Skip to main content

The Immune Response to Transplanted Organs

  • Chapter
  • First Online:
Kidney and Pancreas Transplantation

Part of the book series: Current Clinical Urology ((CCU))

  • 1772 Accesses

Abstract

This chapter discusses the immune response to transplanted solid organs. An overview of the innate immune system and its relationship to the adaptive alloimmune response is provided. Effector mechanisms of the adaptive alloimmune response are discussed. Clinical and pathologic correlates are highlighted in the context of acute and chronic rejection, histocompatibility testing, and immunosuppression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bonventre JV, Zuk A. Ischemic renal failure: an inflammatory disease? Kidney Int 2004;66:480–485.

    Article  PubMed  CAS  Google Scholar 

  2. De Groot H, Rauen U. Ischemia-reperfusion injury: processes in pathogenetic networks. A review. Transplant Proc 2007;39:481–484.

    Article  PubMed  CAS  Google Scholar 

  3. Rabb H, O’Meara YM, Maderna P, Coleman P, Brady HR. Leukocytes, cell adhesion molecules and ischemic acute renal failure. Kidney Int 1997;51:1463–1468.

    Article  PubMed  CAS  Google Scholar 

  4. Koo DD, Welsh KI, Roake JA, Morris PJ, Fuggle SV. Ischemia/reperfusion injury in human kidney transplantation: an immunohistochemical analysis of changes after reperfusion. Am J Pathol 1998;153:557–576.

    Article  PubMed  CAS  Google Scholar 

  5. Land W, Messmer K. The impact of ischemia/reperfusion injury on specific and non-specific, early and late chronic events after organ transplantation. Transplant Rev 1996;10:236–253.

    Article  Google Scholar 

  6. Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 1997;63:968–974.

    Article  PubMed  CAS  Google Scholar 

  7. Terasaki PI, Cecka JM, Gjertson DW, Takemoto S. High survival rates of kidney transplants from spousal and living unrelated donors. NEJM 1995;333:333–336.

    Article  PubMed  CAS  Google Scholar 

  8. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 2006;17:1503–1520.

    Article  PubMed  CAS  Google Scholar 

  9. Linas SL, Whittenburg D, Parsons PE, Repine JE. Ischemia increases neutrophil retention and worsens acute renal failure: role of oxygen metabolites and ICAM-1. Kidney Int 1995;48:1584–1591.

    Article  PubMed  CAS  Google Scholar 

  10. Miura M, Fu X, Zhang Q-W, Remick DG, Fairchild RL. Neutralization of Groα and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury. Am J Pathol 2001;159:2137–2145.

    Article  PubMed  CAS  Google Scholar 

  11. Raab H, Mendiola CC, Saba SR, et al. Antibodies to ICAM-1 protect kidneys in severe ischemic reperfusion injury. Biochem Biophys Res Commun 1995;211:67–73.

    Article  Google Scholar 

  12. Takada M, Nadeau KC, Shaw GD, Marquette KA, Tilney NL. The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. J Clin Invest 1997;99:2682–2690.

    Article  PubMed  CAS  Google Scholar 

  13. Heinzelmann M, Mercer JM, Passmore JC. Neutrophils and renal failure. Am J Kidney Dis 1999;34:384–399.

    Article  PubMed  CAS  Google Scholar 

  14. Welbourn CRB, Goldman G, Paterson IS, Valeri CR, Shepro D, Hechtman HB. Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil. Br J Surg 1991;78:651–655.

    Article  PubMed  CAS  Google Scholar 

  15. Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin-8, a novel cytokine that activates neutrophils. J Clin Invest 1989;84:1045–1049.

    Article  PubMed  CAS  Google Scholar 

  16. Jaeschke H, Smith CW. Mechanisms of neutrophil-induced parenchymal cell injury. J Leuk Biol 1997;61:647–653.

    CAS  Google Scholar 

  17. Colletti LM, Kunkel SL, Walz A, et al. Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein. J Clin Invest 1995;95:134–141.

    Article  PubMed  CAS  Google Scholar 

  18. Cugini D, Azzollini N, Gagliardini E, et al. Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion injury. Kidney Int 2005;67:1753–1761.

    Article  PubMed  CAS  Google Scholar 

  19. Klausner JM, Paterson IS, Goldman G, et al. Postischemic renal injury is mediated by neutrophils and leukotrienes. Am J Physiol 1989;256:F794–F802.

