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Hello. My name is Tom Hawn.
I'm at the University
of Washington
at the Division of Allergy
and Infectious Diseases.
Today's topic is the immunology
underlying tuberculosis.
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The outline for today
is to first frame
the gaps and challenges in
our immunologic
understanding of TB.
Then to drill down on our
understanding currently of
the innate immune response and the
adaptive immune response to TB.
Then bring that together with
insights into pathogenesis,
and then to wrap it up
with trying to understand
the clinical relevance
of immunology
and how it is being
brought into the clinic.
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First to frame some of the
immunologic challenges and gaps.
TB, as it has always been, is a
major cause of death worldwide.
In a population of 7.9 billion,
about a quarter are currently
or have been infected with TB.
Each year around 10 million
people get the active disease
and about 1.3 million die.
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Shown here are the leading causes
of death worldwide in 2010,
and as is the case year by year,
TB is always one of the leading,
if not the top, killers worldwide.
Just for framing,
COVID-19 over the last two years
has numbers that have
exceeded tuberculosis.
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Looking at the basic
imunnopathogenesis of TB,
it begins with exposure to TB,
which gets inhaled
into the lungs,
meets an alveolar
macrophage in the lungs,
spreads to lymph nodes
and can get into
the bloodstream with a
period of bacillemia.
A number of things
can then happen.
Some individuals
are able to resist
infection immediately
or clear it rapidly,
some get infected and
develop symptoms rather
quickly over the course of a
couple of weeks to months,
and then some individuals
have a silent infection
and they're at risk of
reactivating later.
When the bug starts to
replicate it can then progress
and lead to symptoms
most commonly
in the lungs with
pulmonary disease,
but it can affect almost
any organ in the body.
Every step in pathogenesis
on this slide contains
major immunologic
unknowns and gaps.
This will be the topic
that we will touch on
throughout today's discussion.