204:. Immune complexes are better at inducing DC maturation than an antigen on its own. Again, the low affinity of many FcγR for IgG means that only immune complexes, not single antibodies, can induce the FcγR’s signaling cascade. When compared to single antibodies binding to FcγRs, immune complexes binding to FcγRs cause significant changes in internalization and processing of antigen, maturation of the vesicles containing the internalized antigen, and activation in DCs and macrophages. There are multiple classes of macrophages and DCs that express different FcγRs, which have differing affinities for single antibodies and immune complexes. This allows the response of the DC or macrophage to be tuned precisely, subsequently tuning the level of IgG. These diverse FcγRs cause different responses in their DCs or macrophages by initiating different signaling pathways that can either activate or inhibit cellular functions. The binding of the immune complex to the DC’s membrane-bound receptor and internalization of the immune complex and receptor begins the process of antigen presentation, which allows the DC to activate T cells. Via this process, immune complexes cause enhanced T cell activation.
218:
Immunoreceptor
Tyrosine-Based Activation Motif (ITAM) signaling pathway. ITAM is composed of tyrosine which is separated from a leucine or isoleucine by two other amino acids and is located in the cytoplasmic tail of the molecule. Following the clustering by IgG complexes, ITAM is phosphorylated by FcγRs crosslinking. This
212:
Type I FcγRs activation begins a cascade of reactions to eliminate the IgG-opsonized target. Type I FcγRs is another type of IgG constant region receptor, which can bind to IgG immune complexes and lead to the elimination of the opsonized complex. Immune complexes bind to multiple type I FcγRs, which
217:
signaling pathway. Although both activating and inhibitory Type I FcγRs can mediate phagocytosis, but the internalization of IgG-opsonized targets through activating FcγRs is more effective for response. Immune complexes bind to multiple type I FcγRs, which cluster on the cell surface and begin the
104:
cells have low affinity for a singular antibody, and instead need to bind to an immune complex containing multiple antibodies in order to begin their intracellular signaling pathway and pass along a message from outside to inside of the cell. Additionally, the grouping and binding together of
20:
105:
multiple immune complexes allows for an increase in the avidity, or strength of binding, of the FcRs. This allows innate immune cells to get multiple inputs at once and prevents them from being activated early.
529:
Kang, SunAh; Rogers, Jennifer L.; Monteith, Andrew J.; Jiang, Chuancang; Schmitz, John; Clarke, Stephen H.; Tarrant, Teresa K.; Truong, Young K.; Diaz, Marilyn; Fedoriw, Yuri; Vilen, Barbara J. (2016-05-15).
222:
of the ITAM leads to pro-inflammatory signaling that mediates cellular activation which will induce a signaling cascade and eventually leads to elimination of opsonized immune complex.
877:
702:
Guilliams, Martin; Bruhns, Pierre; Saeys, Yvan; Hammad, Hamida; Lambrecht, Bart N. (February 2014). "The function of Fcγ receptors in dendritic cells and macrophages".
96:
The ratio of antigen to antibody determines size and shape of immune complex. This, in turn, determines the effect of the immune complex. Many innate immune cells have
214:
870:
462:
Monteith, Andrew J.; Kang, SunAh; Scott, Eric; Hillman, Kai; Rajfur, Zenon; Jacobson, Ken; Costello, M. Joseph; Vilen, Barbara J. (2016-04-12).
196:
Immune complexes, particularly those made of IgG, also play a variety of roles in the activation and regulation of phagocytes, which include
164:(BCRs) on their surfaces and antigen binding to these receptors begins a signaling cascade that leads to activation. B cells also express
863:
446:
372:
281:
248:
1209:
1204:
532:"Apoptotic Debris Accumulates on Hematopoietic Cells and Promotes Disease in Murine and Human Systemic Lupus Erythematosus"
184:
and cease to express BCR but continue to express FcγRIIb, which allows IgG immune complexes to regulate IgG production via
1147:
140:
57:. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including
1033:
108:
Immune complexes may themselves cause illness when they are deposited in organs, for example, in certain forms of
117:
132:
464:"Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus"
1213:
971:
648:"Fcγ receptors and toll-like receptor 9 synergize to drive immune complex-induced dendritic cell maturation"
53:. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific
23:
1311:
1235:
953:
889:
1182:
1038:
1016:
78:
1199:
1132:
1043:
967:
475:
124:
101:
855:
1306:
1259:
1194:
1177:
1011:
929:
802:
Bournazos, Stylianos; Wang, Taia T.; Dahan, Rony; Maamary, Jad; Ravetch, Jeffrey V. (2017-04-26).
646:
Nelson, Nicole L.J.; Zajd, Cheryl M.; Lennartz, Michelle R.; Gosselin, Edmund J. (November 2019).
