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THE PLAYERS IN THE
Inside you are more than thirty different organs, which include
more than two hundred different cell types and about 100 trillion
cells. Each organ is patrolled by your immune system, which is constantly
performing surveillance for possible threats. Following are
some of the major players.
Bone marrow, the reddish-looking material inside nearly every bone
in the human body, is where all of the blood cells are produced.
Inside the marrow, on an inner framework, lie the bone marrow
stem cells. These cells are constantly dividing, producing huge
numbers of cells that turn into red and white blood cells.
The bone marrow stem cells continue to divide, even as they
keep making red and white blood cells. And just as a couple of
million are being produced every second, the same number are
being gobbled up and destroyed in the spleen, which is, in effect,
the cells' decommissioning center. The spleen is where blood cells
are taken out of circulation once they've completed their useful life
cycle (see below).
This process-birth in the bone marrow, death in the spleen-
should be evenly balanced. If it isn't, you will be prone to a blood
disorder. For example, if your system is destroying more red blood
cells than it's making, you'll become anemic, which will make
you feel tired and appear pale. If you're making more than you are
destroying, you'll become polycythemic, or suffer from blood that is
overcrowded with red blood cells.
Once the cells form in the bone marrow, they remain there and
mature, at which time they exit and enter the bloodstream. There
they circulate, the red cells carrying oxygen and carbon dioxide,
and the white cells patrolling for invaders.
The thymus, located in front of your windpipe in the upper chest
region, is the most mysterious organ in your homeland.
In infants, the thymus is, relatively speaking, huge. It grows
until about puberty and then starts to shrink. By old age, the thymus
has almost completely disappeared.
The thymus serves the role of a kind of boot camp for the
white blood cells called T cells-it's where these cells go to mature.
The thymus is especially active early in life because, during youth,
T cells are constantly being exposed to new things, from new proteins
in your diet to new germs. These T cells need to have a place
to congregate, share information, and learn about threats and
For example, let's say one of the cells in your immune system
comes in contact with a foreign invader. It now has to communicate
that information to other cells so they can become aware of
the invader too. The thymus is where this information is shared
and training occurs.
Why does the thymus later atrophy? Science doesn't know
for certain, but as you grow older, your immune system has less to
learn. So the current thinking is that there may be less need for a
large thymus as we age. But although the thymus is not as big or as
active as it was when we were young, the smaller thymus is still able
to help train T cells well into our eighties, nineties, and beyond.
Another important training center and meeting ground for the
immune system is the spleen. This large organ, about the size of
your fist, is located on the left side of your belly, tucked under
The spleen is a common meeting place for all the immune
system's cells. Blood routes to the spleen, where the cells circulate
and mingle, allowing them to tell each other what they've learned,
what they've seen, what they've killed, and what antibodies they've
The heart pumps the blood around the body about once every
minute, which means each blood cell might find itself in the spleen
about 1,400 times a day. That's a great many trips.
The spleen is also important because it's where the body decides
if a red or a white blood cell has gotten too old. Once the decision
is made, the cell is decommissioned and disassembled and its building
blocks are recycled.
You can live without a spleen; if it ruptures, the liver can take
over its functions. Still, if your spleen is removed or no longer
works, your immunity becomes impaired; people without a spleen
are more susceptible to infections.
Nearly everyone knows about the bloodstream: it's a road map of
blood vessels that allow our blood to circulate through our body.
But few people realize that another important, and completely different,
circulatory system exists in the body-the lymphatic system,
which circulates our lymph.
Lymph is a clear fluid that travels through your body, cleaning
your tissues and keeping them nourished. Just as blood circulates
back to the heart through our veins, lymph must also be recycled
and return to the heart, which it does through the lymphatic
The lymphatic system is something of a secondary transportation
system for your homeland troops. Like the circulatory system,
it is composed of a series of vessels and tubes. The major difference
between the circulatory and the lymphatic systems is that the latter
lacks a pump to move the fluid it carries. For the blood, that
pump is the heart. For lymph, the flow back to the heart is achieved
through a more passive process involving muscle contractions and
You may have noticed that your feet swell during a long journey
on an airplane or in a car. This is due to lack of movement; your
muscles haven't been able to circulate lymph, so because of gravity,
it collects at the lowest part of your body-your feet.
You also may be aware of a condition known as edema, which
is swelling that results from a collection of lymph. Edema occurs
when excess lymph fluid cannot be returned back into circulation.
The bloodstream is extensive, branching out from its main
trunk, the aorta, as well as smaller arteries, arterioles, capillaries,
veins, and venules, but there is still a large portion of our tissues
the capillaries can't reach.
