Complement System in Adaptive Immunity

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Complement System in Adaptive Immunity Background

The serum complement system, which represents a chief component of innate immunity, not only participates in inflammation but also acts to enhance the adaptive immunity. Specific activation of complement via innate recognition proteins or secreted antibody releases cleavage products that interact with a wide range of cell surface receptors found on myeloid, lymphoid and stromal cells.

Current research shows that the soluble and membrane-associated factors of complement system have a much wider reach than initially recognized, and importantly direct adaptive immunity in a variety of ways: complement receptors on B cells and follicular dendritic cells determine the longevity, maturation, and memory of humoral responses, but also T cell responses are influenced by complement factors.

Work published since the early 2000s uncovered an unexpected role for complement as a regulator of T-cell immunity. During cognate interactions between T cells and APCs, both partners upregulate and secrete alternative pathway complement components C3, fB, and fD, produce C5, and upregulate surface expression of C3aR and C5aR. Coengagement of the T-cell receptor and the complement regulator CD46 promotes regulatory IL-10 production to delineate a crucial role for complement in modulating the balance between pathogenic and protective adaptive T-cell responses.

Complement System in Adaptive Immunity References

1. Carroll M C. (2004). The complement system in regulation of adaptive immunity. Nature immunology, 5(10), 981-986.
2. Dunkelberger J R, et al. (2010). Complement and its role in innate and adaptive immune responses. Cell research, 20(1), 34-50.
3. Hoebe K, et al. (2004). The interface between innate and adaptive immunity. Nature immunology, 5(10), 971-974.
4. Mathern D R, et al. (2015). Molecules great and small: the complement system. Clinical Journal of the American Society of Nephrology, 10(9), 1636-1650.