1077 MCB 3020, Spring 2005 Host-Parasite Relationships

1078 Host-parasite relationships I. Normal flora II. Pathogenesis III. Virulence IV. Nonspecific host defenses

1079 I. Normal flora Organisms normally associated with healthy body tissues. most are beneficial (prevent colonization by pathogens) (how else?) TB

1080 A. Skin Not generally hospitable to microbes relatively low pH (4 to 6) often too dry staphylococcus corynebacterium (eg. Propiobacterium acnes ) Normal flora TB

1081 B. Teeth enamel tooth cross-section TB gingival crevice (saliva contains lysozyme) matrix

Plaque Bacteria growing on the teeth 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

1083 Acids, like lactic acid, are produced during sugar fermentations in anaerobic microenvironments.

1084 simulated plaques Picture 21

Plaque bacteria a. Streptococcus mutans colonizes tooth crevices produces dextran for attachment dextran is produced from sucrose (table sugar) TB

1086 S. mutans Picture 22

1087 b. Streptococcus sobrinus colonizes smooth surfaces attaches to glycoproteins that coat the tooth enamel c. Heavy plaque has the anaerobe Actinomyces ( and others) TB

Gastrointestinal tract Stomach (pH ~2) Lactobacilli large intestine (pH 7) Enterococci Bacteroides C. Mucous membranes small intestine (pH 4-5) Lactobacilli Enterococci TB Bacteria = 1/3 weight of fecal matter TB Picture 23

1089 Other gastrointestinal information: normal flora can prevent pathogens from colonizing antibiotics can sterilize the gastrointestinal tract giving opportunistic pathogens a chance to colonize

1090 Picture Upper respiratory tract staphylococci streptococcus pathogens (most are trapped in nasal secretions) TB

Lower respiratory tract (trachea, bronchi, lungs) very few organisms walls of respiratory tracts are lined with cilia that push bacteria up; microbes expelled in saliva and nasal secretions TB

Urogenital tract Bladder few organisms Urethra E. coli Proteus Vagina Lactobacillus acidophilus TB

1093 II. Pathogenesis The process by which a pathogen damages a host. TB

Site of entry Mucous membranes through intact membranes through breaks Skin usually through breaks insect bites A. Entry TB

Specificity for host Pathogens often adhere best to a specific tissue of a specific host TB

1096 Tissue specificity Host specificity intestinal epitheliumMouse Salmonella typhimurium urogenital epitheliumHuman Neisseria gonorrhoeae TB

Adherence factors on microbes Glycocalyx Adherence proteins Lipoteichoic acids Fimbriae TB

1098 B. Growth Factors affecting growth physical conditions nutrient availability eg. iron TB

1099 C. Spread through the bloodstream through the lymph system through tissues can also be localized, eg. pimple TB

1100 D. Virulence factors extracellular proteins produced by pathogens to aid in establishment or maintenance of disease TB

1101 D. Virulence factors hyaluronidase collagenase streptokinase (breaks down fibrin clots in blood) coagulase (promotes clotting) hemolysins (attack cell membranes) leukocidins (lyse white blood cells) TB

1102 E. Exotoxins Proteins excreted from the pathogen that harm the host can travel through the body TB

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 (Death by partial suffocation & tissue destruction) TB

Tetanus toxin protein: neurotoxin blocks muscle relaxation twitching paralysis lockjaw Clostridium tetani deep puncture wounds TB Picture 25

Botulinum toxin Clostridium botulinum protein: neurotoxin blocks muscle contraction flaccid paralysis most poisonous substance known grows in improperly preserved food (death by respiratory or cardiac failure) can? TB

Cholera toxin Vibrio cholera (water contamination) protein enterotoxin (small intestine) activates adenyl cyclase causes diarrhea (death by extreme dehydration)

1107 H2OH2O Na+ intestinal cell Na + bloodstream lumen cholera toxin H2OH2O Cl - TB

1108 F. Endotoxins Gram - lipopolysaccharides Escherichia Salmonella Shigella fever and diarrhea TB

1109 exotoxinsendotoxins highly toxicweakly toxic nonpyrogenicpyrogenic (fever-causing) highly immunogenic weakly TB

1110 III. Virulence 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

1111 Clostridium tetani low invasiveness high toxigenicity Streptococcus pneumonia high invasiveness low toxigenicity TB

1112 C. Measurement of virulence LD 50 Dose (number of cells/animal) that kills 50% of animals infected TB

1113 D. Salmonella virulence factors flagellum virulence plasmid O-antigen fimbriae LPS enterotoxin cytotoxin Inhibits host prot. synth. TB

1114 IV. Nonspecific host defenses A. Anatomical defenses B. Inflammation C. Fever

1115 A. Anatomical defenses Lysozyme skin-physical barrier stomach-low pH cilia normal flora flushing of the urinary tract In tears and other secretions TB

1116 B. Inflammation results from complement activation and phagocytic attack swelling and redness localizes noxious agent often by producing a fibrin clot TB

1117 C. Effects of fever often accelerates immune response low fever high fever often favors the pathogen TB

1118 Study objectives 1. Know that normal flora are organisms normally associated with healthy body tissue. Normal flora are often beneficial. However, under certain conditions 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 

Know how the following invasion enzymes work: a. hyaluronidase breaks down hyaluronic acid, a polysaccharide that cements tissues together 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.