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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,
