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The balance between intestinal immune homeostasis and inflammation

Published on September 28, 2023   35 min

A selection of talks on Immunology

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0:00
Thank you for joining this course. My name is Janneke Samsom. I am a mucosal immunologist with specialism in intestinal immunology. In this course I will discuss how the intestinal immune system maintains tolerance to harmless exogenous substances like food proteins and intestinal bacteria but at the same time retains the capacity to respond and eradicate harmful threats.
0:28
I will place this lecture in the context of inflammatory bowel disease. A chronic intestinal inflammation caused by a loss of homeostasis. As such, I will start by explaining inflammatory bowel disease. I will discuss the differences between intestinal immune responses to commensal and pathogenic bacteria. Thirdly, I will explain the relation between genetic variation and apparent immune responses in IBD. I will end by showing an example of how dysregulated interleukin-10 signaling predisposes to IBD.
1:06
Directly after birth, the intestinal tract is colonized with commensal bacteria and unicellular organisms. These microbiota are needed to digest our food, to prevent colonization of pathogens in our gastrointestinal tract, and to train our immune system. In general, our immune system distinguishes self and non-self and is geared towards protecting self and eliminating non-self. However, in the intestine, our intestinal immune system needs to accept the commensal microbiota, despite the fact that they are non-self. In other words, the intestinal immune system needs to learn to tolerate the commensal microbiota and develop a host bacteria mutualism. In patients with inflammatory bowel disease, hereafter denoted as IBD, the development of the host microbiota, mutualism becomes apparent. IBD is a multifactorial disease with a strong genetic predisposition, a clear role for commensal microbiota, and a contribution of the environment, including nutrition. There are two main clinical subtypes of IBD, ulcerative colitis and Crohn's disease. In ulcerative colitis the inflammation only occurs in the colon and as can be seen from the endoscopy picture below is very superficial. In contrast, in Crohn's disease, the inflammation can be located anywhere in the gastrointestinal tract, including the small intestine and the colon. At endoscopy as can be seen below, Crohn's disease can look different from ulcerative colitis as the inflammation can occur all through the bowel wall. Another key characteristic of Chron's disease is that the disease is patchy, with mixed areas of inflamed and healthy tissue, while lesions are always continuous in ulcerative colitis. The main challenge in treating these diseases is the heterogeneity of the clinical disease at diagnosis, the heterogeneity of the disease on histology in the intestine, and the heterogeneous response to immunosuppressive treatment. As IBD is an immune disease, there is a strong need to classify the heterogeneity of patients on the basis of the individual immune response. The treatment aim is to control the chronicity of the inflammatory CD4+ T cell response, thereby suppressing tissue damage in the intestine. In order to understand these diseases, we need to much better understand the mechanisms that maintain mucosal tolerance in the intestine. When a microbe is encountered,

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The balance between intestinal immune homeostasis and inflammation

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