Immunology WORLD OF MICROBIOLOGY AND IMMUNOLOGY304•
They have also identified many of the actors and processes
that form the immune response.
The immune response recognizes and responds to
pathogens via a network of cells that communicate with each
other about what they have “seen” and whether it “belongs.”
These cells patrol throughout the body for infection, carried by
both the blood stream and the lymph ducts, a series of vessels
carrying a clear fluid rich in immune cells.
The antigenpresenting cells are the first line of the
body’s defense, the scouts of the immune army. They engulf
foreign material or microorganismsand digest them, display-
ing bits and pieces of the invaders—called antigens—for other
immune cells to identify. These other immune cells, called T
lymphocytes, can then begin the immune response that attacks
the pathogen.
The body’s other cells can also present antigens,
although in a slightly different way. Cells always display anti-
gens from their everyday proteins on their surface. When a
cell is infected with a virus, or when it becomes cancerous, it
will often make unusual proteins whose antigens can then be
identified by any of a variety of cytotoxic T lymphocytes.
These “killer cells” then destroy the infected or cancerous cell
to protect the rest of the body. Other T lymphocytes generate
chemical or other signals that encourage multiplication of
other infection-fighting cells. Various types of T lymphocytes
are a central part of the cellular immune response; they are
also involved in the humoral response, encouraging B lym-
phocytesto turn into antibody-producing plasma cells.
The body cannot know in advance what a pathogen will
look like and how to fight it, so it creates millions and millions
of different lymphocytes that recognize random antigens.
When, by chance, a B or T lymphocyte recognizes an antigen
being displayed by an antigen presenting cell, the lymphocyte
divides and produces many offspring that can also identify and
attack this antigen. The way the immune system expands cells
that by chance can attack an invading microbe is called clonal
selection.
Some researchers believe that while some B and T lym-
phocytes recognize a pathogen and begin to mature and fight
an infection, others stick around in the bloodstream for months
or even years in a primed condition. Such memory cells may
be the basis for the immunity noted by the ancient Chinese and
by Thucydides. Other immunologists believe instead that trace
amounts of a pathogen persist in the body, and their continued
presence keeps the immune response strong over time.
Substances foreign to the body, such as disease-causing
bacteria, viruses, and other infectious agents (known as anti-
gens), are recognized by the body’s immune system as
invaders. The body’s natural defenses against these infectious
agents are antibodies—proteins that seek out the antigens and
help destroy them. Antibodies have two very useful charac-
teristics. First, they are extremely specific; that is, each anti-
bodybinds to and attacks one particular antigen. Second,
some antibodies, once activated by the occurrence of a dis-
ease, continue to confer resistance against that disease; clas-
sic examples are the antibodies to the childhood diseases
chickenpox and measles.The second characteristic of antibodies makes it possi-
ble to develop vaccines. Avaccineis a preparation of killed or
weakened bacteria or viruses that, when introduced into the
body, stimulates the production of antibodies against the anti-
gens it contains.
It is the first trait of antibodies, their specificity, that
makes monoclonal antibody technology so valuable. Not only
can antibodies be used therapeutically, to protect against dis-
ease; they can also help to diagnose a wide variety of illnesses,
and can detect the presence of drugs, viral and bacterial prod-
ucts, and other unusual or abnormal substances in the blood.
Given such a diversity of uses for these disease-fighting
substances, their production in pure quantities has long been
the focus of scientific investigation. The conventional method
was to inject a laboratory animal with an antigen and then,
after antibodies had been formed, collect those antibodies
from the blood serum (antibody-containing blood serum is
called antiserum). There are two problems with this method:
It yields antiserum that contains undesired substances, and it
provides a very small amount of usable antibody.
Monoclonal antibody technology allows the production
of large amounts of pure antibodies in the following way. Cells
that produce antibodies naturally are obtained along with a
class of cells that can grow continually in cell culture. The
hybrid resulting from combining cells with the characteristic
of “immortality” and those with the ability to produce the
desired substance, creates, in effect, a factory to produce anti-
bodies that work around the clock.
A myeloma is a tumor of the bone marrow that can be
adapted to grow permanently in cell culture. Fusing myeloma
cells with antibody-producing mammalian spleen cells, results
in hybrid cells, or hybridomas, producing large amounts of
monoclonal antibodies. This product of cell fusion combined
the desired qualities of the two different types of cells, the
ability to grow continually, and the ability to produce large
amounts of pure antibody. Because selected hybrid cells pro-
duce only one specific antibody, they are more pure than the
polyclonal antibodies produced by conventional techniques.
They are potentially more effective than conventional drugs in
fighting disease, because drugs attack not only the foreign
substance but also the body’s own cells as well, sometimes
producing undesirable side effects such as nausea and allergic
reactions. Monoclonal antibodies attack the target molecule
and only the target molecule, with no or greatly diminished
side effects.
While researchers have made great gains in understand-
ing immunity, many big questions remain. Future research
will need to identify how the immune response is coordinated.
Other researchers are studying the immune systems of non-
mammals, trying to learn how our immune response evolved.
Insects, for instance, lack antibodies, and are protected only by
cellular immunity and chemical defenses not known to be
present in higher organisms.
Immunologists do not yet know the details behind
allergy, where antigens like those from pollen, poison ivy, or
certain kinds of food make the body start an uncomfortable,
unnecessary, and occasionally life-threatening immune
response. Likewise, no one knows exactly why the immunewomi_I 5/6/03 3:23 PM Page 304