The immunology underlying tuberculosis

Published on March 22, 2022   40 min

Other Talks in the Series: The Immune System - key concepts and questions

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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.
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.
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.
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.
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.