Pathogen & Defense Against Disease: Fighting the Enemy Within!

1. Pathogen and Defense Against Disease (Topic 6.3 &11.1) Fighting theEnemy Within!

2. 6.3.1  Define pathogen • A pathogen is a disease-causing agent • Example:

3. 6.3.2  Explain why antibiotics are effective against bacteria but not against viruses Antibiotics are substances or compounds that kill or inhibit the growth of bacteria by targeting the metabolic pathways of prokaryotes • Specific prokaryotic features that may be targeted by • antibiotics include key enzymes, 70S ribosomes and the • bacterial cell wall • Because eukaryotic cells do not have these features, • antibiotic can kill bacterial cells without harming humans • (or viruses)

4. 6.3.2  Explain why antibiotics are effective against bacteria but not against viruses • Viruses do not carry out metabolic reactions themselves, but • instead infect host cells and take over their cellular machinery • Viruses need to be treated with specific antiviral agents that • target features specific to viruses (e.g. reverse transcriptase • in retroviruses) http://www.youtube.com/watch?v=Rpj0emEGShQ (How a virus attacks your body) http://www.sumanasinc.com/scienceinfocus/sif_antibiotics.html (The Rise in Antibiotic Resistance)

5. 6.3.2  Explain why antibiotics are effective against bacteria but not against viruses

6. 6.3.3  Outline the role of skin and mucous membranes in defense against pathogens First Line of Defense • The first line of defense against infection are the surface barriers that prevent the entry of pathogenic substances • Examples: skin and mucous membranes

7. 6.3.3  Outline the role of skin and mucous membranes in defense against pathogens Skin • Protects external structures (outer body areas) • A dry, thick and tough region made of predominantly dead surface cells • Contains sebaceous glands - secrete chemicals which inhibit the growth of some bacteria • Releases acidic secretions to lower pH and prevent bacteria from growing

8. 6.3.3  Outline the role of skin and mucous membranes in defense against pathogens Mucous membranes • Protect internal structures (externally accessible cavities and tubes, such as trachea, vagina and urethra) • A thin region containing living surface cells that release fluids to wash away pathogens (mucus, tears, saliva, etc.) • Secretions contain lysozyme, which can destroy cell walls and cause cell lysis • May be ciliated to aid in the removal of pathogens (along with physical actions such as coughing or sneezing)

9. 6.3.4  Outline how phagocytic leukocytes ingest pathogens in the blood and in body tissue Second Line of Defense • The second line of defense against pathogenic invasion • are the non-specific defense mechanisms • Non-specific mechanisms do not differentiate between • types of microorganisms and always invoke the same • response • Examples: phagocytic leukocytes, inflammation, fever and • anti-microbial proteins

10. 6.3.4  Outline how phagocytic leukocytes ingest pathogens in the blood and in body tissue Phagocytic leukocytes (macrophages) circulate in the blood but may move into body tissue in response to infection http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.html Phagocytosis

11. 6.3.4  Outline how phagocytic leukocytes ingest pathogens in the blood and in body tissue • They concentrate at sites of infection due to the release of • histamine from damaged body cells • Pathogens are engulfed when pseudopodia surround the • pathogen and then fuse, sequestering it in an internal vesicle • The vesicle may then fuse with the lysosome to digest the • pathogen • Some of the pathogens antigenic fragments may be • presented on the surface of the macrophage, in order to • help stimulate antibody production • This mechanism is called phagocytosis ('cell-eating')

12. 6.3.5  Distinguish between antigens and antibodies Third Line of Defense • The third line of defense are the specific defenses, • coordinated by a type of leukocyte called lymphocytes • These can recognize and respond specifically to different • types of micro-organism and have memory (can respond • more effectively upon reinfection) Antigen:  A substance that the body recognizes as foreign and that can evoke an immune response Antibody:  A protein produced by certain white blood cells (B lymphocytes, plasma cells) in response to an antigen

13. 6.3.5  Distinguish between antigens and antibodies • Antibodies are made up of 4 polypeptide chains (2 light and • 2 heavy chains) joined together by disulphide bonds to form • a Y-shaped molecule • The ends of the arms are where the antigens bind and these • areas are called the variable regions, as these will differ • between antibodies • Each type of antibody will recognize a unique antigenic • fragment, making this interaction specific (like enzyme- • substrate interactions) 

