Let’s look at the blood and
So here we can see the
And lymphocytes and other blood cells will
be traveling around in the blood circulation.
And they may go to the liver, they may go to the skin,
they may go to the kidney or they might go to the gut.
Following their arrival at these
locations, they can look for antigen.
And they can ultimately leave these
locations and go to the local lymph nodes.
Whether they’re coming from the liver, the skin or
the kidney, they can end up in nearby lymph nodes.
Lymphocytes that are activated in the
Peyer’s patches in the gut can also travel
to the local lymph node and in this
case, it is the mesenteric lymph nodes.
Ultimately, the lymphocytes can leave those lymph
nodes and travel via the lymphatic vessels
to other lymph nodes, because the lymph nodes
are connected to each other via the lymphatics.
So they’ll leave via the efferent
lymphatics for those particular nodes
and then later on enter via the afferent
lymphatics to downstream nodes.
The lymphocytes can also directly
enter into the lymph nodes.
They don’t have to enter via the lymphatic vessels; they
can actually go straight there from the blood circulation.
And they do this by structures within the lymph
nodes called high endothelial venules, HEV.
Ultimately, after seeing whether
or not their antigen is present
in the lymph node, the lymphocytes can leave via the efferent
lymphatics, again travel through the
lymphatic vessels and ultimately
they can rejoin the blood circulation via the thoracic duct.
So let’s have a look
at these two systems.
Really they’re very much like a road system and a
rail system; two different systems but interconnected,
just like you can drive your car to the station,
park at the station and hop on a train.
So lymphocytes can travel around both of these
systems and use the interconnections such as
the high endothelial venules, such as the thoracic
duct to get between one system and another.
Looking now in a little bit more detail at
the events that occur in the lymph node and
particularly, the events occurring as lymphocytes
leave the blood vessels and enter the lymph node.
So at the top, we have a lymphocyte, it’s a
naïve T-cell, it’s not seen antigen before.
And it’s going to enter a lymph node.
But this lymph node in this particular example, it doesn’t
have the antigen that this T-cell is specific for.
So the lymphocyte will enter the lymph
node via the high endothelial venules.
It will have a look, see whether
its antigen is there or not.
And if the antigen isn’t there, it will
actually not hang around in that lymph node.
It will move quite rapidly out of the lymph
node via the efferent lymphatic vessels.
Then it can go to the next
lymph node in the chain.
And maybe that lymph node has got
antigen present that the T-cell
is specific for, because maybe
there’s an infection in the tissues.
And pathogens picked up by dendritic
cells can be carried from the
location of the infection via the
afferent lymphatics into the lymph node.
And when the lymphocyte arrives, lo
and behold, its antigen is there.
So it will stay in that lymph
node and become activated.
It may also be that the lymphocyte
directly entered that node and
will immediately be activated because its antigen is present.
So at the top we have a lymph node without
the antigen, in the middle we have a
lymph node where the antigen is present that
that particular T-cell is specific for.
And that T-cell may have entered via the
lymphatics because it’s come from another
node, or it may enter directly through
the HEV from the blood circulation.
Following interaction with dendritic cells, and stimulation of
the lymphocyte, this naïve lymphocyte then becomes activated.
And the activated lymphocyte can leave
the lymph node via the efferent lymphatic
vessels and ultimately rejoin the blood
circulation via the thoracic duct.
Remember the thoracic duct it’s a
connec-- one of the connections
between the lymphatic circulation and the blood circulation.
Now this T-cell is activated, and it’s
responding to a particular infection.
But it’s no good at being in the lymphatic
vessels or in the blood circulation, it needs to
actually get to where the infection is, so it can
carry out its job of eliminating the infection.
So it will recirculate back to the location
where the antigen originated from and
therefore be able to attack the pathogen
and hopefully get rid of the infection.
In terms of the high endothelial
venules, this is a very specific
process whereby molecules associated
with the high endothelial venules
interact with molecules on the surface of the lymphocyte to
facilitate binding of the lymphocyte
to the high endothelial venule.
And then exit from the venule
into the body of the lymph node.
This is mediated by cell surface
molecules present on the lymphocyte.
So for example, the adhesion molecule,
L-selectin on the surface of the naïve
T-cell interacts with a molecule
called PNAd (Peripheral Node Adresin).
Peripheral Node Adresin - PNAd, on the
surface of the high endothelial venules.
So this is a cell-cell interaction, one
molecule on the surface of the T-cell,
L-selectin interacting with a molecule on
the surface of the endothelial cell, PNAd.
Also there will be soluble cytokines that can bind
to the surface of the high endothelial venule.
And in particular, one type of cytokine,
the chemokine, is key in this process.
As the name suggests, these
are chemotactic cytokines.
And two of them are
Those chemokines are
called CCL19 and CCL21.
And they are recognized by a particular chemokine
receptor on the surface of the naïve T-cell.
And that receptor is called CCR7.
Having then entered the lymph node, those naïve T-cells
can become activated by interaction with dendritic cells.
And then, as we just saw they can leave the
lymph node via the efferent lymphatic vessels.