Transcript Host Microbe Interations

Chapter 17
Host- Microbe Interaction
Biology 261
Medgar Evers College, CUNY
Prof. Santos
Establishing cause of infectious
disease
1- Koch’s postulate
a- the microorganism must be present in every
case of the disease
b- the organism must be grown in pure culture
from dispersed hosts.
c- the same disease must be produced when a
pure culture of the organism is introduced into a
host.
d- the organism must be removed or isolated from
experimentally infected hosts.
Molecular Koch’s postulates
a- the virulence factor or its product should
be found in pathogenic strains of the
organism.
b- mutating the virulence gene to disrupt its
function should reduce the virulence of the
pathogen.
c- reversion of a mutated virulence gene or
replacement with a wild type version
should restore virulence to the strain.
Pathogenicity
• Pathogenicity refers to the ability of an
organism to cause disease (harm the
host). This ability represents a genetic
component of the pathogen and the overt
damage done to the host is a property of
the host-pathogen interactions.
Virulence
• The extend of pathogenicity
Mechanism of pathogenicity
1- establishment of infection
2- invasion and breach of anatomical
barriers
3-avoiding host defense
4-damage to the host
Establishment of infection
• Adherence- the use of adhesin proteins to
bind to host.
• Adhesin proteins are found at tip of pili.
• Pili used for attachment are called
fimbriae.
• The binding of an adhesin to host surface
receptor is highly specific.
Colonization
• Colonization- this involves taking over site that
is already populated by a normal flora. The
pathogen must compete for nutrients, space,
and overcome the host’s immune system.
• Ig A antibodies circulating the host bind to
adhesin proteins of pathogen preventing their
attachment to host receptor.
• To overcome this, a rapid turnover of the pili
occurs, antigenic variation of the pili can occur
and the activation of IgA protease to destroy IgA.
Invasion of Anatomical barriers
I Penetration of skin to get in or get in by
means of a vector such as an arthropod
II Penetration of the mucous membrane by
inducing mucosal epithelial cells to engulf
the bacteria. Some pathogens exploit
antigen sampling processes.
Antigenic sampling
• Special cells called M cells are located
between the intestinal lumen and
secondary lymphoid tissues called peyer’s
patches.
• These M cells sample fluids of the
intestine and if a microbe is detected, it
delivers the microbe to a macrophage that
destroys it. This kind of cell to cell delivery
is called transcytosis.
• Some strains of shigella exploit this
system to get into the mucous membranes
and induce apoptosis in the phagocyte.
Avoiding the host defense
I Hiding inside the host
II Avoiding killing by complement system
proteins
III Avoiding destruction by phagocytosis by
avoiding recognition, attachment, and
eventually escaping from the phagosome.
IV Avoiding antibodies by using proteases to
destroy them, antigenic variation, mimicking
“self cells”.
Avoiding recognition
1- capsule proteins inactivate the C3b
complement component
2- M proteins found in strains of
Streptococcus pyogenes also inactivate
the C3b complement component.
3- Fc receptors found on the surface of
Staphylococcus and Streptococcus bind to
the fc region of an antibody preventing it
from binding correctly!
Damage to the host
3 main mechanisms;
• Release of exotoxins
• Use of endotoxins
• Damaging effect of the Immune system
Exotoxins
These are proteins that have very specific
damaging effects. There are 4 types;
1- A-B toxins, the A subunit is the toxin while the b
subunit binds to specific receptors on target cell.
2- Super-antigens interfere with T cell responses
by causing non-specific activation of T cells. This
leads to a massive release of cytokines that can
promote tissue damage.
Examples of AB toxins
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Cholera exotoxin
Enterotoxins
Pertussis toxin
Anthrax toxin
Botulin toxin
Tetanus toxin
Neutrophil activating protein
Examples of superantigens
1- Toxic shock syndrome toxin-1- secreted
by S. aureus leading to fever, rash and
shock
2- Staphylococcal enterotoxin- secreted by
S.aureus leading to vomiting, fever,
diarrhea, and nausea.
3- Membrane damaging toxins that disrupt
the integrity of the cell membrane by
forming pores or removing the polar head
group on phospholipids
4-Hydrolytic enzymes that can break down
tissues.
Example is exfoliatin toxin secreted by S.
aureus to cause scalded skin syndrome.
Endotoxin
• a toxin that is confined inside the
microorganism and is released only when
the microorganism is broken down or dies.
Endotoxins
• This involves the Lipid A of the LPS of a
cell wall of a bacteria. The host immune
system produces massive amounts of proinflammatory cytokines in response to its
presence.
• The immune system will mount a massive
attack against lipid A. This can lead to
systemic shock or endotoxic shock.
Damaging effect of the immune
system
• An over reaction of the host immune
system can cause the release of enzymes
and toxic products that can damage the
tissues of the host.
• Antigen antibody complexes can cause
kidney and joint damage and cross
reactive antibodies can trigger
autoimmune diseases.