Here is where the lymph comes into play. Nutrients such as glucose
(blood sugar) must be helped so they can reach and nourish
each and every cell, including those the bloodstream can't reach.
That happens via the lymph fluid, which bathes and nourishes all
of the body's tissues. And once those nutrients have been used, the
fluid must be recycled or your body would swell up like the Michelin
Along the course of the lymphatic system are way stations
known as lymph nodes. These are outposts whose sentries make
sure nothing passes through the lymphatic channels that shouldn't.
The lymphatic system could provide easy and direct access for a
germ or microbe to our heart and bloodstream, so to prevent that
from happening, lymphocytes (T cells and B cells) aggregate in
lymph nodes, waiting for something bad to pass by. When they
spot that something, the node cells attack before it can venture
into the heart and bloodstream.
When a problem is stirring in your body, the lymph nodes
become enlarged. For example, if you have swollen glands in the
neck, your nodes may have found some virus that landed in the back
of the throat and is trying to gain access to the lungs or bloodstream.
Lymph nodes responding to some infection can become swollen
almost anywhere: in the groin, neck, chest, abdomen, and so on.
WHITE BLOOD CELLS
Probably the most important cells of our immune system, as well as
the best-known and the most numerous, are the white blood cells.
This term distinguishes them from the red blood cells, the disk-like
cells responsible for carrying oxygen and carbon dioxide from our
lungs throughout the rest of the body.
Most people probably think of white blood cells simply as formless
globules floating through our bloodstream, randomly patrolling
for microbes. But our white blood cells are very purposeful and
deliberate in their surveillance, and there are actually many different
types of white blood cells, each with specialized functions.
And these white blood cells are found not just in the blood, but
throughout our bodies-in each of our organs, from the brain to
the liver to the lungs, as well as throughout the lymphatic system.
The first line of immune cells are the lymphocytes. Cyte means
"cell," so lymphocytes are the lymph or lymphatic cells. The ones
you most need to know about are the B lymphocytes (better known
as B cells) and the T lymphocytes (better known as T cells).
B cells were so named because they were first studied in the bursa
of Fabricius, an organ unique to birds. In humans, B cells actually
originate in the bone marrow.
The B cells have two major jobs: they maintain a memory
database, and they create complex protein structures that are used
as weapons against threats and invaders. These complex structures
are called antibodies, about which more is coming.
B cells keep a record of every single interaction your immune
system has ever had. This means that within your body, a record of
every germ and virus you've ever encountered, every protein you've
ever eaten, every piece of pollen you've ever inhaled, has been
stored in a memory bank-not in your brain, but in your immune
system. Think about it: for each of these interactions, there is a
B cell floating around inside your body that has retained a memory
of the encounter.
Your immune system's memory is, in some ways, more impressive
than your brain's. Most of us can only evoke faint memories
from early childhood. Your immune system, however, remembers
your first vaccination, which probably occurred in the earliest days
of your life. Research now suggests that your immune system even
stores memories from when you were still developing in your mother's
Shortly after birth, you were probably immunized with vaccines
for diphtheria, tetanus, and pertussis (whooping cough).
Although the memory of that immunization may fade somewhat,
and a booster may be needed to remind your immune system, some
remnant of that memory lasts a lifetime.
These stored memories are critically important for your survival;
they are what make you immune to becoming sick more
than once from certain illnesses.
For example, after a bout of chicken pox in childhood, you
become immune-you usually can't catch chicken pox again as an
adult. Likewise, after being immunized with a shot for tetanus, you
won't succumb to the bacterial infection that causes tetanus. Your
B cells now have the memory stored away and prevent you from
coming down with the disease.
A memory of exposure to prior threats is crucial because it
allows your immune system to respond more quickly and effectively
to serious threats if you are re-exposed. Without such a memory,
and a rapid response, exposure to ailments such as tetanus or diphtheria
could be fatal.
It's also important for your immune system to remember prior
contacts and exposures even if they're not potentially lethal, as it
makes your immune system less likely to cause an overwhelming
reaction when encountering nonlethal microbes. If, for example,
your immune system overreacted every time you ate a particular
food, or breathed in a particular pollen, you would forever exist in a
state of immune hyperactivity and unnecessary battle.
One example of an overreaction by our immune system is an
allergy, which can trigger serious problems like asthma or even
anaphylaxis, which can be lethal. We'll talk more about this later.
B cells possess another important function. They make antibodies,
whose role in your internal homeland security is similar to
that of the U.S. Army Corps of Engineers. Here B cells work closely
with T cells to build complex mechanical and chemical structures
that act as deadly weapons to neutralize invaders.
