Transcript Normal flora

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.