589:
Bournazos, Stylianos; Wang, Taia T.; Dahan, Rony; Maamary, Jad; Ravetch, Jeffrey V. (2017-04-26).
1079:
735:
419:
100:, which are membrane-bound receptors that bind the constant regions of antibodies. Most FcRs on
1127:
893:
841:
823:
784:
727:
719:
677:
628:
610:
571:
553:
511:
493:
442:
411:
368:
345:
327:
277:
244:
185:
58:
1247:
1187:
1159:
1154:
1122:
1109:
1099:
831:
815:
774:
766:
711:
667:
659:
618:
602:
561:
543:
501:
483:
401:
335:
319:
169:
120:. Such hypersensitivity progressing to disease states produces the immune complex diseases.
113:
123:
Immune complex deposition is a prominent feature of several autoimmune diseases, including
1142:
819:
606:
273:
266:
219:
161:
479:
1169:
1114:
975:
948:
836:
803:
779:
754:
672:
647:
623:
590:
566:
531:
506:
463:
340:
307:
197:
74:
1300:
1137:
1026:
739:
423:
168:, low affinity receptors specific to the constant region of IgG, on their surfaces.
139:
and subsequent accumulation on the surface of immune cells has been associated with
1104:
1089:
1084:
1021:
919:
389:
66:
62:
663:
406:
303:
181:
156:
Immune complexes can also play a role in the regulation of antibody production.
128:
97:
1227:
980:
886:
755:"Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling"
201:
165:
109:
827:
723:
614:
557:
548:
497:
331:
1285:
990:
488:
177:
86:
845:
788:
731:
681:
632:
575:
515:
349:
176:
for these receptors and immune complex binding to these receptors induces
1275:
1060:
1048:
1006:
960:
924:
415:
323:
136:
70:
50:
42:
1280:
1094:
943:
914:
54:
46:
770:
180:, or cell death. After B cells are activated, they differentiate into
1252:
1240:
985:
936:
390:"Demonstration of Circulating Immune Complexes in Sjögren's Syndrome"
173:
157:
90:
715:
308:"Beyond binding: antibody effector functions in infectious diseases"
19:
18:
859:
82:
400:(3). The American Association of Immunologists: 1382–7.
302:
Lu, Lenette L.; Suscovich, Todd J.; Fortune, Sarah M.;
239:
Cush, John; Kavanaugh, Arthur; Stein, Charles (2005).
1268:
1226:
1168:
1069:
999:
907:
900:
265:
135:. An inability to degrade immune complexes in the
388:Lawley, Thomas; Moustopoulos, Haralampos (1979).
243:. Lippincott Williams & Wilkins. p. 78.
367:(2 ed.). St.Louis: The C.V. Mosby Company.
468:Proceedings of the National Academy of Sciences
85:-coated immune complexes and transport them to
16:Molecule formed binding antigens to antibodies
871:
192:Activation of dendritic cells and macrophages
8:
365:Basic Immunology and its Medical Application
904:
878:
864:
856:
804:"Signaling by Antibodies: Recent Progress"
591:"Signaling by Antibodies: Recent Progress"
213:cluster on the cell surface and begin the
116:in the Gell-Coombs classification, called
835:
778:
671:
622:
565:
547:
505:
487:
405:
339:
208:Elimination of opsonized immune complexes
188:and prevent uncontrolled IgG production.
93:, and return to the general circulation.
241:Rheumatology: Diagnosis and Therapeutics
441:. Oxford University Press. p. 68.
231:
820:10.1146/annurev-immunol-051116-052433
697:
695:
693:
691:
607:10.1146/annurev-immunol-051116-052433
81:-receptors on their surface may bind
7:
297:
295:
293:
45:formed from the binding of multiple
439:The New Sjogren's Syndrome Handbook
14:
152:Regulation of antibody production
1205:Immunoglobulin class switching
1:
664:10.1016/j.cellimm.2019.103962
437:Wallace, Daniel, ed. (2004).
141:systemic lupus erythematosus
112:. This is the third form of
808:Annual Review of Immunology
595:Annual Review of Immunology
407:10.4049/jimmunol.123.3.1382
1328:
1034:Polyclonal B cell response
704:Nature Reviews Immunology
536:The Journal of Immunology
312:Nature Reviews Immunology
264:Goldsby, Richard (2002).
172:immune complexes are the
118:type III hypersensitivity
549:10.4049/jimmunol.1500418
35:antigen-antibody complex
489:10.1073/pnas.1513943113
24:Immune complex diseases
1148:Tolerance in pregnancy
890:adaptive immune system
363:Barret, James (1980).
89:, mostly in liver and
39:antigen-bound antibody
33:, sometimes called an
26:
1183:Somatic hypermutation
1017:Polyclonal antibodies
1012:Monoclonal antibodies
759:Immunological Reviews
394:Journal of Immunology
272:. Macmillan. p.
