Chapter 11 : Complement and Its Receptors in Infection

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Complement and Its Receptors in Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817671/9781555812911_Chap11-1.gif /docserver/preview/fulltext/10.1128/9781555817671/9781555812911_Chap11-2.gif


This chapter focuses on the general modus operandi of complement and its receptors in infection. It discusses the various pathways of complement activation and their microbial triggers and highlights some of the mechanisms and strategies pathogens have evolved to counteract or “hijack” the complement system. A portion examines how the source of complement affects adaptive immunity to infectious agents. Defined by the mode of activation and the subsequent proteolytic cascade in which activation occurs, three activation pathways are recognized: classical, mannan-binding lectin (MBL), and alternative. Complement receptors play an important role in the uptake and clearance of opsonized Ag, enhancing adaptive and innate cellular responses, and inducing inflammatory responses. The role of anaphylatoxin receptors becomes more complicated when relatively recent work describing an attenuating effect of C3aR on inflammation induced by lipopolysaccharides (LPSs) in an in vivo endotoxic shock model is considered. An additional factor that might have promoted cooperation between adaptive immunity and classical complement is the close linkage of some of their hallmark genes on the mammalian genome. To date, myeloid C3 is the only known source with a site-restricted complement function that does not overlap with alternative sources. Its fundamental importance in adaptive immunity in the periphery might make it a factor of consideration in vaccine development or possibly part of standard clinical analyses where serum complement is measured now.

Citation: Verschoor A, Carroll M. 2004. Complement and Its Receptors in Infection, p 219-240. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch11

Key Concept Ranking

Complement System
Adaptive Immune System
Herpes simplex virus 1
Major Histocompatibility Complex
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Schematic overview of the complement cascade. Classical, MBL, and alternative pathways commence from the left side of the figure, leading to the converging point of C3 activation (top right). In every subsequent proteolytic step, the position of the new addition to the antigen complex is shown in black for clarity. From the central C3 activation step downwards, the C3 amplification loop through the alternative pathway is indicated by asterisks. The lytic pathway is initiated with the formation of C5 convertase and leads to the assembly of the C5,6,7,8,()9 MAC that interferes with the target's structural integrity by penetrating the cellular membrane (bottom right).

Citation: Verschoor A, Carroll M. 2004. Complement and Its Receptors in Infection, p 219-240. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Molecular basis for complement enhancement of the humoral response. (1) Ag captured and presented on the FDC surface through CR1/2 or FcR is presented to Ag-specific B cell in the germinal center. (2) Recognition of Ag through the BCR and coligation of the CR2, CD19, CD81-signaling complex through complement leads to Bcell activation and (3) Ag-specific Ab production. (4) Specific Ab complexes with Ag result in (5 and 6) downregulation of the B-cell response by engagement of the cell surface BCR and FcR. Also, formation of Ag– Ab(-C′) complexes results in enhanced trapping of Ag onto the FDC surface through CR and FcR (7), creating a long-term Ag pool.

Citation: Verschoor A, Carroll M. 2004. Complement and Its Receptors in Infection, p 219-240. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Impaired humoral responses in classical complement or complement receptor knockout mice. C3-, C4-, or CR1/2-deficient animals reveal impaired humoral responses upon peripheral HSV infection. Recombinant β-galactosidase-expressing HSV-1 (strain HD-2) was used for inoculation, giving essentially the same results as WT virus but also allowing assessment of the response to β-galactosidase (as reported by ).The results mirror, in a well-controlled way, early immunization experiments with animals that were transiently depleted or naturally deficient in one or more complement factors.

Citation: Verschoor A, Carroll M. 2004. Complement and Its Receptors in Infection, p 219-240. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Local myeloid C3 synthesis is essential for humoral responses to peripheral HSV infection. (a) Peripheral HSV infection leads to robust humoral responses in WT but not C3 animals. (b) Local BM-derived myeloid C3 synthesis can rescue this defect in WT BM → C3 animals. Upon further investigation, local C3 synthesis appears essential, as evidenced by infection of C3 BM →WT animals. (c) C3 BM →WT animals show WT-like levels of circulating C3, but do not respond to HSV. In contrast, WT BM →C3 animals have essentially C3 serum levels, but respond with WT-like humoral responses. i.d., intradermally.

