250:. C1-inhibitor defiency can be hereditary or acquired, resulting in hereditary or acquired angioedema. C1-inhibitor plays the role of inactivating C1r and C1s to prevent further downstream classical complement activity. C1-inhibitor controls the processes involved in maintaining vascular permeability. As a result, C1-inhibitor levels of less than 50% of the standard lead to increased vascular permeability, characteristic of angioedema. Cinryze, a human plasma derived C1-esterase inhibitor, has been approved for use in 2008 for the prevention of hereditary angioedema attacks.
107:
20:
261:. Among the many functions of C1q, C1q triggers clearance of immune complexes and apoptotic cells by activating the classical pathway and binding directly onto phagocytes. Consequently, systemic lupus erythematosus from insufficient amounts of C1q is characterized by the accumulation of autoantibodies and apoptotic cells. Studies are being done to look into antibodies against C1q as a diagnostic marker for systemic lupus erythematosus.
203:
C3b binds to the C3 convertase (C4b2b), to form C5 convertase (C4b2b3b). C5 convertase then cleaves C5 into C5a and C5b. Like C3a, C5a is also an anaphylatoxin that interacts with its cognate C5a receptor (C5aR) to attract leukocytes. Subsequent interactions between C5b and other terminal components
168:
The newly formed C4b cannot stay activated as a highly reactive thioester bond is revealed once C4 has been cleaved. The thioester bond is cleaved by water resulting in its cleavage permanently deactivating the C4b molecule. As a result of this C4b is restricted to only bind to pathogen surfaces.
186:
C3b can act as an opsonin. C3b is very similar to C4 in both structure and function also has a thioester bond that forces it to attach to surface nucleophile of the activator(namely the pathogen or IC). Phagocytes have receptors for C3b and as a result of receptor-ligand binding are able to more
177:
Surface-bound C4b acts as a receptor for the binding of C2. The binding of C2 and C4b results in C2 being cleaved by C1s into C2a and C2b. C2b diffuses into the plasma as a protein inflammatory mediator while C2a remains attached with C4b, forming the C3-convertase (C4b2a). The function of the
138:
region of antibody isotypes IgG or IgM. These globular regions of C1q can also bind to bacterial and viral surface proteins, apoptotic cells, and acute phase proteins. In the absence of these activation factors, C1q is part of the inactive C1 complex which consists of six molecules of C1q, two
224:
Immunotherapies have been developed to detect and destroy cells infected by the HIV virus via classical complement activation. This process involves creating synthetic peptides that target conserved regions in HIV specific proteins and induce an antibody specific immune response through IgG
234:
these IgM were found to be critical in complement activation through the classical pathway and subsequent destruction of the bacteria. Therapies that utilize classical complement activation have been shown to be effective in targeting and killing cancer cells and destroying tumors.
82:
protein. The cleaved products attract phagocytes to the site of infection and tags target cells for elimination by phagocytosis. In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane attack complex
212:
Because of its role in the innate immune system classical complement has been implicated in a number of pathogen related disorders. Complement is responsible for immune inflammatory response in adipose tissues which has been implicated in the development of
239:, a small peptide, has been shown to exhibit these effects. When injected into target tissue encourages recruitment of C1q and activates downstream events, eventually leading to the formation of the C5b-9 complex which damages tumor cells, killing them.
155:
The binding of C1q with pathogen surface or antigen-antibody immune complex leads to conformational changes and the activation of the serine protease C1r. The activated C1r then cleaves and activates the serine protease C1s. Activated C1s cleaves
225:
antibodies. This is important for targeting the virus in its intracellular phase because the antibodies specific to the synthetic peptides can trigger the classical complement pathway and induce the death of HIV infected cells.
169:
They would undergo rapid deactivation in the time it took to travel from the origin of activation where C1q is complexed with an antigen-antibody immune complex(IC) or where C1q is directly attached to the pathogens surface.
722:
An, Jingang; Li, Zhengxiao; Dong, Yingying; Wu, Jiawen; Ren, Jianwen (2015-05-22). "Complement activation contributes to the anti-methicillin-resistant
Staphylococcus aureus effect of natural anti-keratin antibody".
628:
Zhang, Jinhui; Wright, Wendy; Bernlohr, David A.; Cushman, Samuel W.; Chen, Xiaoli (2007-05-01). "Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance".
