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Small peptides for inhibition of central component of immunity: the complement system

1. Director of Research, Apellis Pharmaceuticals
2. Chief Operating Officer, Apellis Pharmaceuticals

The complement system plays a pivotal role in innate and adaptive immune responses (1). It consists of a number of proteins that interact to recognize and kill pathogens or abnormal cells in the body (1).  The complement cascade can be activated through three major pathways: classical, lectin, and alternative pathways that converge on complement C3 (1). It leads to the principal effects of complement activation: opsonization, inflammation, immune activation, and formation of the membrane attack complex. The major effectors are i) C3b, an C3 active fragment which tags cell surfaces for removal from tissues or the bloodstream, ii) C3a and C5a anaphylatoxins that recruit inflammatory cells, influence T- and B-cell phenotypes and functions, and modulate the pro-inflammatory microenvironment, and iii) the membrane attack complex that lyse targeted surfaces (1). Excessive or uncontrolled complement activation, either due to an aging immune system or underlying genetic mutations in complement proteins can lead to a wide range of life-threatening or debilitating disorders (2). Such as the inflammatory chronic diseases associated with aging such as chronic o ...

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