Immunologic Research

, Volume 33, Issue 2, pp 103–112 | Cite as

The role of the complement system in innate immunity

  • Horea RusEmail author
  • Cornelia Cudrici
  • Florin Niculescu


Complement is a major component of innate immune system involved in defending against all the foreign pathogens through complement fragments that participate in opsonization, chemotaxis, and activation of leukocytes and through cytolysis by C5b-9 membrane attack complex. Bacterias and viruses have adapted in various ways to escape the complement activation, and they take advantage of the complement system by using the host complement receptors to infect various cells. Complement activation also participates in clearance of apoptotic cells and immune, complexes. Moreover at sublytic dose, C5b-9 was shown to promote cell survival. Recently it was also recognized that complement plays a key role in adaptive immunity by modulating and modifying the T cell responses. All these data suggest that complement activation constitutes a critical link between the innate and acquired immune responses.


Systemic Lupus Erythematosus Apoptotic Cell Experimental Autoimmune Encephalomyelitis Complement Activation Complement System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Medzhitov R, Janeway CA, Jr: An ancient system of host defense. Curr Opin Immunol 1998; 10: 12–15.PubMedCrossRefGoogle Scholar
  2. 2.
    Carroll MC: A protective role for innate immunity in autoimmune disease. Clin Immunol 2000; 95: S30–38.CrossRefGoogle Scholar
  3. 3.
    Frank MM: Complement system; in Frank MM AK, Claman HN, Unanue ER, (eds): Samter's Immunologic Diseases. Boston, Little, Brown and Company, 1995, pp 331–362.Google Scholar
  4. 4.
    Shin ML, Rus HG, Niculescu FI: Membranes attack by complement: assembly and biology of the terminal complement complexes, in Lee, AG (ed), Biomembranes, vol 4 JAI Press, Greenwitch, CT, 1996, pp. 123–149.Google Scholar
  5. 5.
    Walport MJ: Complement. First of two parts. N Engl J Med 2001; 344: 1058–1066.PubMedCrossRefGoogle Scholar
  6. 6.
    Ahearn JM, Fearon DT: Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). Adv Immunol 1989; 46: 183–219.PubMedGoogle Scholar
  7. 7.
    Krych-Goldberg M, Atkinson JP: Structure-function relationships of complement receptor type 1. Immunol Rev 2001; 180: 112–122.PubMedCrossRefGoogle Scholar
  8. 8.
    Xu Y, Narayana SV, Volanakis JE: Structural biology of the alternative pathway convertase. Immunol Rev 2001; 180: 123–135.PubMedCrossRefGoogle Scholar
  9. 9.
    Fujita T, Endo Y, Nonaka, M: Primitive complement system—recognition and activation. Mol Immunol 2004; 41: 103–111.PubMedCrossRefGoogle Scholar
  10. 10.
    Petersen SV, Thiel S, Jensen L, Vorup-Jensen T, Koch C, Jensenius JC: Control of the classical and the MBL pathway of complement activation. Mol Immunol 2000; 37: 803–811.PubMedCrossRefGoogle Scholar
  11. 11.
    Dahl MR, Thiel S, Matsushita, M, et al.: MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 2001; 15: 127–135.PubMedCrossRefGoogle Scholar
  12. 12.
    Muller-Eberhard HJ: Molecular organization and function of the complement system. Annu Rev Biochem 1988; 57: 321–347.PubMedCrossRefGoogle Scholar
  13. 13.
    Bhakdi S, Tranum-Jensen J: Membrane damage by, complement. Biochim Biophys Acta 1983; 737: 343–372.PubMedGoogle Scholar
  14. 14.
    Mayer MM: Membrane damage by complement. Johns Hopkins Med J 1981; 148: 243–258.PubMedGoogle Scholar
  15. 15.
    Koski CL, Ramm LE, Hammer CH, Mayer MM, Shin ML: Cytolysis of nucleated cells by complement: cell death displays multi-hit characteristics. Proc Natl Acad Sci USA 1983; 80: 3816–3820.PubMedCrossRefGoogle Scholar
  16. 16.
    Papadimitriou JC, Ramm LE, Drachenberg CB, Trump BF, Shin ML: Quantitative analysis of adenine nucleotides during the prelytic phase of cell death mediated by C5b-9. J Immunol 1991; 147: 212–217.PubMedGoogle Scholar
  17. 17.
    Martinou JC, Green DR: Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2001; 2: 63–67.PubMedCrossRefGoogle Scholar
  18. 18.
