Key Points
-
The complement system maintains tissue homeostasis and integrity and forms the first central and immediately acting line of defence against invading infectious microorganisms.
-
Complement activation generates toxic products, which need to be precisely targeted to the surface of invading microorganisms, and initiates effector functions with the goal of clearing tagged foreign cells as well as modified self cells, such as apoptotic particles.
-
Complement activation is tightly regulated by multiple inhibitors that are distributed as integral membrane proteins, surface-bound regulators and soluble effectors in the body fluids and plasma.
-
The central steps of complement activation are controlled by multiple regulators or inhibitors that have redundant activity.
-
Dysregulation of the delicate balance of complement activation products and regulators results in autoimmune diseases.
-
Some pathogenic microorganisms mimic the surface of host cells and can remain unrecognized by the host immune system.
Abstract
The complement system is important for cellular integrity and tissue homeostasis. Complement activation mediates the removal of microorganisms and the clearance of modified self cells, such as apoptotic cells. Complement regulators control the spontaneously activated complement cascade and any disturbances in this delicate balance can result in damage to tissues and in autoimmune disease. Therefore, insights into the mechanisms of complement regulation are crucial for understanding disease pathology and for enabling the development of diagnostic tools and therapies for complement-associated diseases.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Walport, M. J. Complement. First of two parts. N. Engl. J. Med. 344, 1058–1066 (2001).
Walport, M. J. Complement. Second of two parts. N. Engl. J. Med. 344, 1140–1144 (2001).
Volonakis, J. E. & Frank. M. M. The Human Complement System in Health and Disease (Dekker, New York, 1998).
Zipfel, P. F., Wurzner, R. & Skerka, C. Complement evasion of pathogens: common strategies are shared by diverse organisms. Mol. Immunol. 44, 3850–3857 (2007).
Rooijakkers, S. H. & van Strijp, J. A. Bacterial complement evasion. Mol. Immunol. 44, 23–32 (2007).
Ogden, C. A. & Elkon, K. B. Role of complement and other innate immune mechanisms in the removal of apoptotic cells. Curr. Dir. Autoimmun. 9, 120–142 (2006).
Medzhitov, R. & Janeway, C. A. Jr. Decoding the patterns of self and nonself by the innate immune system. Science 296, 298–300 (2002).
Zipfel, P. F., Mihlan, M. & Skerka, C. The alternative pathway of complement: a pattern recognition system. Adv. Exp. Med. Biol. 598, 80–92 (2007).
Holers, V. M. The spectrum of complement alternative pathway-mediated diseases. Immunol. Rev. 223, 300–303 (2008).
Ehrlich, P. Zur Theorie der Lysin Wirkung. Berl. Klin. Wochenschr. 1, 6–9 (1899).
Metschnikow, I. I. Immunität bei Infektionskrankheiten (Fischer, Frankfurt, 1902).
Köhl, J. Self, non-self, and danger. A complementary view. Adv. Exp. Med. Biol. 586, 71–94 (2006).
Gros, P., Milder, F. J. & Janssen, B. J. Complement driven by conformational changes. Nature Rev. Immunol. 8, 48–58 (2008). This article provides an excellent and elegant review of the structural dynamics of complement components upon activation.
Carroll, M. C. The complement system in regulation of adaptive immunity. Nature Immunol. 5, 981–986 (2004). This is a comprehensive review on the role of complement in the T cell-mediated adaptive immune response.
Kemper, C. & Atkinson, J. P. T-cell regulation: with complements from innate immunity. Nature Rev. Immunol. 7, 9–18 (2007).
Janeway, C. A. Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol. Today 13, 11–16 (1992).
Strey, C. W. et al. The proinflammatory mediators C3a and C5a are essential for liver regeneration. J. Exp. Med. 198, 913–923 (2003).
Mukherjee, P., Thomas, S. & Pasinetti, G. M. Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo. J. Neuroinflammation 29, 5 (2008).
