PubMed · 4174142
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K Kouvalainen. 1968. [Immunoglobulins].. https://pubmed.ncbi.nlm.nih.gov/4174142/
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Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with hepatitis C virus. The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission, and its underlying mechanisms are not well understood. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although 70% to 80% of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive hepatitis C carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective hepatitis C virus vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology have engendered novel approaches to the fundamental problems encountered in vaccine development. Current therapy for hepatitis C, although effective in some patients, is problematic and still evolving. Advances in modern biology and immunology promise new therapies for this important disease.
The vaccination route may influence the success of immunization against pathogens. The conventional intramuscular (i.m.) application of a vaccine containing the hepatitis B virus (HBV) surface antigen (HBsAg) led to protective anti-HBs antibody levels in the majority of vaccine recipients. In this study, we vaccinated healthy volunteers and a group of i.m. vaccine nonresponders via the intradermal (i.d.) route and analyzed the HBV-specific B-cell response as well as class-II- and class-I-restricted T-cell responses by (3)H-thymidine uptake, enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT). The results were then compared with i.m. vaccinated controls. I.d. vaccinations were well tolerated and induced neutralizing anti-HBs antibodies in all naive vaccine recipients and, importantly, all but one former i.m. nonresponder developed protective anti-HBs serum antibody levels after 2 or 3 i.d. immunizations. On the cellular level, i.d. vaccine recipients showed significantly higher anti-HBs producing B-cell frequencies and more vigorous class-II-restricted T-helper (Th) cell responses than i.m. controls. However, although the HBsAg-specific T cells were characterized by their cytokine release as Th1-like cells in both groups, human leukocyte antigen (HLA)-A2+ individuals who received the soluble HBsAg via the i.d. route developed higher peptide-specific cytotoxic CD8+ T cell precursor (CTLp) frequencies. In conclusion, i.d. HBsAg vaccination is more effective even in former i.m. vaccine nonresponders with respect to antibody induction and specific B- and T-cell responses. The induction of virus-specific CTLp may provide the rationale to study the i.d. HBsAg vaccine in the treatment of chronic hepatitis B.
Differentiation of focal or extended lymphoid bone marrow infiltrates presents a diagnostic challenge and therefore warrants systematic evaluation of those features which affect this. One of the basic requirements is an appropriate technique of processing the bone marrow specimens. This includes the possibility of enzyme evaluation (naphthol-AS-D-chloroacetate esterase) and immunohistochemistry (set of monoclonal antibodies) and comparison with the corresponding lymph node histology. A number of histological parameters have emerged with a distinctive property for distinguishing between reactive focal lymphoid aggregates and malignant lymphomas. Amongst these the pattern of infiltrates, i.e., histotopography (subcortical infiltrates, paratrabcular-endosteal localization, margination, tandem-like extension between adipocytes and cribriform appearance), content of reticulin fibers, cytology (small lymphocytes versus large blast cells) and, finally, immunohistochemistry (monoclonal versus polyclonal expression of cytoplasmic immunoglobulins, uniform versus mixed population of B or T lymphocytes) are most important. In conclusion, synoptic consideration of several parameters, in particular histotopography and immunohistochemistry provides a most promising approach to differentiate neoplastic from reactive lymphoid lesions in the bone marrow.