Antibodies are complex proteins manufactured to exact specifications. Each antibody is built by the B cells to neutralize one
specific invader. Medical science does not yet fully understand the
way in which these antibodies are made. What is known is that
B cells team up with macrophages in order to create them.
First, what is a macrophage? Phage comes from the Greek
phagon, meaning "to eat." Macro, from the Greek macron, means
"big." Thus a macrophage is a "big eater."
Macrophages constantly patrol the body, which means they
can be considered your body's military police, or MPs. The MPs
are constantly on the lookout, in every organ in your body. Always
moving, they crawl between the trillions of cells in all of your
organs like an amoeba might crawl across a petri dish.
These bloblike, voracious eaters are searching for any invaders
that might have sneaked into your body. When an MP encounters
one, it will capture it, cut it up into a thousand tiny pieces, and then
take the bits and show them around the body to let the other troops,
such as the B cells, know exactly what the invader looks like.
Sound overly dramatic? Actually, it's quite close to the literal
truth. When macrophages encounter an invader, they grab it with
amoebalike fingers and engulf it, swallowing the invader whole so
that it becomes a captive. The macrophage then releases enzymes
to digest it, breaking it down into tiny bits. These little sections
become pieces of proteins-small enough to be moved around
but large enough to provide a unique "fingerprint" identifying the
invader the MP just gobbled up and digested.
The MP next spits up these little digested bits of protein fingerprints
and displays them on its own surface, similar to placing a
"Wanted" poster for the rest of your immune system to see. Now
the B cells move in, going up to that "Wanted" poster, or that piece
of the invader, and learning its shape. They then build an antibody
that suits the shape of the invader perfectly. This antibody
can now recognize and attach itself to the invader the next time it
comes into contact with it.
The B cells next start making millions and millions of copies
of this antibody, releasing them into the bloodstream. They fl oat
through our blood, and if they come into contact with one of these
microbial invaders, the antibodies immediately attach themselves
to it, triggering a series of events that will ultimately kill it.
Our B cells manufacture antibodies to exceptionally tight
specifications so that the antibodies are specific to one particular
germ. And the antibodies must be a perfect fit; otherwise, critical
problems would result, the most important being that the antibody
might not be properly able to recognize and neutralize the threat.
If, for instance, the antibody mistakenly grabbed onto your eye,
you would go blind. If it grasped your brain, you'd suffer brain damage.
As soon as antibodies take hold of something, a chain reaction
is produced, and that thing will either be neutralized or killed.
Once a B cell learns to produce an antibody with the help of
a macrophage, it retains the memory to produce that antibody forever.
So in effect, that B cell is forever programmed to recognize a
specific invader. If it ever encounters that invader again, the B cell
will immediately begin producing millions of copies of its antibody,
and will also reproduce itself thousands of times to create a force of
so-called daughter cells. Each daughter cell also inherits the know-how
to recognize that specific invader and to produce its specific
It is thought that B cells live anywhere from about a year to
about six years. B cells reproduce themselves (by cell division) to
maintain their collective memory, which is crucial for your very
survival. And B cells can also multiply quickly in response to the
recognition of a known threat. This ability to multiply helps build
a formidable antibody response in the event a known invader gains
entry into your body again.
There's a lot of brainpower in the B cells.
The other major group of lymphocytes is the T cells (T stands for
thymus, the body organ in which they mature).
T cells look like B cells under a microscope-they are spherical,
with a big nucleus and not much cytoplasm (the stuff that
surrounds the nucleus). These T cells are the marines of your homeland
security team. Just as every marine has a job classification,
or a military occupational specialty (MOS), every T cell also has
The T cells are divided into occupations such as helper T cells,
suppressor T cells, and cytotoxic T cells. These are all very specialized
functions, analogous to real marines assigned to the bomb
squad, the recon team, and so forth. Some T cells (cytotoxic, or
CD8, cells) attack invaders and infected cells directly, while others
(helper, or CD4, cells and suppressor T cells) help regulate the
immune response and keep it from becoming overactive. Cytotoxic
(or cell-killing) T cells identify foreign organisms inside our cells
and destroy those infected cells by recognizing changes in their
surface proteins. They work in concert with the suppressor and
helper T cells, which regulate the activity of the cytotoxic T cells.
Suppressor T cells help to regulate the immune reaction by preventing
cytotoxic T cells from killing healthy cells. Helper, or CD4,
T cells help cytotoxic cells kill infected cells. You may have heard
of CD4 cells in the context of HIV infection, because these are the
cells targeted by HIV (the human immunodeficiency virus). Low
levels of CD4 cells signal a serious HIV infection.
