vaccine • against polio • attacks motor neurons

  48. Polio epidemics 1994: Americas polio free

  49. Passive immunity • Obtaining antibodies from another individual • Temporary immunity as the body does not learn to make these antibodies. • Fast; antibodies begin to work immediately.

  50. Passive immunity • 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

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