Hostmicrobe interactions

1
Host-microbe interactions 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?)
2
p. 460
3
Skin and mucosa are barriers, but also
host normal flora Symbiotic- benefit
both vitamin B- and K-producing
bacteria generally protective role of normal
flora Commensal- one partner benefits the other
is unaffected Parasite- one benefits, the other
is harmed term usually reserved for protozoa
and helminths
4
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) Infectious dose can be calculated
7
General sequence of events in infectious disease
p. 463 Infection may be localized or systemic
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

9
Molecular postulates virulence FACTORS can be
identified Virulence factor is only in
pathogenic strains If factor is mutated organism
becomes less virulent when transferred to a
non- pathogenic organism, the organism becomes
pathogenic Immune response to pathogenic factor
should be protective
10
Mechanisms of pathogenicity Toxin production
(endotoxin or exotoxin) toxins can be produced
in body or ingested Colonization (usually GI or
respiratory tract) Invasion of tissues (avoids
immune system) Or some combination!
11
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
12
Colonization- requires ability to obtain
food and evade immune mechanisms Antigenic
variation IgA proteases Siderophores Secretion
of substances that enable them to permeate host
cells
13
p. 467
14
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)
15
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
16
Surviving phagocytosis Listeria, Shigella get
out of phagosome Salmonella- prevent fusion
with lysosome IgA proteases Antigenic
variation mimicking host molecules (streptococci
good at this)
17
How do toxins damage host? (see p.
473) Neurotoxins- interfere with transmission of
nervous signal C. botulinum- prevents release
of acetylcholine (flaccid) C. tetani- blocks
inhibitory neurons spastic
18
Enterotoxins- oversecretion of fluids
into intestine- E. coli V. cholerae Cytotoxins
B. anthracis, B. pertussis- oversecretion C.
diphtheriae, E. coli O157H7, S.
dysenteriae inhibit protein synthesis All of
the above are A-B toxins
19
Membrane-damaging toxins have different structure
, directly attacking cell membranes Example
hemolytic bacteria (can lyse other membranes
beside RBC membranes)
20
Superantigens break the rules of
antigen specificity Recall that T cells
recognize antigen presented to them by MHC
Class II on APCs 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
21
Most exotoxins are not heat-stable (except S.
aureus superantigen) Many exotoxins have been
isolated and are used (as toxoids) for
vaccines Endotoxin is actually component of
Gram- negatives (LPS), so cannot be
isolated Damage is due to inflammatory response
to it can be fatal Limulus amoebocyte assay is
used to test for endotoxins
22
Thus immune response itself can contribute to
disease Inflammation Autoimmune disease
(cross-reactive antibodies) Immune complex
disease (type III hypersensitivity)
23
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
24
Many viruses have evolved mechanisms
that neutralize specific immune
functions Influenza, HIV- avoid
interferons (HIV-infect regulatory T
cells!) Block MHC Class I expression Form
syncytia (cells fuse together) Antigenic
variation
25
How do viruses damage cells? Burst
cells Apoptosis (avoids inflammatory response,
too) Inflammatory response
26
Fungal infections Natures saprophytes can
damage living tissue Effect is strong in
immunocompromised patients Toxins Hypersensitiv
ities
27
Helminths and protozoa Depends on organism and
host tissue Malnutrition Damage to colonized
tissue dysfunction associated with that Can
suppress immune response
28
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