22:
1200:Junctional diversity
968:Antigen presentation
324:10.1038/nri.2017.106
125:rheumatoid arthritis
1195:V(D)J recombination
1178:Affinity maturation
930:Antigenic variation
753:Getahun, A (2015).
652:Cellular Immunology
480:2016PNAS..113E2142M
474:(15): E2142–E2151.
69:, or processing by
133:Sjögren's syndrome
27:
1294:
1293:
1222:
1221:
972:professional APCs
771:10.1111/imr.12336
542:(10): 4030–4039.
186:negative feedback
1319:
1188:Clonal selection
1160:Immune privilege
1155:Immunodeficiency
1110:Cross-reactivity
1100:Hypersensitivity
905:
880:
873:
866:
857:
850:
849:
839:
799:
793:
792:
782:
750:
744:
743:
699:
686:
685:
675:
643:
637:
636:
626:
586:
580:
579:
569:
551:
526:
520:
519:
509:
491:
459:
453:
452:
434:
428:
427:
409:
385:
379:
378:
360:
354:
353:
343:
306:(January 2018).
299:
288:
287:
271:
261:
255:
254:
236:
162:B-cell receptors
114:hypersensitivity
1327:
1326:
1322:
1321:
1320:
1318:
1317:
1316:
1297:
1296:
1295:
1290:
1264:
1218:
1164:
1143:Clonal deletion
1071:
1065:
995:
896:
884:
854:
853:
801:
800:
796:
752:
751:
747:
716:10.1038/nri3582
701:
700:
689:
645:
644:
640:
588:
587:
583:
528:
527:
523:
461:
460:
456:
449:
436:
435:
431:
387:
386:
382:
375:
362:
361:
357:
301:
300:
291:
284:
263:
262:
258:
251:
238:
237:
233:
228:
220:phosphorylation
210:
198:dendritic cells
194:
154:
149:
75:Red blood cells
17:
12:
11:
5:
1325:
1323:
1315:
1314:
1309:
1299:
1298:
1292:
1291:
1289:
1288:
1283:
1278:
1272:
1270:
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1265:
1263:
1262:
1257:
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1245:
1244:
1243:
1232:
1230:
1224:
1223:
1220:
1219:
1217:
1216:
1207:
1202:
1197:
1192:
1191:
1190:
1185:
1174:
1172:
1170:Immunogenetics
1166:
1165:
1163:
1162:
1157:
1152:
1151:
1150:
1145:
1140:
1135:
1130:
1118:
1117:
1115:Co-stimulation
1112:
1107:
1102:
1097:
1092:
1087:
1082:
1075:
1073:
1067:
1066:
1064:
1063:
1058:
1056:Immune complex
1052:
1051:
1046:
1041:
1036:
1031:
1030:
1029:
1024:
1019:
1014:
1003:
1001:
997:
996:
994:
993:
988:
983:
978:
976:Dendritic cell
964:
963:
958:
957:
956:
954:Conformational
951:
940:
939:
934:
933:
932:
927:
922:
911:
909:
902:
898:
897:
885:
883:
882:
875:
868:
860:
852:
851:
814:(1): 285–311.
794:
745:
687:
638:
601:(1): 285–311.
581:
521:
454:
447:
429:
380:
373:
355:
289:
282:
256:
249:
230:
229:
227:
224:
209:
206:
193:
190:
153:
150:
148:
145:
31:immune complex
15:
13:
10:
9:
6:
4:
3:
2:
1324:
1313:
1312:Immune system
1310:
1308:
1305:
1304:
1302:
1287:
1284:
1282:
1279:
1277:
1274:
1273:
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1234:
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1211:
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1201:
1198:
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1193:
1189:
1186:
1184:
1181:
1180:
1179:
1176:
1175:
1173:
1171:
1167:
1161:
1158:
1156:
1153:
1149:
1146:
1144:
1141:
1139:
1138:Clonal anergy
1136:
1134:
1131:
1129:
1126:
1125:
1124:
1120:
1119:
1116:
1113:
1111:
1108:
1106:
1103:
1101:
1098:
1096:
1093:
1091:
1088:
1086:
1083:
1081:
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1074:
1068:
1062:
1059:
1057:
1054:
1053:
1050:
1047:
1045:
1042:
1040:
1037:
1035:
1032:
1028:
1027:Microantibody
1025:
1023:
1020:
1018:
1015:
1013:
1010:
1009:
1008:
1005:
1004:
1002:
998:
992:
989:
987:
984:
982:
979:
977:
973:
969:
966:
965:
962:
959:
955:
952:
950:
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946:
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942:
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938:
935:
931:
928:
926:
923:
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917:
916:
913:
912:
910:
906:
903:
899:
895:
891:
888:
881:
876:
874:
869:
867:
862:
861:
858:
847:
843:
838:
833:
829:
825:
821:
817:
813:
809:
805:
798:
795:
790:
786:
781:
776:
772:
768:
764:
760:
756:
749:
746:
741:
737:
733:
729:
725:
721:
717:
713:
710:(2): 94–108.