    PubMed  CAS  Google Scholar 

  20. Seekamp A, Mulligan MS, Till GO, Ward PA. Requirements for neutrophil products and L-arginine in ischemia-reperfusion injury. Am J Pathol 1993;142:1217–1226.

    PubMed  CAS  Google Scholar 

  21. Day Y-J, Huang L, Ye H, Li L, Linden J, Okusa MD. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-γ. J Immunol 2006;176:3108–3114.

    PubMed  CAS  Google Scholar 

  22. Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int 2004;66:486–491.

    Article  PubMed  Google Scholar 

  23. Gueler F, Park J-K, Rong S, et al. Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages. Am J Pathol 2007;170:1192–1199.

    Article  PubMed  CAS  Google Scholar 

  24. Savill J, Dransfield I, Gregory C, Haaslett C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2002;2:965–975.

    Article  PubMed  CAS  Google Scholar 

  25. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783–801.

    Article  PubMed  CAS  Google Scholar 

  26. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007;449:819–826.

    Article  PubMed  CAS  Google Scholar 

  27. Johnson GB, Brunn GJ, Kodaira Y, Platt JL. Receptor-mediated monitoring of tissue well-being via detection of soluble heparin sulfate by Toll-like receptor 4. J Immunol 2002;168:5233–5239.

    PubMed  CAS  Google Scholar 

  28. Park JS, Svetkauskaite D, He Q, et al. Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 2004;279:7370–7377.

    Article  PubMed  CAS  Google Scholar 

  29. Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J Immunol 2001;167:2887–2894.

    PubMed  CAS  Google Scholar 

  30. Tsung A, Klune JR, Zhang Z, et al. HMGB1 release induced by liver ischemia involves Toll-like receptor 4-dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med 2007;204:2913–2923.

    Article  PubMed  CAS  Google Scholar 

  31. Tsung A, Sahai R, Tanaka H, et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med 2005;201:1135–1143.

    Article  PubMed  CAS  Google Scholar 

  32. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 2002;277:15107–15112.

    Article  PubMed  CAS  Google Scholar 

  33. Favre J, Musette P, Douin-Echinard V, et al. Toll-like receptors 2-deficient mice are protected against post-ischemic coronary endothelial dysfunction. Arterioscler Thromb Vasc Biol 2007;27:1064–1071.

    Article  PubMed  CAS  Google Scholar 

  34. Kaczorowski DJ, Nakao A, Mollen KP, et al. Toll-like receptor 4 mediates the early inflammation response after cold ischemia/reperfusion. Trans­plantation 2007;84:1279–1287.

    Article  PubMed  CAS  Google Scholar 

  35. Leemans JC, Stokman G, Claessen N, et al. Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J Clin Invest 2005;115:2894–2903.

    Article  PubMed  CAS  Google Scholar 

  36. Shen X-D, Ke B, Zhai Y, et al. Toll-like receptor and heme oxygenase-1 signaling in hepatic ­ischemia/reperfusion injury. Am J Transplant 2005;5:1793–1800.

    Article  PubMed  CAS  Google Scholar 

  37. Shigeoka AA, Holscher TD, King AJ, et al. TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J Immunol 2007;178:6252–6258.

    PubMed  CAS  Google Scholar 

  38. Wu H, Chen G, Wyburn KR, et al. TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 2007;117:2847–2859.

    Article  PubMed  CAS  Google Scholar 

  39. Kruger B, Krick S, Dhillon N, et al. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci USA 2009;106:3390–3395.

    Article  PubMed  CAS  Google Scholar 

  40. Soos TJ, Sims TN, Barisoni L, et al. CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney. Kidney Int 2006;70:591–596.

    PubMed  CAS  Google Scholar 

  41. Randolph GJ, Ochando J, Partida-Sanchez S. Migration of dendritic cells subsets and their precursors. Annu Rev Immunol 2008;26:293–316.

    Article  PubMed  CAS  Google Scholar 

  42. Sozzani S. Dendritic cell trafficking: more than just chemokines. Cytokine Growth Factor Rev 2005;16:581–592.

    Article  PubMed  CAS  Google Scholar 

  43. Felix NJ, Allen PM. Specificity of T-cell alloreactivity. Nat Rev Immunol 2007;7:942–953.

    Article  PubMed  CAS  Google Scholar 

  44. Felix NJ, Donermeyer DL, Horvath S, et al. Allreactive T cells respond specifically to multiple distinct peptide-MHC complexes. Nat Immunol 2007;8:388–397.