14. 6.3.5  Distinguish between antigens and antibodies

15. 6.3.5  Distinguish between antigens and antibodies

16. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity

17. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity Challenge and Response Challenge: pathogen enters blood Response: - Pathogen engulfed by macrophage - Macrophage takes on the antigen (or epitope - cell surface protein) - Macrophage presents epitope to T cells - Complementary helper T cells are activated - Helper T cell stimulates appropriate B cell - B-cell produces clones - Clones become either plasma cells or memory cells - Plasma cells produce antibodies - Memory cells remain as immunity to the pathogen

18. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity • Clonal Selection • B lymphocytes (B cells) are antibody-producing cells that • develop in the bone marrow to produce a highly specific • antibody that recognizes one type of antigen • When wandering macrophages encounter a pathogen, • they digest it and • present the antigenic • fragments on their • surface to helper • T lymphocytes • (THcells) 

19. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity • Clonal Selection • When antigens are presented to B cells (and TH cells) by • macrophages, only the B cell with the appropriate antibody • will become activated and clone • The majority of B cell clones will differentiate into antibody- • producing plasma cells, a minority will become memory • B cells (BMcells)

20. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity http://www.youtube.com/watch?v=HUSDvSknIgI Fighting infection by clonal selection http://www.sumanasinc.com/webcontent/animations/content/monoclonalantibodies.html Monoclonal antibodies

21. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity • Because pathogens may contain several antigenic • determinants, several B cell clones may become activated • (polyclonal activation)

22. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity Because the adaptive immune response is dependent on clonal expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies

23. 6.3.6 / 11.1.4 Explain antibody production 11.1.2  Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity • If a second infection with the same antigen occurs, • the memory cells react faster and more vigorously than • the initial immune response, such that the symptoms of • the infection do not normally appear • Because the individual no longer presents with the • symptoms of infection upon exposure, the individual is • thus said to be immune

24. 6.3.7  Outline the effect of HIV on the immune system • The human immunodeficiency virus (HIV) is a retrovirus • that infects helper T lymphcytes (TH cells) • Reverse transcriptase allows viral DNA to be produced • from its RNA code, which is integrated into the host cells • genome

25. 6.3.7  Outline the effect of HIV on the immune system • After a number of years of inactivity (during which • infected TH cells have continually reproduced), the virus becomes active and begins to spread, destroying • the TH cells in the process (known as the lysogenic cycle) • This results in lower immunity as antibody production is • compromised - the individual is now susceptible to • opportunistic infections

26. 6.3.7  Outline the effect of HIV on the immune system http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__how_the_hiv_infection_cycle_works.html

27. 6.3.8  Discuss the cause, transmission and social implications of AIDS • Cause • Acquired Immunodeficieny Syndrome (AIDS) is a collection • of symptoms and infections caused by the destruction of the • immune system by HIV • While HIV infection results in a lowering in immunity over • a number of years, AIDS describes the final stages when • observable symptoms develop

28. 6.3.8  Discuss the cause, transmission and social implications of AIDS • Transmission • HIV is transmitted through the exchange of bodily fluids • (including unprotected sex, blood transfusions, breast • feeding, child birth, etc.) • The risk of exposure to HIV through sexual contact can • be reduced by using latex protection (condoms) • A minority of people are immune to HIV infection (they • do not have the CD4+ T cell receptor that HIV needs to • infect the cell)

29. 6.3.8  Discuss the cause, transmission and social implications of AIDS • Social Implications • People with HIV may be stigmatized and discriminated • against, potentially leading to unemployment and poverty • Majority of people who die from AIDS are at a productive • age, which may cripple a country's workforce and • economic growth • It can result in an increased number of orphans, taxing • a country's welfare resources • Poverty may increase transmission of AIDS (due to poor • education and high cost of treatments), creating a moral • obligation for assistance from wealthier countries

30. 11.1.1  Describe the process of blood clotting • Clotting (hemostasis) is a mechanism that prevents the loss • of blood from broken vessels • Damaged cells and platelets release chemical signals called • clotting factors which trigger a coagulation cascade:

31. 11.1.1  Describe the process of blood clotting • Clotting factors convert the inactive zymogen prothrombin into • the activated enzyme thrombin • Thrombin catalyzes the conversion of the soluble plasma • protein fibrinogen into an insoluble form (fibrin) • Fibrin forms an insoluble • mesh of fibers that trap • blood cells at the site • of damage

