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often responsible for triggering diversity in biological responses
and can also serve as a factor that increases the adaptability and
complexity of an immune response [1]. Indeed, it is often a case of
minimizing a noise/signal ratio, and being able to convert “noise” into
meaningful signals. For example, stochastic processes govern many
of the genetic mechanisms that underlie the generation of antibody
diversity. B-cells producing high-affinity antibodies undergo expan-
sion, while low-affinity antibody-producing cells are subject to
negative selection and deletion. In such a way, the signal (high affinity)
is distinguished from the noise (low affinity). Similar stochastic events
dictate various immunological processes such as antibody gene recom-
bination and hypermutation, T-cell selection in the thymus, B-cell
maturation in germinal centers, and immunological tolerance to
self-antigens.
Even though the immune response has been extensively studied
over the years, very little is known about the way in which different
components of this response interact in a “systems” perspective. Our
knowledge of the system's properties, and the pathway associations
that are formed within the immune response, as well as the study of its
dynamics, are still in an early stage. This can be partly attributed to the
fact that researchers have been investigating this complex system only
one gene, or one protein, at a time. It is now becoming evident that the
enormous growth in structural and biomolecular data, generated by
high-throughput methodologies, will force scientists to address
immunology in an integrated “systems” context.
Complement, a pivotal system of the innate immune response,
serves as an ideal paradigm of how traditional immunology is revisit-
ing basic immune processes in a “systems” approach. In the
postgenomic era, our knowledge of this innate immune system is
enriched by findings that point to novel functions that do not strictly
correlate with immunological defense and surveillance, immune mod-
ulation, or inflammation [3]. Several studies indicate that complement
proteins exert functions that are either more complex than previously
thought, or go well beyond the innate immune character of the system.
As we depart from the traditional hallmarks of molecular biology,
such as the genome and the transcriptome, and begin to appreciate
more the “proteome” as the dynamic expression profile of all organ-
isms, novel associations between complement-modulated pathways
and apparently unrelated biological processes are constantly being
revealed. In this respect, recent evidence produced by our laboratory
(and others) suggests that complement components can modulate
diverse biological processes by closely interacting with other intra- and
intercellular networks [3]. Furthermore, the structure and functions of
several complement proteins, as well as the protein-protein inter-
actions that underlie these functions, are now being investigated with
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