    Article  PubMed  CAS  Google Scholar 

  45. Huseby ES, White J, Crawford F, et al. How the T cell repertoire becomes peptide and MHC specific. Cell 2005;122:247–260.

    Article  PubMed  CAS  Google Scholar 

  46. Morris GP, Allen PM. Highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease. J Immunol 2009;182:6639–6643.

    Article  PubMed  CAS  Google Scholar 

  47. Rogers NJ, Lechler RI. Allorecognition. Am J Transplant 2001;1:97–102.

    Article  PubMed  CAS  Google Scholar 

  48. Auchincloss H Jr, Lee R, Shea S, Markowitz JS, Grusby MJ, Glimcher LH. The role of “indirect” recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice. Proc Natl Acad Sci USA 1993;90:3373–3377.

    Article  PubMed  CAS  Google Scholar 

  49. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.

    Article  PubMed  CAS  Google Scholar 

  50. Sauve D, Baratin M, Leduc C, Bonin K, Daniel C. Alloantibody production is regulated by CD4+ T cells’ alloreactive pathway, rather than precursor frequency or Th1/Th2 differentiation. Am J Transplant 2004;4:1237–1245.

    Article  PubMed  CAS  Google Scholar 

  51. Taylor AL, Neugs SL, Negus M, Bolton EM, Bradley JA, Pettigrew GJ. Pathways of helper CD4 T cell allorecognition in generating alloantibody and CD8 T cell alloimmunity. Transplantation 2007;83:931–937.

    Article  PubMed  Google Scholar 

  52. Herrera OB, Golshayan D, Tibbott R, et al. A novel pathway of alloantigen presentation by dendritic cells. J Immunol 2004;173:4828–4837.

    PubMed  CAS  Google Scholar 

  53. Sharpe AH, Abbas A. T-cell costimulation-biology, therapeutic potential, and challenges. NEJM 2006;355:973–975.

    Article  PubMed  CAS  Google Scholar 

  54. Peggs KS, Quezada SA, Allison JP. Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol Rev 2008;224:141–165.

    Article  PubMed  CAS  Google Scholar 

  55. Li XC, Rothstein DM, Sayegh MH. Costimulatory pathways in transplantation: challenges and new developments. Immunol Rev 2009;229:271–293.

    Article  PubMed  CAS  Google Scholar 

  56. Ford ML, Larsen CP. Translating costimulation blockade to the clinic: lessons learned from three pathways. Immunol Rev 2009;229:294–306.

    Article  PubMed  CAS  Google Scholar 

  57. Kishimoto K, Dong VM, Sayegh MH. The role of costimulatory molecules as targets for new immunosuppressives in transplantation. Curr Opin Urol 2000;10:57–62.

    Article  PubMed  CAS  Google Scholar 

  58. Kawai T, Andrews D, Colvin RB, Sachs DH, Cosimi AB. Thromoembolic complications after treatment with monoclonal antibody against CD40 ligand. Nat Med 2000;6:114.

    Article  CAS  Google Scholar 

  59. Weaver TA, Charafeddine AH, Kirk AD. Costimulation blockade: towards clinical application. Front Biosci 2008;13:2120–2139.

    Article  PubMed  CAS  Google Scholar 

  60. Emamaullee J, Toso C, Merani S, Shapiro AMJ. Costimulatory blockade with belatacept in clinical and experimental transplantation-a review. Exp Opin Biol Ther 2009;9:787–796.

    Article  Google Scholar 

  61. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009;27:485–517.

    Article  PubMed  CAS  Google Scholar 

  62. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145–173.

    Article  PubMed  CAS  Google Scholar 

  63. O’Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4 T cells. Science 2010;327:1098–1102.

    Article  PubMed  CAS  Google Scholar 

  64. Burlingham WJ, Love RB, Jankowska-Gan E, et al. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 2007;117:3498–3506.

    Article  PubMed  CAS  Google Scholar 

  65. Williams MA, Bevan MJ. Effector and memory CTL differentiation. Annu Rev Immunol 2007;25:171–192.

    Article  PubMed  CAS  Google Scholar 

  66. Shi L, Mai S, Israels S, Browne K, Trapani JA, Greenberg AH. Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and BraB nuclear localization. J Exp Med 1997;185:855–866.

    Article  PubMed  CAS  Google Scholar 

  67. Chowdhury D, Lieberman J. Death by a thousand cutes: granzyme pathways of programmed cell death. Annu Rev Immunol 2008;26:389–420.

