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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 594))

Abstract

Network theory is increasingly accepted as a basic regulatory mechanism in diverse immunological functions. Heat shock proteins (Hsps) are involved in multiple networks in the immune system. Hsps themselves (foreign or endogenous) activate innate immunity and play important roles to deliver self or nonself materials to antigen presenting cells. However, Hsps are immunodominant antigens during infectious diseases making self Hsps endangered targets of autoimmunity by cross-reactive clones. Therefore, it is not surprising that the mechanism of protection of self Hsps is not clonal deletion in natural self tolerance; rather, self Hsps are protected by active regulating natural autoimmunity. The active regulatory/protective immunity is accomplished by natural autoantibodies and regulatory T cells, both recognizing Hsps. The multiple involvements of Hsps in immune networks make them ideal targets of therapy in autoimmune diseases. Indeed, immunotherapy with Hsps was recently reported to be effective treatment modality against cancer, arthritis or diabetes mellitus.

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References

  1. Matzinger P. The clanger model: A renewed sense of self. Science 2002; 296:301–305.

    Article  PubMed  CAS  Google Scholar 

  2. Binder RJ, Vatner R, Srivastava PK. The heat-shock protein receptors: Some answers and more questions. Tissue Antigens 2004; 64:442–451.

    Article  PubMed  CAS  Google Scholar 

  3. Tsan MF, Gao B. Endogenous ligands of Toll-like receptors. J Leukoc Biol 2004; 76:514–519.

    Article  PubMed  CAS  Google Scholar 

  4. Gao B, Tsan MF. Induction of cytokines by heat shock proteins and endotoxin in murine mac-rophages. Biochem Biophys Res Commun 2004; 317:1149–1154.

    Article  PubMed  CAS  Google Scholar 

  5. Panjwani NN, Popova L, Srivastava PK. Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J Immunol 2002; 168:2997–3003.

    PubMed  CAS  Google Scholar 

  6. Korbelik M, Sun J, Cecic I. Photodynamic therapy induced cell surface expression and release of heat shock proteins: Relevance for tumor response. Cancer Res 2002; 65:1018–1026.

    Google Scholar 

  7. Habich C, Kempe K, Gomez FJ et al. Heat shock protein 60: Identification of specific epitopes for binding to primary macrophages. FEBS Lett 2006; 580:115–120.

    Article  PubMed  CAS  Google Scholar 

  8. Habich C, Kempe K, van der Zee R et al. Heat shock protein 60: Specific binding of lipopolysac-charide. J Immunol 2005; 174:1298–1305.

    PubMed  CAS  Google Scholar 

  9. Byrd CA, Bornmann H, Erdjument-Bromage P et al. Heat shock protein 90 mediates macrophage activation by taxol and bacterial lipopolysaccharide. Proc Natl Acad Sci USA 1999; 96:5645–5651.

    Article  PubMed  CAS  Google Scholar 

  10. Triantafilou K, Triantafilou M, Dedrick RL. A CDl4-independent LPS receptor complex. Nat Immunol 2001; 2:338–342.

    Article  PubMed  CAS  Google Scholar 

  11. Jones DB, Coulson AF, Duff GW. Sequence homologies between Hsp60 and autoantigens. Immunol Today 1993; 14:115–8.

    Article  PubMed  CAS  Google Scholar 

  12. Cohen IR, Young DB. Autoimmunity, microbial immunity and the immunological homunculus. Immunol Today 1992; 12:105–110.

    Article  Google Scholar 

  13. Coutinho A, Kazatchkine MD, Avrameas S. Natural autoantibodies. Curr Opin Immunol 1995; 7:812–821.

    Article  PubMed  CAS  Google Scholar 

  14. Lacroix-Desmazes S, Kaveri SV, Mouthon L et al. Self-reactive antibodies (natural autoantibodies) in healthy individuals. J Immunol Meth 1998; 216:117–137.

    Article  CAS  Google Scholar 

  15. Lacroix-Desmazes S, Mouthon L, Spalter SH et al. Immunoglobulins and the regulation of autoimmunity through the immune network. Clin Exp Rheumatol 1996; 14:S9–S15.

    PubMed  Google Scholar 

  16. Pashov A, Kenderov A, Kyurkchiev S et al. Autoantibodies to heat shock protein 90 in the human natural antibody repertoire. Int Immunol 2002; 14:453–461.

    Article  PubMed  CAS  Google Scholar 

  17. Prohászka Z, Füst G. Immunological aspects of heat shock proteins-The optimum stress of life. Mol Immunol 2004; 41:29–44.

    Article  PubMed  Google Scholar 

  18. Uray K, Hudecz F, Füst G et al. Comparative analysis of linear antibody epitopes on human and mycobacterial 60 kDa heat shock proteins using samples of healthy blood donors. Int Immunol 2003; 15:1229–1236.

    Article  PubMed  CAS  Google Scholar 

  19. Veres A, Prohászka Z, Kilpinen S et al. The promoter polymorphism of the IL-6 gene is associated with levels of antibodies to 60 kDa heat shock proteins. Immunogenetics 2002; 53:851–856.

    Article  PubMed  CAS  Google Scholar 

  20. Pandey JP, Prohászka Z, Veres A et al. Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60-kDa and 65 kDa heat shock proteins. Genes and Immunity 2004; 5:68–71.