Also important are specialized cells known as natural killer
cells (NKs), which are assassins trained to destroy damaged, cancerous,
or infected cells in the body. NK cells are similar to cytotoxic
T cells but are more powerful.
Let's say you are exposed to a virus. One of the reasons viruses
are so dangerous is that they don't just cruise around the tissue or
blood and hide there, waiting for your body to destroy them. They
actually creep inside your cells, and that means your body has to
destroy some of its own cells if they become infected.
Once inside your cells, a virus messes with your DNA, tricking
your cells into reproducing the virus by mingling its own DNA
with yours. Then the virus uses your cells' DNA-processing system
to replicate its own DNA too.
When a cell becomes infected with a virus in this way, the situation starts to resemble the scene from the science-fiction movie
Alien in which the aliens, growing inside the characters' bodies,
burst out, killing them.
Unfortunately, the only way to prevent the dangerous alien
that is a virus from reproducing is to kill the newly infected cell.
That's where the killer T cells come in. Natural killer cells sense a
distress signal from the cells infected by a virus. The call may come
from any type of cell-one that lines the nose or throat, or that
resides in your intestines or in your skin.
When NK cells detect an infected cell, they use a special
weapon to destroy it-a kind of plug that's injected into the cell
membrane (the outside boundary of the cell). The plug, which has
a small hole in it, is a protein called perforin. The NK cell then
injects a substance called granzyme (or, more formally, exogenous
serine protease) through the plug, which destroys the cell like
That's how the natural killer cells work to destroy cells infected
with viruses. Other parts of the immune system attack viruses
directly, but natural killer T cells are those responsible for killing
viral-infected cells, including the ones carrying HIV, which is why
it's important to have a high count of NK cells in your blood.
Natural killer cells are involved in many search-and-destroy
missions for our immune system. They're also important in killing
cancerous cells that crop up in our bodies, ideally before they
can grow into tumors. Cancer in the human body is not as rare as
most people think; cancer cells are actually quite common. But for
a number of reasons, most of these cells are never allowed to grow
into tumors capable of killing us. One of the reasons for this is that
the assassin-like NK cell snuffs them out before they have a chance
Several therapies have been shown to increase NK activity,
such as guided imagery, qigong, special breathing techniques, ginseng,
and certain Chinese herbs.
Besides lymphocytes and macrophages, the third line of immune
cells includes the blood-forming, or hematogenic, cells. Hematogenic
cells are the cells from which our red blood cells, and many
white blood cells, are produced. During a routine physical exam,
your doctor probably performed a blood count, measuring the number
and types of white blood cells seen in a drop of your blood. A
high number (or high concentration) of white blood cells is usually
a sign of some infection or stress on the body.
Many types of white blood cells are visible in a drop of blood.
About half of them are known as neutrophils, aka polymorphonuclear
cells, or polys for short.
I like calling these cells PMs, because that also stands for Pac-
Man, the video game whose little creatures resemble PMs. Like
Pac-Men, PMs sense invaders, chase after them, and once they've
caught their quarry, they literally gobble them up.
Some of the other white blood cells include eosinophils, basophils,
and monocytes. Each of these cells has its own specialized
function. Eosinophils, for example, play a role in allergic reactions,
as well as disorders like asthma. They are also involved in fighting
off parasitic infestations.
As you know now, our immune system contains many specialized
fighters possessing specialized weapons to deal with varied and
sometimes uncommon threats. The ones mentioned above are just a
few of the soldiers who are constantly fighting to keep your personal
homeland safe. Right now, inside your body, they are all at work.
BORDER SECURITY AND THE ALTS
As discussed, one of the major duties of our body's homeland security
system is border security, and it's a big border, including all of
the surfaces that come into contact with the outside world. Invaders
are constantly appearing, with the intent of not just looking
around, but of doing us harm. Therefore, we need more than just a
few cells of our immune system patrolling these borders.
This is where the so-called ALTs, or associated lymphoid tissues,
enter the picture. ALTs are large clusters of immune cells
located at fairly regular distances along our borders. For example,
in the gut we have GALT (the gut-associated lymphoid tissue),
which resembles thousands of strongholds positioned throughout
the gut's lining, protecting the border between us and what's inside
The gut is an especially important border, not only because of
its size (approximately the area of a tennis court when fully flattened),
but also because of the constant barrage of bacteria and
other microbes trying to break through it. The only barrier is a
thin membrane a single cell thick.
