Topic 6.3 Defense against infectious disease

1. Topic 6.3 Defense against infectious disease

2. Defense against pathogens • Essential idea: The human body has structures and processes that resist the continuous threat of invasion by pathogens. • Pathogen = an organism or virus that causes a disease. Streptococcus pneumoniae Giardia

3. Pathogens can be species-specific although others can cross species barriers. • A zoonosis is a pathogen that can cross a species barrier. • Ex. Lyme disease, bird flu, bubonic plague etc. • Bird flu on NovaScienceNow http://www.pbs.org/wgbh/nova/body/pandemic-flu.html

4. Lines of Defense Nonspecific Defense Mechanisms……

5. Nonspecific Defense Mechanisms…… • Skin and mucous membranes • Skin acidity/ dryness • Mucus—traps pathogens • Lysozyme (in tears, saliva, mucus)– enzyme digests cell walls of bacteria • Stomach acidity • Nonspecific Phagocytic and Natural Killer Cells • ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to diseases. (from course guide) • Antimicrobial proteins (complement system) • Inflammation • Blood clotting

6. Histamines • White cells release histamine in response to allergens. • Histamines cause allergic symptoms. • cause blood vessels to dilate and increase in permeability. • Allergy symptoms

7. Blood Clotting Thrombus= medical name for a blood clot • Release of clotting factors by damaged tissue and/or platelets • Causes formation of thrombin • Causes formation of fibrin (fibrinogen  fibrin)

8. Coronary Thrombosis: Blood Clotting gone wrong…. • Application: Causes and consequences of blood clot formation in coronary arteries.

9. Specific Immunity • Essential idea: Immunity is based on recognition of self and destruction of foreign material. • Every organism has unique molecules on the surface of its cells. • Application: Antigens on the surface of red blood cells stimulate antibody production in a person with a different blood group.

10. Specific Immunity • Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity • Antibodies: antigen-binding immunoglobulin, produced by B cells • Lymphocyctes (circulate in blood and lymph.) • Like all blood cells, originate from pluripotent bone marrow stem cells... • B Cells (develop in bone marrow) • T Cells (develop in thymus) • Antigen:a foreign molecule that elicits a response by lymphocytes (found on pathogens) Guidance for SL only: Subgroups of phagocyte and lymphocyte are not required but students should be aware that some lymphocytes act as memory cells and can quickly reproduce to form a clone of plasma cells if a pathogen carrying a specific antigen is re-encountered.

11. Overview of specific immune responses • C:\Documents and Settings\BBAUGHMAN\Desktop\bio powerpoints\Chapter 39 BDOL IC • Animations: Animation of immune system OK…but not great

12. General principles of specific immune response • Challenge and response: Immunity is developed after a disease challenges the immune system. • Clonal selection: When challenged the immune system produces clones of lymphocytes to deal with a specific antigen • Memory cells: These cells are produced to “remember” the antigen. Why?

13. Types of immune responses • Humoral immunity • Occurs in the lymph and blood plasma • B cell activation • Production of antibodies • Cell-mediated immunity • Destroys infected body cells • T cell activation • Binds to and/or lyses cells • NOTE: WE WILL FOCUS ON THE PRODUCTION OF ANTIBODIES

14. Humoral Response: Antibody Production… • Steps: • 1. Antigen Presentation • 2. Activation of Helper T-cells • 3. Activation of B-cells • 4. Production of plasma cells and memory B cells

15. Step 1: Antigen presentation • Macrophages (a type of Phagocytic Leukocyte) take in antigens by endocytosis. • Antigen presentation: Macrophage attaches the antigen to an MHC protein and “presents’ the antigen to a helper T cell. • Helper T cells (TH): bind to proteins displayed by MHC molecules

16. Step 2: Activation of Helper T cells • The helper T-cell has a receptor for the antigen being presented. • When it binds to the antigen, the helper T cell becomes activated.

17. Step 3: Activation of B-cells • Antigen binds to inactive B cell antibody. • This allows helper T cell to bind to the B cell antibody/antigen complex. • Helper T cell sends a signal to B cell causing it to become activated.

18. Step 4: Production of Plasma cells • Activated B cells divide by mitosis (clonal selection) • Many plasma cells are produced • Plasma cells produce the antibody. • Memory B cells are also produced. • Immunity depends upon the persistence of memory cells. • Long-lived cells that allow for a rapid response if the antigen is encountered again.

