Issues in Biology
Self / Non-self
Discrimination of the Immune System
developed a defense mechanism which can adapt to a large variety
of antigens, particles that find their way into our body causing
an immune reaction. Because of the evolutionary relationship among
all living organisms, most antigenic structures of infectious pathogenic
organism are made of (macro-)molecules very similar to ours (this
is also a concern for organ transplantation). As the immune system
must be able to destroy invading pathogens, but not our own cells
that may contain closely related cellular structures, it needs to
learn to distinguish foreign components from its very own. This
is known as the self/non self discrimination of the immune system.
As simple as the concept appears, it comprises a mechanistically
difficult to understand system. The issue is how our immune system
learns to distinguish to make antibodies targeted only against foreign
antigens, but not for self antigens?
From a molecular
view point, one that a structural biochemist may take, this task
seems almost impossible, unless parasitic and infectious organisms
have radically different antigen structures (epitopes) than we have.
While this is true for many bacterial and viral structures, it is
not for all. Worse even, an individual's immune system recognizes
the cellular components of an other person as foreign. Here, we
certainly cannot assume that most of these components are radically
different. In fact, they are very similar and the task of distinguishing
cellular components among individuals of the same species falls
to a few select molecular structures. These structures are often
the sugar portions of cell surfaces, so called glycoproteins and
glycolipids. A familiar specificity is provided by blood group markers.
These provide compatibility between blood donor and recipient and
are based on sugar structures of sphingolipids.
Back to the
immune system. The immune system is partially based on white blood
cells (lymphocytes) that provide the adaptive protection against
novel pathogens. Part of the adaptation is the continuous maturation
of naive cells into mature cells. This maturation process gets trained
in the first few month of our lives not to recognize our own cells.
The body uses a clever strategy offering the immune system samples
of its own cells. Any lymphocyte in the making that will kill such
exposed cells, will be eliminated themselves. Somehow, the immune
systems not to produce any of these self-recognizing lymphocytes.
Cells that do not attack our own sample cells make it through the
we really would like to know how this process works, i.e., understanding
the molecular mechanism. Briefly, the maturing immune cells are
presented with self markers and the interaction with these markers
and the immune cell prevents an attack. Any cell that fails to present
such self markers in addition to markers (antigens) known or unknown
to the immune cells, will be engaged and destroyed. Mechanistically,
this interaction is the result of a long series of multiple one-on-one
interaction among many different (glyco-)proteins. Cells make use
of their ability to cluster and assemble a variety of different
marker to create recognition sites for other cells. Depending on
the combination of markers, the immune fate of cells screened by
lymphocytes lead either to distraction or has no further consequence.
It seems that
the process of this learning by the immune system is well understood.
However, the immune system sometimes attacks its own tissues anyway.
We suffer an auto-immune disease. Familiar examples are lupus and
multiple sclerosis. There are some good ideas of how this could
happen, also almost nothing is know of how to prevent or even cure
autoimmune diseases. The number of occurrences of these diseases
is on the rise. This is surprising at first considering the improved
standard of health and hygiene. But our success in keeping infections
out of our lives may contribute to autoimmune diseases simply because
the immune system has no clear foreign pathogens to 'learn' from.
The antigens it comes in touch with are increasingly similar to
each other and self and non-self discrimination may become harder
or more error prone.
more about the immune system at ImmuneCentral
| Back to Issues
Copyright © 2000-2003 Lukas K. Buehler