Complement Cascade

Stable Identifier
Gallus gallus
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The complement system is the first line of defense against invading microbes. It consists of a large number of distinct proteins, which circulate in the blood stream in functionally inactive states. When activated, complement components assemble on the surface of a target cell. The activation of one component induces its proteolytic function that acts on the next component in the cascade, cleaving it into biologically active fragments. In mammals, the complement system is activated via three distinct pathways: the classical, lectin and alternative pathways. All three pathways merge at the proteolytic cleavage of component C3 to form the key molecule C3b. The activation of the complement system leads to four principal outcomes: (1) opsonization of target cells to enhance phagocytosis (2) lysis of target cells via an assembly of the membrane attack complex (MAC) on the pathogen surface (3) production of anaphylatoxins that are involved in the host inflammatory response (4) clearance of antibody-antigen complexes.

Avian species (chicken, turkey and duck) have been reported to induce functional complement pathways in response to immunization with sheep red blood cells (SRBC) [Ellis MG et al 1989; Koppenheffer TL et al 1999; Baelmans R et al 2005]. Complement activation in chicken was also shown to mediate host response against bacterial and viral infections [Skeeles JK et al 1979a, b; Ohta H et al 1983; Laursen SB and Nielsen OL 2000]. Immune competence of the distinct chicken ecotypes was assessed by measuring complement hemolytic activity after immunization with SRBC [Baelmans R et al 2004; Baelmans R et al 2005]. Both classical Ca2+ dependent complement pathway (CPW) and alternative calcium-independent complement pathway (APW), as well as total Ig (IgG and IgM antibody) responses were detected. However, the type and magnitude of immune response varied for individual chickens even within the same ecotype.

Analysis of genome data revealed that mammals and aves seem to share practically the same set of complement genes [Nonaka M and Kimura A 2006]. Indeed, most of the components of the classical and alternative complement pathways have been found in the chicken genome. However, an absence of some components such as chicken C9, factor D, properdin, MASP-1 has been also reported [Barta O and Hubbert NL 1978; Lynch et al 2005; Koch C 1986; Mikrou A and Zarkadis IK. 2010]. In this project we assume that antimicrobial functions of chicken complement are similar to those of human, although the mechanism of the chicken complement activation remains to be clarified.

This Reactome module refers to the larger complement fragments as "b" and the smaller "a", based on the nomenclature of the complement proteins .

Literature References
PubMed ID Title Journal Year
226048 Infectious bursal disease viral infections. II. The relationship of age, complement levels, virus-neutralizing antibody, clotting, and lesions

Lukert, PD, De Buysscher, EV, Brown, J, Fletcher, OJ, Skeeles, JK

Avian Dis. 0
6315584 Activation of chicken alternative complement pathway by fowlpox virus-infected cells

Kai, C, Ohta, H, Yamanouchi, K, Yoshikawa, Y

Infect. Immun. 1983
226056 Infectious bursal disease viral infections. I. Complement and virus-neutralizing antibody response following infection of susceptible chickens

Lukert, PD, De Buysscher, EV, Brown, J, Fletcher, OJ, Skeeles, JK

Avian Dis. 0
15747855 Haemolytic complement activity and humoral immune responses to sheep red blood cells in indigenous chickens and in eight German Dahlem Red chicken lines with different combinations of major genes (dwarf, naked neck and frizzled) of tropical interest

Baelmans, R, Demey, F, Parmentier, HK, Dorny, P, Berkvens, D, Nieuwland, MG

Trop Anim Health Prod 2005
3646826 The alternative complement pathway in chickens. Purification of factor B and production of a monospecific antibody against it

Koch, C

Acta Pathol Microbiol Immunol Scand C 1986
16896831 Genomic view of the evolution of the complement system

Nonaka, M, Kimura, A

Immunogenetics 2006
15643809 Different serum haemolytic complement levels in indigenous chickens from Benin, Bolivia, Cameroon, India and Tanzania

Baelmans, R, Demey, F, Parmentier, HK, Udo, HM, Dorny, P, Berkvens, D

Trop Anim Health Prod 2004
  Avian Immunology

Davison, F, Kaspers, B, Schat, KA

15814730 Composition of the lectin pathway of complement in Gallus gallus: absence of mannan-binding lectin-associated serine protease-1 in birds

Marston, D, Sandrini, SM, Stover, CM, Schwaeble, WJ, Presanis, JS, Khan, SU, Lynch, NJ

J Immunol 2005
16147546 The complement system of the duck

Koppenheffer, TL, Higgins, DA, Chan, SW

Avian Pathol. 1999
10717281 Mannan-binding lectin (MBL) in chickens: molecular and functional aspects

Laursen, SB, Nielsen, OL

Dev Comp Immunol 2000
697137 Testing of hemolytic complement components in domestic animals

Barta, O, Hubbert, NL

Am J Vet Res 1978
2666975 Characterization of complement activity in turkeys: evidence for classical and alternative complement pathways

Lamont, SJ, Arp, LH, Ellis, MG

Poult. Sci. 1989
  Current Topics in Complement

Lambris, JD

20067805 Cloning of the sixth complement component and, spatial and temporal expression profile of MAC structural and regulatory genes in chicken

Mikrou, A, Zarkadis, IK

Dev Comp Immunol 2010
20720586 Complement: a key system for immune surveillance and homeostasis

Yang, K, Lambris, JD, Hajishengallis, G, Ricklin, D

Nat Immunol 2010
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