Ward, P. A. Functions of C5a receptors. J. Mol. Med. 87, 375–378 (2009).
Stevens, B. et al. The classical complement cascade mediates CNS synapse elimination. Cell 131, 1164–1178 (2007).
Wysoczynski, M. et al. Defective engraftment of C3aR−/− hematopoietic stem progenitor cells shows a novel role of the C3a-C3aR axis in bone marrow homing. Leukemia 23, 1455–1461 (2009).
Fang, C., Zhang, X., Miwa, T. & Song, W. C. Complement promotes the development of inflammatory Th17 cells through synergistic interaction with TLR signaling and IL-6 production. Blood 114, 1005–1015 (2009).
Lambris, J. D. The multifunctional role of C3, the third component of complement. Immunol. Today 9, 387–393 (1988).
Pangburn, M. K. The alternative pathway of complement. Springer Semin. Immunopathol. 7, 163–192 (1984).
Law, S. K. A. & Reid, K. B. M. Complement 2nd edn Oxford Univ. Press (1995).
Fujita, T. Evolution of the lectin–complement pathway and its role in innate immunity. Nature Rev. Immunol. 2, 346–353 (2002).
Degn, S. E., Thiel, S. & Jensenius, J. C. New perspectives on mannan-binding lectin-mediated complement activation. Immunobiology 212, 301–311 (2007).
Huber-Lang, M. et al. Generation of C5a in the absence of C3: a new complement activation pathway. Nature Med. 12, 682–687 (2006).
Nordahl, E. A. et al. Activation of the complement system generates antibacterial peptides. Proc. Natl Acad. Sci. USA 101, 16879–16884 (2004). This is the first paper to describe the antimicrobial activity of the complement activation products C3a and C4a.
Gal, P., Barna, L., Kocsis, A. & Zavodszky, P. Serine proteases of the classical and lectin pathways: similarities and differences. Immunobiology 212, 267–277 (2007).
Pangburn, M. K. & Rawal, N. Structure and function of complement C5 convertase enzymes. Biochem. Soc. Trans. 30, 1006–1010 (2002).
Ward, P. A. Functions of C5a receptors. J. Mol. Med. 87, 375–378 (2009).
Fischetti, F. et al. Selective therapeutic control of C5a and the terminal complement complex by anti-C5 single-chain Fv in an experimental model of antigen-induced arthritis in rats. Arthritis Rheum. 56, 1187–1197 (2009).
Morgan, B. P. Regulation of the complement membrane attack pathway. Crit. Rev. Immunol. 19, 173–198 (1999).
Bhakdi, S. & Tranum-Jensen, J. Damage to cell membranes by pore-forming bacterial cytolysins. Prog. Allergy 40, 1–43 (1988).
Muller-Eberhard, H. J. The membrane attack complex of complement. Annu. Rev. Immunol. 4, 503–528 (1986).
Chen, Y. et al. Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization. Eur. J. Immunol. 37, 167–176 (2007).
Bossi, F. et al. C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function. Blood 113, 3640–3648 (2009).
Bossi, F. et al. Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. J. Immunol. 173, 6921–6927 (2004).
Liszewski, M. K., Fang, C. J. & Atkinson, J. Inhibiting complement activation on cells at the step of C3 cleavage. Vaccines 26 (Suppl. 8), 122–127 (2008).
Ollert, M. W., David, K., Bredehorst, R. & Vogel, C. W. Classical complement pathway activation on nucleated cells. Role of factor H in the control of deposited C3b. J. Immunol. 155, 4955–4962 (1995).
Flierman, R. & Daha, M. R. The clearance of apoptotic cells by complement. Immunobiology 212, 363–370 (2007).
Trouw, L. A., Blom, A. M. & Gasque, P. Role of complement and complement regulators in the removal of apoptotic cells. Mol. Immunol. 45, 1199–1207 (2008).
