Complement, its role in innate immunity and autoimmunity
- M Daha1
© The Author(s) 2003
Published: 12 September 2003
The innate immune system provides essential host defense against a wide variety of microbial pathogens. In addition, the innate immune system is responsible for the recognition of necrotic and apoptotic cells and self-antigens that are released from the large number of cells that undergo apoptosis for the maintenance of physiologic homeostasis. The complement system is essential to initiate and drive the acquired immune response.
Until recently, two pathways for complement activation were recognized, namely the classical pathway and the alternative pathway. Recent studies from a large number of laboratories indicate the existence of a third pathway of complement activation, namely the lectin pathway. This third pathway is initiated by the interaction of, for example, mannan binding lectin and a number of other pattern recognition molecules called ficolins, with carbohydrate domains on a wide variety of pathogens such as bacteria and viruses.
Studies in complement-deficient individuals have indicated a strong association between complement deficiencies and infections or with immune complex disease and autoimmunity. Deficiencies in the lectin pathway are associated with serious bacterial infections in immunocompromised individuals, while deficiencies in the early classical pathway components are associated with immune complex disease and autoimmunity. Especially, deficiencies in C1q, the recognition unit of the classical pathway, are associated strongly with systemic lupus erythematosus. Studies in C1q knockout mice also implicate C1q with autoimmunity. Various studies indicate that C1q, but also a number of other molecules of innate immunity, such as C-reactive protein, serum amyloid P-component, pentraxin-3, and possibly mannan binding lectin and ficolins, all in concert, may be involved in the recognition and clearance of harmfull potentially pathogenic apoptotic and necrotic cells. It is thought that the deficient removal or the mode of presentation of self-antigens may determine whether autoimmune responses take place or whether tolerance is induced. In this scenario, it is suggested that the method of engagement and subsequent signal induction may ultimately determine the final outcome of the ensuring immune response.
These studies were supported in part by the European Union, grant number QLG1-CT-2001-01039.