    Cragg MS, Howatt WJ, Bleodworth L, Anderson VA, Morgan BP, Glennie MJ: Complement mediated cell death is associated with DNA fragmentation. Cell Death Differ 2000; 7: 48–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Cunnion KM, Zhang HM, Frank MM: Availability of complement bound to Staphylococcus aureus to interact with membrane complement receptors influences efficiency of phagocytosis. Infect Immun 2003; 71: 656–662.PubMedCrossRefGoogle Scholar
  20. 20.
    Frank MM: Anhihilating host defense. Nat Med 2001; 7: 1285–1286.PubMedCrossRefGoogle Scholar
  21. 21.
    Jarva H, Jokiranta TS, Wurzner R, Meri S: Complement resistance mechanisms of streptococci. Mol Immunol 2003; 40: 95–107.PubMedCrossRefGoogle Scholar
  22. 22.
    Alitalo A, Meri T, Lankinen H, et al: Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmidencoded outer surface protein E paralogs. J Immunol 2002; 169: 3847–3853.PubMedGoogle Scholar
  23. 23.
    de Haas CJ, Veldkamp KE, Peschel A, et al: Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med 2004; 199: 687–695.PubMedCrossRefGoogle Scholar
  24. 24.
    Frank MM: Complement deficiencies. Pediatr Clin North Am 2000; 47: 1339–1354.PubMedCrossRefGoogle Scholar
  25. 25.
    Drogari-Apiranthitou M, Kuijper EJ, Dekker N, Dankert J: Complement activation and formation of the membrane attack complex on serogroup B Neisseria meningitidis in the presence or absence of serum bactericidal activity. Infect Immun 2002; 70: 3752–3758.PubMedCrossRefGoogle Scholar
  26. 26.
    Joiner KA, Fries LF, Frank MM: Studies of antibody and complement function in host defense against bacterial infection. Immunol Lett 1987; 14: 197–202.PubMedCrossRefGoogle Scholar
  27. 27.
    Sprong T, Brandtzaeg P, Fung M, et al: Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood medel of meningococcal sepsis. Blood 2003; 102: 3702–3710.PubMedCrossRefGoogle Scholar
  28. 28.
    Thiel S, Holmskov U, Hviid L, Laursen SB, Jensenius JC: The concentration of the C-type lectin, mannan-binding protein, in human plasma in creases during an acute phase response. Clin Exp Immunol 1992; 90: 31–35.PubMedCrossRefGoogle Scholar
  29. 29.
    Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, Turner MW: Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000; 68: 688–693.PubMedCrossRefGoogle Scholar
  30. 30.
    Jack DL, Read RC, Tenner AJ, Frosch M, Turner MW, Klein NJ: Mannose-binding lectin, regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis, serogroup B J Infect Dis 2001; 184: 1115–1162.Google Scholar
  31. 31.
    Eisen DP, Minchinton RM: Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003; 37: 1496–1505.PubMedCrossRefGoogle Scholar
  32. 32.
    Garred P, Madsen HO, Balslev U, et al.: Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 1997; 349: 236–240.PubMedCrossRefGoogle Scholar
  33. 33.
    Korb LC, Ahearn JM: Clq binds directly and specifically to surface blebs of apoptotic human keratinocytes.: complement deficiency and systemic lupus erythematosus revisited. J Immunol 1997; 158: 4525–4528.PubMedGoogle Scholar
  34. 34.
    Taylor PR, Carugati A, Fadok VA, et al: A hierarchiacal role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 2000; 192: 359–366.PubMedCrossRefGoogle Scholar
  35. 35.
    Nauta AJ, Trouw LA, Daha MR, et al: Direct binding of Clq to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 2002; 32: 1726–1736.PubMedCrossRefGoogle Scholar
  36. 36.
    Chang MK, Binder CJ, Torzewski M, Witztum JL: C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci USA 2002; 99: 13043–13048.PubMedCrossRefGoogle Scholar
  37. 37.
    Nauta AJ, Raaschou-Jensen N, Roos A, et al: Mannose-binding lectin engagement with late apoptotic and necrotic cells. Eur J Immunol 2003; 33: 2853–2863.PubMedCrossRefGoogle Scholar
  38. 38.
    Gaipl US, Kuenkele S, Voll RE, et al: Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death. Cell Death Differ 2001; 8: 327–334.PubMedCrossRefGoogle Scholar
  39. 39.
    Niculescu F, Niculescu T, Rus H: C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis. Exp Mol Pathol 2004; 76: 17–23.PubMedCrossRefGoogle Scholar
  40. 40.
    Niculescu F, Niculescu T, Nguyen P, et al.: Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs-host disease. Exp Mol Path 2005;PM1D 1597610.Google Scholar
  41. 41.
