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Spleen
The spleen is perhaps the most crucial of our secondary lymphoid
organs. We only have one each so if we damage it our immune system
can be significantly compromised. We can survive without it and
lead a virtually normal life, there are people who have had splenectomies
perhaps because of tumor development or other such extensive damage.
Such people may be more susceptible to pathogenic infection but
the duality of the immune system comes into play and lymph nodes
may take over some of the functioning of the spleen.
The spleen lies in our abdominal cavity on the left hand side
immediately behind the stomach. It is a long thin sac-like structure
contained in a collagenous capsule. As for the thymus and bone
marrow it has a closed circulatory system, one entry and exit
point near the top of the sac. In healthy individuals the spleen
is a deep red/purple color but for those fighting infection or
with a chronic immune response the spleen may turn a red/pink
color. As with the bone marrow when it is challenged with an infection
the color change is due to the accumulation of white lymphocytes
dominating over red blood cells.
To cut a spleen in half you will see changes in color and structure
throughout the tissue. The spleen contains trabeculae like the
thymus. These trabeculae are collagenous extensions from the capsule
deep into the spleen. They are part of the support superstructure.
In addition there is a complex network of reticular fibers which
shoot off from the trabeculae further into the spleen and looks
a lot like a plant root system. On top of this are reticular cells
which reinforce the frame work and hold cells and blood vessels
in place to stop them slopping around. The blood system consists
of arteries and veins, capillaries and sinuses. The spleen also
has a connected "lymphatic" system. The main arteries
and veins run through the middle of the trabeculae and then branch
out on their own into smaller and smaller arterioles. These seem
to end in blind endings in the tissue but there is some argument
about this. Some believe that the arteries are connected to the
sinuses which are in turn connected to the veins which take blood
away from the spleen. Others disagree and say the arteries and
sinuses/veins are not directly connected. If they are not connected
then all the cells that enter the spleen through the blood vessels
must squeeze through the vessel wall and into the spleen tissue
before collecting in the sinuses and veins to leave the spleen.
If the arteries and veins are connected then we must assume that
most blood cells entering the spleen are flushed straight through
and that only selected blood cells push through the artery walls
and into the spleen tissue.
The cells in the spleen called the pulp tissue can be seen arranged
and focused around these arterioles and other vessels. There are
two types of pulp, red and white. Red pulp predominantly contains
red blood cells and white pulp contains mainly lymphocytes. In
healthy people the red pulp will take up 80% of the space in the
spleen but those people facing a chronic infection will expand
their white pulp to take up 50% of the space and correspondingly
reduce the amount of red pulp. White pulp tissue can be seen tightly
focused in a cylinder shape around the blood vessels running through
the spleen. These cylinders of white pulp are also known as the
"periarteriolar lymphoid sheath" (PALS).The spaces in
between these cylinders of white pulp is filled up with red pulp
tissue.
We can further subdivide the white pulp into areas with special
functions. T lymphocytes are found closest to the arterioles.
A little further away the B cells are situated. The spleen is
the major center for B cells to congregate. When the body is defending
against an infection the B cells can be clearly seen to form what
is called a "germinal center". When this happens the
white pulp cells push the arterioles they focus on to one side.
The new center of attention is a region of B cells which rapidly
multiply and mature into adult antibody producing cells.
As I mentioned in chapter three you won't find many B cells
floating around in your blood stream and you would be hard pressed
to find any B cells in healthy tissue and organs. The vast majority
of B cells situate themselves in the spleen and carry out their
functions here. There is no need for them to migrate to sites
of infection and tissue damage unlike T cells which must migrate.
The B cells wait until they are presented with stimulating antigens.
Interspersed throughout the white pulp and into the red pulp too
there are interdigitating cells (antigen presenting cells). These
cells present any antigens of infective pathogens predominantly
to the T cells that are present. Remember that B cells often need
T helper (Th) cell stimulation before they become fully activated.
The activated Th cells send out cytokines to promote the nearby
B cells. The B cells may receive antigen stimulation from antigens
previously processed by the antigen presenting cells and then
released or sometimes the B cells can recognized unprocessed antigen
that was brought to the spleen in the blood plasma. Once stimulated
the B cells become antibody producing plasma cells. The antibodies
are then released to be collected into the veins and lymphatic
vessels to be distributed throughout the body.
