Recent advances in complement biology The complement system, traditionally considered a central arm of innate immunity, consists a set of soluble and cell surface proteins including components, receptors and regulators. Through pattern recognition, the complement system not only plays a major role in host defence and the inflammatory response, but also forms an important link between innate and adaptive arms of immune response [1, 2]. Complement proteins present in serum or fluid, such as C3, C1q and MBL, can bind directly to the surface of certain pathogens and thereby trigger complement activation on their surfaces. Besides initiating the formation of membrane attack complex (C5b–9) that mediates direct microbial killing, cleavage of the pivotal component C3 generates several other biological effectors, including surface-associated fragment C3b and its derivatives (eg C3b, iC3b, C3d) and released activation fragments C3a and C5a, which can bind to their receptors on a variety of cell types participating in microbial elimination and immune regulation. For example, CR3, CR4 and the newly identified CRIg [3], which are present on many leucocytes, recognise C3b-coated or iC3b-coated (opsonised) pathogens and altered self-tissues/molecules leading to uptake by phagocytes. Complement receptors CR1 and CR2 that are present on immune cells (eg B cells and follicular dendritic cells) also recognise (C3b, C3dg) opsonised antigen, augmenting the retention of antigen and facilitating the antigen-specific B cell response in secondary lymphoid tissue. Receptors C3aR and C5aR found on both myeloid and non-myeloid cells, detect the soluble products of complement activation (C3a and C5a). Interaction of C3aR or C5aR and its ligand mediates a series of inflammatory responses, such as contraction of smooth muscle cells, increase in the permeability of blood capillaries and chemotaxis. In addition to their known effector functions in the innate response, evidence for C3a and C5a regulating adaptive immunity has emerged. These data suggest that C3aR (or C5aR)–ligand interactions could influence the function of APCs, subsequently influencing the T cell response [4]. Thus, the relevance of these complement receptor–ligand interactions in the alloreactive T cell response and allograft rejection merits further investigation, as they pose potential targets for therapy in transplant rejection and other immunological disorders.

In the past few years, there have been several advances regarding the understanding of complement activation pathways. Complement can be activated through three main routes, namely the classical, alternative, and mannose-binding lectin (MBL) pathways (Figure 1). The convergence point of the three pathways is the assembly of C3 convertases that cleave C3 into C3a and C3b, subsequently forming C5 convertases that cleave C5 releasing C5a and resulting in C5b–9 formation. Current dogma is that the activation of the classical pathway