709:
705:
698:
696:
694:
692:
688:
683:
679:
674:
669:
665:
661:
657:
653:
649:
642:
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634:
630:
625:
620:
616:
612:
608:
604:
600:
596:
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585:
582:
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573:
568:
563:
559:
555:
550:
545:
541:
537:
533:
525:
522:
517:
513:
508:
503:
499:
495:
490:
485:
481:
477:
473:
469:
465:
458:
455:
450:
448:9780198038481
444:
440:
433:
430:
425:
421:
417:
413:
408:
403:
399:
395:
391:
384:
381:
376:
374:0-8016-0495-8
370:
366:
359:
356:
351:
347:
342:
337:
333:
329:
325:
321:
317:
313:
309:
305:
298:
296:
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290:
285:
283:9780716749479
279:
275:
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257:
252:
250:9780781757324
246:
242:
235:
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203:
199:
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159:
151:
146:
144:
142:
138:
134:
130:
126:
121:
119:
115:
111:
106:
103:
102:innate immune
99:
94:
92:
88:
84:
80:
76:
72:
68:
64:
60:
56:
52:
48:
44:
40:
36:
32:
25:
21:
1105:Inflammation
1090:Alloimmunity
1085:Autoimmunity
1070:Immunity vs.
1055:
1022:Autoantibody
920:Superantigen
811:
807:
797:
765:(1): 66–73.
762:
758:
748:
707:
703:
655:
651:
641:
598:
594:
584:
539:
535:
524:
471:
467:
457:
438:
432:
397:
393:
383:
364:
358:
318:(1): 46–61.
315:
311:
304:Alter, Galit
267:
259:
240:
234:
211:
195:
182:plasma cells
155:
122:
107:
95:
67:phagocytosis
63:opsonization
61:deposition,
38:
34:
30:
28:
1228:Lymphocytes
887:Lymphocytic
202:macrophages
129:scleroderma
1307:Immunology
1301:Categories
1269:Substances
1133:Peripheral
1121:Inaction:
1000:Antibodies
981:Macrophage
894:complement
658:: 103962.
268:Immunology
226:References
200:(DCs) and
110:vasculitis
87:phagocytes
59:complement
51:antibodies
1286:Cytolysin
1276:Cytokines
1123:Tolerance
1072:tolerance
991:Immunogen
828:0732-0582
724:1474-1733
615:0732-0582
558:0022-1767
498:0027-8424
332:1474-1733
178:apoptosis
147:Functions
77:carrying
71:proteases
1236:Cellular
1080:Immunity
1078:Action:
1061:Paratope
1049:Idiotype
1039:Allotype
1007:Antibody
961:Mimotope
925:Allergen
908:Antigens
901:Lymphoid
846:28446061
789:26497513
740:11733324
732:24445665
682:31582169
633:28446061
576:27059595
516:27035940
424:31511399
350:29063907
160:express
137:lysosome
47:antigens
43:molecule
1281:Opsonin
1260:NK cell
1248:Humoral
1128:Central
1095:Allergy
1044:Isotype
944:Epitope
915:Antigen
837:5613280
780:4621791
673:6892604
624:5613280
567:4868781
507:4839468
476:Bibcode
341:6369690
166:FcγRIIb
158:B cells
55:epitope
41:, is a
1253:B cell
1241:T cell
986:B cell
949:Linear
937:Hapten
844:
834:
826:
787:
777:
738:
730:
722:
680:
670:
631:
621:
613:
574:
564:
556:
514:
504:
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416:469255
414:
371:
348:
338:
330:
280:
247:
174:ligand
91:spleen
736:S2CID
420:S2CID
892:and
842:PMID
824:ISSN
785:PMID
728:PMID
720:ISSN
678:PMID
629:PMID
611:ISSN
572:PMID
554:ISSN
512:PMID
494:ISSN
443:ISBN
412:PMID
369:ISBN
346:PMID
328:ISSN
278:ISBN
245:ISBN
215:ITAM
131:and
98:FcRs
1214:HLA
1210:MHC
832:PMC
816:doi
775:PMC
767:doi
763:268
712:doi
668:PMC
660:doi
656:345
619:PMC
603:doi
562:PMC
544:doi
540:196
502:PMC
484:doi
472:113
402:doi
398:123
336:PMC
320:doi
274:381
170:IgG
83:C3b
79:CR1
49:to
37:or
29:An
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Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