Citation: Verschoor A, Carroll M. 2004. Complement and Its Receptors in Infection, p 219-240. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

Model for myeloid C3 enhancement of the humoral response in the periphery. Upon HSV infection (1), viral Ag in the skin encounters complement from various sources, including those that are serum, keratinocyte, or myeloid derived (2). Although serum or keratinocyte C3 is clearly present, C3 BM →WT animals suggest that these sources of C3 do not result in enhancement of the humoral response. Carried by the afferent lymphatics (3),Ag reaches the peripheral lymph nodes in free, complement-complexed or antigen-presenting cell (APC)-processed form.There it is recognized by Ag-specific B- cells (4) that receive T-cell help generated though MHC-restricted APC interaction (5). Gamma interferon (IFNγ) is generated in this process and has been shown to stimulate macrophages to produce complement factors, which then can opsonize drained Ag (6). Opsonized Ag can enhance the B-cell response significantly (7), increasing the amount of specific Ab produced. Specific Ab aids the formation of Ag, Ab, Cʹ immune complexes, structures that are especially immunogenic. SS, subcapsular sinus; IC, immune complex;AFC, antibody-forming cell.

Citation: Verschoor A, Carroll M. 2004. Complement and Its Receptors in Infection, p 219-240. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ahearn, J. M.,, M. B. Fischer,, D. Croix,, S. Goerg,, M. Ma,, J. Xia,, X. Zhou,, R. G. Howard,, T. L. Rothstein,, and M. C. Carroll. 1996. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity 4:251262.
2. Albrecht, J. C.,, and B. Fleckenstein. 1992. New member of the multigene family of complement control proteins in herpesvirus saimiri. J. Virol. 66:39373940.
3. Al-Sharif, W. Z.,, J. O. Sunyer,, J. D. Lambris,, and L. C. Smith. 1998. Sea urchin coelomocytes specifically express a homologue of the complement component C3. J. Immunol. 160:29832997.
4. Barnum, S. R.,, J. L. Jones,, and E. N. Benveniste. 1993. Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells. Glia 7:225236.
5. Barrington, R. A.,, O. Pozdnyakova,, M. R. Zafari,, C. D. Benjamin,, and M. C. Carroll. 2002. B lymphocyte memory: role of stromal cell complement and FcgammaRIIB receptors. J. Exp. Med. 196:11891199.
6. Bianco, C.,, R. Patrick,, and V. Nussenzweig. 1970. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J. Exp. Med. 132:702720.
7. Boackle, S. A.,, V. M. Holers,, and D. R. Karp. 1997. CD21 augments antigen presentation in immune individuals. Eur. J. Immunol. 27:122129.
8. Boackle, S. A.,, M. A. Morris,, V. M. Holers,, and D. R. Karp. 1998. Complement opsonization is required for presentation of immune complexes by resting peripheral blood B cells. J. Immunol. 161:65376543.
9. Brauer, R. B.,, T.T. Lam,, D. Wang,, L. R. Horwitz,, A. D. Hess,, A. S. Klein,, F. Sanfilippo,, and W. M. Baldwin, III. 1995. Extrahepatic synthesis of C6 in the rat is sufficient for complement-mediated hyperacute rejection of a guinea pig cardiac xenograft. Transplantation 59:10731076.
10. Brauer, R. B.,, W. M. Baldwin, III, D.Wang, L. R. Horwitz, A. D. Hess, A. S. Klein, and F. Sanfilippo. 1994. Hepatic and extrahepatic biosynthesis of complement factor C6 in the rat. J. Immunol. 153:31683176.
11. Brooimans, R. A.,, A. A. van der Ark,, W. A. Buurman,, L. A. van Es,, and M. R. Daha. 1990. Differential regulation of complement factor H and C3 production in human umbilical vein endothelial cells by IFN-gamma and IL-1. J. Immunol. 144:38353840.
12. Brooimans, R. A.,, A. P. Stegmann,, W. T. vanDorp,, A. A. vanderArk,, F. J. vanderWoude,, L. A. vanEs,, and M. R. Daha. 1991. Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells. J. Clin. Invest. 88:379384.
13. Carroll, M. C. 1998. CD21, CD35 in B cell activation. Semin. Immunol. 10:279286.
14. Choi, N. H.,, T. Mazda,, and M. Tomita. 1989. A serum protein SP40,40 modulates the formation of membrane attack complex of complement on erythrocytes. Mol. Immunol. 26:835840.
