Download Host-Parasite Relationships

Host-Parasite Relationships
Development of disease
A generalized time model -Death
Illness
Prodromal
Period
Decline Period
Convalescence
Period
Incubation Period
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Host-Parasite Relationships
Pathogenicity
Involves various
Virulence Factors
Virulence Factors
Attributes which
enhance
pathogenicity
NEITHER Virulence nor relative resistance of the host are static. These items
change frequently. Interaction of the Host-Parasite is very dynamic..
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Host-Parasite Relationships
Mechanisms of Bacterial Pathogenicity
Virulence
Quantitative measure
of pathogenicity
Expressed as the
number of pathogen
cells needed to elicit a
pathogenic response
in a host within a given
time period
PATHOGENICITY – ability of the parasite (pathogen) to cause damage to the host
AND the host
resistance or susceptibility to the parasite
Pathogenicity varies greatly among individual pathogens. The quantitative measure
of pathogenicity is VIRULENCE
VIRULENCE = expressed as the cell number (pathogens) that
will elicit a pathogenic response in the host within a given time period.
Can think of VIRULENCE as the relative ability of a pathogen to cause disease.
LD50 or Lethal Dose 50 – ON BOARD\
IN lab culture virulence often lost == ATTNUATED
Why – non virulent strain may grow faster
in lab
so selected for during growth
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Mechanisms of Bacterial Pathogenicity
Entry Into the Host –
Skin
Usually through a wound
Mucus membranes
Respiratory, gastrointestinal and genitourinary
tracts
Starts with entry into the Host – Cant cause disease if ya can’t get in – non-specific
host defense MECHANICAL BARRIER
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Mechanisms of Bacterial Pathogenicity
Specific Adherence –
Adherin
Glycocalyx
Receptor
glycoprotiens
polysaccharides
Bacterium
Enterotoxic E.
coli.
Adherence proteins
M protein
Opa Protein
Grp A Strep
N. gonorrhoeae
Lipoteichoic acid
complex lipids
Grp A Strep
Fimbriae (pili) (fig 21.14)
CFA (colonizing
factor antigen)
urogenital epithilia
intestinal epithilia
Enterotoxic E.
coli
N. gonorrhoeae
Salmonella sp.
(fig 21.13)
Protein – Protein Interaction or Lipid – Protein interactions
Variation and “selectivity” even among epithelium that are adhered to -- SEE M
protein versus Opa protein
Specific adherence factor in HOST SPECIFICITY – bind better to their “normal” host
than to related cells in a “non-normal” host.
M protein of Grp A step binds to receptors on the respiratory mucosa
Opa binds specifically to receptors on the urogenital epithelium
V. Cholerae == Vibiro Cholerae
Group A Strep == Streptococcus pyogenes
N. Gonorrhoeae == Neisseria gonorrhoease
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Mechanisms of Bacterial Pathogenicity
Penetration –
Mucosal Surface colonization –
For bacteria which produce toxins this is enough
Whooping cough, diphtheria, cholera
Most however must penetrate (Invasion)
Also called INVASION in your book
Penetrate into deeper tissues
Also could be at sites distance from original point of entry
carried via blood or the lymphatic system
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Mechanisms of Bacterial Pathogenicity
Colonization and Growth –
Nutrition – MOST important
In host soluble nutrients are limited
Sugars, amino acids
Not all vitamins and growth factors
Minerals
Fe
Bound by transferrin and lactoferrin in
animals.. Bacterial siderophores
Favorable Environment
Temperature, pH, reduction potential
Once a pathogen gains access to tissue it must be able to colonize and grow
Bacterial siderophores
if all Fe bound to transferrin or lactoferrin, then Fe become limiting for
the bacteria
Bacterial siderophores – small MW proteins containing
many OH groups with VERY high affinity for Fe. Can actually strip it away from
Transferrin and lactoferrin –
E. coli siderophore == AEROBACTIN
Once inside may stay localized as they grow, or can become SYSTEMIC if spread
to other sites via blood and lymphatic system.
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Toxicity – ability of an organism to cause disease
by preformed toxin.
Invasiveness – ability of an organism to grown in
host tissue in large numbers.
Clostridium tetanii – tetanus
Stptoccoccus pneumoniae – invasive – major virulence factor == polysacchride –
capsule – prevents host cell phagocytosis.
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Virulence factors which aid in Invasion and
Penetration
hyaluronidase hyaluronic acid
Protease
Lipase
DNase
Collagenase
Streptokinase
fibriolytic enzyme
Coagulase
fibrin clot forming
Phospholipases
hemolysis
Hi Al i ron a dase -- hyaluronic acid – intracellular tissue cement – polysaccharide
Streptokinase – clot dissolving enzyme – Streptococcus pyogenes
Coagulase – S. aureus promotes fibrin clots – very localized infections pimples and
boils
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Exotoxins
Released by bacteria
Three (mostly) Categories
Cytolytic
A-B toxins
Superantigen toxins
Most are proteins
Heat labile
Specific
Potent
Immunogenic
Exotoxins – may travel to very distant sites and cause damage there
Can be coded for chromosomally, via a plasmid, via prophage.. Most are single
genes.
The toxoid maybe able to form a basis for a vaccine
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Exotoxins
Cytolytic Toxins
Hemolysins -- Example is detection of STREPTOCOCCUS spp
Lecithinases
Phospholipases -- can also lyse bacterial cells
Virulence factor which lyse the cell be one or another means
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Exotoxins
A-B Toxins
Diptheria toxin
Inhibits protein synthesis
Tissue necrosis
Diphtheria toxin approximately 62kDa Proteolytic cleavage allows A to enter
(21kDa)
(ADP ribosylation)
EF-2 + NAD => EF-2-ribose-p-p-ribose-adenine + nicotinamide
Corynebacterium diptheriae
EF-2 is Elongation Factor
WILKINSON DRAWING 193A and B 342??
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Exotoxins
A-B Toxins
Botulinum toxin
Clostridium botulinum and Clostridium tetani
Botulinum – most potent biological toxin known
1mg kill 1,000,000 guinea pigs
Blocks acetylcholine release at the motor neuron end plates
Irreversible relation of the muscles == flaccid paralysis
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Exotoxins
A-B Toxins
tetanus toxin
Tetanus
blocks glycine (from inhibitory interneuron)
Irreversible contraction of the muscles == spastic paralysis
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Mechanisms of Bacterial Pathogenicity
Toxicity and
Invasiveness –
Enterotoxins
Act on small
intestine
Massive fluid
secretion into
intestine
Many food
poisoning bacteria
Exotoxins which act on small intestine
Cholera toxin
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Mechanisms of Bacterial Pathogenicity
Toxicity and Invasiveness –
Endotoxins
Lipopolysaccharides
Lipid-polysaccharide
Heat stable
Less potent
General toxic action
Weak immunogens
Lipopolysaccharide part of gram negative bacterial outer cell envelope
Toxic – cell bound
released in large quantity as bacterial cells
die and are lysed
Escherichia, Shigella and Salmonella most studied
endotoxins
Pyrogens = cause fever in host
Diarrhea, decrease in lymphocytes, leukocytes and platelets
Generalized inflammatory response
Lower blood pressure leading to shock
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Mechanisms of Bacterial Pathogenicity
Virulence factors
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Purple bacteria
Cyanobacteria
Actinomyces
Gram-positive
Spirochetes
Escherichia Coli
Clostridium botulinum
Aquiflex
Mycobacterium tuberculosisi
Plantctomyies sp.
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