Chapter 43.

1. phagocytic leukocyte Chapter 43. Immune System lymphocytes attacking cancer cell lymph system

2. Why an immune system? • Attack from outside • animals must defend themselves against unwelcome invaders • viruses protists • bacteria  fungi • we are a tasty vitamin-packed meal • cells are packages of macromolecules • no cell wall • traded mobility for susceptibility • Attack from inside • defend against abnormal body cells = cancers

3. Lines of defense • 1st line: Barriers • broad, innate, external defense • “barbed wire” • skin & mucus membranes • 2nd line: Non-specific patrol • broad, innate, internal defense • “untrained soldiers” • leukocytes (WBCs) • 3rd line: Immune system • specific, acquired immunity • “elite trained units” • lymphocytes & antibodies

4. 1st: External defense • non-specific defense • external barrier • epithelial cells & mucus membranes • skin • respiratory system • digestive system • genito-urinary tract Lining of trachea: ciliated cells & mucus secreting cells

5. 1st: Chemical barriers on epithelium • Skin & mucous membrane secretions • sweat • pH 3-5 • tears • washing action • mucus • traps microbes • saliva • anti-baterial = “lick your wounds” • stomach acid • pH 2-3 • anti-microbial proteins • lysozyme • digests bacterial cell walls

6. 2nd: Internal, broad range patrol leukocytes • innate defense • rapid response • cells & proteins • attack invaders that penetrate body’s outer barriers • leukocytes • phagocytic white blood cells • anti-microbial proteins • inflammatory response • natural killer cells

7. Leukocytes: Phagocytic WBCs • Neutrophils • attracted by chemical signals released by damaged cells (interferon) • enter infected tissue, engulf & ingest microbes • amoeba-like • lysosomes • ~3 day life span • Macrophages • “big eater” • bigger, long-lived phagocytes

8. Phagocytes macrophage yeast

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

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

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

12. Inflammatory response • Damage to tissue triggers local inflammatory response • histamines & prostaglandins released • capillaries dilate, more permeable • lead to clot formation • increased blood supply • swelling, redness & heat of inflammation & infection • delivers WBC, RBC, platelets, clotting factors

13. 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 • 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

14. 3rd: Acquired Immunity • Specific defense • lymphocytes • B lymphocytes (B cells) • T lymphocytes (T cells) • antibodies • immunoglobulins • Responds to… • specific microorganisms • specific toxins • abnormal body cells • antigens

15. Antigens • Proteins that serve as cellular name tags • foreign antigens cause response from WBCs • proteins belonging: • viruses, bacteria, protozoa, parasitic worms, fungi, toxins • non-pathogens: pollen & transplanted tissue • B cells & T cells respond to different antigens • B cells recognize intact antigens • invaders in blood & lymph • T cells recognize antigen fragments • invaders which have infected cells “self” “foreign”

16. Lymphocytes • B cells • mature in bone marrow • humoral response system • “humors” = body fluids • produce antibodies • T cells • mature in thymus • cellular response system • Learn to distinguish “self” from “non-self” antigens during maturation

17. B cells • Humoral response = “in fluid” • defense against attackers circulating freely in blood & lymph • Specific response • recognizes specific antigen • produces antibodies against it • tagging protein = immunogloblin • millions of different B cells, each produces different antibodies,each recognizes a different antigen • types of B cells • plasma cells • immediate production of antibodies • short term release • memory cells • long term immunity

18. 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 • antibodies match molecular shape of antigens • immune system has antibodies to respond to millions of antigens (invaders) • tagging system • “this is foreign!” Y Y Y Y Y variable binding region Y Y Y Y each B cell has ~100,000 antigen receptors

19. How antibodies work

20. 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

21. 1° vs 2° response to disease • Memory B cells allow a rapid, amplified response with future exposure to pathogen

22. How can we have so many antibody proteins & so few genes? Variable region Antibody Constant region Light chain B cell Heavy chain Variable DNA combinations: • 1M different B cells • 10M different T cells Rearrangement of DNA Translation of mRNA Transcription of gene V mRNA 40 genes for Variable region DNA of differentiated B cell D J C C Chromosome of undifferentiated B cell

23. Vaccinations • Active immunity • immune system exposed to harmless version of pathogen • Stimulates immune system to produce antibodies to invader • rapid response if future exposure • Most successful against viral diseases

24. 1914 – 1995 Jonas Salk • Developed first vaccine • against polio April 12, 1955

25. Polio epidemics

26. Passive immunity • Maternal immunity • antibodies pass from mother to baby across placenta or in breast 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

27. T cells • Immune response to infected cells • defense against invaders inside infected cells • viruses & bacteria within infected cells, fungi, protozoa & parasitic worms • defense against “non-self” cells • cancer & transplant cells • Kinds of T cells • helper T cells • stimulate immune system • killer T cells • attack infected body cells

28. T cell How are cells tagged with antigens • Glycoproteins on surface of cells have unique “fingerprint” • major histocompatibility proteins (MHC) • human leukocyte antigens (HLA) • MHC proteins constantly export bits of cellular protein to cell surface • “snapshot” of what is going on inside cell MHC proteins displaying self-antigens

29. T cell How do T cells know a cell is infected • Infected cells digest some pathogens & export pieces to MHC proteins on cell surface • antigen presenting cells (APC) invading pathogen MHC proteins displaying foreign antigens T cell antigen receptors

30. 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 killerT cell activatekiller T cells stimulateB cells &antibodies helperT cell helperT cell helperT cell helperT cell helperT cell Y Y Y Y Y Y Y Y T cell response infected cell interleukin 2 interleukin 1 or activated macrophage interleukin 2

31. Attack of the Killer T cells • Destroys infected body cells • binds to target cell • secretes perforin protein • punctures cell membrane of infected cell Vesicle Killer T cell Killer T cellbinds toinfected cell Perforin puncturescell membrane Cell membrane Cell membrane Infected cell destroyed Target cell

32. Y Y Y Y Y Y Y antibodies Y Y Y Y Immune response pathogen invasionantigenexposure free antigens in blood antigens on infected cells macrophages humoral response cellular response helperT cells B cells T cells plasmaB cells memoryB cells memoryT cells cytotoxicT cells

33. HIV & AIDS • Human Immunodeficiency Virus • virus infects helper T cells • helper T cells don’t activate rest of immune system: T cells & B cells • also destroy T cells • Acquired ImmunoDeficiency Syndrome • infections by opportunistic diseases • death usually from other infections • pneumonia or cancer

34. 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 • diabetes • beta-islet cells of pancreas attacked & destroyed • multiple sclerosis • T cells attack myelin sheath of brain & spinal cord nerves • Allergies • over-reaction to environmental antigens • allergens = proteins on pollen, from dust mites, in animal saliva

35. Key attributes of immune system • 4 attributes that characterize the immune system as a whole • specificity • antigen-antibody specificity • diversity • react to millions of antigens • memory • rapid 2° response • ability to distinguish self vs. non-self • maturation & training process to reduce auto-immune disease