    Article  PubMed  CAS  Google Scholar 

  68. Sabelko-Downes KA, Russell JH. The role of Fas ligand in vivo as a cause and regulator of pathogenesis. Curr Opin Immunol 2000;12:330–335.

    Article  PubMed  CAS  Google Scholar 

  69. Ju ST, Cui H, Panka DJ, Ettinger R, Marshak-Rothstein A. Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and CD8+ cytotoxic T cells. Proc Natl Acad Sci USA 1994;91:4185–4189.

    Article  PubMed  CAS  Google Scholar 

  70. Williams NS, Engelhard VH. Identification of a CD4+ CTL that utilizes a perforin- rather than a Fas ligand-dependent cytotoxic mechanism. J Immunol 1996;156:153–159.

    PubMed  CAS  Google Scholar 

  71. Nelson BH, Willerford DM. Biology of the interleukin-2 receptor. Adv Immunol 1998;70:1–81.

    Article  PubMed  CAS  Google Scholar 

  72. Bradley LM, Watson SR, Swain SL. Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin. J Exp Med 1994;180:2401–2406.

    Article  PubMed  CAS  Google Scholar 

  73. Rosen SD. Ligands for L-selectin: homing, inflammation and beyond. Annu Rev Immunol 2004;22:129–156.

    Article  PubMed  CAS  Google Scholar 

  74. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994;76:301–314.

    Article  PubMed  CAS  Google Scholar 

  75. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 2007;7:678–689.

    Article  PubMed  CAS  Google Scholar 

  76. Muller WA, Randolph GJ. Migration of leukocytes across endothelium and beyond: molecules involved in the transmigration and fate of monocytes. J Leuk Biol 1999;66:698–704.

    CAS  Google Scholar 

  77. Nourshargh S, Krombach F, Dejana F. The role of JAM-A and PECAM-1 in modulating leukocyte infiltration in inflamed and ischemic tissues. J Leuk Biol 2006;80:714–718.

    Article  CAS  Google Scholar 

  78. Luster AD. Chemokines-chemotactic cytokines that mediate inflammation. NEJM 1998;338:436–445.

    Article  PubMed  CAS  Google Scholar 

  79. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. NEJM 2006;354:610–621.

    Article  PubMed  CAS  Google Scholar 

  80. El-Sawy T, Fahmy NM, Fairchild RL. Chemokines: directing leukocyte infiltration into allografts. Curr Opin Immunol 2002;14:562–568.

    Article  PubMed  CAS  Google Scholar 

  81. Hancock WW, Wang I, Ye O, Han R, Lee I. Chemokines and their receptors as markers of allograft rejection and targets for immunosuppression. Curr Opin Immunol 2003;15:479–486.

    Google Scholar 

  82. Hall BM, Dorsch SE. Cells mediating allograft rejection. Immunol Rev 1984;77:31–59.

    Article  PubMed  CAS  Google Scholar 

  83. Hidalgo LG, Halloran PF. Role of IFN-gamma in allograft rejection. Crit Rev Immunol 2002;22:317–349.

    Article  PubMed  CAS  Google Scholar 

  84. Heeger PS. T-cell allorecognition and transplant rejection: a summary and update. Am J Transplant 2003;3:525–533.

    Article  PubMed  CAS  Google Scholar 

  85. Li B, Hartono C, DIng R, et al. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. NEJM 2001;344:947–954.

    Article  PubMed  CAS  Google Scholar 

  86. Hu H, Swun J, Alzenstein BD, Knechtle SJ. Noninvasive detection of acute and chronic injuries in human renal transplant by elevation of multiple cytokines/chemokines in urine. Transplantation 2009;87:1814–1820.

    Article  PubMed  CAS  Google Scholar 

  87. Lefrancois L, Marzo AL. The descent of memory T-cell subsets. Nat Rev Immunol 2006;6:618–623.

    Google Scholar 

  88. Lefrancois L. Development, trafficking, and function of memory T-cell subsets. Immunol Rev 2006;11:93–103.

    Article  Google Scholar 

  89. Ahmed R, Bevan ML, Reiner SL, Fearon DT. The precursors of memory: models and controversies. Nat Rev Immunol 2009;9:662–668.

    Article  PubMed  CAS  Google Scholar 

  90. Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation and maintenance. Annu Rev Immunol 2004;22:745–763.

    Article  PubMed  CAS  Google Scholar 

  91. McHeyzer-Williams LJ, McHeyzer-Williams MG. Antigen-specific memory B cell development. Annu Rev Immunol 2005;23:487–513.

