Biology Reference
In-Depth Information
the aid of cross-disciplinary approaches ranging from mathematics and
biophysics to comparative phylogenesis, molecular modeling, and
proteomics.
The complement system has long been appreciated as a major effec-
tor arm of the innate immune response. It consists of a complex group
of serum proteins and glycoproteins and soluble or membrane-bound
receptors, which play an important role in host defense against infection
[4] (figure 6.1). Complement, a phylogenetically conserved arm of innate
immunity, functions together with the adaptive immune response by
serving as an important inflammatory mediator of antigen-antibody
interactions. It also provides an interface between the innate and adap-
tive immune response by contributing to the enhancement of the
humoral response mounted against specific antigens [5].
Complement can be activated through the classical, alternative, or
lectin pathways (figure 6.1). Antigen-antibody complexes initiate the
activation of the classical pathway, whereas the alternative and lectin
pathways are activated in an antibody-independent fashion through
interaction of complement components with specific carbohydrate
groups and lipopolysaccharides present on the surface of foreign
pathogens (e.g., bacteria) [6]. Complement activation proceeds in
a sequential fashion, through the proteolytic cleavage of a series of
proteins, and leads to the generation of active products that mediate
various biological activities through their interaction with specific
cellular receptors and other serum proteins. During the course of this
cascade, a number of biological processes are initiated by the various
complement components, including inflammation, leukocyte migra-
tion, and phagocytosis of complement-opsonized particles and cells.
The end result of these complement-mediated events is a direct lysis
of target cells and microorganisms as a consequence of membrane-
penetrating lesions (pores).
Currently over 35 complement proteins have been identified, and
deficiencies in any particular components have been frequently associ-
ated with a diminished ability to clear circulating immune complexes
or fight bacterial and viral infection. Here we present a comprehensive
account of how an integrated “systems” approach has contributed to
the elucidation of the structural-functional aspects of C3-ligand inter-
actions and the rational design of small-size complement inhibitors. We
also present critical aspects of our studies on viral molecular mimicry
and immune evasion as well as evolutionary aspects of complement
biology and diversity that are integral to a “systems” overview of the
complement system. Furthermore, we discuss novel associations of
various complement components with developmental pathways and
present our research on the role of complement in tissue regeneration
and early hematopoietic development using an array of genomic,
biochemical, and proteomic approaches.
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