Skip to main content
Top
Published in: Immunologic Research 6/2018

01-12-2018 | Hypothesis

Antibody-initiated beneficial and harmful immune responses

Authors: Arpad Zsigmond Barabas, Chad Douglas Cole, Rene Lafreniere

Published in: Immunologic Research | Issue 6/2018

Login to get access

Abstract

A critical function of the immune system is to maintain tolerance to self by corrective immune responses throughout life, including preventing or correcting changes that may interfere with organ function and architectural integrity. These changes have two broad categories, namely (1) exogenous antigen-induced mishaps (e.g., due to bacterial, viral or fungal infections) and (2) endogenous antigen-caused ailments initiated by modified self-antigens derived from damaged organs following exposure to smoke, certain drugs, chemicals, infectious agents, radiation, etc., resulting in autoimmune diseases or cancer. In some cases, cells of the immune system are unable to respond with a corrective antibody response. For example, presentation of a modified self-antigen can initiate a pathogenic IgG immune response, thereby causing an autoimmune disease. Furthermore, if cancer-associated antigens are not appropriately presented to the cells of the immune system, there is failure to mount a specific pathogenic lytic IgG autoantibody response for recognition and elimination of cancer-associated antigens, and as a consequence, the cancer continues to proliferate.
The third vaccination technique that we have developed and designated a modified vaccination technique (MVT) is able to correct these immunological mishaps. The premise of the MVT is that it can prevent both exogenous (infectious and contagious diseases) and endogenous (autoimmune diseases and cancer) antigen-caused diseases, as well as terminate established diseases. Therefore, by exploiting the immune system’s natural abilities to make corrective responses, it has both prophylactic and therapeutic actions, with minimal side effects.
Literature
1.
go back to reference Avrameas S. Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today. 1991;12(5):154–9.PubMed Avrameas S. Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today. 1991;12(5):154–9.PubMed
2.
go back to reference Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Down-regulation of pathogenic autoantibody response in a slowly progressive Heymann nephritis kidney disease model. Int J Exp Pathol. 2004;85(6):321–34.CrossRef Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Down-regulation of pathogenic autoantibody response in a slowly progressive Heymann nephritis kidney disease model. Int J Exp Pathol. 2004;85(6):321–34.CrossRef
3.
go back to reference Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Production of Heymann nephritis by a chemically modified renal antigen. Int J Exp Pathol. 2004;85(5):277–85.CrossRef Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Production of Heymann nephritis by a chemically modified renal antigen. Int J Exp Pathol. 2004;85(5):277–85.CrossRef
4.
go back to reference Barabas AZ, Lafreniere R. Antigen-specific down-regulation of immunopathological events in an experimental autoimmune kidney disease. Autoimmun Rev. 2005;4(8):565–70.CrossRef Barabas AZ, Lafreniere R. Antigen-specific down-regulation of immunopathological events in an experimental autoimmune kidney disease. Autoimmun Rev. 2005;4(8):565–70.CrossRef
5.
go back to reference Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc. Natl. Acad. Sci. U. S A. 2000;97(3):1184–9.CrossRef Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc. Natl. Acad. Sci. U. S A. 2000;97(3):1184–9.CrossRef
6.
go back to reference Ogden CA, Kowalewski R, Peng Y, Montenegro V, Elkon KB. IgM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity. 2005;38(4):259–64.CrossRef Ogden CA, Kowalewski R, Peng Y, Montenegro V, Elkon KB. IgM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity. 2005;38(4):259–64.CrossRef
7.
