Chapter 39

1. Chapter 39 Immunity: A Summary AP Biology Spring 2011

2. Integrated Responses To Threats • Immunity: body’s capacity to resist and combat infection, began when multicelled eukaryotic species evolved from free-living cells

3. Integrated Responses To Threats • Mutations introduced molecular patterns in membrane proteins that were unique to cells of a given type • Mutations led to mechanisms of identifying those proteins as belonging self- one’s own body • And ability to identify nonself

4. Integrated Responses To Threats • Antigen: any molecule that the body recognizes as nonself that revokes an immune response • Most are proteins, lipids, and oligosaccharides • Pattern receptors: used to detect patterns that are present mainly on pathogenic cells • Anything that became bound to hem induced an animal cell to release complement (a set of about 30 proteins) which circulate in blood and destroy microbes or tag them for phagocytes

5. Integrated Responses To Threats • The microbial pattern receptors and complement offered innate immunity- fast, off-the-shelf responses to a fixed set of nonself cues • Does not protect against novel or unrecognized threats , adapting to them isn’t possible in an individual’s lifetime

7. Integrated Responses To Threats • Evolution of cytokines and lymphocytes • Lymphocytes: specialized class of WBC • Together these signals and cells could tailor defenses to an astounding array of specific threats that an individual encountered during its lifetime • Adaptive immunity

9. Three Lines of Defense • Pathogens cannot do damage unless they can enter the internal environment • Intact skin and lining of body tubes and cavities • Physical and chemical protection • Innate immunity • Starts immediately after antigen has been detected or after a tissue has become damaged • WBC, complement, acute inflammation, and fever • Adaptive immunity • Large populations of WBC form, all sensitized to a specific threat

11. The Defenders • Leukocytes: all WBC that arise from stem cells in bone marrow

12. The Defenders • Many kinds • Neutrophils: most abundant of WBC, fast acting phagocytes • Macrophages: slower, bigger eaters, can get rid of as many as 100 bacterial cells • Dendrite cells: alert immune system to the presence of antigen

13. The Defenders • Many kinds: • Basophils and Mast Cells: circulate in blood (basophils) and tissues (mast cells) and release enzymes and cytokines in response to antigen or injury • Eosinophils: secrete enzymes and toxic proteins that are good at punching holes in larvae of parasitic worms • B and T Lymphocytes: are central to adaptive immunity • Natural killer cells: innate immune response, also participate in adaptive immunity, directly kill body cells that are infected, stressed, or mutated, as by cancerous transformations

15. Immunalogy • http://www.youtube.com/watch?v=T_4TrNRa3v8&feature=related • Watch the video • Draw a diagram to separate innate and adaptive immunity

16. Surface Barriers- The First Line of Defense • Your skin is teeming with about 200 different kinds of microbes • Skin is waterproof covering of dead, keratin packed epithelial cell layers • Normal skin resident populations of microbes have neutral or helpful impacts on health Staphylococcus epidermidis , the most common species on skin and a leading cause of bacterial infections

17. Linings of Tubes and Cavities • Body has defenses that normally keep microbes outside on the surface of linings • Mucus: coating on free surface of epithelial linings • Consists of glycoproteins (mucins) and salts in water • Lysozyme: enzyme that cleaves peptidoglycans in bacterial cell walls and disrupts their structure • Tears have lysozymes

18. Linings of Tubes and Cavities • Breathing in air: • Mucus coated epithelial lining of airways • Coughing expels many cells, lysozymes in mucus kill others • Lining has ciliated cells, cilia beat in synchrony at its free surface, which sweeps the bacteria laden mucus to throat for disposal

19. Linings of Tubes and Cavities • In the mouth • If microbes make it to the stomach, low pH kills most • If make it to small intestine bile salts in intestinal lumen usually kill them • If make it to large intestine, must compete with 500 or so established species and if they do displace the residents a flushing mechanism (diarrhea) usually gets rid of them

20. Linings of Tubes and Cavities • Urinary tract and vagina • Lactic acid, byproduct of fermentation by Lactobacillus • Helps keep vaginal pH beyond range of tolerance for most bacteria and fungi • Flushing action of urination normally keeps most pathogens from colonizing in urinary tract

21. Uneasy Balance • Must keep microbes outside body • Surface barriers are vulnerable • When we become sick or weak with age, changes in physiology may compromise them • Examples: • Acne • Plaque deposits, periodontitis