    Article  PubMed  CAS  Google Scholar 

  92. Peled JU, Kuang FL, Iglesias-Ussel MD, et al. The biochemistry of somatic hypermutation. Annu Rev Immunol 2008;26:481–511.

    Article  PubMed  CAS  Google Scholar 

  93. Ford ML, Kirk AD, Larsen CP. Donor-reactive T-cell stimulation history and precursor frequency: barriers to tolerance induction. Transplantation 2009;87:569–574.

    Article  CAS  Google Scholar 

  94. Valujskikh A, Lakkis F. In remembrance of things past: memory T cells and transplant rejection. Immunol Rev 2003;196:65–74.

    Article  PubMed  CAS  Google Scholar 

  95. Sellin LK, Brehm MA, Naurov YN, et al. Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunity. Immunol Rev 2006;211:164–181.

    Article  Google Scholar 

  96. van Leeuwen EM, Sprent J, Surh CD. Generation and maintenance of memory CD4+ T cells. Curr Opin Immunol 2009;21:167–172.

    Article  PubMed  CAS  Google Scholar 

  97. Wu Z, Bensinger SJ, Zhang J, et al. Homeostatic proliferation is a barrier to transplantation tolerance. Nat Med 2003;10:87–92.

    Article  PubMed  CAS  Google Scholar 

  98. Pearl JP, Parris J, Hale DA, et al. Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant 2005;5:465–474.

    Article  PubMed  CAS  Google Scholar 

  99. Zeevi A, Husain S, Spichty KJ, et al. Recovery of functional memory T cells in lung transplant recipients following induction therapy with alemtuzumab. Am J Transplant 2007;7:471–475.

    Article  PubMed  CAS  Google Scholar 

  100. Chen Y, Heeger PS, Valujskikh A. In vivo helper functions of alloreactive memory CD4+ T cells remain intact despite donor-specific transfusion and anti-CD40 ligand therapy. J Immunol 2004;172:5456–5466.

    PubMed  CAS  Google Scholar 

  101. Kissmeyer-Nielsen F, Olsen S, Petersen VP, Fjeldborg O. Hyperacute rejection of kidney allografts associated with pre-existing humoral antibodies against donor cells. Lancet 1966;2:662.

    Article  PubMed  CAS  Google Scholar 

  102. Williams GM, Hume DH, Hudson J, R. P., Morris P, Kano K, Milgrom F. “Hyperacute” renal-homograft rejection in man. NEJM 1968;279:611.

    Article  PubMed  CAS  Google Scholar 

  103. Patel R, Terasaki P. Significance of the positive crossmatch test in kidney transplantation. NEJM 1969;280:735–739.

    Article  PubMed  CAS  Google Scholar 

  104. Fan X, Ang A, Pollock-Barziv SM, et al. Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation. Nat Med 2004;10:1227–1233.

    Article  PubMed  CAS  Google Scholar 

  105. Halloran PF, Schlaut J, Solez K, Srinivasa NS. The significance of the anti-class I antibody response. II. Clinical and pathologic features of renal transplants with anti-class I-like antibody. Transplantation 1992;53:550–555.

    Article  PubMed  CAS  Google Scholar 

  106. Halloran PF, Wadgymer A, Ritchie S, Falk J, Solez K, Srinivasa NS. The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I mediated rejection. Transplantation 1990;49:85–91.

    Article  PubMed  CAS  Google Scholar 

  107. Feucht HE, Felber E, Gokel MJ, et al. Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Clin Exp Immunol 1991;86:464–470.

    Article  PubMed  CAS  Google Scholar 

  108. Collins AB, Schneeberger EE, Pascual MA, et al. Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol 1999;10:2208–2214.

    PubMed  CAS  Google Scholar 

  109. Feucht HE, Mihatsch MJ. Diagnostic value of C4d in renal biopsies. Curr Opin Nephrol Hypertens 2005;14:592–598.

    Article  PubMed  Google Scholar 

  110. Racusen LC, Colvin RB, Solez K, et al. Antibody-mediated rejection criteria-an addition to the Banff ’97 classification of renal allograft rejection. Am J Transplant 2003;3:708–714.

    Article  PubMed  Google Scholar 

  111. Racusen LC, Haas M. Antibody-mediated rejection in renal allografts: lessons from pathology. Clin J Am Soc Nephrol 2006;1:415–420.

    Article  PubMed  CAS  Google Scholar 

  112. Yamakuchi M, Kirkiles-Smith NC, Ferlito M, et al. Antibody to human leukocyte antigen triggers endothelial exocytosis. Proc Natl Acad Sci USA 104;2007:1301–1306.