go back to reference Quartier P, Potter PK, Ehrenstein MR, Walport MJ, Botto M. Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur J Immunol. 2005;35(1):252–60.CrossRef Quartier P, Potter PK, Ehrenstein MR, Walport MJ, Botto M. Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur J Immunol. 2005;35(1):252–60.CrossRef
8.
go back to reference Barabas AZ, Cole CD, Weir DM & Lafreniere R. (2011) Immunopathological events in an experimental autoimmune kidney disease and how those events can be terminated to regain tolerance to self. In Autoimmune disorders: symptoms, diagnosis and treatment. Petrov M, editor. Hauppauge: Nova Science Publishers, Inc. 35–66. Barabas AZ, Cole CD, Weir DM & Lafreniere R. (2011) Immunopathological events in an experimental autoimmune kidney disease and how those events can be terminated to regain tolerance to self. In Autoimmune disorders: symptoms, diagnosis and treatment. Petrov M, editor. Hauppauge: Nova Science Publishers, Inc. 35–66.
9.
go back to reference Barabas AZ, Cole CD, Barabas AD, Barabas AN, Lafreniere R. Reduced incidence of slowly progressive Heymann nephritis in rats immunized with a modified vaccination technique. Clin Dev Immunol. 2006;13(1):17–24.CrossRef Barabas AZ, Cole CD, Barabas AD, Barabas AN, Lafreniere R. Reduced incidence of slowly progressive Heymann nephritis in rats immunized with a modified vaccination technique. Clin Dev Immunol. 2006;13(1):17–24.CrossRef
10.
go back to reference Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Downregulation of a pathogenic autoantibody response by IgM autoantibodies directed against the nephritogenic antigen in slowly progressive Heymann nephritis. Pathol Int. 2006;56(4):181–90.CrossRef Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Downregulation of a pathogenic autoantibody response by IgM autoantibodies directed against the nephritogenic antigen in slowly progressive Heymann nephritis. Pathol Int. 2006;56(4):181–90.CrossRef
11.
go back to reference Barabas AZ, Cole CD, Kovacs ZB, Lafreniere R. Elevated antibody response by antigen presentation in immune complexes. Med Sci Monit. 2007;13(5):BR119–24.PubMed Barabas AZ, Cole CD, Kovacs ZB, Lafreniere R. Elevated antibody response by antigen presentation in immune complexes. Med Sci Monit. 2007;13(5):BR119–24.PubMed
12.
go back to reference Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Preventative and therapeutic vaccination to combat an experimental autoimmune kidney disease. Biologics. 2007;1(1):59–68.PubMedPubMedCentral Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Preventative and therapeutic vaccination to combat an experimental autoimmune kidney disease. Biologics. 2007;1(1):59–68.PubMedPubMedCentral
13.
go back to reference Barabas AZ, Weir DM, Cole CD, Barabas AD, Bahlis NJ, Graeff RM, et al. Preventing and treating chronic disorders using the modified vaccination technique. Front Biosci. 2009:143892–8. Barabas AZ, Weir DM, Cole CD, Barabas AD, Bahlis NJ, Graeff RM, et al. Preventing and treating chronic disorders using the modified vaccination technique. Front Biosci. 2009:143892–8.
14.
go back to reference Barabas AZ, Cole CD, Graeff RM, Lafreniere R, Weir DM. Tolerance, loss of tolerance and regaining tolerance to self by immune-mediated events. Immunol Res. 2017;65(1):402–9.CrossRef Barabas AZ, Cole CD, Graeff RM, Lafreniere R, Weir DM. Tolerance, loss of tolerance and regaining tolerance to self by immune-mediated events. Immunol Res. 2017;65(1):402–9.CrossRef
15.
go back to reference Barabas AZ, Cole CD, Barabas AD, Bahlis NJ, Lafreniere R. A vaccination technique to combat presently untreatable chronic ailments. Bioprocess J. 2007;6(4):12–8.CrossRef Barabas AZ, Cole CD, Barabas AD, Bahlis NJ, Lafreniere R. A vaccination technique to combat presently untreatable chronic ailments. Bioprocess J. 2007;6(4):12–8.CrossRef
16.
go back to reference Heymann W. Experimental analogues of human nephropathies. In: International Proc. 3rd Int. Congr. Nephrol. New York: Karger, Basel; 1967. p. 164–77. Heymann W. Experimental analogues of human nephropathies. In: International Proc. 3rd Int. Congr. Nephrol. New York: Karger, Basel; 1967. p. 164–77.