Kemper, C., Mitchell, L. M., Zhang, L. & Hourcade, D. E. The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis. Proc. Natl Acad. Sci. USA 105, 9023–9028 (2008).
Taylor, P. R. et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J. Exp. Med. 192, 359–366 (2000).
Gershov, D., Kim, S., Brot, N. & Elkon, K. B. C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J. Exp. Med. 192, 1353–1364 (2000). This manuscript describes how controlled complement activation enhances uptake and clearance of apoptotic particles and limits further inflammatory responses.
Schulze, C. et al. Clearance deficiency — a potential link between infections and autoimmunity. Autoimmun. Rev. 8, 5–8 (2008).
Mihlan, M., Stippa, S., Józsi, M. & Zipfel, P. F. Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting Factor H. Cell Death Differ. 14 August 2009 (doi:10.1038/cdd.2009.103).
Cook, H. T. & Botto, M. Mechanisms of disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nature Clin. Pract. Rheumatol. 2, 330–337 (2006).
Carroll, M. C. A protective role for innate immunity in systemic lupus erythematosus. Nature Rev. Immunol. 4, 825–831 (2004).
Lachmann, P. J. Microbial subversion of the immune response. Proc. Natl Acad. Sci. USA 99, 8461–8462 (2002).
Rooijakkers, S. H. M. et al. Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nature Immunol. 10, 721–729 (2009).
Jozsi, M. & Zipfel, P. F. Factor H family proteins and human diseases. Trends Immunol. 29, 380–387 (2008).
Zipfel, P. F. & Skerka, C. FHL-1/reconectin: a human complement and immune regulator with cell-adhesive function. Immunol. Today 20, 135–140 (1999).
Hourcade, D. E. Properdin and complement activation: a fresh perspective. Curr. Drug Targets 9, 158–164 (2008).
Skidgel, R. A. & Erdos, E. G. Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator. Int. Immunopharmacol. 7, 1888–1899 (2007).
Mueller-Opitz, S.L. et al. Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock. J. Immunol. 182, 6533–6539 (2009).
Davis, A. E., Mejia, P. & Lu, F. Biological activities of C1 inhibitor. Mol. Immunol. 45, 4057–4063 (2008).
Blom, A. M., Villoutreix, B. O. & Dahlback, B. Complement inhibitor C4b-binding protein-friend or foe in the innate immune system? Mol. Immunol. 40, 1333–1346 (2004).
Perry, V. H. & O'Connor, V. C1q: the perfect complement for a synaptic feast? Nature Rev. Neurosci. 9, 807–811 (2008).
Schwarz, M. et al. Potential protective role of apoprotein J (clusterin) in atherogenesis: binding to enzymatically modified low-density lipoprotein reduces fatty acid-mediated cytotoxicity. Thromb. Haemost. 100, 110–118 (2008).
Heinen, S. et al. Factor H related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation. Blood Jun 15 2009 (doi:10/1182/blood-2009-02-205641).
Preissner, K. T. & Seiffert, D. Role of vitronectin and its receptors in haemostasis and vascular remodeling. Thromb. Res. 89, 1–21 (1998).
Caccamo, A. E. et al. Cell detachment and apoptosis induction of immortalized human prostate epithelial cells are associated with early accumulation of a 45 kDa nuclear isoform of clusterin. Biochem. J. 382, 157–168 (2004).
Spitzer, D., Mitchell, L. M., Atkinson, J. P. & Hourcade, D. E. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J. Immunol. 179, 2600–2608 (2007).
Kemper, C. & Hourcade, D. E. Properdin: new roles in pattern recognition and target clearance. Mol. Immunol. 45, 4048–4056 (2008).
Kim, D. D. & Song, W. C. Membrane complement regulatory proteins. Clin. Immunol. 118, 127–136 (2006). This is a comprehensive review on the role of membrane complement regulatory proteins as important modulators of tissue injury in autoimmune and inflammatory disease settings and on their influence on cellular immunity.
