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MCB 3020, Spring 2005 Host-Parasite Relationships 10 77 Host-parasite relationships I. Normal flora II. Pathogenesis III. Virulence IV. Nonspecific host defenses 10 78 I. Normal flora 10 79 Organisms normally associated with healthy body tissues. TB 10 80 A. Skin Not generally hospitable to microbes relatively low pH (4 to 6) often too dry Normal flora staphylococcus corynebacterium (eg. Propiobacterium acnes) TB B. Teeth enamel matrix 10 81 gingival crevice tooth cross-section TB 1. Plaque Bacteria growing on the teeth 10 82 2. Tooth decay (dental caries) Breakdown of tooth enamel caused by acids produced by plaque. Penetration of the matrix of the tooth by bacteria TB Acids, like lactic acid, are produced during sugar fermentations in anaerobic microenvironments. 10 83 simulated plaques Picture 21 10 84 3. Plaque bacteria 10 85 a. Streptococcus mutans • colonizes tooth crevices • produces dextran for attachment • dextran is produced from sucrose (table sugar) TB 10 86 S. mutans Picture 22 b. Streptococcus sobrinus colonizes smooth surfaces 10 87 attaches to glycoproteins that coat the tooth enamel c. Heavy plaque has the anaerobe Actinomyces (and others) TB C. Mucous membranes 1. Gastrointestinal tract Stomach (pH ~2) Lactobacilli small intestine (pH 4-5) Lactobacilli Enterococci large intestine (pH 7) Enterococci Picture Bacteroides 23 TB 10 88 TB Other gastrointestinal information: 10 89 • normal flora can prevent pathogens from colonizing • antibiotics can sterilize the gastrointestinal tract giving opportunistic pathogens a chance to colonize 2. Upper respiratory tract staphylococci streptococcus pathogens 10 90 Picture 24 (most are trapped in nasal secretions) TB 3. Lower respiratory tract (trachea, bronchi, lungs) 10 91 very few organisms TB 4. Urogenital tract Bladder few organisms Urethra E. coli Proteus Vagina Lactobacillus acidophilus 10 92 TB II. Pathogenesis 10 93 The process by which a pathogen damages a host. TB A. Entry 1. Site of entry Mucous membranes through intact membranes through breaks 10 94 Skin usually through breaks insect bites TB 2. Specificity for host 10 95 Pathogens often adhere best to a specific tissue of a specific host TB Tissue specificity 10 96 Host specificity Neisseria urogenital gonorrhoeae epithelium Human Salmonella typhimurium Mouse intestinal epithelium TB 3. Adherence factors on microbes Glycocalyx 10 97 Adherence proteins Lipoteichoic acids Fimbriae TB B. Growth 10 98 Factors affecting growth physical conditions nutrient availability eg. iron TB C. Spread 10 99 through the bloodstream through the lymph system through tissues TB D. Virulence factors 11 00 extracellular proteins produced by pathogens to aid in establishment or maintenance of disease TB D. Virulence factors 11 01 hyaluronidase collagenase streptokinase (breaks down fibrin clots in blood) coagulase (promotes clotting) hemolysins (attack cell membranes) leukocidins (lyse white blood cells) TB E. Exotoxins 11 02 Proteins excreted from the pathogen that harm the host can travel through the body TB 11 03 1. Diphtheria toxin Corynebacterium diphtheriae protein encoded by lysogenized phage beta blocks eukaryotic protein synthesis through ADP-ribosylation of EF-2 (elongation factor-2) potent: one molecule can kill one cell TB 2. Tetanus toxin Clostridium tetani deep puncture wounds protein: neurotoxin blocks muscle relaxation twitching paralysis lockjaw TB 11 04 Picture 25 11 05 3. Botulinum toxin Clostridium botulinum grows in improperly preserved food protein: neurotoxin blocks muscle contraction flaccid paralysis most poisonous substance known TB 4. Cholera toxin 11 06 Vibrio cholera (water contamination) protein enterotoxin (small intestine) activates adenyl cyclase causes diarrhea intestinal cell Na+ lumen H2O Na+ Cl H2O 11 07 bloodstream cholera toxin TB F. Endotoxins Gram lipopolysaccharides Escherichia Salmonella Shigella fever and diarrhea 11 08 TB 11 09 exotoxins endotoxins highly toxic weakly toxic nonpyrogenic pyrogenic (fever-causing) highly immunogenic weakly immunogenic TB 11 III. Virulence 10 The capacity to cause harm A. Invasiveness The capacity to cause harm by entry and spread B. Toxigenicity The capacity to cause harm by toxic effects TB Clostridium tetani low invasiveness high toxigenicity 11 11 Streptococcus pneumonia high invasiveness low toxigenicity TB C. Measurement of virulence 11 12 LD50 Dose (number of cells/animal) that kills 50% of animals infected TB 11 13 D. Salmonella virulence factors cytotoxin LPS Inhibits host prot. synth. virulence plasmid fimbriae O-antigen flagellum enterotoxin TB IV. Nonspecific host defenses A. Anatomical defenses B. Inflammation C. Fever 11 14 A. Anatomical defenses Lysozyme In tears and other secretions skin-physical barrier stomach-low pH cilia normal flora flushing of the urinary tract 11 15 TB B. Inflammation 11 16 swelling and redness results from complement activation and phagocytic attack localizes noxious agent often by producing a fibrin clot TB C. Effects of fever 11 17 low fever often accelerates immune response high fever often favors the pathogen TB Study objectives 11 1. Know that normal flora are organisms normally associated with healthy body tissue. Normal flora are often beneficial. However, under certain conditions18 normal flora can invade and cause disease. 2. Memorize the names of bacterial normal flora adapted to survive in certain regions of the body. 3. Know what plaque is and how it can lead to tooth decay. 4. Understand the basic steps of pathogenesis. 5. Know that the following are adherence factors: glycocalyx, adherence proteins, lipoteichoic acid, fimbriae. Continued 6. Know how the following invasion enzymes work: 11 a. hyaluronidase breaks down hyaluronic acid, a polysaccharide that cements tissues together 19 b. collagenase breaks down the fibrous protein collagen, which normally supports tissues c. streptokinase breaks down fibrin clots. Hosts sometimes form fibrin clots to wall off the invader. d. coagulase is a fibrin-clotting enzyme may offer protection against host defenses e. hemolysins, usually lipases, breakdown the lipids, and thereby lyse cells f. leukocidins lyse white blood cells impairing host defenses that rely on defenses mediated by these cells. 7. Know the details about the following exotoxins: tetanus toxin, botulism toxin, and enterotoxins (cholera toxin) 8. Know that endotoxin is lipopolysaccharide and be able to compare and contrast endo- and exotoxins. 9. Know how toxigenicity and virulence contribute to disease. 10. Know the Salmonella virulence factors. 11. Understand the nonspecific host defenses: anatomical, inflammation, fever.