15. Cochrane, C. G.,, and H. J. Muller-Eberhard. 1968. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J. Exp. Med. 127:371386.
16. Coico, R. F.,, B. S. Bhogal,, and G. J. Thorbecke. 1983. Relationship of germinal centers in lymphoid tissue to immunologic memory.VI.Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin. J. Immunol. 131:22542257.
17. Cooper, N. R. 1985.The classical complement pathway: activation and regulation of the first complement component. Adv. Immunol. 37:151216. Da Costa, X. J., M. A. Brockman, E. Alicot, M.
18. Da Costa, X. J.,, M. A. Brockman,, E. Alicot,, M. Ma,, M. B. Fischer,, X. Zhou,, D. M. Knipe,, and M. C. Carroll. 1999. Humoral response to herpes simplex virus is complement-dependent. Proc. Natl. Acad. Sci. USA 96:1270812712.
19. Dempsey, P.W.,, M. E. Allison,, S. Akkaraju,, C. C. Goodnow,, and D.T. Fearon. 1996. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271:348350.
20. DiasDaSilva, W.,, and I. H. Lepow. 1967. Complement as a mediator of inflammation. II. Biological properties of anaphylatoxin prepared with purified components of human complement. J. Exp. Med. 125:921946.
21. Donaldson, V. H.,, F. S. Rosen,, and D. H. Bing. 1977. Role of the second component of complement (C2) and plasmin in kinin release in hereditary angioneurotic edema (H.A.N.E.) plasma. Trans. Assoc. Am. Physicians 90:174183.
22. Drouin, S. M.,, D. B. Corry,, J. Kildsgaard,, and R. A. Wetsel. 2001. Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy. J. Immunol. 167:41414145.
23. Ebenbichler, C. F.,, N. M. Thielens,, R. Vornhagen,, P. Marschang,, G. J. Arlaud,, and M. P. Dierich. 1991. Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific sites in the transmembrane glycoprotein gp41. J. Exp. Med. 174:14171424.
24. Eden, A.,, C. Bianco,, and V. Nussenzweig. 1971.A population of lymphocytes bearing a membrane receptor antigen-antibody-complement complexes. II. Specific isolation. Cell. Immunol. 2:658669.
25. Ember, J.,, M. Jagels,, and T. Hugli,. 1998. Characterization of complement anaphylatoxins and their biological responses, p. 241284. In J. Volanakis, and M. Frank (ed.), The Human Complement System in Health and Disease. Marcel Dekker, Inc., New York, N.Y..
26. Erdei, A.,, E. Spaeth,, J. Alsenz,, E. Rude,, T. Schulz,, J. Gergely,, and M. P. Dierich. 1984. Role of C3b receptors in the enhancement of interleukin- 2-dependent T-cell proliferation. Mol. Immunol. 21: 12151221.
27. Fang, Y.,, C. Xu,, Y. X. Fu,, V. M. Holers,, and H. Molina. 1998. Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response. J. Immunol. 160:52735279.
28. Fearon, D.T. 1993.The CD19-CR2-TAPA-1 complex, CD45 and signaling by the antigen receptor of B lymphocytes. Curr. Opin. Immunol. 5:341348.
29. Fischer, E.,, C. Delibrias,, and M. D. Kazatchkine. 1991. Expression of CR2 (the C3dg, EBV receptor, CD21) on normal human peripheral blood T lymphocytes. J. Immunol. 146:865869.
30. Fischer, M. B.,, M. Ma,, S. Goerg,, X. Zhou,, J. Xia,, O. Finco,, S. Han,, G. Kelsoe,, R. G. Howard,, T. L. Rothstein,, E. Kremmer,, F. S. Rosen,, and M. C. Carroll. 1996. Regulation of the B cell response to Tdependent antigens by classical pathway complement. J. Immunol. 157:549556.
31. Fischer, M. B.,, M. Ma,, N. C. Hsu,, and M. C. Carroll. 1998. Local synthesis of C3 within the splenic lymphoid compartment can reconstitute the impaired immune response in C3-deficient mice. J. Immunol. 160:26192625.
32. Gadjeva, M.,, A. Verschoor,, M. A. Brockman,, H. Jezak,, L. M. Shen,, D. M. Knipe,, and M. C. Carroll. 2002. Macrophage-derived complement component C4 can restore humoral immunity in C4- deficient mice. J. Immunol. 169:54895495.