22. Innate Immune Response • Phagocytes: • Macrophages arrive first: engulf and digest anything other than undamaged body cells • Their pattern receptors recognize and bind to pathogen secreting cytokines which signal more macrophages and neutrophils

23. Innate Immune Response • Complement Proteins: • Also arrive first • Bind to circulating microbes or to antigen being displayed at phagocyte’s surface which causes a positive feedback mechanism • One bound molecule becomes activated  then activates a few molecules of a different type of complement  then activates some of a different type, etc. • Cascading reactions yield high concentrations of activated complement in localized tissue region

24. Innate Immune Response • Activated complement proteins have many effects • Chemotactic: attract phagocyte cells (phagocytes follow gradients to site of damage, where complement is most concentrated) • Some bind to microbes: microbes coated with complements will get recognized and engulfed faster by phagocytes • Some assemble into attack complexes in cell wall or plasma membrane and promote bacterium’s lysis • Also function in adaptive immunity

25. Innate Immune Response • Acute Inflammation: swift response from to tissue irritation or tissue damage • Cytokines secretions from macrophages and activated complement trigger this • Symptoms: redness, warmth, swelling, pain

26. Innate Immune Response • Steps of acute inflammation • Mast cells respond to complement cascades or to antigen • Secrete histamine and cytokines into interstitial fluid • Histamine makes arterioles in tissue dilate  increases blood flow to the area (causes warmth and redness) • Histamine makes blood capillaries in the tissue “leaky” to plasma proteins that usually do not leave blood • Causes endothelial cells of capillary wall to shrink, cells pull further apart at clefts between them • Plasma proteins and phagocytes slip out

27. Innate Immune Response • Steps of acute inflammation continued • Osmotic pressure in interstitial fluid rises, fluid balance across the capillary wall shifts, localized edema (swelling) • Swollen tissue cause free nerve endings to give rise to sensations of pain; suppresses voluntary movements (allows for tissue repair) • Other plasma proteins leaking into interstitial fluid include clotting factors, macrophage secretions activate them

28. Innate Immune Response • Fever: rise in body temperature above the normal set point on a built in thermostat in hypothalamus • Macrophages bring about fever as innate immune response • Secrete pyrogenic cytokines which stimulates brain to synthesize and release several kinds of prostaglandins • Prostaglandins act in hypothalamus to raise thermostat set point • Fever of 39 degrees C, enhances immunity by increasing enzyme activity and speeding metabolism (formation and action of phagocytes accelerates, so does tissue repair) • Also pop. Of many microbes grow slowly at high temp.s

29. Features of Adaptive Immunity • Four characteristics of vertebrate active immunity • Self/nonself recognition • Specificity • Diversity • Memory

30. Features of Adaptive Immunity • Self versus nonself recognition • Every cell or virus has its own identity • Human cells have markers: human leukocyte antigens (HLA), also known as MHC markers (major histocompatibility complex) • T cells have TCRs: antigen receptors at their surface • T cells normally do not target body cell that has bare MHC markers, but will act against it if those markers have antigen bits attached

31. Features of Adaptive Immunity • Specificity • New B or T cell makes receptors for one kind of antigen • Diversity: • Refers to collection of antigen receptors on all B and T cells is the body • Potentially billions of different antigen receptors, gives potential to counter billions of different threats

32. Features of Adaptive Immunity • Memory • Immune system’s capacity to “remember” antigen that it vanquished • First time lymphocytes recognize an antigen, takes a few days to for their populations to form • When the same antigen shows up again, system makes faster, hightened response

33. First Step: The Antigen Alert • Recognition stimulates repeated mitotic cell divisions • Result is large populations of B and T cells, primed to recognize antigen

34. First Step: The Antigen Alert • Macrophages, B cells, dendritic cells are antigen presenting cells and find antigens and present them to T cell (receptors recognize antigens) • First engulf anything bearing antigen, vesicles move into the cytoplasm • Vesicle fuses with lysomes, enzymes digest antigens • Some fragments bind to MHC markers • Antigen-MHC complexes shuttled to plasma membrane and are displayed

35. First Step: The Antigen Alert • When a cell’s MHC markers become paired with antigen fragments, it becomes a call to arms • Odds are at least one T cell has receptors that can bind • Binds, becomes activated and secretes cytokines that induce divisions of B or T cells sensitive to same antigen • Effector cells: differentiated lymphocytes that act immediately against antigen • Memory cells: long lived B and T cells that develop during first exposure and set aside for future encounters

