Infection and Disease II

1
Infection and Disease II

• Pathogenicity and Infection

2
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.
3
HIV Indirect ELISA animation

• http//www.biology.arizona.edu/immunology/activiti
  es/elisa/technique.html?

4
Pathogenicity and Infection

• Non-specific host defenses
• Entry of the pathogen into the host
• Colonization and growth
• Virulence
• Toxins

5
(No Transcript)
6
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

7
Non-specific host defenses

• Anatomical defenses
• Effect of age, stress, and diet on susceptibility

8
Physical Barriers and Anatomical Defenses
9

• 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. 664917-4923.)

10
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)

11
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 dont 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

12
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
13
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.

14
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)
15
(No Transcript)
16
Adherence, colonization, invasion, growth, disease
17
(No Transcript)
18
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
19
Intestinal Infection by Enteropathogenic bacteria
Enteropathogenic E. coli infection animation
Salmonella invasion animation (Howard Hughes
Institute web site http//www.hhmi.org/grants/lec
tures/biointeractive/animations.html)
20
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 cant adhere to
  _______ cells or hosts.

21

• 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.

22
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.

23
(No Transcript)
24
Summary of virulence factors important in
Salmonella pathogenesis
25
Some pathogens are much more virulent than others
26
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 lt infectious dose
  no infection
• If number of cells gtgt inf. dose more
  rapid __________

27
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) dont
  generally ______________ very much in infected
  tissues but instead release potent neurotoxins.

28
Action of Tetanus Neurotoxin

• Tetanus causes irreversible muscle
  _________________ (spastic paralysis or
  lockjaw)

29
Action of Botulinum Neurotoxin

• Botulinum toxin, the most poisonous substance
  known, causes irreversible muscle
  _________________ (flaccid paralysis).

30
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.

31
(No Transcript)
32
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

33
Action of cholera enterotoxin
34
Action of cholera enterotoxin (cont.)
35
Patterns of Infection