This article comments on my trajectory first from Havana as a medical student, to Pittsburgh as a pathology intern, then to La Jolla. It reviews my initial experience in immunology research at the Scripps Research Institute in the early 1960s. Under Frank Dixon, my work examined how antibodies to the glomerular basement membrane (GBM) cause disease. I present these studies in the broader context of immunological renal injury. The early studies by Dixon and his group examining the models of acute or chronic serum sickness were major for our understanding of renal and vascular pathology. I review them because of their historical importance in immunopathology and also cover facets of Dixon's overall contributions to immunology. The studies in serum sickness and anti-GBM nephritis led to an understanding of autoimmune glomerulonephritides, the first proven autoantibody-induced diseases.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Unanue ER. 1.  2006. From antigen processing to peptide-MHC binding. Nat. Immunol. 7:1277–79 [Google Scholar]
  2. Schlesinger S, Schlesinger M. 2.  2006. Conversations with Sondra Schlesinger St. Louis: private press228 [Google Scholar]
  3. Oldstone MAO. 3.  2009. Frank James Dixon (1920–2008): A Biographical Memoir Washington, DC: Natl. Acad. Sci. [Google Scholar]
  4. Warren S, Dixon FJ. 4.  1948. Antigen tracer studies and histologic observations in anaphylactic shock in the guinea pig. Am. J. Med. Sci. 216:136–45 [Google Scholar]
  5. Dammin GJ, Bukantz SC, Dixon FJ, Talmage DW. 5.  1951. The metabolism of I-131 labelled proteins in rabbits: the sensitivity of the antigen elimination rate as an indicator of antibody. J. Clin. Investig. 30:634–35 [Google Scholar]
  6. Dixon FJ, Bukantz SC, Talmage DW, Dammin GJ. 6.  1951. Radiosensitivity of the immune response. Am. J. Pathol. 27:679–80 [Google Scholar]
  7. Dixon FJ, Moore RA. 7.  2002. Testicular tumors—a clinicopathological study. J. Urol. 167:896–918 [Google Scholar]
  8. von Pirquet CE. 8.  1911. Allergy. Arch. Inst. Med. 7:259–436 [Google Scholar]
  9. Opie EL.9.  1924. Inflammatory reaction of the immune animal to antigen and its relation to antibodies. J. Immunol. 9:231–45 [Google Scholar]
  10. Rich AR.10.  1956. The pathology and pathogenesis of experimental anaphylactic glomerulonephritis in relation to human acute glomerulonephritis. Bull. Johns Hopkins Hosp. 98:120–51 [Google Scholar]
  11. Hawn CVZ, Janeway CA. 11.  1947. Histological and serological sequences in experimental hypersensitivity. J. Exp. Med. 85:571–90 [Google Scholar]
  12. Dixon FJ, Vazquez JJ, Weigle WO, Cochrane CG. 12.  1958. Pathogenesis of serum sickness. Arch. Pathol. 65:18–28 [Google Scholar]
  13. Germuth FG Jr, Senterfit LB, Pollack AD. 13.  1967. Immune complex disease. I. Experimental acute and chronic glomerulonephritis. Johns Hopkins Med. J. 120:225–51 [Google Scholar]
  14. McCluskey RT, Benacerraf B, Potter JL, Miller F. 14.  1960. The pathologic effects of intravenously administered soluble antigen-antibody complexes. I. Passive serum sickness in mice. J. Exp. Med. 111:181–94 [Google Scholar]
  15. Dixon FJ, Feldman JD, Vazques JJ. 15.  1961. Experimental glomerulonephritis: the pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J. Exp. Med. 113:899–920 [Google Scholar]
  16. Kim JM, Wu H, Green G, Winkler CA, Kopp JB. 16.  et al. 2003. CD2-associated protein haploinsufficiency underlies susceptibility to glomerular disease. Science 300:1298–300 [Google Scholar]
  17. Grunkemeyer JA, Kwoh C, Huber TB, Shaw AS. 17.  2005. CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency. J. Biol. Chem. 280:29677–81 [Google Scholar]
  18. Coons AH.18.  1961. The beginnings of immunofluorescence. J. Immunol. 87:499–503 [Google Scholar]
  19. Vazquez JJ, Dixon FJ. 19.  1956. Studies on the immunohistochemical composition of inflammatory and degenerative lesions. Am. J. Pathol. 32:615–16 [Google Scholar]
  20. Coons AH, Kaplan MH. 20.  1950. Localization of antigen in tissue cells: improvements in a method for the detection of antigen by means of fluorescent antibody. J. Exp. Med. 91:1–13 [Google Scholar]
  21. Cochrane CG, Weigle WO. 21.  1958. The cutaneous reaction to soluble antigen-antibody complexes. A comparison with the Arthus phenomenon. J. Exp. Med. 108:591–604 [Google Scholar]
  22. Weigle WO, Chiller JM, Habicht GS. 22.  1972. Effect of immunological unresponsiveness on different cell populations. Transplant. Rev. 8:3–25 [Google Scholar]
  23. Müller-Eberhard HJ, Nilsson U. 23.  1960. Relation of a β(1)-glycoprotein of human serum to the complement system. J. Exp. Med. 111:217–34 [Google Scholar]
  24. Dutton RW, Eady JD. 24.  1964. An in vitro system for the study of the mechanism of antigenic stimulation in the secondary response. Immunology 7:40–53 [Google Scholar]
  25. Hammer DK, Dixon FJ. 25.  1963. Experimental glomerulonephritis. II. Immunologic events in the pathogenesis of nephrotoxic nephritis in the rat. J. Exp. Med. 117:1019–34 [Google Scholar]