Khera, R. & Das, N. Complement receptor 1: disease associations and therapeutic implications. Mol. Immunol. 46, 761–772 (2009).
Isaak, A., Prechl, J., Gergely, J. & Erdei, A. The role of CR2 in autoimmunity. Autoimmunity 39, 357–366 (2006).
Roozendaal, R. & Carroll, M. C. Complement receptors CD21 and CD35 in humoral immunity. Immunol. Rev. 219, 157–166 (2007).
Spendlove, I., Ramage, J. M., Bradley, R., Harris, C. & Durrant, L. G. Complement decay accelerating factor (DAF)/CD55 in cancer. Cancer. Immunol. Immunother. 55, 987–995 (2006).
Seya, T. & Atkinson, J. P. Functional properties of membrane cofactor protein of complement. Biochem. J. 264, 581–538 (1989).
Kimberley, F. C., Sivasankar, B. & Paul Morgan, B. Alternative roles for CD59. Mol. Immunol. 44, 73–81 (2007).
He, J. Q., Wiesmann, C. & van Lookeren Campagne, M. A role of macrophage complement receptor CRIg in immune clearance and inflammation. Mol. Immunol. 45, 4041–4047 (2008). This article provides a detailed description of a new human complement regulator.
Dempsey, P. W., Allison, M. E., Akkaraju, S., Goodnow, C. C. & Fearon, D. T. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271, 348–350 (1996).
Springer, T., Galfre, G., Secher, D. S. & Milstein, C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur. J. Immunol. 9, 301–306 (1979).
Vik, D. P. & Fearon, D. T. Cellular distribution of complement receptor type 4 (CR4): expression on human platelets. J. Immunol. 138, 254–258 (1987).
Benard, M. et al. Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Mol. Immunol. 45, 3767–3774 (2008).
Köhl, J. et al. A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma. J. Clin. Invest. 116, 783–796 (2006). This study shows that C5aR regulates or enhances T helper 2 cell-polarized immune responses in asthma.
Scola, A. M., Johswich, K. O., Morgan, B. P., Klos, A. & Monk, P. N. The human complement fragment receptor, C5L2, is a recycling decoy receptor. Mol. Immunol. 46, 1149–1162 (2009).
Karp, C. L. et al. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nature Immunol. 1, 221–226 (2000).
Rittirsch, D. et al. Functional roles for C5a receptors in sepsis. Nature Med. 14, 551–557 (2008). This is a comprehensive functional characterization of the role of the C5a receptors C5aR and C5L2 in an animal model of sepsis using antibody-induced blockade of C5a receptors and knockout mice. The authors show that C5L2 is a functional receptor rather than merely a default receptor.
Zutter, M. M. & Edelson, B. T. The α2β1 integrin: a novel collectin/C1q receptor. Immunobiology 212, 343–353 (2007).
Tarr, J. & Eggleton, P. Immune function of C1q and its modulators CD91 and CD93. Crit. Rev. Immunol. 25, 305–330 (2005).
Kang, Y. S. et al. A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Cell 125, 47–58 (2006). This report identifies SIGNR1 as a receptor for C1q, and shows that this lectin surface protein contributes to innate immune responses through a previously unknown C3 activation pathway.
Sanchez-Corral, P., Gonzalez-Rubio, C., Rodriguez de Cordoba, S. & Lopez-Trascasa, M. Functional analysis in serum from atypical hemolytic uremic syndrome patients reveals impaired protection of host cells associated with mutations in factor H. Mol. Immunol. 41, 81–84 (2004).
Manuelian, T. et al. Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. J. Clin. Invest. 111, 1181–1190 (2003).
Ferreira, V. P. & Pangburn, M. K. Factor H mediated cell surface protection from complement is critical for the survival of PNH erythrocytes. Blood 110, 2190–2192 (2007). References 86–88 describe the protective role of the complement regulator factor H on the surface of host cells and erythrocytes.