217:. Obesity in turn results in an abnormally high level of complement activation via production of the C1 component of the classical pathway, which can lead to tissue inflammation and eventually
228:
Classical complement activation has also been shown to combat
Methicillin-resistant Staphylococcus aureus. Certain variants of the IgM antibody were found to bind the Methicillin-resistant
114:
The classical pathway is distinct from the other complement pathways in its unique activation triggers and cascade sequence. Activation of the complement pathway through the classical,
812:
Cugno, Massimo; Zanichelli, Andrea; Foieni, Fabrizio; Caccia, Sonia; Cicardi, Marco (2009). "C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress".
955:
1016:
Taylor, Philip R.; Carugati, Anna; Fadok, Valerie A.; Cook, H. Terence; Andrews, Mark; Carroll, Michael C.; Savill, John S.; Henson, Peter M.; Botto, Marina (2000-08-07).
673:"Synthetic immunotherapy induces HIV virus specific Th1 cytotoxic response and death of an HIV-1 infected human cell line through classic complement activation"
178:
membrane-bound C3-convertase is the cleavage of many many molecules of C3 into C3a and C3b. C3a is a smaller fragment of C3 is a potent inflammatory mediator.
513:
Ahearn, Joseph M.; Fearon, Douglas T. (1989-01-01). "Structure and
Function of the Complement Receptors, CR1 (CD35) and CR2 (CD21)". In Dixon, Frank J. (ed.).
1209:
758:
Chen, Jinguo; Xu, Xue-Ming; Underhill, Charles B.; Yang, Shanmin; Wang, Luping; Chen, Yixin; Hong, Shuigen; Creswell, Karen; Zhang, Lurong (2005-06-01).
1075:"Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis"
1650:
981:
Stegert, Mihaela; Bock, Merete; Trendelenburg, Marten (2015). "Clinical presentation of human C1q deficiency: How much of a lupus?".
204:
C6, C7, C8, and C9 form the membrane attack complex or the C5b-9 complex which forms pores on the target cell membranes to lysing.
1202:
906:"Cinryze as the first approved C1 inhibitor in the USA for the treatment of hereditary angioedema: approval, efficacy and safety"
63:
364:
Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit (February 2017). "Complement in autoimmune diseases".
1864:
1195:
574:
Rus, Horea; Cudrici, Cornelia; Niculescu, Florin (2005-11-01). "The role of the complement system in innate immunity".
84:
530:
1541:
464:
Thielens, Nicole M.; Tedesco, Francesco; Bohlson, Suzanne S.; Gaboriaud, Christine; Tenner, Andrea J. (June 2017).
1643:
1683:
1536:
270:
135:
119:
110:
The classical complement pathway leading into a complement cascade that is shared with the alternative pathway.
1479:
87:). The membrane attack complex creates a pore on the target cell's membrane, inducing cell lysis and death.
1018:"A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo"
960:
258:
2065:
1636:
1365:
1073:
Chi, Shuhong; Yu, Yunxia; Shi, Juan; Zhang, Yurong; Yang, Jijuan; Yang, Lijuan; Liu, Xiaoming (2015).
130:
The classical complement pathway can be initiated by the binding of antigen-antibody complexes to the
1919:
1187:
40:
1999:
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1834:
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1719:
1714:
1545:
1303:
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131:
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1285:
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79:
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1971:
1966:
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1514:
1370:
1348:
230:
1981:
1976:
1531:
1464:
1375:
1299:
195:(C3aR) to recruit leukocytes, C3b contributes to further downstream complement activation.
8:
1958:
1938:
1928:
1777:
1591:
1526:
1509:
1343:
1261:
122:
is followed by a cascade of reactions eventually leading to the membrane attack complex.
95:
849:"Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica"
1411:
1168:
1133:
1109:
1074:
1050:
1017:
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994:
864:
825:
671:
Pleguezuelos, Olga; Stoloff, Gregory A; CaparrĂłs-Wanderley, Wilson (2013-04-04).
481:
242:
Lack of regulation of the classical complement pathway through the deficiency in
1678:
1501:
1446:
1387:
1307:
1280:
736:
641:
558:
275:
115:
587:
377:
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59:
36:
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2009:
2004:
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1002:
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833:
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708:
657:
603:
499:
443:
385:
343:
243:
192:
1091:
1033:
760:"Tachyplesin Activates the Classic Complement Pathway to Kill Tumor Cells"
540:
23:
Classical and alternative pathways shown with their corresponding proteins
236:
1884:
1709:
1559:
1312:
1218:
257:
protein of the classical complement pathway can lead to development of
247:
74:
component of the cleaved C3 binds to C3 convertase (C4b2b) to generate
922:
19:
1787:
1617:
1322:
1217:
670:
106:
91:
1628:
1132:
Mahler, Michael; van
Schaarenburg, Rosanne; Trouw, Leendert (2013).
