Transcript Pathogen

Infection and Disease II
Pathogenicity and Infection
Antibody-based detection methods
ELISA -- Enzyme-Linked Immunosorbent
Assay
Direct ELISA -- detects __________ (i.e. virus,
bacterium)
Indirect ELISA -- detects ______________ to
the antigen. HIV ELISA is an example.
HIV Indirect ELISA animation
http://www.biology.arizona.edu/immunology/
activities/elisa/technique.html?
Pathogenicity and Infection
•
Non-specific host defenses
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Entry of the pathogen into the host
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Colonization and growth
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Virulence
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Toxins
Some terms
Pathogen (or ‘true pathogen’) -- can cause infection and
disease in a _____________ host
Opportunistic pathogen -- only pathogenic to non______________ individuals or when introduced into a
normally ___________ part of the body
Virulence -- degree of __________________ of a parasite
Virulence factors -- _________________ of the pathogen
which allow it to successfully invade and colonize a host
Non-specific host defenses
•
Anatomical defenses
•
Effect of age, stress, and diet on
susceptibility
Physical Barriers and Anatomical Defenses
Compound in Saliva Protects Against E. coli
Scientists from the University of Calgary have identified a protein produced by
salivary glands that, when administered orally, can significantly reduce
diarrhea and weight loss associated with Escherichia coli infection. They
report their findings in the October 1998 issue of the journal Infection and
Immunity.
In the study, the researchers investigated the ability of the protein, known as
epidermal growth factor (EGF), to protect rabbits from the effects of an
experimental E. coli infection. The researchers found that daily treatment with
EGF prevented the occurrence of diarrhea and weight loss. They also found
lower colonization rates in the intestines of treated rabbits.
"The findings demonstrate that oral EGF administration inhibits the production of
diarrhea and reduction in weight gain seen in weanling rabbits infected with
attaching-effacing E. coli, " say the researchers. "These observations suggest a
role for EGF in protecting the gastrointestinal tract from colonization from
bacterial pathogens.”
(A. Buret, M.E. Olson, D. Grant Gall, and J.A. Hardin. 1998. Effects of orally administered epidermal growth factor on
enteropathogenic Escherichia coli infection in rabbits. Infection and Immunity. 66:4917-4923.)
Susceptibility to Infectious Disease
Age -- ___________ and ____________ more susceptible. Why?

infants -- undeveloped normal flora,undeveloped immune system

elderly -- immune response declines, anatomical changes
Stress -- in rats: fatigue, exertion, poor diet, dehydration, drastic
climatic changes increase_________________
and___________________ of infections.

Hormone imbalance plays important role.
Diet -- famine and infectious disease correlated (e.g. cholera).
Overeating may have also an effect.

Key may be disruption of __________________ ______________

Not eating a particular substance needed by normal flora can have effect
(e.g. a vitamin)
How they get in
Tissue specificity (of the pathogen) is a serious barrier to the
entry of most microorganisms (more on this later)


Discussed in viruses, also true of other pathogenic
microorganisms: often (usually) only infect specific tissues and cell
types.
Notable (mainly bacterial) exceptions exist, e.g. Streptococcus
pyogenes and Staphylococcus aureus.
So, how do microorganisms “get into” (colonize and establish
in) the host??