Perkins, S. J. et al. Solution structures of complement components by X-ray and neutron scattering and analytical ultracentrifugation. Biochem. Soc. Trans. 30, 996–1001 (2002).
Hakulinen, J., Junnikkala, S., Sorsa, T. & Meri, S. Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form. Eur. J. Immunol. 34, 2620–2629 (2004).
Noris, M. & Remuzzi, G. Hemolytic uremic syndrome. J. Am. Soc. Nephrol. 16, 1035–1050 (2005).
Skerka, C., Jozsi, M., Zipfel, P. F., Dragon-Durey, M. A. & Fremeaux-Bacchi, V. Autoantibodies in haemolytic uraemic syndrome (HUS). Thromb. Haemost. 101, 227–232 (2009).
Smith, R. J. et al. New approaches to the treatment of dense deposit disease. J. Am. Soc. Nephrol. 18, 2447–2456 (2007).
de Jong, P. T. Age-related macular degeneration. N. Engl. J. Med. 355, 1474–1485 (2006).
Klein, R. J. et al. Complement factor H polymorphism in age-related macular degeneration. Science 308, 385–389 (2005). This is the first genetic analysis to show that a common polymorphism in the factor H gene is strongly associated with the risk for the retinal disease AMD.
Truedsson, L., Bengtsson, A. A. & Sturfelt, G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 40, 560–566 (2007).
Donin, N. et al. Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid. Clin. Exp. Immunol. 131, 254–263 (2003).
Lambris, J. D., Ricklin, D. & Geisbrecht, B. V. Complement evasion by human pathogens. Nature Rev. Microbiol. 6, 132–142 (2008). This is a comprehensive review on the evasion strategies used by human pathogenic microorganisms.
Zipfel, P. F., Heinen, S., Jozsi, M. & Skerka, C. Complement and diseases: defective alternative pathway control results in kidney and eye diseases. Mol. Immunol. 43, 97–106 (2006).
Gold, B. et al. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nature Genet. 38, 458–462 (2006).
Hageman, G. S. et al. Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann. Med. 38, 592–604 (2006).
Zipfel, P. F. et al. Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS Genet. 3, e41 (2007).
Venables, J. P. et al. Atypical haemolytic uraemic syndrome associated with a hybrid complement gene. PLoS Med. 3, e431 (2006).
Hughes, A. E. et al. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nature Genet. 38, 1173–1177 (2006). References 102–104 show that a deletion of an 84-kb chromosomal fragment, which includes the two human genes CFHR1 and CFHR3 , is associated with various diseases. This deletion is a risk factor in aHUS but has a protective role in AMD.
Daha, M. R., Fearon, D. T. & Austen, K. F. C3 nephritic factor (C3NeF): stabilization of fluid phase and cell-bound alternative pathway convertase. J. Immunol. 116, 1–7 (1976).
Wu, J. et al. Structure of complement fragment C3b-factor H and its implications for host protection by complement regulators. Nature Immunol. 10, 728–734 (2009).
Skerka, C. et al. Defective complement control of factor H (Y402H) and FHL-1 in age-related macular degeneration. Mol. Immunol. 44, 3398–3406 (2007).
Sethi, S. et al. Glomeruli of dense-deposit disease contain components of the alternative and terminal complement pathway. Kidney Int. 75, 952–960 (2009).
Crabb, J. W. et al. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc. Natl Acad. Sci. USA 99, 14682–14687 (2002). References 108 and 109 are the first proteomic analyses of renal dense deposits and retinal drusen, respectively. The two deposits, which develop in different organs, show related protein profiles in the form of inflammatory proteins and components of the terminal complement pathway.
Carroll, M. C. A protective role for innate immunity in systemic lupus erythematosus. Nature Rev. Immunol. 4, 825–831 (2004).
Robson, M. G. & Walport, M. J. Pathogenesis of systemic lupus erythematosus (SLE). Clin. Exp. Allergy 31, 678–685 (2002).
