Conclusion
In conclusion, until the cellular biology of hepatitis B virus infection is understood and until the technology for the development of suitable virus infected autologous target cells is available, it will not be possible to definitively establish the mechanism involved in the pathogenesis of hepatitis B virus induced hepatocellular injury. Clearly, considerable effort must now be focused on the basic biology of virus infection, replication, and effects on hepatocellular metabolism before it will be possible to perform the definitive experiments to elucidate the role played by the immune system in the pathogenesis of this disease.
Article PDF
Similar content being viewed by others
References
Agarwal SS, Blumberg BB, Gerstley BJS, London WT, Millman I, Sutmek AI, Loeb LA (1971) Lymphocyte transformation and hepatitis. I. Impairment of thymidine incorporation and DNA polymerase activity. Proc Soc Exp Biol Med 137: 1498
Alberti A, Realdi G, Tremolodi F, Spiver GP (1976) Liver cell surface localization of hepatitis B antigen and immunoglobulins in acute and chronic hepatitis and liver cirrhosis. Clin Exp Immunol 25: 396
Alberti A, Realdi G, Bortolotti F, Rigoli AM (1977) T-lymphocyte cytotoxicity to HBsAg-coated target cells in hepatitis B virus infection. Gut 18: 1004
Alexander JJ, Bey EM, Geddes EW, Lecatsas G (1976) Establishment of a continuous growing cell line from primary carcinoma of the liver. S Afr Med J 50: 2124
Bang FB, Warwick A (1960) Mouse macrophages as host cells for the mouse hepatitis virus and the genetic basis of their susceptibility. Proc Natl Acad Sci USA 46: 1
Barker LF, Shulman WR, Murray R, Hirschman RJ, Ratner F, Diefenback WCL, Geller HM (1970) Transmission of serum hepatitis. JAMA 211: 1509
Behrens UH, Paronetto F (1979) Studies on liver-specific antigens. 1. Evaluation of the liver specificity of “LSP” and “LP-2”. Gastroenterology 77: 1045
Blumberg BS, Sutnick AI, London WT (1970) Australia antigen as a hepatitis virus. Variation in host response. Am J Med 48: 1
Le Bouvier GL (1971) The heterogeneity of Australia antigen. J Infect Dis 123: 671
Chang RS (1954) Continuous subcultivation of epithelial-like cells from normal tissue. Proc Soc Exp Biol Med 87: 440
Charpentier B, Guttmann RL, Shuster J, P Gold (1977) Augmentation of proliferation of human mixed lymphocyte culture by human α-fetoprotein. J Immunol 119: 897
Chisari FV (1977) Immunoregulatory properties of human plasma in very low density lipoprotein. J Immunol 119: 2129
Chisari FV (1978) Regulation of human lymphocyte function by a soluble extract from normal human liver. J. Immunol 121: 1279
Chisari FV (1979) Liver-specific protein in perspective. Gastroenterology 7: 168
Chisari FV, Anderson DS (1979) Cytotoxic and suppressor cell function in hepatitis. Clin Res 27: 470A
Chisari FV Edginton TS (1975) Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein. J Exp Med 142: 1092
Chisari FV, Routenberg JA, Edgington TS (1976) Mechanisms responsible for defective human T lymphocyte sheep erythrocyte rosette function associated with hepatitis B virus infections. J Clin Invest 57: 1227
Chisari FV, Gealy WJ, Edgington TS (1977) Recovery of soluble sheep eythrocyte receptor from the T lymphocyte surface by proteolytic cleavage. J Immunol 118: 1138
Chisari FV, Routenberg JA, Fiala M, Edgington TS (1977) Extrinsic modulation of human T-lymphocyte E rosette function associated with prolonged hepatocellulax injury after viral hepatitis. J Clin Invest 59: 134
Chisari FV, Routenberg JA, Anderson DS, Edgington TS (1978) Cellular immune reactivity in hepatitis B virus-induced liver disease in viral hepatitis. In: Vyas GW, Cohen SW, Schmid R (eds) Viral hepatitis. Franklin Press, Philadelphia, PA. p 245
Chisari FV, Bieber MS, Josepho CA, Xavier C, Anderson DS (1981) Functional properties of lymphocytes subpopulations in hepatitis B virus infection II. Cytotoxic effector cell killing of targets which naturally express hepatitis B surface antigen and liver specific lipoprotein. J Immunol 126: 45
Chisari FV, Castle KL, Xavier C, Anderson DS (1981) Functional properties of lymphocyte subpopulations in hepatitis B virus infection. I. Suppressor cell control of T lymphocyte responsiveness. J Immunol 126: 38
Cochrane AMB, Moussouros A, Thomson AD, Eddleston ALWF, Williams R (1976) Antibody dependent cell-mediated (K cell) cytotoxicity against isolated hepatocytes in chronic active hepatitis. Lancet 1: 441
Colombo M, Vernace SJ, Paronetto F (1977) T and B lymphocytes in patients with chronic active hepatitis. Clin Exp Immunol 30: 4
Dehoratius RJ, Strickland RG, Williams RC (1974) T and B lymphocytes in acute and chronic hepatitis. Clin Immunol Immunopathol 2: 353
Doherty PC, Gotze D, Trinchieri G, Zinkernagel RM (1976) Models for recognition of virally modified cells by immune thymus-derived lymphocytes. Immunogenetics 3: 517
Doherty PC, Solert D, Knowles BB (1977) H-2 gene expression is required for T cell-mediated lysis of virus-infected target cells. Nature 266: 361
Dudley FJ, Fox RA, Sherlock S (1971) Relationship of hepatitis associated antigen (H.A.A.) to acute and chronic liver injury. Lancet I: 12
Dudley FJ, Fox RA, Sherlock S (1972) Cellular immunity and hepatitis-associated Australia antigen liver disease. Lancet 1: 723
Dudley FJ, Giustino V, Sherlock S (1972) Cell mediated immunity in patients positive for hepatitis associated antigen. Br Med J 4: 754
Eddleston ALWF (1975) Lymphocyte cytotoxicity to isolated hepatocytes in active chronic hepatitis. The role of T and B cells. Chronic Hepatitis International Symposium Montecatini, Italy p 117
Eddleston ALWF, Williams, R (1976) The role of immunological mechanisms in chronic hepatitis. Ann Clin Res 8: 162
Edgington TS, Chisari FV (1975) Immunologic aspects of hepatitis B virus infection. Am J Med Sci 270: 213
Edginton TS, Chisari FV, Curtiss LK (1976) Regulation of lymphocyte function in HBV infection. Immunopathology International Symposium. Schwabe and Co, Basel/Stuttgart, p 173
Edgington TS, Curtiss LK, DeHeer DH (1976) Immunoregulatory characteristics of LDL-In a species of normal low density lipoprotein.Clin Res 24: 445
Edginton TS, Henney CH, Curtiss LK (1976) The bioregulatory properties of the low density lipoprotein inhibitor (LDL-In) on the generation of killer T cells. In: Miescher PA (ed) Proceedings of the 11th Leukocyte Culture Conference. Schwabe and Co, Basel/Stuttgart, p 173
El Sheikh N, Osman CG, Cullens H, Eddleston ALWF, Williams R (1978) T lymphocyte-mediated cytotoxicity in HB,Ag positive liver disease. Clin Exp Immunol 31: 158
Facchini A, Stefanni GF, Bernardi M, Miglio F, Gasbarini G, Labo G (1978) Lymphocytotoxicity test against rabbit hepatocytes in chronic liver diseases. Gut 19: 189
Fernandez-Cruz E, Escartin P, Bootello A, Kreisler H, Segovia De Arana JM (1978) Hepatocyte damage induced by lymphocytes from patients with chronic liver diseases as detected by LDH release. Clin Exp Immunol 31: 436
Gershon RK (1974) T cell control of antibody production. Contemp Top Immunol 3: 1
Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18: 723
Girmann G, Pees H, Shwartze G, Scheurlen PG (1976) Immunosuppression by micromolecular fibrinogen degradation products in cancer. Nature 259: 399
Gocke DJ (1975) Extrahepatic manifestations of viral hepatitis. Am J Med Sci 270: 49
Good RA, Page AR (1960)Fatal complications of virus hepatitis in two patients with agammaglobulinemia. Am J Med 29: 804
Ha TY, Waksman BH (1973) Role of the thymus in tolerance X. Suppressor activity of antigenstimulated rat thymocytes transferred to normal recipients. J Immunol 110: 1290
Hodgson HJF, Wands JR, Isselbacher KJ (1978) Alteration in suppressor cell activity in chronic active hepatitis. Proc Natl Acad Sci USA 75: 1549
Hopf U, Meyer Zum Buschenfelde KH, Freudenberg J (1974) Liver specific antigens of different species. II. Localization of a membrane antigen at cell surface of isolated hepatocytes. Clin Exp Immunol 16: 117
Ibrahim AB, Vyas GN, Perkins HA (1975) Immune response to hepatitis B surface antigen. Infect Immun 11: 137
Jensen DM, McFarlane IG, Portmann BS, Eddleston ALWF, Williams R (1978) Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis. N Engl J Med 299: 1
Joseph BS, Oldstone MBA (1975) Antibody induced redistribution of measles virus antigens on the cell surface. J Immunol 113: 1205
Kakumu S, Hara T, Goku H, Sakamoto N (1978) Lymphocyte cytotoxicity against Chang liver cells in chronic active hepatitis. Cell Immunol 36: 46
Kongshaven PAL, Hawkins D, Shuster J (1976) The biology of the immune response. In: Freedman SO, Gold P (eds) Clinical immunology. Harper and Row, Maryland, p 1
Krugman S, Giles JK (1970) Viral hepatitis: new light on an old disease. JAMA 212: 1019
Laughter AH, Twomey JJ (1977) Suppression of lymphoproliferation by high concentrations of normal human mononuclear leukocytes. J Immunol 119: 173
Lee WM, Reed WP, Mitchell CG, Galbraith RM, Eddleston ALWF, Zuckerman AJ Williams R (1975) Cellular and humoral immunity to hepatitis B surface antigen in active chronic hepatitis. Br Med J 1: 705
Lee WM, Reed WD, Osman CG, Vahrman J, Zuckerman AJ, Eddleston ALWF, Williams R (1977) Immune responses to the hepatitis B surface antigen and liver specific lipoprotein in acute type B hepatitis. Gut 18: 250
Levo Y (1979) Extrahepatic manifestations of hepatitis B virus infection. Isr J Med Sci 15: 726
Levy GA, Edgington TS (1980) Lymphocyte collaboration is required for the generation of procoagulant activity. J Exp Med 151: 1232
Magnius LO, Espmark JA (1972) New specificities in Australia antigen positive sera distinct from the Le Bouvier determinants. J Immunol 109: 1017
McFarlane G, Wojcicka BM, Zucker GM, Eddleston ALWF, Williams R (1977) Purification and characterization of human liver-specific membrane lipoprotein (LSP). Clin Exp Immunol 27: 381
Melnick JL, Dreesman GR, Hollinger FB (1977) Viral hepatitis. Scientific American 44: 237
Meyer Zum Buschenfelde KH, Hopf U (1974) Studies of the pathogenesis of experimental chronic active hepatitis in rabbits. 1. Induction of the disease and protective effect of allogeneic liver specific proteins. Br J Exp Pathol 55: 498
Meyer Zum Buschenfelde KB, Meixcher PA (1972) Liver specific antigens. Purification and characterization. Clin Exp Immunol 10: 89
Meyer Zum Buschenfelde KH, Kossling FK, Miescher PA (1972) Experimental chronic active hepatitis in rabbits following immunization with human liver proteins. Clin Exp Immunol 10: 99
Meyer Zum Buschenfelde KH, Alberti A, Arnold W, Freudenberg J (1975) Organ specificity and diagnostic value of cell mediated immunity against a liver-specific membrane protein: Studies in hepatic and non-hepatic diseases. Klin Wochenschr 53: 1061
Miller KB, Schwartz RS (1979) Familial abnormalities of suppressor cell function in systemic lupus erythematosus. N Engl J Med 301: 803
Miller J, Smith MGM, Mitchell CG, Reed WD, Eddleston ALWF, Williams R (1972) Cell mediated immunity to a liver specific antigen in patients with active chronic hepatitis and primary biliary cirrhosis. Lancet 2: 296
Miller DJ, Duyer JM, Klatskin G (1977) Identification of lymphocytes in percutaneous liver biopsy cores. Gastroenterology 72: 1199
Miyakawa Y, Mayumi M (1978) Characterization and clinical significance of HBcAg. In: Vyas G, Cohen SN, Schmid R (eds) Viral hepatitis. The Franklin Institute Press, Philadelphia, p 193
Mogensen SC (1979) Role of macrophages in natural resistance to virus infection. Microbiol Rev 43: 1
Moretta L, Webb SR, Grossi CE, Lydyard PM, Cooper DM (1977) Functional analysis of two human T cell subpopulations: help and suppression of B cell responses by T cells bearing receptor for IgM and IgG. J Exp Med 146: 184
Mortensen RF, Osmand AP, Gewarz H (1975) Effects of C. reactive protein on the lymphoid system. J Exp Med 141: 821
