Infection presence of microorganisms

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Infection - presence of microorganisms Disease -
alteration in physical state of the body will
infection result in disease? dosage of
microorganisms ID50 host resistance pathogenici
ty of the organism pathogenicity - ability
to cause disease due to virulence factors which
allow them to invade and disrupt body
functions host may attenuate so symptoms are not
overt
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To confirm an organism is a pathogen Robert
Koch - anthrax Kochs postulates 1.
Organism present in every case of the disease 2.
Organism isolated and grown in pure culture 3.
Healthy animal inoculated with organism has
disease 4. Organism re-isolated from test
case Problems T. pallidum Mycobacterium
leprae Rickettsia similar syndrome with
several pathogens e.g., nephritis, pneumonia,
meningitis ETHICS!!
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Virulence how potent a pathogen
depends on survival during transmission
depends on Invasiveness and Toxigenicity
depends on host resistance Opportunists not
pathogens, but often associated with the body
a change in body function or status may result
in disease e.g., other diseases - diabetes,
AIDS, CF antibiotic therapy burns transfer of
organism to an abnormal spot catheters,
surgery (E. coli and UTI) Survival - adaptation
to hosts immune system response successful
pathogen not too virulent
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Virulence depends upon Invasiveness ability
to invade and attach to tissues, to
multiply (normal flora non-invasive for surfaces
they inhabit) (some cause superficial
infections, others deeper) may be attenuated
by the immune system Toxigenicity ability to
produce toxins which disrupt cell function or
destroy cells or tissues may cause death (may
not need organisms botulism S. aureus)
LD50 lethal dose for 50 of test cases
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Portals of entry Mucous membranes
respiratory inhaled in air GI food, water,
objects put in mouth GU sexual contact,
catheters, hand transfer conjunctiva - air
Skin pores (sweat glands) hair follicles
Parenteral damage to barrier punctures,
insect bites, cuts, scrapes, dry skin body
piercings, tattoos
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Colonization set up focus of infection
Adherence - attachment to tissue adhesins
ligands, carbohydrate residues (mannose)
requires surface receptor on host cell
receptors typically lectins (glycoproteins)
capsules - S. mutans cell wall
components fimbriae N. gonorrhea
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Defeating host defenses Invade host cells -
evade immune system Shigella, E. coli,
Legionella prevent lysosome fusion
protected from digestive enzymes Inhibit
phagocytosis or destruction by phagocytes capsule
s of S. pneumoniae, H. influenzae, Y.
pestis cell wall and cell envelope components
S. pyogenes M protein - resists phagocytosis
M. tuberculosis waxes - resists digestion
endotoxin lipopolysaccharide (LPS) pili -
inhibit phagocytosis present on many
Gram-negative organisms
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Defeating host defenses secretion of toxins
EXOTOXINS specific organism specific
effects distinctive clinical symptoms heat
sensitive proteins, so most are denatured
easily POTENT!!
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Bacterial Toxins Toxin Dose
(mg) Host Botulinum D
0.8x10-8 mouse Tetanus
4x10-8 mouseShigella neurotoxin
2.3x10-6 rabbit Diphtheria
6x10-5 guinea pigEndotoxin
3x107 mouse
1x107 rabbit
2x104 guinea pigSnake venom
3x105 mouse
1x105 rabbit
2x102 guinea pig
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PROTEIN TOXINSA. Neurotoxins C. botulinum
progenitor toxin C. tetani tetanospasmin B.
Enterotoxins V. cholerae cholaragen S.
aureus enterotoxin C. Cytotoxins - cell death to
cell lysis protein synthesis inhibitor C.
diphtheriae and P. aeruginosa hemolytic
toxins (Staphylococcus, Streptococcus,
Clostridium) RBC ?, ?, ? hemolysis WBC
leukocidin (S. aureus) dermonecrotic toxin
(S. aureus) necrotizing fasciitis (S.
pyogenes)
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PROTEIN TOXINSD. Exoenzymes protease
breaksdown protein phospholipase damages
cell membranes hyaluronidase breaksdown
connective tissue collagenase breaksdown
connective tissue fibrinolysin
Streptokinase, Staphylokinase coagulase
clots plasma exfoliatin scalded skin
syndrome
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