Conveners
Models for chronic immune lesions: Lessons from atherosclerosis and tuberculosis
- Mary Myerscough (University of Sydney)
Description
Immune lesions are produced by the body in response to a wide variety of stimuli and can occur in many different parts of the body. Chronically inflamed lesions contain populations of macrophages that undergo apoptosis and are consumed by other macrophages via the process of efferocytosis. If apoptotic macrophages fail to be consumed, or die in an uncontrolled way, this produces necrotic regions in the lesion which may make lesion resolution even more problematic. Because the lipid content of macrophages is recycled during efferocytosis, these necrotic regions can contain a substantial amount of free lipids, including cholesterol. As an inflamed lesion grows it may distort the surrounding tissue.
One of the most significant examples of lipid-rich chronically inflamed lesions are atherosclerotic plaques, that form in the walls of major arteries in response to an invasion of modified low density lipoproteins. Vascular disease caused by atherosclerosis is one of the most common causes of death worldwide. Another important example of a lipid-rich chronic lesion is tuberculous granulomas that can form in many part of the body in response to infection by Mycobacterium tuberculosis, which is the number one cause of death due to infectious disease in the world.
This minisymposium brings together modelers who study atherosclerotic plaques and tuberculosis granulomas where macrophage dynamics and lipid trafficking are important and where there is potential for plaque or granuloma expansion into the surrounding tissues. The aim of this minisymposium is to promote cross-fertilization between different modelers both within and beyond non-infectious and infectious diseases.
Speakers will present a variety of different types of models that include PDE models for spatial pattern in lesion, PDE models for lipid accumulation in macrophages and agent-based models that are hybrid (including PDEs and ODEs) and also multiscale in nature.
The arterial wall is composed of three distinct layers: the innermost intima, the media, and the adventitia. Atherosclerosis is an inflammatory disease of the artery characterized mainly by an expansion of the intima. In 1987, Seymour Glagov quantified arterial remodelling as atherosclerosis progressed. He found that the remodelling occurred in two stages: first a compensatory phase in which...
Atherosclerosis is among the leading causes of death worldwide due to its implication in heart attacks and strokes. The disease is characterised by the localised thickening of artery walls due to the buildup of fatty cholesterol-filled streaks. A key factor in determining whether an atherosclerotic plaque becomes problematic is the interplay between low density lipoprotein (LDL) and high low...
Tuberculosis (TB) is the number one cause of death world-wide due to infection. 2 billion are infected and 10 million die each year. Understanding the immune response to TB is crucial to developing vaccines and improving treatment strategies. The immune response to infection with Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, results in the formation of granulomas, spherical...
Inflamed tissues are densely populated with macrophages that influence the balance between inflammation amplification and resolution. Macrophages that accumulate immunogenic substances such as cholesterol (in atherosclerosis) and uric acid (in gout) become pro-inflammatory and drive inflammatory responses that never resolve.
I use in vitro experiments to show that substances dynamically...