33. Gewurz, H.,, H. S. Shin,, and S. E. Mergenhagen. 1968. Interactions of the complement system with endotoxic lipopolysaccharide: consumption of each of the six terminal complement components. J. Exp. Med. 128:10491057.
34. Green, T. D.,, B. R. Newton,, P. A. Rota,, Y. Xu,, H. L. Robinson,, and T. M. Ross. 2001. C3d enhancement of neutralizing antibodies to measles hemagglutinin. Vaccine 20:242248.
35. Gustavsson, S.,, T. Kinoshita,, and B. Heyman. 1995. Antibodies to murine complement receptor 1 and 2 can inhibit the antibody response in vivo without inhibiting T helper cell induction. J. Immunol. 154:65246528.
36. Hashimoto, K.,, T. Nakanishi,, and Y. Kurosawa. 1992. Identification of a shark sequence resembling the major histocompatibility complex class I alpha 3 domain. Proc. Natl. Acad. Sci. USA 89:22092212.
37. Hinds, K. R.,, and G.W. Litman. 1986. Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution. Nature 320:546549.
38. Hugli, T. E.,, and H. J. Muller-Eberhard. 1978. Anaphylatoxins: C3a and C5a. Adv. Immunol. 26:153.
39. Humbles, A. A.,, B. Lu,, C. A. Nilsson,, C. Lilly,, E. Israel,, Y. Fujiwara,, N. P. Gerard,, and C. Gerard. 2000.A role for the C3a anaphylatoxin receptor in the effector phase of asthma. Nature 406:9981001.
40. Hung, S. L.,, C. Peng,, I. Kostavasili,, H. M. Friedman,, J. D. Lambris,, R. J. Eisenberg,, and G. H. Cohen. 1994.The interaction of glycoprotein C of herpes simplex virus types 1 and 2 with the alternative complement pathway. Virology 203:299312.
41. Kapadia, S. B.,, B. Levine,, S. H. Speck,, and H. W. T. Virgin. 2002. Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infection. Immunity 17:143155.
42. Katz, Y.,, M. Revel,, and R. C. Strunk. 1989. Interleukin 6 stimulates synthesis of complement proteins factor B and C3 in human skin fibroblasts. Eur. J. Immunol. 19:983988.
43. Kelsoe, G. 1996.The germinal center: a crucible for lymphocyte selection. Semin. Immunol. 8:179184.
44. Kerekes, K.,, J. Prechl,, Z. Bajtay,, M. Jozsi,, and A. Erdei. 1998. A further link between innate and adaptive immunity: C3 deposition on antigen-presenting cells enhances the proliferation of antigen-specific T cells. Int. Immunol. 10:19231930.
45. Kildsgaard, J.,, T. J. Hollmann,, K.W. Matthews,, K. Bian,, F. Murad,, and R.A. Wetsel. 2000. Cutting edge: targeted disruption of the C3a receptor gene demonstrates a novel protective anti-inflammatory role for C3a in endotoxin-shock. J. Immunol. 165:54065409.
46. Kipnis, T. L.,, K. A. Joiner,, W. D. da Silva,, M. T. Rimoldi,, C. H. Hammer,, and A. Sher. 1988. Identification of membrane components of Trypanosoma cruzi modulators of complement system.Mem. Inst. Oswaldo Cruz 83(Suppl. 1):571575.
47. Kohl, J. 2001.Anaphylatoxins and infectious and noninfectious inflammatory diseases. Mol. Immunol. 38:175187.
48. Kopf, M.,, B. Abel,, A. Gallimore,, M. Carroll,, and M. F. Bachmann. 2002. Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat. Med. 8:373378.
49. Kotwal, G. J.,, and B. Moss. 1988. Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins. Nature 335:176178.
50. Krych-Goldberg, M.,, J. M. Moulds,, and J. P. Atkinson. 2002. Human complement receptor type 1 (CR1) binds to a major malarial adhesin. Trends Mol. Med. 8:531537.
51. Kurtz, C. B.,, E. O'Toole,, S. M. Christensen,, and J. H. Weis. 1990. The murine complement receptor gene family. IV. Alternative splicing of Cr2 gene transcripts predicts two distinct gene products that share homologous domains with both human CR2 and CR1. J. Immunol. 144:35813591.