Varela, J. C., Atkinson, C., Woolson, R., Keane, T. E. & Tomlinson, S. Upregulated expression of complement inhibitory proteins on bladder cancer cells and anti-MUC1 antibody immune selection. Int. J. Cancer 123, 1357–1363 (2008).
Markiewski, M. M. et al. Modulation of the antitumor immune response by complement. Nature Immunol. 9, 1225–1235 (2008).
S ivasankar, B. et al. CD59 blockade enhances antigen-specific CD4+ T cell responses in humans: a new target for cancer immunotherapy? J. Immunol. 182, 5203–5207 (2009).
Nurnberger, J. et al. Eculizumab for atypical hemolytic-uremic syndrome. N. Engl. J. Med. 360, 542–544 (2009).
Gruppo, R. A. & Rother, R. P. Eculizumab for congenital atypical hemolytic-uremic syndrome. N. Engl. J. Med. 360, 544–546 (2009). References 115 and 116 report the first, impressive results on the use of eculizumab, a humanized monoclonal antibody that binds to the C5 inhibitor in aHUS.
Rossmann, E. et al. Dual binding specificity of a Borrelia hermsii-associated complement regulator-acquiring surface protein for factor H and plasminogen discloses a putative virulence factor of relapsing fever spirochetes. J. Immunol. 178, 7292–7301 (2007).
Hammel, M. et al. A structural basis for complement inhibition by Staphylococcus aureus. Nature Immunol. 8, 430–437 (2007). This manuscript gives a mechanistic insight based on structural data into how pathogen-encoded inhibitors bind to C3 and block further C3 conformational changes.
Schneider, M. C. et al. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature 458, 890–893 (2009).
Johri, A. K. et al. Group B Streptococcus: global incidence and vaccine development. Nature Rev. Microbiol. 4, 932–942 (2006).
Pizza, M., Donnelly, J. & Rappuoli, R. Factor H binding protein, a unique meningococcal vaccine antigen. Vaccine 26, 146–148 (2008).
Ricklin, D. & Lambris, J. D. Complement-targeted therapeutics. Nature Biotech. 25, 1265–1275 (2007).
Acknowledgements
The work of both the authors is supported by the Deutsche Forschungsgemeinschaft, Germany. P.F.Z.'s work is also supported by Kidneeds, Iowa, USA, the National Institutes of Health, USA, and ProRetina, Germany.
Author information
Authors and Affiliations
Corresponding author
Related links
Glossary
- Zymogen
-
An inactive pre-form of a protease that by itself lacks proteolytic activity. Upon processing or proteolytic cleavage the protein displays enzymatic activity. Using such inactive pre-forms allows targeting of protein activity to the right place at the right time. Most complement proteins, but also components of the coagulation cascade and other proteases, exist and circulate as inactive pre-forms and require modification and proteolytic processing to be converted into an active form.
- Opsonization
-
The deposition of activation products, for example the C3 activation fragment C3b, on the surface of a target to mark the target and facilitate and enhance recognition and uptake by phagocytic cells. Phagocytosis eliminates the particle from the circulation and aids in its destruction.
Rights and permissions
About this article
Cite this article
Zipfel, P., Skerka, C. Complement regulators and inhibitory proteins. Nat Rev Immunol 9, 729–740 (2009). https://doi.org/10.1038/nri2620
Published:
Issue Date:
DOI: https://doi.org/10.1038/nri2620
This article is cited by
-
The complement cascade in lung injury and disease
Respiratory Research (2024)
-
A guide to complement biology, pathology and therapeutic opportunity
Nature Reviews Immunology (2024)
-
Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins
Nature Nanotechnology (2024)
-
New insights into the immune functions of podocytes: the role of complement
Molecular and Cellular Pediatrics (2023)
-
The role of complement in kidney disease
Nature Reviews Nephrology (2023)