    Article  PubMed  CAS  Google Scholar 

  113. Zhang X, Reed EF. Effect of antibodies on endo-thelium. Am J Transplant 2009;9:2459–2465.

    Article  PubMed  CAS  Google Scholar 

  114. Lee C-Y, Reynolds M, Garyu J, Baldwin WM, III, Wasowska BA. The involvement of FcR mechanisms in antibody-mediated rejection. Transplantation 2007;84:1324–1334.

    Article  PubMed  CAS  Google Scholar 

  115. Millington TM, Madsen JC. Innate immunity in heart transplantation. Curr Opin Organ Transplant 2009;14:571–576.

    Article  PubMed  Google Scholar 

  116. Benzaquen LR, Nicholson-Weller A, Halperin JA. Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. J Exp Med 1994;179:985–992.

    Article  PubMed  CAS  Google Scholar 

  117. Hattori R, Hamilton KK, McEver RP, Sims PJ. Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J Biol Chem 1989;264:9053–9060.

    PubMed  CAS  Google Scholar 

  118. Wehner J, Morrell CN, Reynolds T, Rodriguez ER, Baldwin WM 3 rd. Antibody and complement in transplant vasculopathy. Circ Res 2007;100:191–203.

    Article  PubMed  CAS  Google Scholar 

  119. Locke JE, Magro CM, Singer AL, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant 2008;9:231–235.

    Article  PubMed  Google Scholar 

  120. Nimmerjahn R, Anthony RM, Ravetch JV. Agalctosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci USA 2007;104:8433–8437.

    Article  PubMed  CAS  Google Scholar 

  121. Benson MJ, Dillon SR, Castigli E, et al. The dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J Immunol 2008;180:3655–3659.

    PubMed  CAS  Google Scholar 

  122. O’Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med 2004;199:91–98.

    Article  PubMed  CAS  Google Scholar 

  123. Kaliss N, Sinclair NR, Cantrell JL. Immunological enhancement of a murine tumor allograft by passive alloantibody IgG and F(ab′)2. Eur. J Immunol 1976;6:38–42.

    Article  PubMed  CAS  Google Scholar 

  124. Batchelor JR. The riddle of kidney graft enhancement. Transplantation 1978;26:139–141.

    Article  PubMed  CAS  Google Scholar 

  125. Platt JL. C4d and the fate of organ allografts. J Am Soc Nephrol 2002;13:2417–2419.

    Article  PubMed  Google Scholar 

  126. Haas M, Rahman MH, Kraus ES, et al. C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings. Am J Transplant 2006;6:1829–1840.

    Article  PubMed  CAS  Google Scholar 

  127. Brodsky SV, Nadasdy GM, Pelletier R, et al. Expression of the decay-accelerating factor (CD55) in renal transplants-a possible prediction marker of allograft survival. Transplantation 2009;27:457–464.

    Article  CAS  Google Scholar 

  128. Fillatreau S, Gray D, Anderton SM. Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol 2008;8:391–397.

    Article  PubMed  CAS  Google Scholar 

  129. Chapman JR, O’Connell PJ, Nankivell BJ. Chronic renal allograft dysfunction. J Am Soc Nephrol 2005;16:3015–3026.

    Article  PubMed  Google Scholar 

  130. Waaga AM, Gasser M, Laskowski I, Tilney NL. Mechanisms of chronic rejection. Curr Opin Immunol 2000;12:517–521.

    Article  PubMed  CAS  Google Scholar 

  131. Weiss MJ, Madsen JC, Rosengard BR, Allan JS. Mechanisms of chronic rejection in cardiothoracic transplantation. Front Bioschi 2008;13:1290–2988.

    Google Scholar 

  132. Mannon RB. Therapeutic targets in the treatment of allograft fibrosis. Am J Transplant 2006;6:867–875.

    Article  PubMed  CAS  Google Scholar 

  133. Segerer, S, Nelson PJ, Schlondorff D. Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol 2000;11:152–176.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William M. Baldwin III .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Baldwin, W.M., Valujskikh, A., Lalli, P.N., Fairchild, R.L. (2011). The Immune Response to Transplanted Organs. In: Srinivas, T., Shoskes, D. (eds) Kidney and Pancreas Transplantation. Current Clinical Urology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-642-9_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-642-9_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-641-2

  • Online ISBN: 978-1-60761-642-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics