Transcript Types of Infection

Mechanisms in Pathogenesis
Pathogenicity
Ability of an organism to cause disease to a
host that it infects
Virulence
The degree of pathogenicity- the relative capacity
of a pathogen to invade and harm host cells
Avirulence
Not pathogenic
Molecular Biology and Biotechnology: A Comprehensive Desk Reference
Robert A. Meyers (editor) VCH Publishers, New York
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Virulence Continuum
Highly virulent
Francisella tularensis
Rabbit fever
Virulence factors
Opportunistic Pathogens
Pseudomonas aeruginosa
Lung infections of cystic
fibrosis patients
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How Many Cells Does it Take to Cause an Infection?
Most organisms require minimum number before
infectious
Infectious capacity of lethal pathogens can be
expressed in terms of number of organisms required to
kill 50% of animals challenged with infection - LD50
Infectious capacity of non-lethal pathogens can be
expressed as number of organisms required to cause
disease in 50% of animals challenged with infection ID50
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Sequence of Pathogenesis
Microbe must gain access to host
Attachment to host tissues critical to gaining access
Must also penetrate or evade host defenses
Skin
Immune cells
Must compete with Normal Flora
Become established
Cause damage
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Portals of Entry - Mucous Membranes
Mucous membranes
Line respiratory, GI, & genitourinary tracts plus conjunctiva
(eye)
Respiratory tract most accessible and commonly infected
Microbes inhaled in droplets and dust particles
GI tract infected by contaminated food, water
Most organisms killed by gastric acid, bile, or digestive
enzymes
Some species can survive and cause disease
Genitourinary tract
STD’s, UTI’s, may require abrasion, some only require
attachment
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Portals of Entry - Parenteral Route (other
than through GI and Respiratory Route)
Involves depositing organisms directly beneath surface of skin
Requires penetration or injury to skin
May be mechanical means of trauma
Surgery, bite, cuts, punctures, injections
May be due to physiological breach
Drying, swelling, chapped lips
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Portals of Entry - Skin
Largest organ in body, first line of defense
Impenetrable by most organisms if unbroken
Some organisms can infect through hair follicles or
sweat gland ducts (e.g., Staphylococcus aureus)
Few organisms can bore through skin (not bacteria)
Hookworm
Some fungi can grow in keratin layer or infect skin
itself (e.g., tinea pedis) (Low aw)
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Adhesion Factors
Specialized structures or
attachment proteins
Viruses & bacteria have
lipoproteins & glycoproteins
Ligands:
Bind to complementary
receptors on host cells
Adhesins is a bacterial term
Attachment proteins is a viral term
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Found on
fimbriae (pili),
flagella &
Neisseria gonorrhoeae glycocalyxes of
STD – causes gonorrhea
pathogenic
Adhesins on pili
bacteria
Stick to cells lining urethra & vagina
Adhesion Factors
Bordetella pertussis
Whooping cough
Filamentous hemagglutinin antigen binds to
membranes of cells of upper respiratory
tract… cells then produce toxins that kill
ciliary cells of host and allow invasion
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Extracellular Enzymes
Maintain infection, invade
the host further, and
avoid immune system
Coagulase
Many pathogens
produce enzymes
that degrade
structural
molecules in the
host.
Collagenase
Coagulates blood proteins
Promotes blood clots (Staph) Degrades collagen
Hyaluronidase
Degrades hyaluronic acid
Kinases
Digest blood clots
Hemolysins
Cause lysis of red blood cells
Others… keratinase, mucinase
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Toxins
Damage tissues or incite the host
immune responses that cause
further damage.
Distinction between extracellular enzymes and
toxins is not always clear. Some toxins are
enzymes and some enzymes have toxins and some
toxins have enzymatic activity.
Toxemia:
Toxins enter the
bloodstream and
are carried to
other parts of the
body.
Fever, cardiovascular effects,
diarrhea, shock, damage to
nervous system, cell membranes,
blood cells, and blood vessels
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Exotoxins
Proteins or peptides, most are enzymes, soluble,
and diffusable… High toxicity!
Cytotoxins - kill host cells or inhibit function
Neurotoxins - interfere with normal nerve
impulse transmission
Enterotoxins - Affect epithelial cells of GI tract
mainly cause diarrhea
Produced mostly by Gram-positive and some Gram-negative
bacteria
Many toxin genes carried on plasmids or prophages (e.g.,
Corynebacterium diphtheriae and phage β)
Damage host cells by inhibiting specific metabolic function
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Generally these do not cause fever
Exotoxins
Often the exotoxin causes the disease and not the bacterium
Killing of bacteria is insufficient to alleviate disease, must
clear toxin
Requires host production of antibodies that neutralize toxin
ANTITOXIN
Immunization against disease caused by toxins use inactivated
toxins
TOXOIDS
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Two separate components
A B Toxins
Subunit A is responsible for the
enzymatic activity
Cholera toxin,
Subunit B is binds to a specific receptor
diphtheria toxin,
and pertussis toxin on the host cell membrane and
transfers subunit A across the
membrane
www-structmed.cimr.cam.ac.uk/.../SLT/ABtoxin.gif
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Diphtheria Toxin - Cytotoxin
Corynebacterium diphtheriae
Two subunits: A (catalytic) & B (binding)
Toxin produced and secreted
B subunit(s) attaches to target cell
Toxin internalized, translocates to cytosol
A subunit catalyzes reactions inhibiting protein synthesis
or some other damaging reaction
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Vibrio Enterotoxin
Vibrio cholerea
AB toxin family
B subunit binds to epithelial cells of intestine
A subunit catalyzes formation of cAMP from ATP
cAMP signals cells to discharge large amounts of fluids into
intestinal lumen
Causes extremely watery diarrhea… leads to dehydration very
quickly
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Botulinum Toxin - Neurotoxin
Produced by Clostridium botulinum when spores germinate
Released upon lysis of cells in log phase
Binds to motor nerve cells, prevents release of acetylcholine
Causes paralysis, cause of death is suffocation
Once toxin is bound to neuron, no treatment is effective
Most potent toxin known to date, 10 ng (ng = 10-9 g) sufficient
to kill
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Tetanus Toxin - Neurotoxin
Produced by Clostridium tetani
Binds to motor neurons
Prevents transmission of nerve impulses that allow muscles to
relax
Causes uncontrollable muscle contraction
Muscle contractions can be violent enough to break bones
Also extremely potent toxin - only 50 ng required to kill
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Endotoxins
Gram negative cell wall has an
outer membrane composed of
lipopolysaccharide,
phospholipids and proteins.
Lipid A
Lipid portion of LPS
Lipid A is released
when bacterial cells
die or are digested
by phagocytic cells.
Lipid A causes the host to release
chemicals that incite fever,
inflammation, diarrhea, hemorrhaging,
shock, and blood coagluation
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Endotoxin Shock
Low toxicity but
fatal in high concentrations
www.kcom.edu/.../Website/Lects/bact7.jpg
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Mechanism of Endotoxin Action
Bacteria engulfed by macrophage, digested in lysosome
Endotoxin induces macrophage to make interleukin 1 (IL-1)
IL-1 travels to the hypothalamus and triggers production of
prostaglandin
Prostaglandin causes increase in body temperature
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Endotoxin-Induced Shock
Sepsis causes macrophages to produce tumor necrosis
factor (TNF)
Designed to eliminate tumor cells
TNF causes damage to capillaries that increases
permeability
Fluid loss accompanied by dangerous drop in blood
pressure - SHOCK
Serious affect on kidneys, lungs, and GI tract
Requires large amount of endotoxin, massive bacterial
infection
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Antiphagocytic Factors
1. Inhibit Phagocytosis
2. Kill or Injure Phagocytes
3. Avoid Phagocytes
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What is phagocytosis?
An important defense
against infection
Process in which phagocytes engulf
and digest microorganisms and
other cellular debris
Material is taken into the
cell in specialize vesicles
called phagocytes
Macrophage
Lysozymes fuse and release
tissue
digestive enzymes
Pseudopodium
Bacterial cells
Neutrophils
blood
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Avoid Phagocytes
Confined to regions inaccessible to phagocytes
Does not illicit an overwhelming inflammatory
response
Inhibits phagocyte chemotaxis
Covers the antigenic surface with host cell
proteins
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Inhibit Phagocytosis
Polysaccharide capsules
Group A streptococci M
protein and pili
Capsules
Protect the bacterial cell
Evade the host’s immune
system
Slippery
Retard digestion
Pseudomonas aeruginosa
biofilm slime
E. coli O polysaccharide
associated with LPS
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Kill or Injure Phagocytes
Pseudomonas aeruginosa exotoxin A kills
macrophages
Pathogenic staphylococci produce leukocidin
Pathogenic streptococci produce streptolysin
Gram-positive pyogenic cocci, produce hemolysins
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Inhibition of fusion of
the phagocytic
lysosomes with the
phagosome
Survival inside the
phagolysosome
Escape from the
phagosome
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Antigens
Whole cells,
viruses and
complex
molecules elicit
the immune
response.
