You live in a world of germs and you're at war. Your body's constant, warm
environment, rich in nutrients, is an ideal home, where tiny organisms can
thrive.Their aim is to get in. Your body's job is to keep them out.
Keeping infectious microorganisms out and destroying any that get in is the
mission of your immune system.
Just 20 years ago, scientists had only fragments of information about how the
many cells that make up your immune system interact to protect you against
disease. Through advances in cancer research, scientists now believe more than
100 million immune cells exist. For every virus or bacterium, there seems to
be an immune cell specifically designed to hunt down and destroy it.
This understanding is leading to new ways to defend against diseases such as
cancer. With use of advanced technologies, scientists are developing drugs and
techniques that modify your body's immune response.
But bacteria and viruses are cunning adversaries--constantly devising new ways
to breach your immune system's defenses. Sometimes scientists develop a new
drug, only to discover later the microorganism has assumed a dangerous new
disguise (see "Are epidemics a thing of the past?").
Here's a look inside your immune system--at its remarkably intricate defense
mechanisms, its vulnerabilities and its future capabilities to fend off
today's invincible enemies.
Aligned for battle on all fronts
Your immune system is a complex array of organs, cells and molecules
distributed throughout your body. Each part of the system contributes to the
growth, development or activation of lymphocytes, sophisticated white blood
cells that play a major role in your immune response.
White blood cells originate in bone marrow. Some then migrate to your thymus
where they develop into specialized types of immune cells.
>From bone marrow and thymus, some white blood cells gather in lymph nodes and
other immune organs, including your spleen, tonsils, adenoids, appendix and
small intestine. Other white blood cells circulate throughout your blood and
lymphatic vessels.
Lymphatic vessels transport lymph, a colorless fluid that carries
microorganisms and dead cells from distant infections into lymph nodes where
they can be eliminated. Lymphatic vessels also transport white blood cells to
sites of infection.
Your immune army's "soldier cells"
The key to your immune response is a remarkable arsenal of white blood cells.
The main defenders include:
B cells and T cells--These white blood cells bear major responsibility for
your immune response. They recognize and coordinate an attack against specific
microorganisms.
B cells work chiefly by producing antibodies. Each B cell is designed to make
a specific antibody. And each antibody is designed to battle a specific
microorganism. B cells also develop into plasma cells that secrete thousands
of identical antibodies.
T cells coordinate immune defenses and kill organisms in cells on contact.
They also work by secreting potent chemicals called lymphokines, which direct
the immune response. Lymphokines are particularly good at attacking cancerous
cells or those infected by viruses.
Phagocytes--The name for these white blood cells comes from the Greek word
meaning "eaters." Their main function is to gobble up everything unwanted,
from a speck of dust or pollen to a virus.
The macrophage is one type of phagocyte that plays a versatile role. As
scavengers, macrophages rid your body of worn-out cells and other debris. They
also play a vital role in initiating the immune response.
Chemical killers--Other white blood cells--neutrophils, eosinophils and
basophils--are also "cell eaters." In addition, they release powerful
chemicals that destroy microorganisms.
Scouting the enemy
Whether the invader is a life-threatening bacterial pneumonia or a relatively
harmless cold virus, destruction by your immune system must be total. A single
infectious microorganism that survives can multiply and cause illness.
Common infectious organisms include bacteria, viruses, and parasites such as
fungi, worms and single-cell protozoa. Some of these infectious organisms
resemble your body's own cells. How do immune cells know which to attack and
which to ignore?
Picture an immune cell, holed up in a lymph node, armed and ready for the
enemy. As it lies in wait, it's constantly bumping up against millions of
substances in your blood--red blood cells, other white blood cells, proteins
and hormone molecules. Who's the enemy?
The marvel of your immune system is its ability to distinguish between what's
"you" and belongs from what's "new" and doesn't belong. Any "new" substance
that triggers an immune response is an antigen. As immune cells learn to
recognize and ignore your body's own cells, they learn to recognize and
destroy antigens.
Only within the past decade have scientists discovered how this recognition
works. Every substance--from a dust mite to the flu virus to one of your own
cells--carries its own "chemical ID card," marked by a unique molecular
pattern on its surface. All your body's cells have the same molecular pattern.
White blood cells learn to recognize and ignore cells identified by your
body's own pattern. During the learning process, many immune cells "fail the
test"; they react against your body's own cells and become inactivated. White
blood cells that ignore your own cells and react strongly against antigens
become "soldiers" in your "immune army."
Front-line defenses
Your immune system is equipped with elaborate defenses to fend off antigens.
As antigens attempt to invade your body, they meet with increasingly
sophisticated layers of protective defenses.
Your first lines of protection include:
Physical barriers--Your skin effectively shields your body from all invaders,
whether they're harmful or not. Your respiratory system also helps keep out
antigens. Defenses include trapping irritants in nasal hairs and mucus,
carrying mucus upward and outward on cilia (tiny hairlike projections lining
your respiratory tract), coughing and sneezing.
