Unit 4a – Almost done!

1. Unit 4a – Almost done!

2. Chapter 15: Microbial Mechanisms of Pathogenicity • How microbes cause disease (figure 15.9)

3. Remember? • Pathogenicity: The ability to cause disease. • Virulence: The extent of pathogenicity.

4. Most pathogenshave a preferredportal of entry • Salmonella typhiswallowed vs. rubbed • Strep pneumoniainhaled vs. swallowed

5. Numbers of Invading Microbes • _____: Infectious dose for 50% of a sample population. • _____: Lethal dose (toxin) for 50% of a sample population. • actual number depends on: • virulence of pathogen • strength of host defenses • for same pathogen and same person, infective dosage varies from day to day with strength of body defenses

6. Clickers… • What is the LD50 for the bacterial toxin tested in the experiment below? • Dilution # of animals # of animals mg/kg that died that survived • 6 0 6 • 12.5 0 6 • 25 3 3 • 50 4 2 • 100 6 0

7. Virulence factors: how pathogens cause disease • Many pathogens have multiple virulence factors • Virulence factors have 5 general effects • adherence to host cells • entering into host cells • destruction of host cells • avoiding phagocytosis • evading immune responses Good Essay Question!

8. Adherence factors • for attachment to host cells

9. attachment by capsule • Remember Unit 1 discussion of Biofilms?

10. attachment by filaments

11. attachment by hook

12. attachment by viral spikes

13. Some exoenzymes of virulence • 1. collagenase: dissolves collagen (protein fibers in connective tissue); softens up a tissue so infection can spread • Clostridium’s spread of gas gangrene • 2. IgA proteases • Destroy our IgA antibodies • Gonorrhoea and meningococcal meningitis can do • 3. hyaluronidase: dissolves hyaluronic acid (glue-like substance that holds cells together); helps infection to spread • Streptococcus sp.

14. hyaluronidase dissolving hyaluronic acid

15. 4. lecithinase: dissolves cell membranes; pathogen can digest cell contents

16. enzymes of virulence • 5. coagulases: Help MAKE blood clot; fibrin fibers coat pathogen, prevent phagocytosis • Staph (to wall off boils) • 6. leukocidins: kill white blood cells • Staph aureus • 7. kinases: Help REMOVE blood clots (e.g. streptokinase) • 8. hemolysins: cause hemolysis (lysis of red blood cells) • test for hemolysis on blood agar

17. alpha hemolysis: partial hemolysis, causes greenish zone around colony on blood agar

18. beta hemolysis: complete hemolysis, causes clear, colorless zone around colony

19. gamma hemolysis: NO hemolysis

20. Other virulence factors • _________: prevents phagocytosis, helps pathogen attach to host cell

21. Toxins • Toxin: Substances that contribute to pathogenicity. • Toxigenicity: Ability to produce a toxin. • Toxemia: Presence of toxin in the host's blood. • Antitoxin: Antibodies our body produces against a specific toxin. • Toxoid: Inactivated toxin used in a vaccine. • When toxoids are injected as a vaccine, they stimulate antitoxin production so that immunity is produced • Diphtheria and tetanus toxoid vaccination

22. Exotoxins • Fig. 15.4

23. Endotoxins: Fig. 15.4

24. Endotoxins and the pyrogenic responsefigure 15.6

26. Sepsis and Septic Shock: pp. 639-641 (10thed) • Although blood is normally sterile, if the defenses of the cardiovascular and lymphatic systems fail, microbes could enter blood/lymph • Septicemia: proliferation of pathogens in the blood • Fever • Sometimes causes organ damage • Sepsis: systemic inflammatory response syndrome (SIRS) • Mediators of inflammation into the blood stream • Fever • rapid heart or respiratory rates • High count of white blood cells • Lymphangitis:inflamed lymph vessels

27. Fig. 23.2 Relationship between the cardiovascular and lymphatic systems

28. Sepsis and Septic Shock continued • life-threatening systemic response to a bacterial infection • First stage is sepsis • Fever, chills and accelerated breathing & heart rate • Overwhelming infection leads to low blood pressure and low blood flow. • Shock • Vital organs, such as the brain, heart, kidneys, and liver may not function properly or may fail. Decreased urine output from kidney failure may be one symptom. • Severe sepsis to septic shock

29. Types • Gram-Negative Sepsis • Endotoxic shock • 750,000 cases/ yr in US; at least 225,000 are fatal (textbook pg. 640) • Gram-Positive Sepsis • Staph, Strep & Enterococcus • Puerperal Sepsis • Childbirth fever • Nosocomial infection • Strep. pyogenesmost frequent cause

30. high risk patients: • Burns • Age >60 or the very young • post-surgery (especially intestinal) • abdominal trauma • advanced cancer • diabetes

31. septic shock • mechanism: pathogens release endotoxins, exotoxins: • these products stimulate release of chemicals from various host cells that produce the symptoms: • low blood pressure, especially when standing • rapid, weak pulse • fever (hypothermia in burn patients) • Low urine output • Agitation, confusion

32. septic shock • symptoms: • sudden high fever • disorientation, confusion, irritability, somnolence • edema (swelling): face, hands, feet • dyspnea • edema may constrict pharynx • bronchioles contract • death by asphyxiation may result • circulatory stagnation • inadequate blood volume causes low blood pressure, rapid weak pulse, possible total stagnation of bloodflow

33. septic shock • treatment (not necessarily in this order) • inject epinephrine • open airway (intubation or tracheostomy) • oxygen if needed • restore blood volume: rapid IV • draw blood for blood gases and to culture pathogen • broad spectrum drug (until pathogen is known) • monoclonal antibodies against endotoxin

34. Back to figure 15.9

35. In summary: Damage to host cells • 1. By using the host’s nutrients • Siderophores: proteins pathogens produce to get the iron they need from the host • 2. By causing direct damage in the immediate vicinity of the invasion • 3. By producing toxins

36. Portals of ExitRespiratory tractCoughing and sneezingGastrointestinal tractFeces and salivaGenitourinary tractUrine and vaginal secretionsSkinBloodBiting arthropods and needles or syringes