17.
go back to reference Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Production of a new model of slowly progressive Heymann nephritis. Int J Exp Pathol. 2003;84(6):245–58.CrossRef Barabas AZ, Cole CD, Barabas AD, Lafreniere R. Production of a new model of slowly progressive Heymann nephritis. Int J Exp Pathol. 2003;84(6):245–58.CrossRef
18.
go back to reference Weir DM, Pinckard RN, Elson CJ, Suckling DE. Naturally occurring anti-tissue antibodies in rat sera. Clin Exp Immunol. 1966;1(4):433–42.PubMedPubMedCentral Weir DM, Pinckard RN, Elson CJ, Suckling DE. Naturally occurring anti-tissue antibodies in rat sera. Clin Exp Immunol. 1966;1(4):433–42.PubMedPubMedCentral
20.
go back to reference Manson JJ, Mauri C, Ehrenstein MR. Natural serum IgM maintains immunological homeostasis and prevents autoimmunity. Springer Semin Immunopathol. 2005;26(4):425–32.CrossRef Manson JJ, Mauri C, Ehrenstein MR. Natural serum IgM maintains immunological homeostasis and prevents autoimmunity. Springer Semin Immunopathol. 2005;26(4):425–32.CrossRef
21.
go back to reference Barabas AZ, Cole CD, Graeff RM, Morcol T, Lafreniere R. A novel modified vaccination technique produces IgG antibodies that cause complement-mediated lysis of multiple myeloma cells carrying CD38 antigen. Human Antibodies. 2017;24(3–4):45–51.CrossRef Barabas AZ, Cole CD, Graeff RM, Morcol T, Lafreniere R. A novel modified vaccination technique produces IgG antibodies that cause complement-mediated lysis of multiple myeloma cells carrying CD38 antigen. Human Antibodies. 2017;24(3–4):45–51.CrossRef
22.
go back to reference Zwart B, Ciurana C, Rensink I, Manoe R, Hack CE, Aarden LA. Complement activation by apoptotic cells occurs predominantly via IgM and is limited to late apoptotic (secondary necrotic) cells. Autoimmunity. 2004;37(2):95–102.CrossRef Zwart B, Ciurana C, Rensink I, Manoe R, Hack CE, Aarden LA. Complement activation by apoptotic cells occurs predominantly via IgM and is limited to late apoptotic (secondary necrotic) cells. Autoimmunity. 2004;37(2):95–102.CrossRef
23.
go back to reference Barabas AZ, Cole CD, Barabas AD, Barabas AN, Lafreniere R. Effect of rat kidney fraction 3 (rKF3) antigen and specific IgM antibody against rKF3 on the progression of slowly progressive Heymann nephritis. Pathol Int. 2006;56(9):516–29.CrossRef Barabas AZ, Cole CD, Barabas AD, Barabas AN, Lafreniere R. Effect of rat kidney fraction 3 (rKF3) antigen and specific IgM antibody against rKF3 on the progression of slowly progressive Heymann nephritis. Pathol Int. 2006;56(9):516–29.CrossRef
24.
go back to reference Hogan SL, Muller KE, Jennette JC, Falk RJ. A review of therapeutic studies of idiopathic membranous glomerulopathy. Am J Kidney Dis. 1995;25(6):862–75.CrossRef Hogan SL, Muller KE, Jennette JC, Falk RJ. A review of therapeutic studies of idiopathic membranous glomerulopathy. Am J Kidney Dis. 1995;25(6):862–75.CrossRef
25.
go back to reference Perna A, Schieppati A, Zamora J, Giuliano GA, Braun N, Remuzzi G. Immunosuppressive treatment for idiopathic membranous nephropathy: a systematic review. Am J Kidney Dis. 2004;44(3):385–401.CrossRef Perna A, Schieppati A, Zamora J, Giuliano GA, Braun N, Remuzzi G. Immunosuppressive treatment for idiopathic membranous nephropathy: a systematic review. Am J Kidney Dis. 2004;44(3):385–401.CrossRef
26.
go back to reference Heymann W, Hackel DB, Harwood S, Wilson SG, Hunter JLP. Production of nephritic syndrome in rats by Freund’s adjuvant and rat kidney suspensions. Proc Soc Exp Biol Med. 1959:100660–4. Heymann W, Hackel DB, Harwood S, Wilson SG, Hunter JLP. Production of nephritic syndrome in rats by Freund’s adjuvant and rat kidney suspensions. Proc Soc Exp Biol Med. 1959:100660–4.
27.
