IMMUNE COMPLEX DISEASE IN CHRONIC VIRAL INFECTIONS

1971 ◽  
Vol 134 (3) ◽  
pp. 32-40 ◽  
Author(s):  
Michael B. A. Oldstone ◽  
Frank J. Dixon
Keyword(s):  
Immune Complex ◽  
Complex Disease ◽  
Viral Infections ◽  
Immune Complex Disease ◽  
Chronic Viral Infections ◽  
Hog Cholera ◽  
B Virus ◽  
Human Disorders ◽  
Antiviral Antibody ◽  
Murine Infections

Chronic viral infections of animals associated with immune complex disease resemble a number of human disorders. At present, on the basis of showing (a) virus, host antiviral antibody, and C3 deposited in a granular pattern along the glomerular capillary wall and in the mesangia and (b) virus-host Ig (presumably antiviral antibody) complexes in the circulation, immune complex disease occurs in chronic murine infections with LCM, LDV, MSV, and ADM. In addition, granular deposits in the glomeruli in Coxsachie B, polyoma, other leukemic viral infections in mice, equine anemia, and hog cholera suggest that immune complex disease also occurs in these infections. In transplacental LCM infections maternal antiviral antibody transferred in utero or via milk induces very early and severe immune complex disease. The severity of immune complex nephritis in mice neonatally or transplacentally infected with LCM virus is directly proportional to the amount of Ig elutable from the kidney and to the proportion of this Ig which reacts with the infecting virus.

INFECTIOUS VIRUS-ANTIBODY COMPLEXES: INTERACTION WITH ANTI-IMMUNOGLOBULINS, COMPLEMENT, AND RHEUMATOID FACTOR

1971 ◽  
Vol 134 (3) ◽  
pp. 41-51 ◽  
Author(s):  
Abner Louis Notkins
Keyword(s):  
Rheumatoid Factor ◽  
Immune Complex ◽  
Complex Disease ◽  
Infectious Virus ◽  
Immune Complex Disease ◽  
Virus Antibody ◽  
Extensive Coverage ◽  
Antiviral Antibody

Interaction of antiviral antibody with the virion can result in the formation of infectious VA complexes. These complexes have been recovered from the blood of chronically infected animals and have been produced in vitro. Incubation of infectious VA complexes with specific anti-immunoglobulins or the purified first and fourth components of complement resulted in neutralization. With subneutralizing concentrations of the first and fourth components of complement, neutralization was enhanced by the addition of the second and third components of complement. RF attached to infectious VA complexes but failed to produce neutralization. The attachment of RF to VA complexes, however, increased the susceptibility of these complexes to neutralization by complement. These findings support the hypothesis that anti-immunoglobulins and complement result in neutralization by more extensive coverage of the surface of the virion than occurs with antiviral antibody alone. Other experiments showed that antiviral antibody increased the sedimentation of radio-labeled virus and that rate-zonal centrifugation could be used to purify VA complexes and to study factors which influence the association and dissociation of these complexes. Our experiments suggest that in vivo the attachment of accessory factors to infectious VA complexes might enhance virus neutralization and play a role in the pathogenesis of virus-induced immune complex disease.

scholarly journals DISEASE ACCOMPANYING IN UTERO VIRAL INFECTION

1972 ◽  
Vol 135 (4) ◽  
pp. 827-838 ◽  
Author(s):  
Michael B. A. Oldstone ◽  
Frank J. Dixon
Keyword(s):  
Viral Infection ◽  
Immune Complex ◽  
Infected Mouse ◽  
Complex Disease ◽  
In Utero ◽  
Immune Complex Disease ◽  
Immune Complex Glomerulonephritis ◽  
Viral Antibody ◽  
Glomerular Deposits ◽  
Antiviral Antibody

Early, after in utero infection with LCM virus, SWR/J and HA/ICR mice developed manifestations of immune complex disease. Observations based on nursing such mice with virus-infected, immune, or noninfected mouse mothers indicated that maternal antiviral antibody was responsible for the early immune complex glomerulonephritis. Despite comparable viral persistance, in utero-infected offspring failed to develop glomerulonephritis when nursed by noninfected mouse mothers, but did when suckled by virus-infected mouse mothers. Nursing by mouse mothers carrying high titers of anti-LCM viral antibody markedly enhanced the Ig glomerular deposits and the resultant nephritis.

scholarly journals C1q nephropathy: a true immune complex disease or an immunologic epiphenomenon?

2009 ◽  
Vol 2 (4) ◽  
pp. 285-291
Author(s):  
M. Muorah ◽  
M. D. Sinha ◽  
C. Horsfield ◽  
P. J. O'Donnell
Keyword(s):  
Immune Complex ◽  
Complex Disease ◽  
Immune Complex Disease ◽  
C1q Nephropathy

Immunopathology of Immune Complex Disease

1983 ◽  
pp. 371-390
Author(s):  
U. E. Nydegger ◽  
M. D. Kazatchkine ◽  
P. H. Lambert ◽  
P. A. Miescher
Keyword(s):  
Immune Complex ◽  
Complex Disease ◽  
Immune Complex Disease

scholarly journals Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice

2016 ◽  
Vol 90 (19) ◽  
pp. 8563-8574 ◽  
Author(s):  
Marianna Di Scala ◽  
Itziar Otano ◽  
Irene Gil-Fariña ◽  
Lucia Vanrell ◽  
Mirja Hommel ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Chronic Hepatitis B ◽  
Viral Infections ◽  
Chronic Viral Infections ◽  
B Virus ◽  
Interleukin 15

ABSTRACTIn chronic hepatitis B (CHB), failure to control hepatitis B virus (HBV) is associated with T cell dysfunction. HBV transgenic mice mirror many features of the human disease, including T cell unresponsiveness, and thus represent an appropriate model in which to test novel therapeutic strategies. To date, the tolerant state of CD8+T cells in these animals could be altered only by strong immunogens or by immunization with HBV antigen-pulsed dendritic cells; however, the effectors induced were unable to suppress viral gene expression or replication. Because of the known stimulatory properties of alpha interferon (IFN-α) and interleukin-15 (IL-15), this study explored the therapeutic potential of liver-directed gene transfer of these cytokines in a murine model of CHB using adeno-associated virus (AAV) delivery. This combination not only resulted in a reduction in the viral load in the liver and the induction of an antibody response but also gave rise to functional and specific CD8+immunity. Furthermore, when splenic and intrahepatic lymphocytes from IFN-α- and IL-15-treated animals were transferred to new HBV carriers, partial antiviral immunity was achieved. In contrast to previous observations made using either cytokine alone, markedly attenuated PD-L1 induction in hepatic tissue was observed upon coadministration. An initial study with CHB patient samples also gave promising results. Hence, we demonstrated synergy between two stimulating cytokines, IL-15 and IFN-α, which, given together, constitute a potent approach to significantly enhance the CD8+T cell response in a state of immune hyporesponsiveness. Such an approach may be useful for treating chronic viral infections and neoplastic conditions.IMPORTANCEWith 350 million people affected worldwide and 600,000 annual deaths due to HBV-induced liver cirrhosis and/or hepatocellular carcinoma, chronic hepatitis B (CHB) is a major health problem. However, current treatment options are costly and not very effective and/or need to be administered for life. The unprecedented efficacy of the strategy described in our paper may offer an alternative and is relevant for a broad spectrum of readers because of its clear translational importance to other chronic viral infections in which a hyporesponsive antigen-specific T cell repertoire prevents clearance of the pathogen.

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