956:"Approval History, Letters, Reviews and Related Documents - CINRYZE"
557:
Janeway, Ca Jr (2001). "The complement system and innate immunity".
1948:
1782:
1607:
1392:
1380:
1338:
1292:
1256:
410:"The complement system: History, pathways, cascade and inhibitors"
1612:
1426:
1275:
1246:
1134:"Anti-C1q Autoantibodies, Novel Tests, and Clinical Consequences"
214:
55:
221:, however the exact mechanisms that causes this is yet unknown.
1584:
1572:
1317:
1268:
463:
134:
protein. The globular regions of C1q recognize and bind to the
1990:
187:
easily recognize and engulf pathogen molecules. While the
630:
American
Journal of Physiology. Endocrinology and Metabolism
1994:
1923:
1817:
1131:
811:
627:
90:
The classical complement pathway can also be activated by
1813:
1741:
1736:
408:
Nesargikar, Prabhu; Spiller, B.; Chavez, R. (June 2012).
144:
140:
71:
980:
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363:
359:
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560:
Immunobiology: The Immune System in Health and
Disease
288:
198:
403:
401:
399:
397:
395:
350:
757:
725:
573:
39:. The classical complement pathway is initiated by
853:Neurology: Neuroimmunology & Neuroinflammation
310:"Overview of Complement Activation and Regulation"
308:Noris, Marina; Remuzzi, Giuseppe (November 2013).
414:European Journal of Microbiology & Immunology
392:
2057:
847:Levy, Michael; Mealy, Maureen A. (2014-06-01).
181:
172:
150:
1644:
1203:
1072:
807:
805:
803:
512:
307:
31:is one of three pathways which activate the
1651:
1637:
1210:
1196:
721:
567:
563:(5th ed.). New York: Garland Science.
1167:
1149:
1108:
1090:
1049:
931:
921:
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846:
800:
775:
698:
688:
489:
433:
333:
466:"C1q: A fresh look upon an old molecule"
207:
105:
18:
556:
2058:
1658:
1632:
1191:
459:
457:
455:
453:
101:
1022:The Journal of Experimental Medicine
903:
623:
621:
552:
550:
163:
66:referred C4b2a), which cleaves the
13:
517:. Vol. 46. pp. 183–219.
450:
199:Formation of C5 convertase and MAC
54:Following activation, a series of
14:
2077:
618:
547:
515:Advances in Immunology Volume 46
326:10.1016/j.semnephrol.2013.08.001
1125:
1066:
1009:
974:
948:
897:
840:
751:
715:
1537:Immunoglobulin class switching
664:
506:
271:Alternative complement pathway
120:alternative complement pathway
1:
777:10.1158/0008-5472.CAN-04-2253
523:10.1016/s0065-2776(08)60654-9
281:
125:
78:(C4b2b3b), which cleaves the
995:10.1016/j.molimm.2015.03.007
961:Food and Drug Administration
904:Lunn, Michael (2010-08-24).
865:10.1212/nxi.0000000000000005
826:10.1016/j.molmed.2008.12.001
814:Trends in Molecular Medicine
482:10.1016/j.molimm.2017.05.025
259:systemic lupus erythematosus
29:classical complement pathway
7:
264:
182:C3b function and structure.
173:Formation of C3-convertase.
151:Formation of C4b convertase
94:cells, necrotic cells, and
43:with the antibody isotypes
16:Aspect of the immune system
10:
2082:
1366:Polyclonal B cell response
737:10.1016/j.bbrc.2015.03.182
642:10.1152/ajpendo.00664.2006
58:are recruited to generate
41:antigen-antibody complexes
2020:
1957:
1920:Decay-accelerating factor
1904:
1857:
1796:
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1692:
1666:
1600:
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1500:
1401:
1331:
1239:
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910:Journal of Blood Medicine
378:10.1016/j.cca.2016.12.017
1151:10.3389/fimmu.2013.00117
690:10.1186/1743-422x-10-107
426:10.1556/EuJMI.2.2012.2.2
1138:Frontiers in Immunology
191:C3a interacts with its
143:, and two molecules of
35:, which is part of the
1480:Tolerance in pregnancy
1222:adaptive immune system
314:Seminars in Nephrology
111:
24:
1515:Somatic hypermutation
1349:Polyclonal antibodies
1344:Monoclonal antibodies
1034:10.1084/jem.192.3.359
231:Staphylococcus aureus
208:Clinical significance
109:
22:
1959:Complement receptors
1532:Junctional diversity
1300:Antigen presentation
983:Molecular Immunology
576:Immunologic Research
470:Molecular Immunology
366:Clinica Chimica Acta
246:results in episodic
96:acute phase proteins
1527:V(D)J recombination
1510:Affinity maturation
1262:Antigenic variation
1092:10.1155/2015/450351
588:10.1385/IR:33:2:103
160:into C4a and C4b.
