Armando Hasandungan Biology and Medicine Videos,
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in this video we'll look at the mucosal immune system of the gut (so the intestinal tract)
before continuing on, if you haven't watched [uh] the overview of the mucosal
immune system, I suggest you watch that first before watching this.
So we begin by learning about the mucosal immune system of the gut
by firstly learning about the mesenteric lymph nodes.
Mesenteric lymph nodes are like any other lymph nodes
in that they contain arteries and veins coming out of them
and they also have lymph vessels coming in and out of them
which connects to the surrounding intestinal tissues (the submucosas)
Mesenteric lymph nodes are important to initiate an immune response.
particularly an adaptive immune response
Mesenteric lymph nodes, like the normal lymph nodes, contain lymphocytes
naïve lymphocytes or inactivated lymphocytes
they contain naïve CD8 and CD4 T cells
there are areas in the lymph node known as follicles where naïve B cells reside
these naïve B cells typically express IgM and sometimes IgD antibodies
the mesenteric lymph nodes connect with areas around the gastrointestinal tract
here we have the lymph vessel connecting to the regions around the body
especially to regions below the mucosal surface of the gut
because we are talking about the gut mucosal immune system
these are the mucosal surface cells, the epithelial cells,
and they form crypts, and they also contain villi which are important for food absorption.
therefore, this area up here is known as the intestinal lumen
because the lumen is where the food passes through, as well as where the bacteria is present.
Now, there are regions all across, all around the gut tract, especially in the small intestines
known as the Peyer's patches.
Peyer's patches are lymphoid tissues
and therefore they contain immune cells
Peyer's patches are important in protecting the body from invasion
and initiating an immune response.
another important area is known as a lamina propria, which is also below the mucosal surface
Lamina Propria are - is basically connective tissue which has many types of immune cells
particularly the activated immune cells such as the CD8 and CD4 T cells
now let's talk about Peyer's patches in a bit more detail.
Peyer's patches contain special cells (epithelial cells) on the mucosal surface
known as follicle-associated epithelial cells
within this area we also have other special cells known as microfold cells or M cells
M cells are important in antigen sampling, in taking in antigens to initiate an immune response
Peyer's patches also contain follicles where B cells predominantly reside in
as well as T cells in the surrounding area
dendritic cells are also found here because dendritic cells are important in initiating, or activating, the adaptive immune response.
we'll learn about the Peyer's patches more later on.
now let's talk about the lamina propria.
lamina propria, as I mentioned, is our connective tissue
and they contain a vast array of actually activated immune cells
the lymph vessels also connect to the lamina propria, where the immune cells can go in and out.
the lamina propria contains macrophages, phagocytes, and also activated CD8 and CD4 T cells
or T-Killer or T-Helper cells.
they also contain plasma cells which are the activated B cells.
and therefore the lamina propria is very important in essentially preventing infection beforehand
Now the question is, where do these immune cells come from?
particularly these naïve immune cells such as the naïve lymphocytes
Well they come from the high endothelial venules, from the bloodstream.
from the thymus and the bone marrow, the naïve lymphocytes actually circulate around the body
and they're not predetermined to go to the gut
they can go anywhere depending on where the signal takes them
for example all lymphoid tissues secrete chemokines which attract the lymphocytes
now, the receptors CCR7 and L-Selectin of the lymphocytes
are attracted to chemokines CCL21 and CCL19, 
which are secreted by lymphoid tissues
including the Peyer's patches
but also the chemokines can be secreted by other lymphoid tissues such as
the spleen and the lymph nodes
so these lymphocytes can literally go anywhere where these chemokines are being secreted from
So here we have a lymphocyte in the high endothelial venules with L-selectin
and the CCR7 receptor, which has attracted the CCL21 and CCL19 chemokines
coming from the Peyer's patches
the lymphocytes will enter the Peyer's patches
if it's a naïve T cell it will stay within the outside of the follicle
and if it was a naïve B cell it would be within the follicle
now if no antigen is present within the Peyer's patches,
or there's no antigen presented to the lymphocyte for the dendritic cells
the lymphocytes will re-circulate through the bloodstream.
because they still have these CCR7 and L-selectin receptors
so they will re-circulate to other lymphoid tissues such as the lymph nodes or the spleen
So what happens if an antigen is present, what happens to these lymphocytes?
and how does an antigen get presented to these lymphocytes?
well the M cells play a critical role here
the M cells take up the antigen - a process known as "antigen sampling"
and they transport it across to dendritic cells
where the dendritic cells can then present it to the lymphocytes.
So how does this process occur - how does the M-cell take up the antigen
and essentially tell the dendritic cell that there is an antigen
and where is the communication between the M cell and the dendritic cell
Well, if here we have the associated follicle epithelial cells and here have the M cell
here the intestinal lumen where the food passes through and where the pathogens are, and the antigens of the pathogens
and here are the Peyer's patches where all the immune cells are residing - or some of them
so the antigen and pathogen - if the antigen and pathogen is present, the cells
particularly the follicle-associated epithelial cells, will begin secreting chemokines
CCL20 and CCL19
and remember, these are the chemokines that attract the lymphocytes
but they also attract dendritic cells
they attract the dendritic cells with the receptors CCR6 and CCR1.
so now the dendritic cells knows that an antigen is present
and that the M cell is about to take it up
the M cell takes it up through phagocytosis (also known as endocytosis)
and the process where it is transported from the lumen to the Peyer's patches is known as transcytosis
"trans" as in "across"
so it transports this molecule, the antigen, from the lumen
to the Peyer's patches where they will just excrete it out
and now the dendritic cells, which are there, can engulf it
and present it on the Major Histocompatibility Complex
and present it to the adaptive immune cells
Now let's look at the bigger picture.
Because the antigen is present now, because the M cell has already taken it up and brought it into the Peyer's patch,
the lymphocytes will lose the receptors L-selectin and the CCR7
and now, and therefore it cannot leave the Peyer's patches per se.
so this dendritic cell with the antigen will now activate this naïve T cell
and it can be a naïve CD8 or naïve CD4 T cell
the dendritic cells also uses retinol and converts it to retinoic acid in the process to activate the T cells.
Why does it do this?
it does this in order for the T cells to begin expressing new receptors
these new receptors are known as "homing receptors"
which will tell where the lymphocytes have to go next
now if this activated T cell were a CD4 cell,
it would become an activated T helper cell.
which can then activate naïve B cells within the follicles.
the naïve B cells, as I mentioned earlier, only express typically IgM antibodies and sometimes IgD antibodies.
but once activated, particularly in the mucosal immune system,
they begin expressing IgA antibodies
IgA antibodies are important for the mucosal immune system because IgA antibodies are the antibodies which prevent infection.
The activated CD8, the activated CD4, and the activated B cell will then leave the Peyer's patches and travel through the body
via the lymph vessel
they will travel around the body and typically end up in the lamina propria, if you remember,
the other area beneath the mucosal surface.
so after the antigen-presenting cells interact with the lymphocytes
the lymphocytes begin expressing the homing receptors
which will direct them to the lamina propria
homing receptors are induced by the retinoic acid
and by dendritic cells
so remember the lymphocytes lost their initial receptors CCR7 and L-selectin
which brought them to lymphoid tissues
and once these lymphocytes are activated they begin expressing homing receptors
here - these homing receptors
which will allow them to leave the Peyer's patches through the lymphatic vessel.
and head to the mesenteric lymph nodes, and following that to the lamina propria
or other areas around the body
so here are the activated CD8 and the activated CD4 cells in the mesenteric lymph nodes now, travelling from the Peyer's patches
as well as the activated B cell