36. Two Arms of Adaptive Immunity • Antibody Mediated Immune Response • Pathogens in blood or interstitial fluid intercepted by phagocytes and B cells • B cells execute most of this response • T cells support

37. Two Arms of Adaptive Immunity • Cell mediated immune response • Intracellular pathogens • Vulnerable only for brief time when they slip out of one cell and infect another • This response does not acquire antibodies • Starts after antigen becomes positioned at surface of infected or altered body cells where phagocytes and cytotoxic T cells detect it

38. Intercepting and Clearing Out Antigens • After engulfing antigen, dendritic cells and macrophages enter a lymph node • In lymph node, both kinds of phagocytes alert the T cells to the threat • Free antigen in interstital fluid enters lymph vessels which deliver it to lymph nodes where it passes B cells, macrophages, and dendritic cells that can bind, process, and present it to T cells • Lymph nodes trap most antigen- some could circulate to blood! Spleen helps filter again!

39. Intercepting and Clearing Out Antigens • During infection: • Antigen-presenting T cells become trapped briefly in lymph nodes • Swollen lymph nodes sign of illness and lymphocyte activity • Immune response subside once antigen is cleared away

40. B Cells: The Antibodies • Antibodies: proteins synthesized only by B cells that encounter and bind antigen • Many Y shaped • Most circulate in blood and enter interstitial fluid during inflammation • Each acts spcifically against the antigen that promoted its synthesis

41. B Cells: The Antibodies • Structure of Antibodies: • Four polypeptide chains • Two identical “light” ones • Two identical “heavy” ones • Each chain has constant region, forms molecules backbone • One end of each chain has variable region- domain for one antigen

42. B Cells: The Antibodies • 5 structural classes of antibodies called Immunoglobulins (Igs) • IgG • IgA • IgM • IgE • IgD • B cell secretes them, circulate alone or in clumps

43. B Cells: The Antibodies • IgG • 80% of all immunoglobulins in blood • Induces complement cascades, neutralizes toxins • Crosses placenta, protects fetus with mother’s aquired immunities • Secreted into early milk (colostrum)

44. B Cells: The Antibodies • IgA • Main immunoglobulin in exocrine gland secretions • Tears, saliva, milk • In mucus of respiratory, digestive, and reproductive tracts

45. B Cells: The Antibodies • IgE • Induces inflammation after pathogen invasions • Constant regions of its heavy chains become anchored to mast cells, basophils, monocytes, or dendritic cells • Makes these cells release histamines and cytokines • Factor in allergic reactions and HIV infection

46. B Cells: The Antibodies • IgM • First to be secreted in primary response and first made by newborns • Surface of each new B cell is covered with hundreds of thousands of IgM or IgD antibodies, each of which recognizes the same antigen • Antibodies are B cell receptors, surface immunoglobulins that function as B cell’s antigen receptors

47. The Making of Antigen Receptors • B cells • Before new B cell leaves bone marrow, already synthesizing unique antigen receptors • Constant region of each is positioned in lipid bilayer of B cell’s plasma membrane • Two variable arms project above it • B cell will have 100,000 antigen receptors • “naïve” B cell- has not yet met its antigen

48. B Cells: The Antibodies • T cells: • Form inside bone marrow • Do not mature until they take a tour through thymus gland • After exposure to thymic hormones, get receptors for MHC proteins • Also get TCR’s, unique antigen receptors by gene splicing • These recombination’s are random , some TCRs end up recognizing MHC markers rather than antigen, many will not

49. B Cells: The Antibodies • To get a functional set of T cells • Thymus cells produce small peptides that are derived from a variety of the body’s proteins • Peptides get attached to MHC markers, act as built in quality controls to weed out “bad” TCRs • Any T cell that binds too tightly to one of complexes, has TCRs that recognize self peptide • T cells that do not bind at all cannot recognize MHC markers • Both types die • By the time naïve T cells leave the thymus, their surface contains functional TCRs

50. The Antibody Mediated Response • Main targets of antibody mediated response are extracellular pathogens and toxins freely circulating in blood and interstitial fluid • Nick your finger, staphlococcus aureus invades • Complement in interstitial fluid latches on to carbohydrates in their bacterial cell wall and activates cascading reactions • Complement coats bacteria • Bacteria move through lymph vessels to lymph node, where paraded past naïve B cells