1788:Factor P/Properdin
1693:Activators/enzymes
636:(5): E1433–E1440.
253:Deficiency in the
219:insulin resistance
112:
102:Complement cascade
25:
2066:Complement system
2053:
2052:
1900:
1899:
1660:Complement system
1626:
1625:
1554:
1553:
1304:professional APCs
923:10.2147/jbm.s9576
770:(11): 4614–4622.
164:Regulation of C4b
33:complement system
2073:
2034:immune adherence
1697:
1696:
1653:
1646:
1639:
1630:
1629:
1520:Clonal selection
1492:Immune privilege
1487:Immunodeficiency
1442:Cross-reactivity
1432:Hypersensitivity
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677:Virology Journal
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1953:
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1853:
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1657:
1627:
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1596:
1550:
1496:
1475:Clonal deletion
1403:
1397:
1327:
1228:
1216:
1186:
1185:
1130:
1126:
1079:Disease Markers
1071:
1067:
1014:
1010:
979:
975:
966:
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902:
898:
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764:Cancer Research
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128:
104:
17:
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2018:
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2015:
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2013:
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2007:
1997:
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1502:Immunogenetics
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1447:Co-stimulation
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1429:
1424:
1419:
1414:
1407:
1405:
1399:
1398:
1396:
1395:
1390:
1388:Immune complex
1384:
1383:
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1373:
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1356:
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1335:
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1308:Dendritic cell
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1286:Conformational
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1234:
1230:
1229:
1215:
1214:
1207:
1200:
1192:
1184:
1183:
1124:
1065:
1028:(3): 359–366.
1008:
973:
947:
896:
839:
799:
750:
731:(1): 142–147.
714:
663:
617:
582:(2): 103–112.
566:
546:
531:
505:
449:
420:(2): 103–111.
391:
349:
320:(6): 479–492.
286:
285:
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276:Lectin pathway
273:
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9:
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2019:
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2000:Anaphylatoxin
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1866:
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1860:
1856:
1850:
1849:C5-convertase
1847:
1845:
1844:C3-convertase
1842:
1841:
1836:
1833:
1831:
1828:
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1359:Microantibody
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189:anaphylatoxin
179:
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139:molecules of
137:
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123:
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99:
97:
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81:
77:
76:C5 convertase
73:
70:protein. The
69:
65:
61:
60:C3 convertase
57:
52:
50:
46:
42:
38:
37:immune system
34:
30:
21:
2045:Opsonization
2040:inflammation
2028:Cytotoxicity
1945:
1935:
1915:C1-inhibitor
1911:
1774:
1755:
1706:
1673:
1437:Inflammation
1422:Alloimmunity
1417:Autoimmunity
1402:Immunity vs.
1354:Autoantibody
1252:Superantigen
1141:
1137:
1127:
1082:
1078:
1068:
1025:
1021:
1011:
986:
982:
976:
965:. Retrieved
959:
950:
913:
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899:
856:
852:
842:
820:(2): 69–78.
817:
813:
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728:
724:
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680:
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666:
633:
629:
579:
575:
569:
559:
514:
508:
473:
469:
417:
413:
369:
365:
317:
313:
252:
244:C1-inhibitor
241:
229:
227:
223:
211:
202:
193:C3a receptor
185:
176:
167:
154:
129:
113:
89:
64:historically
53:
28:
26:
1560:Lymphocytes
1219:Lymphocytic
989:(1): 3–11.
372:: 123–130.
237:Tachyplesin
1905:Inhibitors
1601:Substances
1465:Peripheral
1453:Inaction:
1332:Antibodies
1313:Macrophage
1226:complement
1085:: 450351.
967:2015-01-21
916:: 163–70.
683:(1): 107.
282:References
248:angioedema
126:Initiation
2038:Inducing
1618:Cytolysin
1608:Cytokines
1455:Tolerance
1404:tolerance
1323:Immunogen
1160:1664-3224
1101:0278-0240
1042:0022-1007
873:2332-7812
859:(1): e5.
786:0008-5472
650:0193-1849
596:0257-277X
476:: 73–83.
