Delayed Hypersensitivity in Hepatitis B: Clinical Correlates of in Vitro Production of Migration Inhibition Factor

Abstract

Delayed hypersensitivity to hepatitis B surface antigen (HBsAg) in patients with disease from the clinical spectrum of hepatitis and in controls was examined by an indirect assay of macrophage migration inhibitory factor. Activity was demonstrated in cases of acute or persistently active hepatitis. Steroids and pregnancy had a suppressive effect. Samples from a patient with transfusion-related HBsAg hepatitis were also assayed. A broad clinical spectrum of disease is associated with the presence of hepatitis B surface antigen (HBsAg) in the blood. It has been suggested that the host's immune response is related to the clinical type of disease [1-4]. Delayed hypersensitivity, a cellular immune response to antigenic stimulation, is recognized as an important immunological phenomenon in the pathogenesis and/or prevention of many diseases. Skin testing has been the classical method of studying delayed hypersensitivity to many antigens in animals and humans. In 1951 Henle et al. [5] reported skin reactions in humans to am

Immune responses to the hepatitis B surface antigen and liver-specific lipoprotein in acute type B hepatitis.

“…Extensive washing of the lymphocytes often restores their cytotoxic potential (Currie and Basham, 1972) and it may be that differences in methods of preparing leucocytes and in antigen concentrations are responsible for the variation in the reported frequency of positive results in the leucocyte migration test with HBsAg as antigen in the early stages of acute hepatitis (Dudley et al, 1972b;Frei et al, 1973;Yeung Laiwah et al, 1973;Irwin et al, 1974;Ibrahim et al, 1975). In vivo, this blocking effect might act to prevent T cell damage to infected hepatocytes and, while this could be important in the maintenance of infection in patients with chronic liver disease, it is probably irrelevant in acute hepatitis at the time of clinical presentation as immunofluorescent examination of liver biopsies usually shows that there are no remaining infected cells (Portmann et al, 1976).…”

“…Several lines of evidence suggest that the hepatitis B virus is not cytopathogenic and that liver damage may be the result of immune-mediated destruction of infected hepatocytes (Dudley et al, 1972a;Eddleston, 1976). In almost all patients with acute hepatitis B infection a cell-mediated response to HBsAg can be demonstrated after recovery (Yeung Laiwah et al, 1973;Irwin et al, 1974;Reed et al, 1974), but there is conflicting evidence as to how early in the illness this can be detected. We report here the results of a serial prospective study of the cellular and humoral immune response to HBsAg in 21 cases of acute hepatitis type B, all of whom were followed from the time of presentation until antigen clearance was complete and the standard biochemical liver function tests had returned to normal.…”

Autoimmune reaction to a liver specific membrane antigen during acute viral hepatitis.

“…Recent studies using the lymphocyte transformation (Laiwah, 1971) and leucocyte migration tests (Irwin et al, 1974;Reed et al, 1974) have shown that sensitization to the hepatitis B surface antigen can be detected in the majority of cases of antigen positive hepatitis. This, together with the recent demonstration of HBsAg on the surface of hepatocytes during acute hepatitis B infection (Alberti et al, 1975), supports the concept that a T-cell mediated immune reaction directed against virus bearing hepatocytes is responsible for the liver damage (Dudley et al, 1972).…”

T cell-mediated cytotoxicity against HBsAg-coated Chang cells in patients with chronic hepatitis: Evidence for cytotoxicity mediated by delayed hypersensitivity T cell reaction.

“…Several recent investigations reported that cell-mediated reactions to HBsAg were observed in about half of the patients with chronic hepatitis, using a lymphocyte stimulation test, macrophage migration inhibition test and leukocyte migration inhibition test (Dudley et al 1972b;Irwin et al 1974; Lee et al 1975;Tong et al 1975;Ohta et al, 1976Frei et al 1978. These suggest that the cell-mediated immune response to HBsAg may be responsible for elimination of this antigen from the liver.…”