52. Lakkis, F. G. 2002.Transplant rejection: mind your Tcell language. Nat. Med. 8:1043; author reply 10431044.
53. Lay, W. H.,, and V. Nussenzweig. 1968. Receptors for complement of leukocytes. J. Exp. Med. 128:9911009.
54. Liu, Y. J.,, J. Xu,, O. de Bouteiller,, C. L. Parham,, G. Grouard,, O. Djossou,, B. de Saint-Vis,, S. Lebecque,, J. Banchereau,, and K.W. Moore. 1997. Follicular dendritic cells specifically express the long CR2/CD21 isoform. J. Exp. Med. 185:165170.
55. Lu, J. H.,, S. Thiel,, H. Wiedemann,, R. Timpl,, and K. B. Reid. 1990. Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q. J. Immunol. 144:22872294.
56. Malhotra, R.,, S. Thiel,, K. B. Reid,, and R. B. Sim. 1990. Human leukocyte C1q receptor binds other soluble proteins with collagen domains. J. Exp. Med. 172:955959.
57. Mandel, T. E.,, R. P. Phipps,, A. P. Abbot,, and J. G. Tew. 1981. Long-term antigen retention by dendritic cells in the popliteal lymph node of immunized mice. Immunology 43:353362.
58. Marschang, P.,, J. Sodroski,, R. Wurzner,, and M. P. Dierich. 1995. Decay-accelerating factor (CD55) protects human immunodeficiency virus type 1 from inactivation by human complement. Eur. J. Immunol. 25:285290.
59. Martin, D. R.,, R. L. Marlowe,, and J. M. Ahearn. 1994. Determination of the role for CD21 during Epstein-Barr virus infection of B-lymphoblastoid cells. J.Virol. 68:47164726.
60. Matsushita, M.,, Y. Endo,, M. Nonaka,, and T. Fujita. 1998. Complement-related serine proteases in tunicates and vertebrates. Curr. Opin. Immunol. 10:2935.
61. McGreal, E.,, and P. Gasque. 2001. Structure-function studies of the receptors for complement C1q. Biochem. Soc.Trans. 30:10101014.
62. McPhaden, A. R.,, and K. Whaley. 1993. Complement biosynthesis by mononuclear phagocytes. Immunol. Res. 12:213232.
63. Miller, L. J.,, R. Schwarting,, and T. A. Springer. 1986. Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. J. Immunol. 137:28912900.
64. Mold, C.,, B.M. Bradt,, G. R. Nemerow,, and N. R. Cooper. 1988. Epstein-Barr virus regulates activation and processing of the third component of complement. J. Exp. Med. 168:949969.
65. Molina, H.,, V. M. Holers,, B. Li,, Y. Fung,, S. Mariathasan,, J. Goellner,, J. Strauss- Schoenberger,, R. W. Karr,, and D. D. Chaplin. 1996. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc. Natl. Acad. Sci. USA 93:33573361.
66. Naughton, M. A.,, M. Botto,, M. J. Carter,, G. J. Alexander,, J. M. Goldman,, and M. J. Walport. 1996a. Extrahepatic secreted complement C3 contributes to circulating C3 levels in humans. J. Immunol. 156:30513056.
67. Naughton, M. A.,, M. J. Walport,, R. Wurzner,, M. J. Carter,, G. J. Alexander,, J.M. Goldman,, and M. Botto. 1996b. Organ-specific contribution to circulating C7 levels by the bone marrow and liver in humans. Eur. J. Immunol. 26:21082112.
68. Nikaido, H.,, and T. Nakae. 1979.The outer membrane of Gram-negative bacteria. Adv. Microb. Physiol. 20:163250.
69. Nonaka, M.,, K. Azumi,, X. Ji,, C. Namikawa- Yamada,, M. Sasaki,, H. Saiga,, A.W. Dodds,, H. Sekine,, M. K. Homma,, M. Matsushita,, Y. Endo,, and T. Fujita. 1999. Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi. J. Immunol. 162:387391.
70. Norris, K.A.,, B. Bradt,, N. R. Cooper,, and M. So. 1991. Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor. J. Immunol. 147:22402247.
71. Ohkuro, M.,, M. Ogura-Masaki,, K. Kobayashi,, M. Sakai,, K. Takahashi,, and S. Nagasawa. 1995. Effect of iC3b binding to immune complexes upon the phagocytic response of human neutrophils: synergistic functions between Fc gamma R and CR3. FEBS Lett 373:189192.