    Article  PubMed  CAS  Google Scholar 

  21. Prohászka Z. Gene-gene interactions in immunology as exemplified with studies on autoantibodies against 60 kDa heat shock protein. In: Falus A, ed. Immunogenomics. London: Wiley and Sons, 2005.

    Google Scholar 

  22. Menoret A, Chandawarkar RY, Srivastava PK. Natural autoantibodies against heat-shock proteins hsp70 and gp96: Implications for immunotherapy using heat-shock proteins. Immunology 2000; 101:364–370.

    Article  PubMed  CAS  Google Scholar 

  23. Kocsis J, Veres A, Vatay Á et al. Antibodies against the human heat shock protein hsp70 in patients with severe coronary artery disease. Immunol Invest 2002; 31:219–231.

    Article  PubMed  CAS  Google Scholar 

  24. Pockley AG, Shepherd J, Corton JM. Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol Invest 1998; 27:367–377.

    PubMed  CAS  Google Scholar 

  25. Pockley AG, Bulmer J, Hanks BM et al. Identification of human heat shock protein 60 (Hsp60) and anti-Hsp60 antibodies in the peripheral circulation of normal individuals. Cell Stress Chap 1999; 4:29–35.

    Article  CAS  Google Scholar 

  26. Dybdahl B, Wahba A, Lien E et al. Inflammatory response after open heart surgery: Release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation 2002; 105:685–90.

    Article  PubMed  CAS  Google Scholar 

  27. Clayton A, Turkes A, Navabi H et al. Induction of heat shock protein sin B-cell exosomes. J Cell Sci 2005; 118:3631–3638.

    Article  PubMed  CAS  Google Scholar 

  28. Srivastava PK. Immunotherapy of human cancer: Lessons from mice. Nat Immunol 2000; 1:363–6.

    Article  PubMed  CAS  Google Scholar 

  29. Quintana FJ, Cohen IR. Heat shock proteins as endogenous adjuvants in sterile and septic inflammation. J Immunol 2005; 175:2777–2782.

    PubMed  CAS  Google Scholar 

  30. Prakken BJ, Roord S, Ronaghy A et al. Heat shock protein 60 and adjuvant arthritis: A model for T cell regulation in human arthritis. Springer Semin Immunopathol 2003; 25:47–63.

    Article  PubMed  CAS  Google Scholar 

  31. Cohen IR. Peptide therapy for Type I diabetes: The immunological homunculus and the rationale for vaccination. Diabetologia 2002; 45:1468–1474.

    Article  PubMed  CAS  Google Scholar 

  32. van Eden W, Thole JE, van der Zee R et al. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 1988; 331:171–173.

    Article  PubMed  Google Scholar 

  33. Anderton SM, van der Zee R, Noordzij A et al. Differential mycobacterial 65-kDa heat shock protein T cell epitope recognition after adjuvant arthritis-inducing or protective immunization protocols. J Immunol 1994; 152:3656–3664.

    PubMed  CAS  Google Scholar 

  34. Paul AG, van Kooten PJ, van Eden W et al. Highly autoproliferative T cells specific for 60-kDa heat shock protein produce IL-4/IL-10 and IFN-gamma and are protective in adjuvant arthritis. J Immunol 2000; 165:7270–7277.

    PubMed  CAS  Google Scholar 

  35. Elias D, Markovits D, Reshef T et al. Induction and therapy of autoimmune diabetes in the nonobese diabetic (NOD/LT) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci USA 1990; 87:576–1580.

    Article  Google Scholar 

  36. Elias D, Reshef T, Birk OS et al. Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65 kD heat shock protein. Proc Natl Acad Sci USA 1991; 88:3088–3091.

    Article  PubMed  CAS  Google Scholar 

  37. Raz I, Elias D, Avron A et al. Beta-cell function in new-onset type 1 diabetes and immunomodulation with heat-shock protein peptide (DiaPep277): A randomized, double-blind, phase II trial. Lancet 2001; 358:1749–1753.

    Article  PubMed  CAS  Google Scholar 

  38. van Eden W, Koets A, van Kooten P et al. Immunopotentiating heat shock proteins: Negotiatiors between innate danger and control of autoimmunity. Vaccine 2003; 21:897–901.

    Article  PubMed  Google Scholar 

  39. Jerne N. Towards a network theory of the immune system. Ann Inst Pasteur Immunol 1974; 125C:435–441.

    Google Scholar 

  40. Varela FJ, Coutinho A. Second generation immune networks. Immunol Today 1991; 12:159–166.

    PubMed  CAS  Google Scholar 

  41. Avrameas S. Natural autoantibodies: From ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today 1991; 12:154–158.

    PubMed  CAS  Google Scholar 

  42. Coutinho A. Will the idiotypic network help to solve natural tolerance? Trends Immunol 2003; 24:53–54.

    Article  PubMed  CAS  Google Scholar 

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© 2007 Landes Bioscience and Springer Science+Business Media

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Prohászka, Z. (2007). Chaperones As Part of Immune Networks. In: Csermely, P., Vígh, L. (eds) Molecular Aspects of the Stress Response: Chaperones, Membranes and Networks. Advances in Experimental Medicine and Biology, vol 594. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39975-1_14

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