Transcript Routes of Bacterial Infection

Routes of Bacterial Infection
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Respiratory tract
Gastrointestinal Tract
Genitourinary tract
Unnatural routes opened
up by breaks in mucous
membranes or skin
• Different levels of host
defense mechanisms are
enlisted depending on the
number of organisms
entering and their
virulence.
Immune Response to Bacteria
• Extracellular Bacteria
– Humoral immune response
– Humoral antibodies produced by plasma cells
in regional lymph nodes and submucosa of
respiratory and gastrointestinal tracts
– The antibodies remove the bacteria and
inactivate bacterial toxins to protect the host
cell from invading organisms.
• Antibody neutralizes
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bacterial toxins
Complement activation
Antibody and
complement split product
C3b bind to bacteria,
serving as opsonins to
increase phagocytosis.
C3a and C5a induce local
mast cell degranulation
Other complement split
products are chemotactic
for neutrophils and
macrophages.
Immune Response to Bacteria
• Intracellular Bacteria
– Cell-mediated immune response (Delayedtype hypersensitivity)
– Activate Natural Killer (NK) cells provide early
defense against bacteria.
• In delayed type
hypersensitivity,
cytokines secreted by
CD4+ T cells, such as
IFN gamma, activate
macrophages to kill
ingested pathogens
more effectively.
Bacterial Evasion of Host Defense
Mechanism
• Four Steps in Bacterial Infection
– Attachment to host cells
– Proliferation
– Invasion of host tissue
– Toxin-induced damage to host cell
Many bacteria have developed ways to
overcome some of these host defense
mechanisms
Contribution of the Immune
Response to Bacterial Pathogenesis
• Disease can also be caused by the
immune response to the pathogen.
• Pathogen-stimulated overproduction of
cytokines can lead to symptoms of
bacterial septic shock, food poisoning, and
toxic shock syndrome.
Contribution of the Immune
Response to Bacterial Pathogenesis
• Bacteria that can survive intracellularly within
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infected cells can result in chronic antigenic
activation of CD4+ T-cells, leading to tissue
destruction by a cell-mediated response with
characteristics of a delayed type hypersensitivity
reaction
Cytokines secreted by CD4+ cells can
accumulate, leading to the formation of
granulomas. The concentrations of lysosomal
enzymes in the granulomas can cause tissue
necrosis.
Diphtheria (Corynebacterium
diphtheriae)
• Gram positive, rod-like
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organism
Bacterial disease caused by a
secreted exotoxin.
Spread via airborne respiratory
droplets
Exotoxin destroys underlying
tissue, forming a tough,
fibrous membrane compose of
fibrin, white blood cells and
dead respiratory cells
Also responsible for systemic
manifestations.
Symptoms of Diphtheria
• Damage to different organs
such as the heart, liver,
kidneys and nervous system.
• Choking layer of bacteria and
dead cells in the respiratory
system, accompanied by an
unworldly stench
• Difficulty swallowing and
breathing
• Pus and blood discharge
through nostrils following
death from asphyxiation
More info on diphtheria……
• The exotoxin is encoded by the tox gene carried by
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phage B (beta)
Some strains can exist in the state of lysogeny.
Exotoxin has two disulfide linked chains, a binding chain
and a toxin chain. The binding chain interacts with
ganglioside receptors on susceptible cells, facilitating
internalization of the exotoxin.
Inhibitory effect of toxin chain on protein synthesis leads
to toxicity.
Removal of the binding chain prevents exotoxin from
entering the cell.
How We Treat This Bad Boy….
• Toxoid prepared by treating diphtheria toxin with
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formaldehyde.
Reaction with formaldehyde cross-links the toxin,
resulting in loss of toxicity and enhancement in its
antigenicity.
Usually administered with tetanus toxoid and inactivated
Bordetelal pertussis in a combined vaccine that is given
to children 6-8 weeks of age.
Immunization with toxoid induces production of
antibodies which bind to the toxin and neutralize its
activity.
The reaction
that results
from the
vaccine
Photo Ops of Diphtheria (Smile!)