72. Papamichail, M.,, C. Gutierrez,, P. Embling,, P. Johnson,, E. J. Holborow,, and M. B. Pepys. 1975. Complement dependence of localisation of aggregated IgG in germinal centres. Scand. J. Immunol. 4:343347.
73. Pepys, M. B. 1972. Role of complement in induction of the allergic response. Nat. New Biol. 237:157159.
74. Petry, F.,, M. Botto,, R. Holtappels,, M. J. Walport,, and M. Loos. 2001. Reconstitution of the complement function in C1q-deficient (C1qa-/-) mice with wild-type bone marrow cells. J. Immunol.167:40334037.
75. Pinter, C.,, A. G. Siccardi,, R. Longhi,, and A. Clivio. 1995a. Direct interaction of complement factor H with the C1 domain of HIV type 1 glycoprotein 120. AIDS Res. Hum. Retrovir. 11:577588.
76. Pinter, C.,, A. G. Siccardi,, L. Lopalco,, R. Longhi,, and A. Clivio. 1995b. HIV glycoprotein 41 and complement factor H interact with each other and share functional as well as antigenic homology. AIDS Res. Hum. Retrovir. 11:971980.
77. Podack, E. R.,, K.T. Preissner,, and H. J. Muller- Eberhard. 1984. Inhibition of C9 polymerization within the SC5b-9 complex of complement by Sprotein. Acta Pathol. Microbiol. Immunol. Scand. Suppl. 284:8996.
78. Pratt, J. R.,, S. A. Basheer,, and S. H. Sacks. 2002. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat. Med. 8:582587.
79. Qin, D.,, J. Wu,, M. C. Carroll,, G. F. Burton,, A. K. Szakal,, and J. G. Tew. 1998. Evidence for an important interaction between a complement-derived CD21 ligand on follicular dendritic cells and CD21 on B cells in the initiation of IgG responses. J. Immunol. 161:45494554.
80. Radoux, D.,, C. Kinet-Denoel,, E. Heinen,, M. Moeremans,, J. De Mey,, and L. J. Simar. 1985. Retention of immune complexes by Fc receptors on mouse follicular dendritic cells. Scand. J. Immunol. 21:345353.
81. Ramos, O. F.,, M. Patarroyo,, E. Yefenof,, and E. Klein. 1989. Requirement of leukocytic cell adhesion molecules (CD11a-c/CD18) in the enhanced NK lysis of iC3b-opsonized targets. J. Immunol. 142:41004104.
82. Reynes, M.,, J. P. Aubert,, J. H. Cohen,, J. Audouin,, V. Tricottet,, J. Diebold,, and M. D. Kazatchkine. 1985. Human follicular dendritic cells express CR1, CR2, and CR3 complement receptor antigens. J. Immunol. 135:26872694.
83. Ridker, P. M.,, N. Rifai,, L. Rose,, J. E. Buring,, and N. R. Cook. 2002. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N. Engl. J. Med. 347:15571565.
84. Robson, M. G.,, H. T. Cook,, M. Botto,, P. R. Taylor,, N. Busso,, R. Salvi,, C. D. Pusey,, M. J. Walport,, and K. A. Davies. 2001. Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice. J. Immunol. 166:68206828.
85. Ross, T. M.,, Y. Xu,, R. A. Bright,, and H. L. Robinson. 2000. C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge. Nat. Immunol. 1:127131.
86. Ross, T. M.,, Y. Xu,, T. D. Green,, D. C. Montefiori,, and H. L. Robinson. 2001. Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins. AIDS Res. Hum. Retrovir. 17:829835.
87. Saifuddin, M.,, C. J. Parker,, M. E. Peeples,, M. K. Gorny,, S. Zolla-Pazner,, M. Ghassemi,, I. A. Rooney,, J. P. Atkinson,, and G. T. Spear. 1995. Role of virion-associated glycosylphosphatidylinositol- linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1. J. Exp. Med. 182:501509.
88. Sato, S.,, A. S. Miller,, M. C. Howard,, and T. F. Tedder. 1997. Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19. J. Immunol. 159:32783287.
89. Schnizlein, C. T.,, A. K. Szakal,, and J. G. Tew. 1984. Follicular dendritic cells in the regulation and maintenance of immune responses. Immunobiology 168:391402.
