Porcine reproductive and respiratory syndrome virus (PRRSV) causes immune dysregulation during the Critical Window of Immunological Development. We hypothesize that thymocyte development is altered by infected thymic antigen presenting cells (TAPCs) in the fetal/neonatal thymus that interact with double-positive thymocytes causing an acute deficiency of T cells that produces "holes" in the T cell repertoire allowing for poor recognition of PRRSV and other neonatal pathogens. The deficiency may be the result of random elimination of PRRSV-specific T cells or the generation of T cells that accept PRRSV epitopes as self-antigens. Loss of helper T cells for virus neutralizing (VN) epitopes can result in the failure of selection for B cells in lymph node germinal centers capable of producing high affinity VN antibodies. Generation of cytotoxic and regulatory T cells may also be impaired. Similar to infections with LDV, LCMV, MCMV, HIV-1 and trypanosomes, the host responds to the deficiency of pathogen-specific T cells and perhaps regulatory T cells, by "last ditch" polyclonal B cell activation. In colostrum-deprived PRRSV-infected isolator piglets, this results in hypergammaglobulinemia, which we believe to be a "red herring" that detracts attention from the thymic atrophy story, but leads to our second independent hypothesis. Since hypergammaglobulinemia has not been reported in PRRSV-infected conventionally-reared piglets, we hypothesize that this is due to the down-regulatory effect of passive maternal IgG and cytokines in porcine colostrum, especially TGFβ which stimulates development of regulatory T cells (Tregs).
- MeSH
- hypergamaglobulinemie krev etiologie metabolismus MeSH
- imunoglobulinové izotypy krev imunologie MeSH
- interakce hostitele a patogenu imunologie MeSH
- náchylnost k nemoci MeSH
- pandemie MeSH
- prasata MeSH
- protilátky virové krev imunologie MeSH
- reprodukční a respirační syndrom prasat krev epidemiologie etiologie MeSH
- T-lymfocyty cytologie imunologie metabolismus MeSH
- thymocyty cytologie imunologie metabolismus MeSH
- thymus imunologie metabolismus MeSH
- virus reprodukčního a respiračního syndromu prasat fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The objectives of this study were to evaluate patients with aortic abdominal aneurysm (AAA) with regard to immunoglobulin (Ig)G4-related disease (IgG4-RD). IgG4-RD represents a recently defined condition comprised of a collection of disorders characterized by IgG4 hypergammaglobulinemia, the presence of IgG4-positive plasma cells in organs affected with fibrotic or sclerotizing changes and typical histopathological features. It was identified as a possible cause of vasculitis in large vessels. Studies have been published on a possible association between inflammatory aortic or cardiovascular disease and IgG4-RD. We examined 114 patients with AAA requiring surgery in order to identify findings which are characteristic of IgG4-RD. Aneurysm samples from seven patients showed histopathological features consistent with IgG4-RD and the presence of IgG4+ plasma cells. Only two of these seven patients showed elevated IgG4 serum levels higher 1·35 g/l. In five of the patients, the concentration of serum IgG4 was lower than 1·20 g/l, with the number of IgG4+ plasma cells being higher than 50/high-power field. These findings were consistent with AAA being a heterogeneous group of inflammatory diseases with different pathogenesis.
- MeSH
- aneurysma břišní aorty krev imunologie patologie MeSH
- aorta imunologie metabolismus patologie MeSH
- hypergamaglobulinemie krev imunologie patologie MeSH
- IgG4 asociovaná nemoc krev imunologie patologie MeSH
- imunoglobulin G krev imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plazmatické buňky imunologie metabolismus patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- MeSH
- hypergamaglobulinemie diagnóza krev moč MeSH
- imunoelektroforéza statistika a číselné údaje trendy MeSH
- imunologické testy metody statistika a číselné údaje trendy MeSH
- lidé MeSH
- paraproteinemie diagnóza krev moč MeSH
- paraproteiny krev moč MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- artritida etiologie MeSH
- B-lymfocyty fyziologie MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- horečka etiologie MeSH
- hypergamaglobulinemie imunologie komplikace krev MeSH
- imunofenotypizace využití MeSH
- imunoglobulin D krev MeSH
- lidé MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