19. Helper T Cell Activity • http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter48/animations.html

20. Antibody Action • C:\Documents and Settings\BBAUGHMAN\Desktop\bio powerpoints\Chapter 39 BDOL IC • Shows pathogens docking on a cell and then shows antibodies attaching to pathogen and preventing entry. Then white blood cell destruction of pathogenhttp://catalog.nucleusinc.com/generateexhibit.php?ID=15529

21. Types of Immune Responses • Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen • Secondary immune response: stronger, faster immune response if the individual is exposed to the same antigen at some later time.

22. Immunity in Health & Disease • Passive immunity: transfer of immunity from one individual to another • natural: mother to fetus; breast milk • artificial: rabies antibodies • Active immunity/natural: conferred immunity by recovering from disease • Active immunity/artificial: vaccines contain antigens that trigger immunity but do not cause the disease. Produces a primary response and memory cells.

23. Nature of science: • Consider ethical implications of research—Jenner tested his vaccine for smallpox on a child. (4.5) Jenner chose James Phipps, the eight-year old son of his gardener.

24. Vaccination: Applications and Skills • Application: Smallpox was the first infectious disease of humans to have been eradicated by vaccination. • International-mindedness: • The World Health Organization initiated the campaign for the global eradication of smallpox in 1967. The campaign was deemed a success in 1977, only 10 years later. • Skill: Analysis of epidemiological data related to vaccination programmes. (see page 471- 473 for examples) Utilization: • Human vaccines are often produced using the immune responses of other animals.

25. Monoclonal Antibodies • How to make monoclonal antibodies: • Fuse a tumor cell with a B cell that produces a specific antibody • This makes a HYBRIDOMA cell • Culture hybridoma cells to get many clones • Isolate the antibody they produce. • http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter48/animations.html#

26. a) HIV antigen is attached to the plate. b) HIV antibody from patients serum. c) A second antibody specific to the HIV antibody is added. This second antibody has an enzyme attached. d) Chromagen dye is added. e) The enzyme changes the chromagen dye color More color change = more HIV antibodies. Monoclonal Antibody Uses: • Diagnosis: • Can be used to detect antigens/substances. • Ex. Pregnancy test detects HCG. • Ex. Diagnosis of malaria. • Ex. HIV antibody detection • Animation (ELISA) http://highered.mheducation.com/sites/0072556781/student_view0/chapter33/animation_quiz_1.html • Treatment: • Cancer treatments • Treatment of rabies/anthrax. http://www.mayoclinic.com/health/monoclonal-antibody/CA00082 Article: cancer treatment

28. Antibiotics • Explain why they are effective vs. bacteria but not viruses. • Antibiotics attack metabolic pathways in bacteria. • Viruses do not have these metabolic pathways, so antibiotics can’t be used. • These metabolic pathways aren’t found in eukaryotes (no harm done to host)

29. Application: Florey and Chain’s experiments to test penicillin on bacterial infections in mice. After these 8 mice, they tested on people and it worked!

30. Nature of science: Risks associated with scientific research—Florey and Chain’s tests on the safety of penicillin would not be compliant with current protocol on testing. • Why? • Not enough animal testing • Side effects could have occurred from penicillin or impurities.

31. AIDS • Caused by HIV (human immunodeficiency virus) • Infects cells with CD4 molecules (helper T cells, macrophages and some B-lymphocytes) • Causes a reduction in the # of active lymphocytes and an inability to produce antibodies. *treatments – DNA synthesis inhibitors, reverse transcriptase inhibitors, protease inhibitors (prevent HIV enzyme protease from functioning properly) • http://highered.mcgraw-hill.com/olc/dl/120088/micro41.swf HIV Replication • http://highered.mcgraw-hill.com/olc/dl/120088/treatmentHIV.swf HIV Treatment http://www.hhmi.org/biointeractive/disease/hiv_life_cycle.html

33. Discuss cause, transmission, social implications. • UN Article on AIDS orphans (2004) http://www.unaids.org/bangkok2004/GAR2004_html/GAR2004_05_en.htm • Same article in word document

34. End of IB

35. Vaccination: Benefits and Dangers • Benefits: • Epidemic/pandemic/death prevention • Eradication of fatal/debilitating diseases (ex. smallpox) • Reduced disability due to diseases (ex. Blindness and deafness in babies due to rubella infection of their unvaccinated mothers.) • Vaccines = carefully tested for safety. • Serious adverse reactions (allergic) are very rare. • Dangers: • Some controversial concerns… (discussion) • “The medical and scientific communities have carefully and thoroughly reviewed the evidence concerning the vaccine-autism theory and have found no association between vaccines and autism.” • Citation: http://www.cdc.gov/Features/AutismDecision/ • Guillain-Barré syndrome (GBS) = rare disorder (immune system damages their nerve cells, causing muscle weakness and sometimes paralysis.) Note: Very low risk and unlikely to be causal