    Gaipl US, Brunner J, Beyer TD, Voll RE, Kalden JR, Herrmann M: Disposal of dying cells: a balancing act between infection and autoimmunity. Arthritis Rheum 2003;48:6–11.PubMedCrossRefGoogle Scholar
  42. 42.
    Mevorach D, Mascarenhas JO, Gershov D, Elkon KB: Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 1998;188:2313–2320.PubMedCrossRefGoogle Scholar
  43. 43.
    Verbovetski I, Bychkov H, Trahtemberg U, et al.: Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7. J Exp Med 2002;196:1553–1561.PubMedCrossRefGoogle Scholar
  44. 44.
    Vandivier RW, Fadok VA, Ogden CA, et al.: Impaired clearance of apoptotic cells from cystic fibrosis airways. Chest 2002;121:89S.PubMedCrossRefGoogle Scholar
  45. 45.
    Gaipl US, Voll RE, Sheriff A, Franz S, Kalden JR, Herrmann M: Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun Rev 2005;4:189–194.PubMedCrossRefGoogle Scholar
  46. 46.
    Botto M: Clq knock-out mice for the study of complement deficiency in autoimmune disease. Exp Clin Immunogenet 1998;15:231–234.PubMedCrossRefGoogle Scholar
  47. 47.
    Gommerman JL, Oh DY, Zhou X, et al.: A role for CD21/CD35 and CD19 in responses to acute septic peritonitis: a potential mechanism for mast cell activation. J Immunol 2000;165:6915–6921.PubMedGoogle Scholar
  48. 48.
    Rus HG, Niculescu F, Shin ML: Sublytic complement attack induces cell cycle in oligodendrocytes. J Immunol 1996;156:4892–4900.PubMedGoogle Scholar
  49. 49.
    Dashiell SM, Rus H, Koski CL: Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis. Glia 2000;30:187–198.PubMedCrossRefGoogle Scholar
  50. 50.
    Niculescu T, Weerth S, Niculescu F, et al.: Effects of complement C5 on apoptosis in experimental autoimmune encephalomyelitis. J Immunol 2004;172:702–5706.Google Scholar
  51. 51.
    Soane L, Rus H, Niculescu F, Shin ML: Inhibition of oligodendrocyte apoptosis by sublytic C5b-9 is associated with enhanced synthesis of bcl-2 and mediated by inhibition of caspase-3 activation. J Immunol 1999;163: 6132–6138.PubMedGoogle Scholar
  52. 52.
    Soane L, Cho HJ, Niculescu F, Rus H, Shin ML: C5b-9 terminal complement complex protects oligodendrocytes from death by regulating Bad through phosphatidylinositol 3-kinase/Akt pathway. J Immunol 2001;167: 2305–2311.PubMedGoogle Scholar
  53. 53.
    Fearon DT: Innate immunity—beginning to fulfill its promise? Nat Immunol 2000;1:102–103.PubMedCrossRefGoogle Scholar
  54. 54.
    Carroll MC: The role of complement in B cell activation and tolerance. Adv Immunol 2000;74:61–88.PubMedCrossRefGoogle Scholar
  55. 55.
    Smith KG, Fearon DT: Receptor modulators of B-cell receptor signalling—CD19/CD22. Curr Top Microbiol Immunol 2000;245:195–212.PubMedGoogle Scholar
  56. 56.
    Cherukuri A, Shoham T, Sohn HW, et al.: The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts. J Immunol 2004;172: 370–380.PubMedGoogle Scholar
  57. 57.
    Youd ME, Ferguson AR, Corley RB: Synergistic roles of IgM and complement in antigen trapping and follicular localization. Eur J Immunol 2002;32:2328–2337.PubMedCrossRefGoogle Scholar
  58. 58.
    Verschoor A, Brockman MA, Gadjeva M, Knipe DM, Carroll MC: Myeloid C3 determines induction of humoral responses to peripheral herpes simplex virus infection. J Immunol 2003;171:5363–5371.PubMedGoogle Scholar
  59. 59.
    Ochsenbein AF, Pinschewer DD, Odermatt B, Carroll MC, Hengartner H, Zinkernagel RM: Protective T cell-independent antiviral antibody responses are dependent on complement. J Exp Med 1999;190:1165–1174.PubMedCrossRefGoogle Scholar
  60. 60.
    Heyman B: Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu Rev Immunol 2000;18:709–737.PubMedCrossRefGoogle Scholar
  61. 61.
    Boes M: Role of natural and immune IgM antibodies in immune responses. Mol Immunol 2000;37:1141–1149.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Horea Rus
    • 1
    • 2
    Email author
  • Cornelia Cudrici
    • 1
  • Florin Niculescu
    • 3
  1. 1.Department of NeurologyUniversity of Maryland School of MedicineBaltimore
  2. 2.Multiple Sclerosis Center of ExcellenceVeterans Administration Maryland Health Care SystemBaltimore
  3. 3.Division of Rheumatology and Clinical ImmunologyUniversity of Maryland School of MedicineBaltimore

Personalised recommendations