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MCB 3020, Spring 2005

Host-Parasite Relationships

2Host-parasite relationshipsI. Normal floraII. PathogenesisIII. VirulenceIV. Nonspecific host defenses

3I. Normal flora

Organisms normally associated with healthy body tissues.

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4A. SkinNot generally hospitable to microbes

relatively low pH (4 to 6)often too dry

staphylococcuscorynebacterium

(eg. Propiobacterium acnes)

Normal flora

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5B. Teeth

enamel

tooth cross-sectionTB

gingival crevice

matrix

61. PlaqueBacteria growing on the teeth

2. Tooth decay (dental caries)Breakdown of tooth enamel causedby acids produced by plaque.

Penetration of the matrix of the toothby bacteria

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Acids, like lactic acid, are producedduring sugar fermentationsin anaerobic microenvironments.

8simulated plaques

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93. Plaque bacteria

a. Streptococcus mutans

• colonizes tooth crevices• produces dextran for attachment

• dextran is produced from sucrose (table sugar)

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10S. mutans

Picture22

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b. Streptococcus sobrinuscolonizes smooth surfaces

attaches to glycoproteins that coatthe tooth enamel

c. Heavy plaque has the anaerobe Actinomyces (and others)

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1. Gastrointestinal tractStomach (pH ~2)

Lactobacilli

large intestine (pH 7)

EnterococciBacteroides

C. Mucous membranes

small intestine (pH 4-5)

LactobacilliEnterococci

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TBPicture

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13Other gastrointestinal information:

• normal flora can prevent pathogens from colonizing

• antibiotics can sterilize the gastrointestinal tract giving opportunistic pathogens a chance to colonize

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2. Upper respiratory tractstaphylococcistreptococcuspathogens

(most are trapped in nasal secretions)

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153. Lower respiratory tract

(trachea, bronchi, lungs)

very few organisms

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164. Urogenital tract

Bladderfew organisms

UrethraE. coliProteus

VaginaLactobacillus acidophilus

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17II. Pathogenesis

The process by which a pathogendamages a host.

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1. Site of entryMucous membranes

through intact membranesthrough breaks

Skinusually through breaksinsect bites

A. Entry

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192. Specificity for host

Pathogens often adhere best to a specific tissue of a specific host

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Tissuespecificity

Hostspecificity

intestinalepithelium Mouse

Salmonella typhimurium

urogenitalepithelium Human

Neisseria gonorrhoeae

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213. Adherence factors on microbesGlycocalyx

Adherence proteins

Lipoteichoic acids

Fimbriae

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22B. Growth

Factors affecting growthphysical conditionsnutrient availability

eg. iron

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23C. Spread

through the bloodstreamthrough the lymph systemthrough tissues

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24D. Virulence factors

extracellular proteins produced by pathogens to aid in establishmentor maintenance of disease

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25D. Virulence factors

hyaluronidase collagenasestreptokinase (breaks down fibrin clots in blood)coagulase (promotes clotting)hemolysins (attack cell membranes)leukocidins (lyse white blood cells)

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26E. Exotoxins

Proteins excreted from the pathogenthat harm the host

can travel through the body

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271. Diphtheria toxinCorynebacterium diphtheriaeproteinencoded by lysogenized phage betablocks eukaryotic protein synthesis

through ADP-ribosylation of EF-2 (elongation factor-2)

potent: one molecule can kill one cellTB

282. Tetanus toxin

protein: neurotoxinblocks muscle relaxation

twitching paralysislockjaw

Clostridium tetanideep puncture wounds

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293. Botulinum toxinClostridium botulinum

protein: neurotoxinblocks muscle contractionflaccid paralysismost poisonous substance known

grows in improperly preserved food

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304. Cholera toxin

Vibrio cholera (water contamination)proteinenterotoxin (small intestine)activates adenyl cyclasecauses diarrhea

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H2ONa+

intestinal cell

Na+

bloodstreamlumen

cholera toxin

H2OCl-

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32F. EndotoxinsGram - lipopolysaccharides

EscherichiaSalmonellaShigella

fever and diarrhea

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exotoxins endotoxins

highly toxic weakly toxic

nonpyrogenic pyrogenic(fever-causing)

highlyimmunogenic immunogenic

weakly

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34III. VirulenceThe capacity to cause harm

A. InvasivenessThe capacity to cause harmby entry and spread

B. ToxigenicityThe capacity to cause harm by toxic effects

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35Clostridium tetani

low invasivenesshigh toxigenicity

Streptococcus pneumoniahigh invasivenesslow toxigenicity

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36C. Measurement of virulence

LD50

Dose (number of cells/animal) that

kills 50% of animals infected

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37D. Salmonella virulence factors

flagellum

virulenceplasmid

O-antigen

fimbriae

LPS

enterotoxin

cytotoxinInhibits host prot. synth.

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38IV. Nonspecific host defenses

A. Anatomical defenses

B. Inflammation

C. Fever

39A. Anatomical defensesLysozyme

skin-physical barrierstomach-low pHcilia normal floraflushing of the urinary tract

In tears and other secretions

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40B. Inflammation

results from complement activation and phagocytic attack

swelling and redness

localizes noxious agentoften by producing a fibrin clot

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41C. Effects of fever

often accelerates immune response

low fever

high fever

often favors the pathogen

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42Study objectives1. 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.

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436. 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.