Lecture 12

1. Lecture 12 Microbial Mechanisms of Disease

2. Normal Flora of Human Body • Normal flora: population of microorganisms routinely found growing on the body of healthy individuals • Many different species of microorganisms make up normal flora and they occur in large numbers

3. Figure 19.1

4. Importance of normal flora • Protection against potentially harmful microorganisms • Stimulate the immune system • Flora of intestine stays stable- beneficial to both human and bacteria

5. Relationship between normal flora and host

6. Pioneers in discovering and studying disease caused by microorganisms • Germ theory of disease: microorganisms can cause disease and it can spread and reemerge • Louis Pastuer (1822): proved yeast are living organisms, fermenting wine • Robert Koch (1876): proved bacteria actually cause disease

7. Koch’s postulates • Microorganism must be present in every case of the disease • Organism must be grown in pure culture from the diseased host • Same disease must be produced when a pure culture of organism is injected into another host • Same organism must be recovered from the experimentally infected host

10. Classifying Infectious Diseases • Symptoms: changes in body function • Signs: physician can observe and measure • Communicable disease vs. contagious disease vs. non-communicable disease

11. Occurrence of a disease • Incidence: # of people in a population who develop the disease during a certain time period • Prevalence: # of people in a population that have the disease at a specified time

12. Occurrence of a disease • Sporadic disease: occurs only occasionally • Endemic disease: constantly present in the population • Epidemic disease: many people in a given area get disease in a short time period • Pandemic disease: world-wide epidemic

13. Severity or duration of a disease Primary Infection: initial infection, may leave person predisposed to get a Secondary Infection • Acute Infection: characterized by symptoms that have rapid onset, last short time • Chronic Infection: develops more slowly, lasts longer • Latent Infection: remains inactive, then becomes active again to produce symptoms

14. Extent of host involvement • Local infection: microbes limited to small area of body • Systemic infection: microbes or products throughout the body • Sepsis: toxic inflammatory condition • Septecemia: systemic infection

15. Development of disease • Incubation period- time interval between initial infection and the first appearance of any signs or symptoms • Prodomal period- early mild symptoms • Period of illness- when disease is most acute • Period of decline- signs and symptoms decline • Period of convalescence- person regains strength and body returns to prediseased state

17. Establishment of Disease

18. Microorganisms causing disease • To cause disease microorganisms must: • Transmit disease to host • Enter the body • Adhere to host tissues • Penetrate or evade host defenses • Damage the host tissues

19. Transmission of disease • Microorganisms can be transmitted from the reservoir of infection to a susceptible host by three principle routes • Contact • Vehicles • Vectors

20. Contact transmission • Contact transmission= • Direct contact transmission-physical contact between microorganisms source and susceptible host • Indirect contact transmission- when microorganism transmitted from reservoir to susceptible host by means of nonliving object • Droplet transmission- microorganisms spread by droplets that travel only short distance

21. Vehicle transmission • Vehicle transmission= • Waterborne transmission- water contaminated usually with untreated or poorly treated sewage • Foodborne transmission- food that is usually incompletely cooked, poorly refrigerated, or prepared under unsanitary conditions • Airborne transmission- transmission via droplets that travel more than 1 meter from reservoir to host

22. Vector • Vector= • Arthropods most important group • Mechanical transmission- passive transport of the pathogens on insects feet or other body parts • Biological transmission- active process

23. Enter the Body • Portals of Entry: • Mucous membranes: often respiratory tract • Skin: must enter through openings • Parenteral Route: deposited directly into tissues beneath the skin or mucous membranes

24. Adherence • Adhesins or ligands on microbe bind to receptors on host cells • Adhesions may be located on glycocallyx or other microbial surfaces such as pili, or flagella

25. How bacterial pathogens penetrate host defenses • Several ways: • Capsules • Components of cell wall • Enzymes • Antigenic variation • Penetration into host cell cytoskeleton

26. Capsules • Some bacteria make a glycocallyx that is outside of the cell wall • This impairs phagocytosis • Immune sytstem can overcome this • Some strains of the same bacteria have glycocallyx others do not

27. Components of cell wall • Some components of cell wall contribute to pathogenicity: • M protein • Fimbrae • Waxes

28. Enzymes • Coagulases: form blood clot • Kinases: break down fibrin and dissolve blood clots formed by the body to isolate infection • Hyaluronidase: breaks down polysaccharide that holds together connective tissue • Collagenase: breaks down collagen

29. Antigenic Variation • Antigens= • Antibodies= • Some pathogens can alter surface antigens • Makes it more difficult for immune system to fight against it

30. Penetration into host cell cytoskeleton • Microbes attach by adhesions • Triggers signals in host cell that activates factors that results in the entry of some bacteria • Bacteria produce invasions, which rearrange actin • Causes cytoskeleton disruption • Allows bacteria to enter

31. How Bacterial Pathogens Damage Host Cells • If pathogen overcomes host defenses then microorganism can damage host cells by: • Using host cell nutrients • Causing direct damage • Inducing hypersensitivity reactions • Producing toxins

32. Using Host Cell Nutrients • Bacteria require iron • Most iron in body tightly bound to iron-transport proteins • Some bacteria produce siderophores- take iron away from iron-transport proteins

33. Direct Damage • Use host cell for nutrients and produce waste products • As pathogens metabolize and multiply in cells, cells usually rupture • Then move onto other cells

34. Inducing hypersensitivity reactions • Hypersensitivity= • Occurs in people who have been sensitized by a previous encounter with an antigen • When exposed to again, their immune system reacts to it in a damaging manner

35. Production of Toxins • Toxins= • Produce fever, cardiovascular disturbances, diarrhea, and shock • Also inhibit protein synthesis, destroy red blood cells, disrupt nervous system • Two types: Endotoxins and Exotoxins

37. Exotoxins • Produced inside some bacteria as part of growth and metabolism and then secreted • Diffuse easily within blood and rapidly travel throughout body • Destroy parts of host cells or inhibit metabolic functions

38. Exotoxins • Three principal types: • A-B toxins • Membrane-disrupting toxins • Superantigens

39. A-B toxins

40. Membrane-disrupting toxins • Cause lysis of host cells by disrupting plasma membrane • Two ways: • Form protein channels in plasma membrane • Disrupt phospholipid portion of plasma membrane

41. Superantigens • Provoke very strong immune response • Immune system produces too many immune cells • Produce fever, vomiting, diarrhea, sometimes even shock and death

42. Most Notable Exotoxins • Diphtheria toxin • Botulinum toxin • Tetanus toxin

43. Endotoxins • Part of outer membrane of G- bacteria • Endotoxins released when G- bacteria die • Exert affect by stimulating macrophages to release cytokines at very high levels

45. Epidemiology

46. Descriptive Epidemiology • Collecting all data that describe the occurrence of the disease under study • Retrospective

47. Analytical Epidemiology • Analyzes a particular disease to find it’s probable cause • Case control method • Cohort method

48. Experimental Epidemiology • Hypothesis about disease • Experiments to test hypothesis conducted on group of people

49. CDC • Morbidity and Mortality Weekly Report • Morbidity: incidence of specific notifiable diseases • Mortality: number of deaths from these diseases • Notifiable diseases: those physicians are required to report