The spleen has another function involving the red blood cells.
All cells found in the spleen pulp must pass through the arteries
in the white pulp. Once in the pulp they are subjected to a filtering
mechanism. The spleen wants to make sure the right cells go to
the right places. Lymphocytes don't have to move far. They head
directly for the appropriate areas of white pulp immediately surrounding
the arteries. Red blood cells however have a more tortuous path
to follow. They must pass through the white pulp and enter the
red pulp area. In doing so they are subjected to close examination
by numerous macrophages dispersed through the spleen (These cells
can also function as antigen presenting cells). Any red blood
cells that have defects are promptly phagocytosed. Only healthy
red blood cells reach the red pulp. This examination of red blood
cells has two roles. The red blood cells may have non-self antigens
attached to them if they passed through an area of infection or
damaged tissue. In which case the macrophages need to obtain that
antigen for presentation to T cells. Second, the spleen plays
a supportive role to the liver in cleaning the blood of damaged
and decaying red blood cells.
Once the red blood cells reach the red pulp they may cross into
a network of veins to take them away from the spleen. The lymphocytes
must also enter into the red pulp to leave the spleen via the
sinuses and veins.
Lymphatic
system
Lymph nodes are numerous and widespread throughout our body. They
form a network linked together by the lymphatic system of vessels.
You are aware of the blood system which is the bodies transportation
system for nutrients, waste material and cellular transportation.
We also have a system of vessels that is virtually a dedicated transport
system for tissue plasma. The lymphatic system is just as extensive
as the blood artery/vein network. Lymphatic vessels can be found
almost everywhere there is tissue except for the brain and spinal
cord, skin epithelium, mucous membranes, some regions of the eye,
bone marrow and cartilage.
Like blood vessels the lymphatic ducts are made from endothelial
cells and form a branching system getting ever smaller as they penetrate
deep into the tissue. They end as blind capillaries and their particular
focus of attention are the skin dermis and the respiratory, genitourinary
tracts, those areas of tissue most likely to be the entry point
for pathogens. Unlike the blood system the lymphatic vessels are
not a circular loop. For the blood system the arteries that leave
the heart branch out into the tissue. Blood cells then return to
the heart via the veins and so move round the blood system in a
circular motion. The lymphatic system is strictly a one way street.
It is a drainage system taking away excess tissue fluid.
Strictly speaking there are two lymphatic drainage systems. One,
called the right lymphatic duct, drains the upper right side of
the body including the heart, lungs and the right side of the head.
These lymphatic vessels fuse into one duct that opens into the right
subclavian vein just above the heart. The rest of the body is drained
by another system of ducts called the thoracic duct. This drains
into the left subclavian vein just before entering the heart.
At its simplest the lymphatic system is used to drain excess fluids
from organs and tissue. The fluid is mainly plasma that has been
squeezed out of the blood capillaries because of blood pressure.
A small amount of the fluid is produced by the tissue cells as a
waste product from respiration. Because the fluid in the lymphatic
ducts is drained from tissue it conveniently provides a method for
the immune system of monitoring the health status of different areas
of the body. The immune system can check what kind of soluble antigenic
material is being produced in different areas of the body by checking
the lymph fluid draining from that region.
The lymphatic system has also been utilized by the immune system
as a communication and transport network for lymphocytes and antigen
presenting cells culminating in regional repositories of immune
cells called lymph nodes.
Lymph
nodes
Along the length of the lymphatic vessels are smooth, oval lymph
nodes. They are frequently situated at the junction between several
lymphatic ducts and consist of densely packed immune system cells,
in particular antigen presenting cells, B and T lymphocytes. Each
lymphnode is plumbed into the lymphatic system with several, ducts
extending from it. There is at least one and more likely several
afferent lymphatic ducts bringing cells and plasma to the node.
There are efferent lymphatic ducts leaving the lymphnode ultimately
to drain back into the blood stream. Each lymphnode also has an
enclosed blood network of arteries and veins. The key lymph nodes,
and the largest in size, are the axillary nodes under the armpits,
the inguinal nodes in the groin, the mesenteric lymph nodes close
to the gut, and the lymph nodes in the neck. Normally these lymph
nodes are about an inch in diameter but they enlarge to twice the
size when challenged by an infection.