Your skin and the mucous membranes lining your respiratory and digestive
tracts also contain macrophages and antibodies. Fluids such as saliva, sweat
and tears contain destructive enzymes. Stomach acid kills most microorganisms
ingested in food or water.
General defenses--Antigens that slip through physical barriers are met by
scavenger cells circulating through your blood and lymphatic vessels. These
cells attack all antigens in a general way; they don't employ specific
mechanisms against particular antigens.
One general defense mechanism is the inflammatory response. It halts disease-
causing microorganisms early in their invasion and confines them to a
localized area.
When you're injured, bacteria begin to multiply at the site. Immune cells
cause small blood vessels near the injury to widen (dilate). The increased
blood flow leads to redness and warmth. Swelling occurs when immune cells
cause blood vessels to leak fluid into the surrounding tissue.
Nearby lymph nodes then trap microorganisms and trigger production of more
immune cells that kill bacteria and help contain the infection. Macrophages
clean up dead bacteria and damaged tissue.
Complement--This complex series of circulating proteins "complements" the work
of antibodies. When complement contacts an invading organism, each component
of the complement system is activated in turn ("complement cascade"). The
result is a protein complex that attaches to the organism's surface and
destroys it by puncturing its cell membrane.
Tougher enemies take stronger defenses
Antigens that pass through the front lines of defense confront two layers of
more sophisticated defenses. These defenses rely mainly on B cells and T cells
to recognize a specific antigen and tailor an attack.
Antibody-antigen defense--Each antibody made by a B cell fits a particular
antigen as a key fits a lock. Antibodies are particularly suited for ambushing
bacteria but can't penetrate cells where viruses hide.
Scientists long wondered how your body could store enough antibodies to
counter the millions of different antigens. Because immune cells never know
which potential disease-causing antigen they'll encounter next, they must be
prepared at all times.
Unraveling this mystery earned researchers the 1987 Nobel Prize. Scientists
found antibodies are capable of mixing and matching DNA in "mini-gene"
segments, similar to building with different-colored snap-and-lock blocks. The
mini-genes combine and recombine into the optimum pattern to make antibodies
that fit any particular antigen.
Cellular defenses--T cells concentrate on trickier assignments, such as
finding viruses that hide inside your body's cells. For help in finding the
foe, macrophages act as "undercover agents," moving among cells to help
identify antigen. Macrophages engulf the antigen, break it down and display
fragments of antigen as markers on their surfaces.
Once a virus is identified, some T cells release proteins that bind to the
infected cells and direct the attack.
Victory means future immunity
When you were born, your immune system was relatively weak. As you grew
through infancy and childhood, your natural immunity matured and became
stronger.
Time also strengthens your immune system by giving you another form of
immunity--the kind of protection you acquire through having an infection or
being vaccinated against it.
Each time you're exposed to an antigen, your immune system forms T and B
"memory" cells. After you recovered from chickenpox, for example, your immune
system stored a few B and T memory cells for chickenpox. The next time you
contacted the virus, memory cells multiplied rapidly to stop the infection
before it started.
Vaccines also work because of your immune system's ability to "remember." When
you're vaccinated, killed or weakened live forms of an infectious organism
stimulate an immune response without causing the accompanying illness. Memory
cells provide immunity for years or even your lifetime.
Factors that affect your immune response
The strength of your immune response depends on several factors, including the
specific antigen, your health and your genetic makeup. If your immune system
is healthy, it can make enough immune cells to destroy most infections. Yet
even a normal immune system faces obstacles that can weaken its response:
Age--In general, immune defenses are preserved and may even be enhanced with
age. For example, you acquire immunity to more diseases, such as viral
illnesses, as you grow older.
However, some immune responses are more susceptible to age-related decline.
With age, the number of immune cells doesn't necessarily decrease. Yet immune
cells, especially T cells, may respond less quickly and effectively to
invading organisms.
Heredity--Genes determine the molecular ID pattern that properly marks all
body cells as your own. Genes also shape the makeup of antibodies and other
immune cells. Genetic differences may help explain why you can resist an
infection while your spouse can't or why allergies run in families.
When your immune system doesn't work
Not only can your immune system be weakened, it can also be overwhelmed. These
conditions can occur when your immune system simply doesn't work as it should:
Allergy--This response is an overreaction by your immune system to an
otherwise harmless substance, such as pollen or pet dander.
Contact with an allergy-causing substance triggers production of a specific
kind of antibody (immunoglobulin E). IgE causes immune cells in the mucous
lining of your eyes and airways to release inflammatory substances, including
histamine. Release of histamine leads to the familiar symptoms of allergy and
asthma--redness and swelling of your eyes, sneezing, difficult breathingand
hives.
Autoimmune diseases--In these conditions, your body makes antibodies and T
cells directed against your own cells.