Small molecules, simple
molecules, and large
but repetitive
molecules can evade
the immune system.
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Antigenic Variation
Alter proteins in fimbriae
or fibriae tips.
Alter the outer membrane
proteins.
Alter capsule proteins.
Delicately controlled
expression of the genes.
Many different strains of
Salmonella typhimurium
with unique cell wall (O)
antigens or flagellar (H)
antigens.
Some bacterial species
periodically alter their
surface antigens to avoid the
host antibody response
Neisseria gonorrhoeae
changes fimbrial proteins.
There are greater than 100
strains of Streptococcus
pneumoniae based on capsule
antigens.
textbookofbacteriology.net
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Streptococcus
Diverse group of Gram positive, facultatively
anaerobic cocci arranged in pairs or chains.
Group A
Bacterial pharyngitis, scarlet & rheumatic fever
b-hemolysis
Utilize several
virulence
factors
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M proteins
Attachment & interferes with host
immune response
Hyaluronic acid capsule
Camouflages the bacterium
Streptokinases
Dissolves blood clots
Peptidases
Degrades proteins involved in immune response
Pyrogenic toxins
Stimulate fever, rash & shock
Streptolysins
Lyse erythrocytes, leukocytes & platelets
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Neisseria gonorrhoeae
A Gram-negative coccus
Adhere to
columnar
epithelial
cells
Fimbriae
antigenic
variation
textbookofbacteriology.net
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Types of Infection
1. Localized Infection
2. Systemic Infection
3. Focal Infection
4. Mixed Infection (Polymicrobial Disease)
5. Primary and Secondary Infections
6. Acute Infections
7. Chronic Infections
8. Asymptomatic (Subclinical) Infections
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Types of Infection (continued)
9. Communicable
10. Contagious – Highly communicable
11. Non-communicable
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Process of Clinical Infection
4 General Stages
1. Incubation period
2. Prodromal Stage
3. Period of Invasion
4. Convalescent Period
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How Microbes are Transferred
Reservoir: primary habitat of the pathogen in
the natural world
Source: Where pathogen actually came from
Carrier: Usually person with asymptomatic
infection that spreads disease (e.g.
“Typhoid Mary) but can be incubation and
convalescent carriers as well
“Passive Carrier”- you could be one!
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How Microbes are Transferred
(More terms)
Vector: Living organism that transfers
pathogen (e.g., mosquitoes, ticks, etc.)
2 types
1) Biological- participates in the
pathogens life cycle
2) Mechanical- not part of pathogen’s life
cycle… simply carries pathogen
mechanically (e.g., horseflies)
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How Microbes are Transferred
(More terms)
Vehicle: inanimate material that transmits infectious
agents (e.g., air, water)
Common vehicle: a single material that is a
source of infection for many individuals
Fomite: inanimate objects that harbors and transmits
pathogens (e.g., doorknobs)
Epidemiology: the study of the frequency and
distribution of disease and other health-related
factors in defined human populations
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Nosocomial Infections
Why so prevalent?
Some patients come in with infections… at least some
are going to communicable
Almost all patients are compromised to some degree (e.g.,
through surgery etc.)
Many portals of infection are vulnerable and compromised
Many “passive” carriers are present
Many fomites are present
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Nosocomial Infections (continued)
Genitourinary tract- 39% E. coli,
Klebsiella, Pseudomonas
Respiratory – 18%
Surgical Infections- 17%
Skin – 8%
Septicemia – 6%
Other – gastroenteritis, meningitis, etc.
12%
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Nosocomial Infections (continued)
Organisms Involved- Mainly
opportunists!
Bacteria: Gram-negatives include
E. coli, Klebsiella, Pseudomonas
Gram-positives include Staphylococcus
and Streptococcus
Fungi: Candida albicans
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