We noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Loss of mucosal tolerance
- What mechanisms maintain mucosal tolerance in the intestine?
- Each bacterium can be recognized by its specific pattern of molecular structures
- Pathogens elicit a different cocktail of inflammatory mediators
- Immune system recruitment (1)
- Immune system recruitment (2)
- Bridging innate to adaptive immunity
- T cells will differentiate depending on cues provided by the antigen presenting phagocyte
- Commensal-driven immunological response
- Pathogen-driven immunological response
- Which pathways are derailed in IBD?
- Source of heterogeneity: GWAS studies
- IBD susceptibility genes
- Placing IBD susceptibility genes in pathways
- Learning from intestinal inflammation in monogenic deficiency with very early onset IBD (VEO-IBD)
- Common disease pathways between monogenic disease and adolescent/adult onset IBD
- Pathobiology of monogenic VEO-IBD to classify polygenic adolescent IBD
- Defective IL-10 signaling causes spontaneous therapy resistant intestinal inflammation
- Both APC and T cells can express the IL-10 R
- Mice with deficiency of IL10R in APC
- IL-10 inhibits IFNγ-secreting T cells indirectly
- IL-10 controls effector T cells indirect manner
- What about the polygenic adolescent pediatric IBD patients?
Topics Covered
- Inflammatory bowel disease (IBD)
- Clinical subtypes of IBD
- Ulcerative colitis
- Crohn’s disease
- Commensal and pathogenic bacteria in the intestinal mucosa
- Role of innate and adaptive immunity in the intestine mucosa
- Immune pathways involved in IBD
- IBD susceptibility genes
- Very early onset IBD (VEO-IBD)
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Samsom, J. (2023, September 28). The balance between intestinal immune homeostasis and inflammation [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 9, 2024, from https://doi.org/10.69645/BHVB3420.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Dr. Janneke Samsom has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
The balance between intestinal immune homeostasis and inflammation
Published on September 28, 2023
35 min
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
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,