The immune system is the body's surveillance and defense
system that protects us against invasion by organisms such as bacteria and
viruses. Normally a critical part of immune system function is the ability to
differentiate between the body, or self, from foreign invaders, or non-self.
This function is accomplished by the immune system's ability to identify
portions of proteins, called
Before birth, immune cells
that may potentially recognize the tissues of the body are deleted so that they
will not be around later to damage normal tissues. The state of not reacting to
one's own body is called tolerance. It is thought that in conditions such as
rheumatoid arthritis as well as other
autoimmune diseases, some immune cells that mistake
normal parts of the body for foreign organisms may somehow escape the deletion
process. As a result, later in life they recognize parts of the joint as
something that should be attacked and eliminated. Alternatively, infectious
agents such as viruses may be able to fool the immune system into thinking that
a part of the body is foreign, thus breaking tolerance and leading the immune
system to attack the body instead of the inciting infection. The inclination to
lose tolerance to one's own body is probably determined by the genetics of the
To understand why tolerance breaks down in
autoimmune diseases, it is first necessary to understand the process by which
the immune system finds and attacks foreign substances. Within the ranks of the
immune system, there are three primary types of cells that mount the detection
macrophage is the first cell type to act as a sentinel to detect and report
about what it finds in the environment around it. Macrophage means "big eater."
The macrophage is constantly eating up a little bit of whatever surrounds it,
cutting the ingested proteins up into small pieces (the antigens mentioned
above), and then displaying these pieces of protein on its surface.
The macrophage is said to
present these antigens to the T cell, which is the next cell in the chain and
the primary decision maker in the immune process. T cells are highly
specialized. In fact, each of the thousands of T cells within your body is
different from every other one. On their surface, T cells express a protein
called the T cell receptor, which will bind to only one or a few antigens out
of the thousands that are possible. When a macrophage and a T cell encounter
one another, they see whether any of the antigens on the surface of the
macrophage fit into the T cell receptor. Most of the time the antigens don't
fit. But if the antigens do match the T cell receptor, then the cells stick to
one another. Through the action of chemical messengers, the T cell becomes
turned on, or activated.
Activated T cells then call in the last cell in the chain, which is the B
cell. Like T cells, each B cell is unique. Instead of making specific surface
proteins, though, B cells make proteins called
antibodies that can be released from the B cell into
the bloodstream where they travel until they bind to the antigen that fits.
After an infecting organism is coated with antibodies, it is tagged for
recognition by the immune cells that destroy foreign substances.
One complication of this system is that the macrophage eats and presents
everything that it encounters, whether friend or foe. So the interaction
between the macrophage and the T cell is an especially critical encounter since
the body needs to ensure that no T cells bind to and become activated in
response to self antigens. There are two safety mechanisms that help to prevent
the activation of T cells by self antigens.
June 5, 2012
Anne C. Poinier, MD - Internal Medicine
& Nancy Ann Shadick, MD, MPH - Internal Medicine, Rheumatology
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