  26. Seegal BC, Bevans M. 26.  1957. The production of glomerulonephritis by immunologic methods. J. Chronic Dis. 5:153–72 [Google Scholar]
  27. Unanue ER, Dixon FJ. 27.  1964. Experimental glomerulonephritis. IV. Participation of complement in nephrotoxic nephritis. J. Exp. Med. 119:965–82 [Google Scholar]
  28. Unanue ER, Dixon FJ. 28.  1965. Experimental glomerulonephritis. V. Studies on the interaction of nephrotoxic antibodies with tissues of the rat. J. Exp. Med. 121:697–714 [Google Scholar]
  29. Unanue ER, Dixon FJ. 29.  1965. Experimental glomerulonephritis. VI. The autologous phase of nephrotoxic serum nephritis. J. Exp. Med. 121:715–25 [Google Scholar]
  30. Unanue ER, Dixon FJ, Lee S. 30.  1966. Experimental glomerulonephritis. VIII. In vivo fixation of heterologous nephrotoxic antibodies to, and their exchange among, tissues of rat. Int. Arch. Allergy Appl. Immunol. 29:140–50 [Google Scholar]
  31. Cochrane CG, Unanue ER, Dixon FJ. 31.  1965. A role of polymorphonuclear leukocytes and complement in nephrotoxic nephritis. J. Exp. Med. 122:99–116 [Google Scholar]
  32. Cochrane CG, Weigle WO, Dixon FJ. 32.  1959. The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis. J. Exp. Med. 110:481–94 [Google Scholar]
  33. Humphrey JH.33.  1955. The mechanism of Arthus reactions. I. The role of polymorphonuclear leukocytes and other factors in reversed passive Arthus reactions in rabbits. Br. J. Exp. Pathol. 36:268–82 [Google Scholar]
  34. Cochrane CG, Aikin BS. 34.  1966. Poplymorphonuclear leukocytes in immunologic reactions. The destruction of vascular basement membrane in vivo and in vitro. J. Exp. Med. 124:733–52 [Google Scholar]
  35. DiStasi MR, Ley K. 35.  2009. Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. Trends Immunol. 30:547–56 [Google Scholar]
  36. Lange K, Wachstein M, McPherson SE. 36.  1961. Immunologic mechanism of transmission of experimental glomerulonephritis in parabiotic rats. Proc. Soc. Exp. Biol. Med. 106:13–16 [Google Scholar]
  37. Unanue ER, Lee S, Dixon FJ, Feldman JD. 37.  1965. Experimental glomerulonephritis. VII. The absence of autoimmunity in nephrotoxic nephritis of the rat. J. Exp. Med. 122:565–78 [Google Scholar]
  38. Steblay RW. 38.  1962. Glomerulonephritis induced in sheep by injections of heterologous glomerular basement membrane and Freund's complete adjuvant. J. Exp. Med. 116:253–72 [Google Scholar]
  39. Steblay RW. 39.  1963. Glomerulonephritis induced in monkeys by injections of heterologous glomerular basement membrane and Freund's adjuvant. Nature 197:1173–76 [Google Scholar]
  40. Heymann W, Hackel DB, Harwood S, Wilson SG, Hunter JLP. 40.  1959. Production of nephritic syndrome in rats by Freund's adjuvants and rat kidney suspension. Proc. Soc. Exp. Biol. Med. 100:660–64 [Google Scholar]
  41. Glassock RJ. 41.  2010. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am. J. Kidney Dis. 56:157–67 [Google Scholar]
  42. Lerner RA, Dixon FJ. 42.  1966. Transfer of ovine experimental allergic glomerulonephritis (EAG) with serum. J. Exp. Med. 124:431–42 [Google Scholar]
  43. Rudofsky V, Steblay RW. 43.  1966. Studies on autoimmune nephritis in sheep. II. Passive transfer of nephritis in sheep by plasma. Fed. Proc. 25:569 [Google Scholar]
  44. Unanue ER, Dixon FJ. 44.  1967. Experimental allergic glomerulonephritis induced in the rabbit with heterologous renal antigens. J. Exp. Med. 125:149–62 [Google Scholar]
  45. Unanue ER, Dixon FJ, Feldman JD. 45.  1967. Experimental allergic glomerulonephritis induced in rabbit with homologous renal antigens. J. Exp. Med. 125:163–76 [Google Scholar]
  46. Lerner RA, Glassock RJ, Dixon FJ. 46.  1967. The role of anti-glomerular basement membrane antibody in pathogenesis of human glomerulonephritis. J. Exp. Med. 126:989–1004 [Google Scholar]
  47. Witebsky E, Rose NR, Terplan K, Paine JR, Egan RW. 47.  1957. Chronic thyroiditis and autoimmunization. J. Am. Med. Assoc. 164:1439–47 [Google Scholar]
  48. Doniach D, Hudson RV, Roitt IM. 48.  1960. Human auto-immune thyroiditis: clinical studies. Br. Med. J. 1:365–73 [Google Scholar]
  49. Miescher PA, Grabar P. 49.  1967. Immunopathology, Fifth International Symposium Punta Ala Italy: [Google Scholar]
  50. Tan EM, Schur PH, Carr RI, Kunkel HG. 50.  1966. Deoxyribonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J. Clin. Investig. 45:1732–40 [Google Scholar]
  51. Grabar P, Miescher PA. 51.  1963. Immunopathology, Third International Symposium New York: Grune & Stratton [Google Scholar]
  52. Unanue ER, Askonas BA. 52.  1968. The immune response of mice to antigen in macrophages. Immunology 15:287–96 [Google Scholar]
  53. Unanue ER, Cerottini J-C. 53.  1970. The immunogenicity of antigen bound to the plasma membrane of macrophages. J. Exp. Med. 131:711–25 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error