36. Nonspecific Phagocytic and Natural Killer Cells • Neutrophils 60-70% WBCs; engulf and destroy microbes at infected tissue • Monocytes • 5% WBCs; develop into…. • Macrophages(largest phagocytes) • enzymatically engulf and destroy microbes • Eosinophils 1.5% WBCs; destroy large parasitic invaders (blood flukes)– discharge destructive enzymes • Natural killer (NK) cells destroy virus-infected body cells & abnormal cells (no phagocytosis)

37. Antimicrobial proteins • Complement system– about 20 serum proteins that carry out a cascade of steps that lead to lysis of microbes, and attracting phagocytes. • Interferons– secreted by virus-infected cells– influence nearby cells so they won’t spread virus. • Actual AP MC question: There is some evidence that interferon may be effective against certain forms of cancer. This finding suggests that some cancers may involve • A.Viruses • B. Bacteria • C. Uric acid deposition • D. Allergic reactions • E. An overproduction of white blood cells

38. The Inflammatory Response • 1- Tissue injury; release of chemical signals~ • histamine (released by basophils/mast cells): causes Step 2... • prostaglandins: increases blood flow & vessel permeability • 2/3- Dilation and increased permeability of capillary~ • chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs • 4- Phagocytosis of pathogens~ pyrogens: leukocyte-released molecules increase body temperature (fever)– also toxins may induce fever

39. Antibody Structure & Function • Epitope: region on antigen surface recognized by antibodies • 2 heavy chains and 2 light chains joined by disulfide bridges • Antigen-binding site (variable region)

40. 5 classes of Immunoglobulins • IgM: 1st to circulate; indicates infection; too large to cross placenta • IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement • IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration • IgD: do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells • IgE: very large; small quantity; releases histamines-allergic reaction

41. Antibody-mediated Antigen Disposal • Neutralization– antibody binds to antigen and blocks its activity • opsonization: bound antibodies enhance macrophage attachment and phagocytosis. • Agglutination: antigen clumping • Precipitation: cross-linking of soluble antigens • Complement fixation: activation of 20 serum proteins (complement system), through cascading action, lyse viruses and pathogenic cells. Helps form membrane attack complex (MAC)

42. Cell-mediated: cytotoxic T cells • Destroy cells infected by intracellular pathogens and cancer cells • Class I MHC molecules (nucleated body cells) expose foreign proteins • Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC) • TC cell releases perforin, a protein that forms pores in the target cell membrane; cell lysis and pathogen exposure to circulating antibodies

43. Cytotoxic T Cell Activity http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter48/animations.html

44. Self/Nonself Recognition • Self-tolerance: capacity to distinguish self from non-self • Autoimmune diseases: failure of self-tolerance; multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus • Major Histocompatability Complex (MHC): body cell surface antigens coded by a family of genes • Class I MHC molecules: found on all nucleated cells • Class II MHC molecules: found on macrophages, B cells, and activated T cells • Antigen presentation: process by which an MHC molecule “presents’ an intracellular protein to an antigen receptor on a nearby T cell • Cytotoxic T cells (TC): bind to protein fragments displayed on class I MHC molecules • Helper T cells (TH): bind to proteins displayed by class II MHC molecules

45. Humoral response: B cells • Stimulated by T-dependent antigens (help from helper T cells) • Macrophage (APCs) with class II MHC proteins • Helper T cell (CD4 protein) • Activated T cell secretes IL-2 (cytokines) that activate B cell • B cell differentiates into memory and plasma cells (make antibodies)

46. Helper T lymphocytes • Function in both humoral & cell-mediated immunity • Stimulated by antigen presenting cells (APCs) • T cell surface protein CD4 enhances activation (attaches to MHC II) • Cytokines secreted (peptides that stimulate other lymphocytes): a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells b) interleukin-1 (IL-1): activates helper T cell to produce IL-2

47. Clonal selection • Effector cells: short-lived cells that combat the antigen • Memory cells: long-lived cells that bear receptors for the antigen • Clonal selection: antigen-driven cloning of lymphocytes • “Each antigen, by binding to specific receptors, selectively activates a tiny fraction of cells from the body’s diverse pool of lymphocytes; this relatively small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating the antigen.”

48. Abnormal immune function • Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine • Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus http://video.yahoo.com/video/play?vid=1111690282&fr=yfp-t-462Immunodeficiency disease: SCIDS (severe combined immunodeficiency); A.I.D.S.