Such a big assignment requires a large force, which is why the
GALT alone accounts for about half of all the cells in our immune
system. Most of these cells are T cells, but B cells, as well as macrophages,
are also stationed in the GALT.
However, the borders of our homeland extend beyond the gut.
There's also our skin, and the mucous membranes that line our
nose, mouth, sinuses, throat, and lungs. Each of these boundaries
needs its own defense force, so like the gut's GALT, we also have
a SALT, a NALT, a TALT, and a BALT, whose acronyms stand for
the skin-, nose-, throat- (or tonsils), and bronchial-associated lymphoid
tissue. These aggregations of lymphoid tissue represent more
than 70 percent of our immune system.
THE COMPLEMENT SYSTEM
We've already seen a number of ways our immune system's cells can
fight off threats. For example, an MP (macrophage) or a PM (poly)
can gobble up a germ, or an NK (natural killer) can inject a granzyme
grenade into an infected cell.
There are several additional ways the immune system kills off
bodily threats, using more sophisticated tools that allow it to rid
the body of more than one invader at a time. After all, if faced with
an invasion by billions of enemies, hand-to-hand combat alone
One of these tools is a chemical weapon known as an antibody,
which is produced by the B cells. Yet another process occurs when
the antibody nabs its target. The same handle, or tail, that signals
to the immune system that it's caught something also triggers the
deployment of a system of chemical weapons known as the complement
The complement system is an exceedingly convoluted system
of chemical warfare. In simple terms, think of the complement as
something akin to an arsenal of nuclear weapons. The complement
system is always present in our body, but its different components,
of which there are at least thirty, are generally disassembled.
These complement components are produced mainly in the
liver, but also by macrophages and other cells of the immune system.
Separately, each of the complement components is harmless.
But if the entire array is assembled, watch out! A nuclear reaction
will take place.
The trigger for the complement construction transpires when
those antibody pitchforks skewer so much prey it becomes clear
additional help is needed. That critical level of battle initiates the
assembly, or activation, of the complement system.
Activation of the complement system is one of the body's most
impressive functions. Luckily, it is triggered only by severe issues,
such as pneumococcal pneumonia or meningitis. It also occurs in
organ transplantation-normally our immune system produces
such a vigorous reaction to a transplanted organ that it causes
organ rejection, which is why drugs must be given to suppress complement
As in a nuclear reaction, once the complement system is activated,
a process of events is triggered that is hard to stop and usually
results in the death of the invaders.
That destruction takes the form of leaking capillaries, swelling,
accumulation of lymph fluid, and the release of distress signals
that attract even more fighters from all over the body, as well as the
release of pyrogens (chemicals that raise body temperature, causing
a fever) and general deployment of all available weapons, including
nitric oxide and free radicals.
This entire process makes you feel very sick. If it continues, due
to an overwhelming threat, it can lead to shock, organ failure, and
death. Complement activation is therefore generally reserved for
only the most serious circumstances.
THE COMMUNICATIONS SYSTEM
The final part of the homeland security detail you need to appreciate
is the communications link.
For a battle in the outside world to go well, good communications
are required: satellites, cell phones, radios, and microwave
systems all communicate strategies as well as locate the enemy so it
can be outflanked.
Your body has a similar kind of communications system.
The main category of communications devices is composed of
the cytokines, of which more than one hundred have been discovered.
Cytokines are proteins-such as interleukins, interferons, TNFs
(tumor necrosis factors), pyrogens, and shock proteins-that send
signals through your body to distant parts of the immune system.
Let's say you develop an ingrown toenail. First the Pac-Men
engage with the enemy in the toe. But if they discover, say, an
infection too powerful for them to fight on their own, they send
out a message through the bloodstream that acts as both a distress
and a homing signal, calling for reinforcements to the toe. This
signal goes out in the form of cytokines.
Cytokines tell the rest of the immune cells where to go, and
they follow the cytokines' scent just as a bloodhound sniffs out a
trail, leading them right to the toe where the infection is wreaking
Drug companies are constantly researching cytokines and how
to turn them on or off to treat different conditions. Cytokines are
used to treat some infectious diseases, such as hepatitis, which is
caused by a virus. For example, people are given interferon treatments
if they are infected with hepatitis C. In autoimmune diseases
such as rheumatoid arthritis or colitis, cytokine blockers including
Enbrel, Humira, and Remicade are used to block the effects of the
cytokines activating the immune system.
The immune system is so complicated that it would take volumes
to explain all its details. But this brief introduction should provide
you with a basic understanding. Knowing how your immune system
operates can save your life-the more you know about it, the
better you will treat it, and, in return, the better it will treat you.
© 2007 by Mark Liponis, MD