90. Simpson, A. J.,, and S. R. Smithers. 1980. Characterization of the exposed carbohydrates on the surface membrane of adult Schistosoma mansoni by analysis of lectin binding. Parasitology 81:115.
91. Stalenheim, G.,, and S. Castensson. 1971. Protein A from Staphylococcus aureus conversion of complement factor C3 by aggregates between IgG and protein A. FEBS Lett. 14:7981.
92. Stoiber, H.,, C. Pinter,, A. G. Siccardi,, A. Clivio,, and M. P. Dierich. 1996. Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF, CD55). J. Exp. Med. 183:307310.
93. Strunk, R. C.,, D. M. Eidlen,, and R. J. Mason. 1988. Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways. J. Clin. Invest. 81:14191426.
94. Suradhat, S.,, R. P. Braun,, P. J. Lewis,, L. A. Babiuk,, S. van Drunen Littel-van den Hurk,, P. J. Griebel,, and M. E. Baca-Estrada. 2001. Fusion of C3d molecule with bovine rotavirus VP7 or bovine herpesvirus type 1 glycoprotein D inhibits immune responses following DNA immunization. Vet. Immunol. Immunopathol. 83:7992.
95. Takizawa, F.,, S. Tsuji,, and S. Nagasawa. 1996. Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett. 397:269272.
96. Tang, S.,, W. Zhou,, N. S. Sheerin,, R.W. Vaughan,, and S. H. Sacks. 1999. Contribution of renal se- creted complement C3 to the circulating pool in humans. J. Immunol. 162:43364341.
97. Terui, T.,, K. Ishii,, M. Ozawa,, N. Tabata,, T. Kato,, and H. Tagami. 1997. C3 production of cultured human epidermal keratinocytes is enhanced by IFNgamma and TNFalpha through different pathways. J. Invest. Dermatol. 108:6267.
98. Thornton, B. P.,, V. Vetvicka,, and G. D. Ross. 1994. Natural antibody and complement-mediated antigen processing and presentation by B lymphocytes. J. Immunol. 152:17271737.
99. Thornton, B. P.,, V. Vetvicka,, and G. D. Ross. 1996. Function of C3 in a humoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells. Clin. Exp. Immunol. 104:531537.
100. van den Berg, R. H.,, M. C. Faber-Krol,, J. A. van de Klundert,, L.A. van Es,, and M. R. Daha. 1996. Inhibition of the hemolytic activity of the first component of complement C1 by an Escherichia coli C1q binding protein. J. Immunol. 156:44664473.
101. Varsano, S.,, M. Kaminsky,, M. Kaiser,, and L. Rashkovsky. 2000. Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line. Thorax 55:364369.
102. Verschoor, A.,, M. A. Brockman,, D. M. Knipe,, and M. C. Carroll. 2001. Cutting edge: myeloid complement C3 enhances the humoral response to peripheral viral infection. J. Immunol. 167:24462451.
103. von Andrian, U. H.,, and C. R. Mackay. 2000. T-cell function and migration.Two sides of the same coin. N. Engl. J. Med. 343:10201034.
104. Walport, M. J. 2001a. Complement. First of two parts. N. Engl. J. Med. 344:10581066.
105. Walport, M. J. 2001b. Complement. Second of two parts. N. Engl. J. Med. 344:11401144.
106. Walport, M. J. 2002. Complement and systemic lupus erythematosus. Arthritis Res. 4(Suppl. 3):S279S293.
107. Wilson, J. G.,, T. F. Tedder,, and D.T. Fearon. 1983. Characterization of human T lymphocytes that express the C3b receptor. J. Immunol. 131:684689.
108. Zalman, L. S.,, L. M. Wood,, and H. J. Muller- Eberhard. 1986. Isolation of a human erythrocyte membrane protein capable of inhibiting expression of homologous complement transmembrane channels. Proc. Natl. Acad. Sci. USA 83:69756979.
109. Zhang, L.,, K. Jacobsson,, J. Vasi,, M. Lindberg,, and L. Frykberg. 1998. A second IgG-binding protein in Staphylococcus aureus. Microbiology 144(Pt. 4):985991.
110. Ziccardi, R. J.,, and N. R. Cooper. 1977.The subunit composition and sedimentation properties of human C1. J. Immunol. 118:20472052.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error