Lymph nodes are highly organized and similar in construction to
the spleen. When cut in half the lymphnode can be seen to be bound
by a collagenous capsule with trabeculae extending from it into
the core of the node. From these trabeculae reticular cells and
fibers create a complex meshwork to provide a scaffold support for
other cells. The cells are primarily T and B lymphocytes plus antigen
presenting cells (APCs) such as macrophages and dendritic cells.
Other cell types have restricted access to the lymph nodes. Unlike
the spleen there are no erythrocytes in lymph nodes. The periphery
of a node (the cortex) has the highest concentration of lymphocytes
and the cells are usually aggregated into tightly packed nodules
called follicles. The center of a lymphnode is called the medulla.
This region also contains lymphocytes but not nearly so concentrated
as the peripheral cortex. Follicles in the periphery are mainly
B lymphocytes and when responding to an antigenic challenge these
follicles become sites of B cell proliferation and activation. The
T cells situate them selves in between the follicles in what is
called (surprise) the interfollicular region.
The immune cells may arrive in the lymphnode via the blood system.
They squeeze through the endothelium wall of blood vessels in the
cortical region. The lymph node blood vessels selectively only allow
certain cell types to penetrate the vessel walls and enter the tissue
of the node within the cortical area. Cells that can penetrate through
vessel walls into the lymph nodes have been found to express special
antigens on their cell surface called cell adhesion molecules. These
are receptors which allow the cells to bind to the vessel endothelium
running through the cortex. The blood vessels running through the
medulla do not allow cell adhesion to their surface and so limit
access to the cortex of lymph nodes.
However, above we mentioned that the immune system has adapted
the lymphatic system as a transport network. Immune cells, particularly
T lymphocytes and APCs, can also enter a lymphnode via the afferent
lymphatic ducts. In addition to draining tissue of fluids, lymph
ducts also act as highways for lymphocytes and APCs to leave the
tissue. As well as providing fluid to the lymphnode the ducts also
supply immune cells. All cells leaving the lymph node must leave
via the efferent lymphatic ducts. They rarely, if ever enter, back
into the blood vessels in the node. So the cell density in the lymphatic
ducts becomes increasingly concentrated with each lymph node encountered
on the way from the tissue to ducts opening into the subclavian
veins.
Lymph nodes are very dynamic organs. The bulk of the cells are
mobile, with large volumes entering and leaving the nodes each day.
So, there are two methods by which antigen may be supplied to a
lymphnode. Soluble antigens may be free in the lymph fluid or they
may be contained by antigen presenting cells suspended in the lymph.
As the lymph fluid enters a lymph node it enters what's called the
"subcapsular sinus". This is a fluid space immediately
underneath the lymph node capsule and acts as a reservoir for lymph.
The lymph is then passed down numerous trabecular sinuses through
the cortex and medulla to enter the efferent lymphatic duct and
leave the lymphnode. The walls of subcapsular sinus and trabeculae
sinuses are covered with phagocytic cells which pick up any free
floating antigens in the lymph. These cells, plus APCs already in
the lymph, are able to present the antigens they have picked up
to any T and B cells present in the node.
Normally the migration of T cells and APCs through a lymph node
is continuous, but when a foreign stimulatory antigen is encountered
in a lymph node the movement of cells in and out of the node is
prohibited for up to 24 hours. This gives APCs in the node carrying
the foreign antigen enough time to circulate through the node and
present the antigen to the T lymphocytes. Those cells able to respond
to the antigen become activated. B cells in their densely packed
cortex follicles begin to proliferate. The follicles become larger
and change their composition such that they have a center of immature
B cells and a periphery of more mature cells. In this state the
follicles are called secondary follicles. T cells in the interfollicular
regions are also presented with antigen and responsive T cells proliferate
accordingly.
Once the cells have been presented with antigen, multiplied and
differentiated into adult cells, they migrate to the medulla of
a lymphnode. B cells are now blast cells, actively producing antibody
which is released into the lymph fluid to be taken out of the node.
T cytotoxic and helper cells leave the node via the efferent lymphatics
to move on to other nodes and ultimately to migrate to the source
of the stimulatory antigen to carry out their defense actions. Many
APCs, some B cells and T helper cells also leave the node to enter
other nodes downstream and help with stimulating other B and T cells.
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