Insulin-dependent diabetes, for example, may be partly caused by an attack on
the pancreas by a person's own antibodies. Self-destructive antibodies are
also associated with chronic muscle weakness (myasthenia gravis) and
rheumatoid arthritis.
No one knows what causes the immune system's recognition process to break down
this way. Scientists believe multiple factors--heredity, viruses, certain
drugs or even sunlight--may play a role.
Immune-deficiency diseases--These conditions occur when one or more parts of
the immune system is deficient or missing. The defects can be inherited or
acquired from a viral infection such as AIDS. They also can be caused by the
toxic effects of radiation or some drugs.
Cancers of your immune system--When immune cells reproduce uncontrollably, the
result is a cancer of the immune system such as leukemia, multiple myeloma or
lymphoma.
New understanding spurs promising treatments
Even though understanding of the immune system has advanced during the last
decade, the knowledge reveals just a small piece of an intricate puzzle. Yet
doctors are using what they do know in a wide range of new investigational
treatments.
The strategies underlying most of these treatments are similar: Capitalize on
the immune system's ability to fight disease by enhancing its response. Or, in
the case of an autoimmune disease, by suppressing the immune response to stop
progression of disease. These new strategies are developing hand-in-hand with
advances in biotechnology, such as recombinant DNA technology.
Recombinant DNA technology is a process in which scientists mass-produce a
specific protein to treat a disease. The technology has led to more than 20
new treatments, drugs and vaccines and several hundred in various stages of
investigation.
DNA technology has helped doctors develop a cancer treatment that stimulates
the immune system using synthetic versions of the proteins released by T cells
(interferons). It has also enabled scientists to make growth factors that
cause bone marrow to produce more blood cells. Doctors can use synthetic
growth factors to regenerate blood cells after a bone-marrow transplant and in
treatment for AIDS.
Advances in biotechnology and research are also driving developments in these
areas:
Rheumatoid arthritis--Last year, British scientists discovered a protein
called tumor necrosis factor. TNF may be an important cause of inflammation
that can lead to joint damage.
Using recombinant DNA technology, scientists developed an antibody that
inactivates the inflammatory protein. People given large doses of the antibody
experienced significant improvement in their symptoms.
Organ transplantation--Thousands of Americans are alive because they have
transplanted tissue and organs including bone marrow, kidney, heart, lung,
liver, pancreas and, recently, small bowel. But a transplanted organ provokes
a furious response by your immune system, which treats the transplanted tissue
as foreign.
Researchers are working to develop drugs and other techniques that dampen this
side of your immune response, but still allow your body to defend against
infection.
Cancer--Because cancer develops within your own cells, it's not easily
recognized by your immune system. Once cancer becomes established, it may
block the action of some defense mechanisms that would normally attack the
cancer. The result is suppression of your immune response. Research focuses on
development of cancer vaccines that trigger a strong immune response early
enough to prevent cancer cells from becoming established.
A clinical trial for a vaccine against the skin cancer melanoma is now in its
final stage. And intensive work to find a vaccine against AIDS is helping the
development of vaccines against certain types of leukemia and lymphoma, caused
by a similar type of virus.
But doctors predict cancer vaccines ultimately will be used in combination
with traditional treatments to kill off the few cancer cells remaining after
surgery, chemotherapy or radiation therapy.
Other new treatments for cancer use recombinant DNA technology to increase the
numbers of immune cells. In one treatment, doctors remove lymphokines and
activated T cells from the person, cause them to multiply in the laboratory,
then reintroduce them into the person. A large multicenter trial found
replacement of these immune cells reduced cancer cell activity in people with
terminal kidney cancer.
Another experimental treatment uses a type of lymphokine called interleukin 2
to enhance immune response. After synthesis in the laboratory, interleukin 2
is injected into a person with cancer to cause remission by stimulating
production of immune cells. However, the treatment has many serious side
effects such as fever, chills, low blood pressure and joint pain.
Researchers are also using B cells to make large numbers of identical
antibodies (monoclonal antibodies) designed to attack a specific cancer. When
combined with drugs, toxins or radioactive materials, monoclonal antibodies
also can carry chemicals to destroy specific cancer cells.
At Mayo Clinic and two other centers, researchers are using gene therapy to
boost immune response in people with colon cancer. Investigators inject a gene
into tumor cells that causes the cells to display a stronger "foreign" ID
marker. The hope is that this use of gene therapy will enable the immune
system to recognize and destroy the tumor cells more easily.
The battle rages on
Your immune system is an intricate and remarkable defense mechanism. Through
diverse research efforts, scientists continue to unravel the mysteries of
immunity and to harness some of its unique capabilities.
But, like the buildup of armaments on opposing sides of a war, each new or
drug-resistant microorganism presents another challenge to the immune
defenses. Escalation on both sides moves in lock-step toward infinite
complexity.