In the first place some of them don’t have to “get in” to be
pathogenic… How can this be?
They might already be there (in the normal flora or as latent
infections) Called infection from an “endogenous” source
Exogenous infections
Skin: portals are bites, digestive
enzymes, needles, surgery, wounds,
and catheters.
GI tract: ________ production (e.g.
Staph. aureus, Clostridium
perfringens) or directly through
intestinal (and stomach, in the case
of Helicobacter) epithelium
Respiratory tract: location (upper or
lower) somewhat dependent on size,
attachment. Portal of entry to the
greatest ________________ of
pathogens.
High speed photo of unstifled sneeze
Exogenous Infectious Agents
• Entering via the skin: Staph. aureus; Strep. pyogenes; herpes
simplex type I, HIV, and various viruses; assorted fungi; Clostridium
tetani and C. perfringens; Haemophilus aegyptum, Acanthamoeba and
assorted protozoa, etc.
• Entering through the GI tract: various Gram-negative rods
(Salmonella, Campylobacter, E. coli, Shigella dysenterae, Vibrio
cholerae, etc.); assorted viruses (poliovirus, hepatitis A, rotaviruses)
• Entering via the respiratory tract: Group A Strep. pyogenes;
meningitis-causing bacteria such as Neisseria meningitidis, and
Haemophilus influenzae; Corynebacterium diphtheriae; Bordetella
pertussis; pneumonia-causing agents like Strep. pneumoniae and
various viruses and fungi; Mycobacterium tuberculosis; viruses of
chickenpox, measles, mumps, rubella, influenza, and common cold.
Exogenous infections (cont.)
Urogenital: Enter through skin or mucosa of penis,
vagina, urethra, etc. Syphilis (Treponema
pallidum), gonorrhea (Neisseria gonorrhoeae),
genital warts, chlamydia, herpes simplex Type II,
HIV, etc.
Birth-related infections: Placental (e.g. syphilis) or
during birth: STORCH (syphilis, toxoplasmosis,
other [HIV, hepatitis B, chlamydia], rubella,
cytomegalovirus, herpes simplex II virus)
Adherence, colonization, invasion, growth, disease
Adherence
Fimbriae (non-sex pili) of enteropathogenic E. coli
Enteropathogenic strains are able to colonize the ___________
intestine and cause ________________ by expressing specific
colonization factor antigens (proteins) on their fimbriae
http://www.bc.ic.ac.uk/mcbap.html
Intestinal Infection by
Enteropathogenic bacteria
Enteropathogenic E. coli infection animation
Salmonella invasion animation
(Howard Hughes Institute web site:
http://www.hhmi.org/grants/lectures/biointeractive/animations.html)
Tissue and host specificity as factors in
infection
Pathogens must first become established at site of infection. _____________ must
be compatible with the microorganism.
An infecting microorganism can’t adhere to _______ cells or hosts.
Disease
Tissue infected
Organism
Diphtheria
Throat epithelium
Gonorrhea
Urogenital
epithelium
Small intestine
epithelium
Oral epithelium
Corynebacterium
diphtheriae
Neisseria
gonorrhoeae
Vibrio cholerae
Cholera
Dental caries
Spontaneous abortion
(cattle)
AIDS
Malaria
Placenta
T helper
lymphocytes
Blood (erythrocytes)
Strpetococcus
mutans, S.
sobrinus, S.
sanguis, S. mitis
Brucella abortus
HIV
Plasmodium sp.
Some cells are pathogenic due to the toxins
they produce (e.g. Clostridia) but most
need to actually ___________ and
______________ in host tissues in order
to cause disease.
Colonization, Growth, and Virulence
Colonization -- ____________________ of a
microorganism after it has attached to host tissues
or other surfaces
The initial inoculum of cells is rarely sufficient to cause
disease; needs to ____________.
Must therefore find appropriate nutrients and
environment. This not always as easy as it appears (e.g.
iron)
Virulence factor -- any characteristic of a pathogen
that enables it to establish itself and cause disease.
These are often extracellular enzymes such as hemolysin,
hyaluronidase, collegenase, and coagulase. The first 3
of these allow for spread (and nutrition, to some
extent), the 4th promotes localization and, probably,
protection.
Summary of virulence factors important in
Salmonella pathogenesis
Some pathogens are much more virulent than
others
Infectious Dose -- minimum number of
agents (cells, viruses) needed to cause disease
Varies from 1 Rickettsia cell in Q fever to 10 cells in
tuberculosis to 103 cells in gonorrhea, 104 cells in
typhoid, and 109 cells in cholera.
Smaller infectious dose = more _________ pathogen
If number of cells < infectious dose
If number of cells >> inf. dose
no infection
more rapid __________
Toxins
Exotoxin -- toxin ___________ into tissue
Diphtheria toxin -- extremely potent (one molecule will kill a
cell). Disrupts _____________ synthesis. Caused by
lysogenic phage in Corynebacterium diphtheriae.
Tetanus and botulism toxins -- Causal organisms (Clostridium
tetani and C. botulinum) don’t generally ______________
very much in infected tissues but instead release potent
neurotoxins.
Action of Tetanus Neurotoxin
Tetanus causes irreversible muscle _________________
(‘spastic paralysis’ or ‘lockjaw’)
Action of Botulinum Neurotoxin
Botulinum toxin, the most poisonous substance known, causes
irreversible muscle _________________ (‘flaccid paralysis’).
Toxins (cont.)
Endotoxin -- toxin released only upon cell ________ and lysis
These are lipopolysaccharides and thus are found only in Gram-negative
organisms. Most studied in Salmonella, E. coli, and Shigella.
Toxins (cont.)
Enterotoxin -- toxin that acts specifically on
the ______________.
 Enterotoxins
are found in S. aureus,
enteropathogenic E. coli, Clostridium
perfringens, Salmonella spp., etc.
 Most
studied: cholera toxin from Vibrio
cholerae
Action of cholera enterotoxin
Action of cholera enterotoxin (cont.)
Patterns of Infection