Nelson DL, Bundy BM, Pitchon HE, Blaese RM, Strober W (1976) The effector cells in human peripheral blood mediating mitogen induced cellular cytotoxicity and antibody dependent cellular cytotoxicity. J Immunol 117: 1472
Neurath AR, Strick N (1977) Host specificity of a serum marker for hepatitis B: Evidence that “e antigen” has the properties of an immunoglobulin. Proc Natl Acad Sci USA 74: 1702
Nowolaski A, Krawczynski T, Nazarewicsz T, Scusarcyzk Y (1975) Immunologic aspects of hepatitis B virus infection. Am J Med Sci 270: 229
Paronetto F, Vernace S (1975) Immunological studies in patients with chronic active hepatitis. Clin Exp Immunol 19: 99
Pfizemaier K, Trostman H, Rollinghoff M, Wagner H (1976) Cell mediated immunity in lymphocytic choriomeningitis I. The specificty of cytotoxic lymphocytes. Z Immunitaetsforsch 151: 224
Redeker AG (1975) Viral hepatitis: Clinical aspects. Am J Med Sci 270: 9
Sabesin SM, Koff RS (1974) Pathogenesis of experimental viral hepatitis. N Engl J Med 290: 944
Sakane T, Green I (1977) Human suppressor T cells induced by concanavalin A: suppressor T cells belong to distinctive T cell subclasses. J Immunol 119: 1169
Seidel D, Alaupovic P, Furman RH (1969) A lipoprotein characterizing obstructive jaundice, method for quantitative separation and identification of lipoproteins in jaundiced subjects. J Clin Invest 48: 1211
Sell S, Skelly H, Leffert HL, Mueller-Eberhard W, Kida S (1975) Relationship of the Biosynthesis of a fetoprotein, albumin, hemopexin and haptoglobin to the growth state of fetal rat hepatocyte cultures. Ann NY Acad Sci 259: 45
Shif 1, Bang FB (1970) In vitro interaction of mouse hepatitis virus and macrophages from genetically resistant mice. I. Adsorption of virus and growth curves. J Exp Med 131: 843
Sorrell MF, Leevy CM (1972) Lymphocyte transformation and alcoholic liver injury. Gastroenterology 63: 1020
Stevens JG, Cook ML (1974) Maintenance of latent herpetic infection: an apparent role for anti-viral IgG. J Immunol 113: 1685
Tavassolie H, Kawanishi H (1978)Serum factors inhibition of lymphocyte proliferation and suppressor T cell function in alcoholic and chronic active liver disease. Gastroenterology 75: 990
Tomasi TB, (1977) Serum factors which suppress the immune response. In: Lucas DO (ed) regulatory mechanisms in lymphocyte activation. Academic Press, New York, p 219
Tong MJ, Wallace AM, Peters RL, Reynolds TB (1975) Lymphocyte stimulation in hepatitis B infections. N Engl J Med 293: 318
Vierling JM, Nelson PK, Strober W, Bundy BM, Jones EA (1977) In vitro cell-mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis, Dysfunction of spontaneous cell-mediated cytotoxicity in primary biliary cirrhosis. J Clin Invest 60: 1116
Vogten AJM, Hadzic N, Shorter RG, Summerskill WHJ, Taylor WF (1978) Cell-mediated cytotoxicity in chronic active liver disease: A new test system. Gastroenterology 74: 883
Wands JR, Isselbacher FJ (1975) Lymphocyte cytotoxicity to autologous liver cells in chronic active hepatitis. Proc Natl Acad Sci USA 72: 1301
Wands JR, Perrotto JL, Alpert E, Isselbacher KJ (1975) Cell-mediated immunity in acute and chronic hepatitis J Clin Invest 55: 921
Warnatz H, Rosch W, Gerlich W, Gutmann W (1979) Antibody-dependent cell-mediated cytotoxicity to HBsAg coated target cells in patients with hepatitis B and chronic hepatitis (CAH). Clin Exp Immunol 35: 133
Williams R, Eddleston ALWF (1979) Chronic active hepatitis: Immunopathogenesis and immunotherapy. Isr J Med Sci 15: 261
Zinkernagel RM, Doherty PC (1974) Restriction of in vitro T cell mediated cytotoxicity in lymphocyte choriomeningitis within a synergeneic or semiallogeneic system. Nature 248: 702
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Levy, G.A., Chisari, F.V. Theimunopathogenesis of cronic HBV inducedliver disease . Springer Semin Immunopathol 3, 439–459 (1981). https://doi.org/10.1007/BF01951492
Issue Date:
DOI: https://doi.org/10.1007/BF01951492