Tuberculosis (Mycobacterium
tuberculosis)
• Bacilli shaped organism
• Pulmonary infection by inhalation
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of small droplets of respiratory
secretions containing a few bacilli
Inhaled bacilli are ingested by
alveolar macrophages and
multiply intracellulary by inhibiting
formation of phagolysomes.
Macrophages lyse and large
numbers of bacilli are released.
Cell mediated response by CD4+
T cells may be responsible for
much of the tissue damage of the
disease.
Most common infection of
tuberculosis is pulmonary
tuberculosis.
Symptoms of Tuberculosis
• Symptoms of TB depend on where
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in the body the TB bacteria are
growing. TB bacteria usually grow
in the lungs. TB in the lungs may
cause
– a bad cough that lasts longer
than 2 weeks
– pain in the chest
– coughing up blood or sputum
(phlegm from deep inside the
lungs)
Other symptoms of TB disease are
– weakness or fatigue
– weight loss
– no appetite
– chills
– fever
– sweating at night
Immune Response to Tuberculosis
• Cytokines produced by CD4+ T cells activate
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macrophages, which kill the bacilli or inhibits their
growth.
High levels of interleukin-2 (IL-2), produced by
macrophages, stimulates Th 1-mediated responses.
IL-2 may also contribute to resistance by inducing
production of chemokines that attract macrophages to
the site of infection.
CD4+ T cell mediated response mounted by those
exposed to M. tuberculosis controls the infection and
protects against later infection.
Treatment and Vaccines
• Tuberculosis is treated with
several drugs including
isoniazid, rifampin,
streptomycin, pyrazinamide,
and ethambutol.
• Drug therapy must continue for
at least 9 months to get rid of
the bacteria since the
intracellular growth of M.
tuberculosis makes it difficult
for the drugs to reach the
bacilli.
• Vaccine : attenuated strain of
M. bovis called BCG (Bacillus
Calmette-Guerin) Most
effective against
extrapulmonary tuberculosis.
Not used in the U.S. though.
Sorry!
Tuberculosis Links! Yay!
• http://www.phppo.cdc.gov/PHTN/tbmodul
es/modules1-5/m1/anim.htm
• http://www.phppo.cdc.gov/PHTN/tbmodul
es/modules1-5/m3/photos/3photo3.9.htm
• http://www.phppo.cdc.gov/PHTN/tbmodul
es/modules1-5/m3/photos/3photo3.8.htm
• http://www.cdc.gov/ncidod/diseases/subm
enus/sub_tuberculosis.htm
Lyme Disease (Borrelia burgdoferi)
• Helical shaped bacteria
• Disease spread by bite
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from an infected deer tick
Enters the bloodstream
and spreads to different
organs in the body
Arthritic symptoms and
neurologic symptoms can
develop. Most people
complain of headaches
and some people develop
meningitis or encephalitis.
Immune Response
• Antibodies to a protein associated
with the flagella of B. burgdorferi is
usually detected after infection and
may contribute to pathogenesis.
• Antigen-antibody complexes can
activate complement system,
resulting in direct lytic damage to
the joints or vasculature.
• Interleukin 1 (IL-1) said to be
involved in pathogenesis of Lyme
disease, since Borrelia has a cell
wall containing lipopolysaccharide
(LPS) and LPS is a well known
inducer of IL-1
• Most humans develop antibodies to
a flagellar antigen, while mice
develop antibodies to two proteins
on the outer surface of the bacterial
envelope.
How do we treat it?
• Lyme disease can be
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successfully treated with
broad-spectrum
antibiotics such as
penicillin and tetracycline.
A vaccine based on outersurface protein A
suggests that it offers
significant protection.
The vaccine was
approved for use in
January 1999.
Online Information on Lyme
Disease
• http://www.cdc.gov/ncidod/dvbid/lyme/in
dex.htm
– This is just some general info on Lyme
Disease
• http://phil.cdc.gov/Phil/detail.asp?id=2417
– This is a up close and personal picture of
Borrelia burgdorferi