Biomedical Engineering Reference
In-Depth Information
A general conclusion of these studies is that cell function is dependent on precise
kinetic and mechanical properties of their adhesion receptors and tight regulation of
these parameters.
1.2.4 I
MMUNE
R
ECOGNITION
The immune system provides particularly important models of biological recogni-
tion. The task of immune cells consists of detecting foreign and potentially harmful
particles or molecules to destroy them. Foreign particles may be pathogens, cancer
cells, or damaged cells that may release harmful metabolites. Immune recognition
is of utmost importance and failure may entail devastating consequences. Indeed, a
marked immune deficiency is known to result in lethal infection within a few days or
even hours after birth. Conversely, excessive immune activation may result in death
as may be observed in allergic conditions or autoimmune diseases. It is probably
because of this utmost importance that three complementary recognition mechanisms
evolved and remain active in higher vertebrates.
Antibodies
are protein molecules that may be generated by injecting animals with
foreign substances that are consequently called
antigens
(which means antibody gen-
erators). Antibodies share remarkable structural properties shared by the plasma pro-
teins called
immunoglobulins
. Each antibody molecule possesses between 2 and 10
identical antigen binding sites called
paratopes
. There seems to be no limit to the
recognition capacity of antibodies: They can specifically bind to proteins, carbo-
hydrates, lipids, nucleic acids, and even totally artificial structures such as dinitro-
phenol. Further, antibody efficiency is dependent on quantitative properties of bind-
ing sites such as affinity constant or association kinetics [53] [73], as explained
below. Antibodies bind antigens with an affinity constant that may be as high as
10
10
10
12
M
−
1
and their specificity is illustrated by their capacity to discriminate
between antignenic sites (called
epitopes
) differing by a single amino acid. The study
of antibodies was long made difficult by the high heterogeneity of antibodies raised
after injecting animals with a given antigen. However, monoclonal antibodies pro-
vide a highly efficient basis for studying molecular recognition [131].
The specific antigen receptors born by T lymphocytes (
T cell receptors
or TCRs)
represent a different recognition system. As exemplified in Figure 1.3, a major task
of T lymphocytes consists of detecting cells containing foreign material such as viral
proteins. The recognition principle is remarkable: Most cells express on their sur-
face on the order of 10,000 oligopeptides of 10-15 amino acids nearly randomly
sampled from the proteins they synthesize. Each oligopeptide appears as a few units
bound to specialized membrane molecules encoded by genes belonging to the
major
histocompatibility complex
[131].
It is remarkable that a T lymphocyte can detect a few or even a single foreign
oligopeptide on a cell after scanning its membrane for 5-10 minutes [19]. Another
remarkable point is that a number of studies strongly supported the hypothesis that
the outcome of the recognition of a foreign oligopeptide by a T lymphocytes is
dependent on the physical properties of TCR/ligand interaction. Indeed, the life-
time of individual TCR/ligand bonds might be a key determinant of T lymphocyte
−
Search WWH ::
Custom Search