92:apoptotic
2060:Category
2030:(by MAC)
2021:Function
1949:Factor H
1929:Factor I
1783:Factor D
1778:Factor B
1667:Pathways
1568:Cellular
1412:Immunity
1410:Action:
1393:Paratope
1381:Idiotype
1371:Allotype
1339:Antibody
1293:Mimotope
1257:Allergen
1240:Antigens
1233:Lymphoid
1178:23717311
1119:26549923
1060:10934224
1003:25846716
942:22282695
891:25340061
834:19162547
794:15930279
745:25862372
709:23557359
658:17244723
612:46096567
604:16234578
500:28601358
444:24672678
386:28040558
344:24161035
265:See also
62:(C4b2b,
56:proteins
1613:Opsonin
1592:NK cell
1580:Humoral
1460:Central
1427:Allergy
1376:Isotype
1276:Epitope
1247:Antigen
1169:3653116
1144:: 117.
1110:4621353
1051:2193213
933:3262319
882:4202676
700:3626621
541:2551147
491:5582005
435:3956958
335:3820029
215:obesity
1797:Middle
1585:B cell
1573:T cell
1318:B cell
1281:Linear
1269:Hapten
1176:
1166:
1158:
1117:
1107:
1099:
1058:
1048:
1040:
1001:
940:
930:
889:
879:
871:
832:
792:
784:
743:
707:
697:
656:
648:
610:
602:
594:
539:
529:
498:
488:
442:
432:
384:
342:
332:
116:lectin
1991:CD11c
1987:CD11b
1763:MASP2
1759:MASP1
1700:Early
608:S2CID
1995:CD18
1939:C4BP
1924:CD59
1912:CLA:
1858:Late
1818:iC3b
1224:and
1174:PMID
1156:ISSN
1115:PMID
1097:ISSN
1083:2015
1056:PMID
1038:ISSN
999:PMID
938:PMID
887:PMID
869:ISSN
830:PMID
790:PMID
782:ISSN
741:PMID
705:PMID
654:PMID
646:ISSN
600:PMID
592:ISSN
537:PMID
527:ISBN
496:PMID
440:PMID
382:PMID
340:PMID
47:and
27:The
2010:C5a
2005:C3a
1982:CR4
1977:CR3
1972:CR2
1967:CR1
1936:CL:
1870:C5b
1865:MAC
1835:C5b
1830:C5a
1814:C3b
1809:C3a
1768:MBL
1742:C4b
1737:C4a
1725:C1s
1720:C1r
1715:C1q
1546:HLA
1542:MHC
1164:PMC
1146:doi
1105:PMC
1087:doi
1046:PMC
1030:doi
1026:192
991:doi
928:PMC
918:doi
877:PMC
861:doi
822:doi
772:doi
733:doi
729:461
695:PMC
685:doi
638:doi
634:292
584:doi
519:doi
486:PMC
478:doi
430:PMC
422:doi
374:doi
370:465
330:PMC
322:doi
255:C1q
145:C1s
141:C1r
132:C1q
118:or
85:MAC
72:C3b
49:IgM
45:IgG
2062::
1946:A:
1890:C9
1885:C8
1880:C7
1875:C6
1825:C5
1804:C3
1775:A:
1756:L:
1749:C2
1732:C4
1710:C1
1707:C:
1306::
1172:.
1162:.
1154:.
1140:.
1136:.
1113:.
1103:.
1095:.
1081:.
1077:.
1054:.
1044:.
1036:.
1024:.
1020:.
997:.
987:67
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958:.
936:.
926:.
912:.
908:.
885:.
875:.
867:.
855:.
851:.
828:.
818:15
816:.
802:^
788:.
780:.
768:65
766:.
762:.
739:.
727:.
703:.
693:.
681:10
679:.
675:.
652:.
644:.
632:.
620:^
606:.
598:.
590:.
580:33
578:.
549:^
535:.
525:.
494:.
484:.
474:89
472:.
468:.
452:^
438:.
428:.
416:.
412:.
394:^
380:.
368:.
352:^
338:.
328:.
318:33
316:.
312:.
290:^
158:C4
147:.
136:Fc
98:.
80:C5
68:C3
51:.
1993:/
1989:/
1922:/
1816:/
1761:/
1684:A
1679:L
1674:C
1652:e
1645:t
1638:v
1544:/
1302:/
1211:e
1204:t
1197:v
1180:.
1148::
1142:4
1121:.
1089::
1062:.
1032::
1005:.
993::
970:.
944:.
920::
914:1
893:.
863::
857:1
836:.
824::
796:.
774::
747:.
735::
711:.
687::
660:.
640::
614:.
586::
543:.
521::
502:.
480::
446:.
424::
418:2
388:.
376::
346:.
324::
83:(
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