32. 11.1.1  Describe the process of blood clotting • Clotting factors also cause platelets to become sticky, which • then adhere to the damaged region to form a solid plug called • a clot • The clot prevents further blood loss and blocks entry to foreign • pathogens

33. 11.1.3  Define active and passive immunity Active immunity: Immunity due to the production of antibodies by the organism itself after the body's defense mechanisms are stimulated by antigens Passive immunity:  Immunity due to the acquisition of antibodies from another organism in which active immunity has been stimulated. ex: placenta, colostrum or by injection (e.g. blood transfusions)

34. 11.1.3  Define active and passive immunity

35. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • Monoclonal antibodies (mAb) are antibodies derived • from a single B cell clone • An animal (typically a mouse) is injected with an antigen • and produces specific plasma cells

36. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • The plasma cells are removed and fused (hybridized) with • tumor cells capable of endless divisions (immortal cell line) • The resulting hybridoma is capable of synthesizing large • quantities of specific antibodies, for use in diagnosis and • treatment Monoclonal antibodies https://www.youtube.com/watch?v=sOTdqLDMvcg

37. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • Diagnostic Use: • Monoclonal antibodies can be used to test for • 1) pregnancy via the presence of human chorionic • gonadotrophin (hCG) • 2) HIV via Elisa test

38. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • Pregnancy Test • An antibody specific to hCG is made and is tagged to an • indicator molecule (e.g. chromatophore or pigment • molecule) http://www.sumanasinc.com/webcontent/animations/content/pregtest.html Pregnancy Test

39. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • When hCG is present in the urine, it binds to the anti-hCG • monoclonal antibody and this complex will move with the • fluid until it reaches a second group of fixed antibodies • When the complex binds to the fixed antibodies, they will • appear as a blue line (positive result) due to the presence • of the indicator molecule

40. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • Elisa Test • A tray is coated with antigens for a pathogen. • Serum samples are taken from a patient. • If samples contain the antibodies, a color change occurs • which shows the patient is carrying the pathogen and the body • is trying to fight it. Elisa Test https://www.youtube.com/watch?v=lNxZxJtvB94

41. 11.1.5  Describe the production of monoclonal antibodies and their use in diagnosis and treatment • Treatment Use: • Monoclonal antibodies can be used for the emergency • treatment of rabies • Because the rabies virus is potentially fatal in non-vaccinated • individuals, injecting purified quantities of antibody is an • effective emergency treatment for a very serious viral infection

42. 11.1.6  Explain the principle of vaccination • Vaccinations induce artificial active immunity by stimulating the • production of memory cells  • A vaccine contains weakened or attenuated forms of the • pathogen and is (usually) injected into the bloodstream • Because a modified form of the pathogen is injected, the • individual should not develop disease symptoms

43. 11.1.6  Explain the principle of vaccination • The body responds to the vaccine by initiating a primary • immune response, resulting in the production of memory cells • When exposed to the actual pathogen, the memory cells trigger • a secondary immune response that is much faster and stronger • Vaccines confer long-term immunity, however because memory • cells may not survive a life time, booster shots may be required

44. 11.1.7  Discuss the benefits and dangers of vaccination • Benefits: • Vaccination results in active immunity • It can limit the spread of infectious diseases (pandemics / • epidemics) • Diseases may be eradicated entirely (e.g. smallpox) • Vaccination programs may reduce the mortality rate of a disease • as well as protect vulnerable groups (e.g. youth, elderly) • Vaccinations will decrease the crippling effects of certain • diseases (e.g. polio)  • It will decrease health care costs associated with treating • disease conditions

45. 11.1.7  Discuss the benefits and dangers of vaccination • Risks: • Vaccinated individuals may produce (mild) symptoms of the • disease • There may be human error in the preparation, storage or • administration of the vaccine • Individuals may react badly to vaccines (e.g. hypersensitive / • allergic reactions) • Immunity may not be life long - booster shots may be required • There may be possible toxic effects of mercury-based • preservatives used in vaccines

46. Make a concept map of adaptive immune response using ALL words below: • Pathogen (carrying antigen or epitope) • Macrophage • Macrophage presenting epitope • Helper T cells • Cytotoxic T cells • B cells • Plasma cells • Memory cells • Antibodies • Clonal selection • phagocytosis