go back to reference Barabas AZ, Cole CD, Barabas AD, Lafreniere R & Weir DM. (2011) Four aspects of autoimmunity and how to regain tolerance to self from an autoimmune disease utilizing the modified vaccination technique. In Autoimmune disorders - current concepts and advances from bedside to mechanistic insights. Huang FP, editor. Rijeka, Croatia: InTech 569–590. Barabas AZ, Cole CD, Barabas AD, Lafreniere R & Weir DM. (2011) Four aspects of autoimmunity and how to regain tolerance to self from an autoimmune disease utilizing the modified vaccination technique. In Autoimmune disorders - current concepts and advances from bedside to mechanistic insights. Huang FP, editor. Rijeka, Croatia: InTech 569–590.
28.
go back to reference Blank M, Shoenfeld Y. B cell targeted therapy in autoimmunity. J Autoimmun. 2007;28(2–3):62–8.CrossRef Blank M, Shoenfeld Y. B cell targeted therapy in autoimmunity. J Autoimmun. 2007;28(2–3):62–8.CrossRef
29.
go back to reference Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19.CrossRef Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19.CrossRef
30.
31.
go back to reference Nahta R, Esteva FJ. Trastuzumab: triumphs and tribulations. Oncogene. 2007;26(25):3637–43.CrossRef Nahta R, Esteva FJ. Trastuzumab: triumphs and tribulations. Oncogene. 2007;26(25):3637–43.CrossRef
32.
go back to reference Rommer PS, Dudesek A, Stuve O, Zettl UK. Monoclonal antibodies in treatment of multiple sclerosis. Clin Exp Immunol. 2014;175(3):373–84.CrossRef Rommer PS, Dudesek A, Stuve O, Zettl UK. Monoclonal antibodies in treatment of multiple sclerosis. Clin Exp Immunol. 2014;175(3):373–84.CrossRef
33.
go back to reference Andreakos E, Taylor PC, Feldmann M. Monoclonal antibodies in immune and inflammatory diseases. Curr Opin Biotechnol. 2002;13(6):615–20.CrossRef Andreakos E, Taylor PC, Feldmann M. Monoclonal antibodies in immune and inflammatory diseases. Curr Opin Biotechnol. 2002;13(6):615–20.CrossRef
34.
go back to reference Becker BN, Fuchs H, Hakim R. Intravenous immune globulin in the treatment of patients with systemic lupus erythematosus and end-stage renal disease. J Am Soc Nephrol. 1995;5(10):1746–50.PubMed Becker BN, Fuchs H, Hakim R. Intravenous immune globulin in the treatment of patients with systemic lupus erythematosus and end-stage renal disease. J Am Soc Nephrol. 1995;5(10):1746–50.PubMed
35.
go back to reference Feldmann M, Steinman L. Design of effective immunotherapy for human autoimmunity. Nature. 2005;435(7042):612–9.CrossRef Feldmann M, Steinman L. Design of effective immunotherapy for human autoimmunity. Nature. 2005;435(7042):612–9.CrossRef
36.
go back to reference Leandro MJ, Edwards JC, Cambridge G, Ehrenstein MR, Isenberg DA. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum. 2002;46(10):2673–7.CrossRef Leandro MJ, Edwards JC, Cambridge G, Ehrenstein MR, Isenberg DA. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum. 2002;46(10):2673–7.CrossRef
37.
go back to reference Mok CC. Rituximab for the treatment of rheumatoid arthritis: an update. Drug Des Devel Ther. 2013:887–100. Mok CC. Rituximab for the treatment of rheumatoid arthritis: an update. Drug Des Devel Ther. 2013:887–100.
38.
go back to reference Townsend MJ, Monroe JG, Chan AC. B-cell targeted therapies in human autoimmune diseases: an updated perspective. Immunol Rev. 2010;237(1):264–83.CrossRef Townsend MJ, Monroe JG, Chan AC. B-cell targeted therapies in human autoimmune diseases: an updated perspective. Immunol Rev. 2010;237(1):264–83.CrossRef
39.
go back to reference Barabas AZ, Cole CD, Lafreniere R, Weir DM. Regaining tolerance to a self-antigen by the modified vaccination technique. Clin Rev Allergy Immunol. 2013;45(2):193–201.CrossRef Barabas AZ, Cole CD, Lafreniere R, Weir DM. Regaining tolerance to a self-antigen by the modified vaccination technique. Clin Rev Allergy Immunol. 2013;45(2):193–201.CrossRef
Metadata
Title
Antibody-initiated beneficial and harmful immune responses
Authors
Arpad Zsigmond Barabas
Chad Douglas Cole
Rene Lafreniere
Publication date
01-12-2018
Publisher
Springer US
Published in
Immunologic Research / Issue 6/2018
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-018-9037-0

Other articles of this Issue 6/2018

Immunologic Research 6/2018 Go to the issue