Introduction to microbes and infectious disease

1
Introduction to microbes and infectious
disease Most microbes do NOT cause disease
(whats the difference, i.e., what is a
virulence factor?) Microbes cause different
diseases (why?) How do microbes get into the
body (portals of entry) and spread (portals of
exit)?
2
Why do some organisms cause disease
while others do not? Pathogens cause
disease evade immune system cause tissue
damage Other organisms harmlessly colonize the
body (Ch. 22-28 why do organisms cause disease
in a particular part of the body?)
3
p. 460
4
Resident? Transient?
p. 461 locations for normal flora
5
Pathogenesis of infectious disease How does an
organism cause disease? (impairment of
function) What is the course of disease? How is
disease spread? How is the organism shown to be
pathogenic? Is it always pathogenic (primary
pathogen) or only is susceptible people
(opportunistic) How virulent is the infectious
organism?
6
Contagious (communicable) diseases are
easily spread Sometimes the infectious dose is
very low (therefore easier to spread) Example
dose is high for Salmonella low for Shigella
(both cause diarrhea) Infectious dose can be
calculated
7
General sequence of events in infectious disease
p. 463 Infection may be localized or
systemic Time course can be short or long
8

• Kochs postulates- classical way to determine
• if a particular organism causes disease
• Microbe is present in all affected individuals
• Organism is isolated from a sick individual
• When organism is introduced into new hosts,
• they get sick, too- and same organism is
• isolated from them.
• Not all organism can be grown in pure culture
• or tested
• Postulates are applied on molecular level
• (what microbial product causes disease)

9
Mechanisms of pathogenicity Toxin production
(endotoxin or exotoxin) toxins can be produced
in body or ingested Colonization (usually GI or
respiratory tract) acquire food, overcome normal
flora Invasion of tissues (avoid immune
system) Or some combination!
10
How do bacteria establish infections? Adhesion
(adherence) is often a necessary first
step Adhesins bind to specific molecules on
cell surface- contributes to tissue
specificity i.e., E.coli in urinary tract
Neisseria in repro- ductive tract
11
How do microbes invade body Skin- through
lesions or vectors (bites) Many bacteria have
developed ways to get through innate immune
barriers or by crossing epithelia (cells
specialized for engulfment and/or
transport) Some bacteria hide inside host
cells (e.g., Listeria)
12
Avoiding immune mechanisms Gram-positive
organisms are not sensitive to complement-mediate
d lysis Some Gram-negatives use complement
receptors or special glycosylation Avoiding
phagocytosis capsules complement
inactivation streptococci, staphylococci
13
Surviving phagocytosis Listeria, Shigella get
out of phagosome Salmonella- prevent fusion
with lysosome IgA proteases Antigenic
variation mimicking host molecules (streptococci
good at this)
14
Pathogenic mechanisms

• Toxins
• A-B (B attaches to cell (specificity)
• A part is the toxin
• Cytotoxins damage cells membranes
• Superantigens aggravate immune response
• Other damage specific tissues

15
How do toxins damage host? (see p. 473) A-B
toxins examples I. Neurotoxins- interfere with
transmission of nervous signal C. botulinum-
prevents release of acetylcholine (flaccid) C.
tetani- blocks inhibitory neurons spastic
16
II. Enterotoxins- oversecretion of fluids
into intestine- E. coli V. cholerae III.
Cytotoxins B. anthracis, B. pertussis-
oversecretion C. diphtheriae, E. coli O157H7,
S. dysenteriae inhibit protein synthesis
17
Membrane-damaging toxins have different structure
, directly attacking cell membranes (Have
different structure than A-B toxins) Example
hemolytic bacteria (can lyse other membranes
beside RBC membranes)
18
Superantigens break the rules of
antigen specificity (also act differently than
other exotoxins) Recall that T cells recognize
antigen presented to them by MHC Class II on
APCs (see p. 475) Superantigens bind
differently can activate may different T cells
simultaneously Excess stimulation can cause
nausea, vomiting and sometimes shock S. aureus
toxin is well characterized (TSS)
19
Most exotoxins are not heat-stable (except S.
aureus superantigen) Many exotoxins have been
isolated and are used (as toxoids) for
vaccines See p. 477 for comparison with
endotoxin
20
Endotoxin is actually component of
Gram- negatives (LPS), so cannot be
isolated like an exotoxin can Damage is due to
inflammatory response to it can be fatal (septic
shock) Heat-stable not autoclavable Limulus
amoebocyte assay is used to test for endotoxins
21
Thus immune response itself can contribute to
disease Inflammation Hypersensitivity Autoimmun
e disease (cross-reactive antibodies) Immune
complex disease can lead to kidney damage
22
Viral pathogenesis All viruses must live within
cell some can cause chronic or latent
infections Viruses bind to specific receptors on
cells and (in animals) are endocytosed May
stick to one type of tissue or spread
23
Many viruses have evolved mechanisms
that neutralize specific immune
functions Influenza, HIV- avoid
interferons (HIV-infects regulatory T
cells!) Block MHC Class I expression Form
syncytia (cells fuse together) Antigenic
variation
24
How do viruses damage cells? Burst
cells Apoptosis (avoids inflammatory response,
too) Inflammatory response (Most, but not,
rashes associated with infectious disease are
caused by viruses)
25
Fungal infections Remember how fungi eat! Fungi
can damage living tissue, too Effect is strong
in immunocompromised patients Toxins Hypersensi
tivities
26
Helminths and protozoa Depends on organism and
host tissue Malnutrition Damage to colonized
tissue dysfunction associated with that Can
suppress immune response
27
Study of pathogenesis involves Identification
of virulence factors Understanding host range of
organisms Normal host response to organism and
how pathogen deals with it Strategies for
prevention and treatment