Zwitterionic polysaccharides of the normal flora bacteria represent a novel class of antigens in that they correct systemic CD4؉ T-cell deficiencies and direct lymphoid organogenesis during colonization of the host. Presentation of these polysaccharides to CD4؉ T cells depends on major histocompatibility complex class IIand DM-dependent retrograde transport from lysosomes to the cell surface. Yet the phenotype and clonality of the immune response to the polysaccharide in the mature host immune system have not been studied. Capsular polysaccharides of the human physiologic bacterial flora are immunogenic components that first encounter the human immune system during initial colonization and at the time that the immune system is developing and maturing. As opposed to common negatively charged polysaccharides, the biologic activities of certain commensal bacterial polysaccharides are unique in their ability to stimulate CD4 ϩ T cells in vivo and in vitro. They direct the development of the systemic cellular immune response by correcting CD4 ϩ T-cell deficiencies and TH1/TH2 imbalances toward a TH1 immune response. Responses to the polysaccharides are conferred by CD4 ϩ T cells, not B cells or other T cells (14,18,28,(31)(32)(33). Examples of such bacteria are the ubiquitous anaerobic member of the gut flora Bacteroides fragilis, Staphylococcus aureus as a temporary member of the skin and mucosal flora, and Streptococcus pneumoniae of the upper respiratory tract flora. CD4 ϩ T-cell activation induced by these polysaccharides depends on their unique electrical charge: each repeating unit has a minimum of one positive and one negative charge, leading to their common three-dimensional configuration characterized by a right-handed helix with repeating negatively charged grooves, with the positive charges being on the outer surface of the lateral boundaries (5,14,31,36). Presentation of the so-called zwitterionic polysaccharide (ZPS) from S. pneumoniae serotype 1 (Sp1) by major histocompatibility complex (MHC) class II molecules requires its retrograde transport from lysosomes to the cell surface within tubules as a ZPS-MHC class II complex and also requires the DM molecule (12,22). DM is known to catalyze and edit the exchange of the self-peptide CLIP with processed antigen in MHC class II compartments. The requirement of DM for Sp1 presentation via MHC class II suggests presentation within the antigen binding groove, which is supported by recent studies demonstrating that binding of the ZPS PS A1 from B. fragilis to MHC class II molecules can be competed by peptides known to be presented in the antigen binding cleft (7).For protein-derived T-cell antigens, it is well established that their presence in the MHC class II binding groove leads to the recognition of their antigenic epitopes by the T-cell receptor (TCR), within the CDR3 antigen binding domain of the -chain variable (BV) region, and to subsequent T-cell activation and oligoclonal T-cell proliferation. However, for ZPS, besides the requirement of engaging the ...
A 9-year-old body with X-linked agammaglobulinemia developed chronic enteroviral meningoencephalitis (CEMA) caused by echovirus type 6. Intravenous treatment with selected immunoglobulin charges containing high titers against echovirus type 6 or combination with beta-interferon did not result in improvement. After implantation of a Rickham reservoir and periodical administration of intraventricular and intravenous immunoglobulin the virus recurred rapidly each time treatment was stopped. After 20 months of treatment the patient received a combined therapy with beta-interferon and selected immunoglobulin. Both drugs were given by lumbar puncture, intravenously and via Rickham reservoir. Subsequently echovirus type 6 could not be isolated in culture or PCR. Cerebrospinal fluid pleocytosis disappeared. The remission is lasting for more than three years. Intrathecal and intraventricular beta-interferon therapy for CEMA is being reported for the first time. Facing the unfavourable prognosis of the disease this mode of treatment is a new therapeutic approach following failure of other therapies.
A new, modular Western blot (immunoblot) system for human immunodeficiency virus (HIV) antibodies (ABN WesPage; Wellcome) was compared with enzyme immunoassays (Wellcome, Behringwerke, and Abbott) and with a U.S. Food and Drug Administration (FDA)-licensed Western blot (DuPont) in a multicenter study. A total of 649 serum samples from HIV patients at different stages of the disease, as well as from high-risk patients, from patients with conditions unrelated to AIDS, and from healthy blood donors, were used in the evaluation along with nine seroconversion panels. For evaluation of Western blot reactivity, both Centers for Disease Control (CDC) and FDA criteria were used. With the DuPont Western blot as the reference assay, the overall sensitivity and specificity of the ABN WesPage were 100 and 99.1%, respectively, when indeterminate results were not taken into account and when both tests were interpreted in accordance with CDC criteria. The DuPont Western blot detected significantly more antibodies to pol and gag gene products than the ABN WesPage. The ABN WesPage showed a higher positive rate of detection of viral envelope band gpl60. When both Western blots were interpreted in accordance with CDC criteria, the ABN WesPage and the DuPont Western blot yielded 9.3 and 10.4% indeterminate results, respectively. When the DuPont Western blot was interpreted in accordance with the manufacturers instructions (FDA criteria), 25.7% of the samples tested were regarded as indeterminate. The choice of interpretation criteria is of paramount importance for the evaluation of HIV Western blot patterns.
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