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 ex. Influenzaex. Influenza

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 Bacterial proteinsBacterial proteins

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

44. G- bacteria are ingested by phagocytes They degrade bacteria and LPS of bacterial cell wall released These endotoxins cause macrophages to produce a cytokine called interleukin-1 This is carried by blood to the hypothalamus (temp. control portion of the brain) IL-1 induces hypothalamus to release lipids called prostaglandins, these reset thermostat in the hypothalamus at a higher temperature Result is a fever Bacterial cell death caused by antibiotics or lysis can also cause fever by this mechanism Both aspirin and acetaminophen reduce fever by inhibiting synthesis of prostaglandinsG- bacteria are ingested by phagocytes They degrade bacteria and LPS of bacterial cell wall released These endotoxins cause macrophages to produce a cytokine called interleukin-1 This is carried by blood to the hypothalamus (temp. control portion of the brain) IL-1 induces hypothalamus to release lipids called prostaglandins, these reset thermostat in the hypothalamus at a higher temperature Result is a fever Bacterial cell death caused by antibiotics or lysis can also cause fever by this mechanism Both aspirin and acetaminophen reduce fever by inhibiting synthesis of prostaglandins

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