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Printable Handouts
Navigable Slide Index
- Introduction
- TB immunology outline
- Part 1: TB in 2022
- Infectious causes of death worldwide 2010
- Immunopathogenesis gaps
- Immunologic challenges and gaps in knowledge
- Part 2: TB & innate immunity
- Mtb resides in phagolysosome compartment with escape to cytosol
- Innate immunity & Mtb
- Mycobacteria cell wall: a potent stimulus
- But with clinical consequences
- Mtb & macrophages: the standoff
- Mtb & Esx1: an escape mechanism
- Phagocytosis and autophagy: Mtb killing pathways
- …that can be subverted
- Trained immunity and BCG vaccine
- TB innate immunity summary
- Part 3: TB & adaptive immunity
- Additional adaptive immune mechanisms
- Dendritic cells & Ag presentation
- IFNg, & Mycobacteria: A unique immunogenetic relationship
- Does Mtb benefit from T-cell recognition?
- TH1 TB IFNg Myopia?
- Mtb & the granuloma: a lifelong relationship
- The Mtb granuloma: the standoff
- TB adaptive immunity summary
- Part 4: TB immunology and pathogenesis
- Immunology and pathogenesis
- T-cell response and immunodiagnostics
- Diagnosis: immune tests
- Early events: can individuals resist Mtb infection?
- Myeloid cell immunometabolism regulates resister (RSTR) phenotype
- Initial infection targets alveolar macrophages
- Delayed T-cell response benefits Mtb
- Mechanism of delayed T cell response in lung and lymph nodes
- Incipient TB: predicting progression with whole blood RNA signatures
- The correlate of risk targeted intervention study (CORTIS)
- Pulmonary TB and immunopathology
- Immunology and pathogenesis (2)
- Pathogenesis summary
- Part 5: Clinical relevance
- TB vaccines
- M72/AS01E
- Treatment challenges
- TB treatment: the drug & Rx course timeline
- Shortening trials: what can we learn?
- HDTs and macrophages
- TB HDTs & Phase II RCTs: possible immunopathology improvement
- Clinical relevance summary
- TB immunology: why does Mtb survive?
- New reasons for hope to tame TB
Topics Covered
- The immunologic challenges of tuberculosis and the gaps in knowledge
- Tuberculosis and innate immunity
- Mycobacterium tuberculosis and how it affects macrophages, granulomas, neutrophils and DCs
- Tuberculosis and adaptive immunity
- The role of IFNgamma
- The T-cell response and immunodiagnostics
- The progress of TB vaccines
- Host-directed therapies
Links
Series:
Categories:
Therapeutic Areas:
External Links
Talk Citation
Hawn, T.R. (2022, March 22). The immunology underlying tuberculosis [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 4, 2024, from https://doi.org/10.69645/AZOE1308.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Thomas R. Hawn has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
0:00
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.
0:11
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.
0:37
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.
0:60
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.
1:19
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.