The effect of colostral maternal antibodies (Abs), acquired via colostrum, on passive protection and development of systemic and mucosal immune responses against rotavirus was evaluated in neonatal calves. Colostrum-deprived (CD) calves, or calves receiving one dose of pooled control colostrum (CC) or immune colostrum (IC), containing an IgG1 titer to bovine rotavirus (BRV) of 1:16,384 or 1:262,144, respectively, were orally inoculated with 105.5 FFU of IND (P[5]G6) BRV at 2 days of age. Calves were monitored daily for diarrhea, virus shedding and anti-BRV Abs in feces by ELISA. Anti-rotavirus Ab titers in serum were evaluated weekly by isotype-specific ELISA and virus neutralization (VN). At 21 days post-inoculation (dpi), all animals were euthanized and the number of anti-BRV antibody secreting cells (ASC) in intestinal and systemic lymphoid tissues were evaluated by ELISPOT. After colostrum intake, IC calves had significantly higher IgG1 serum titers (GMT=28,526) than CC (GMT=1195) or CD calves (GMT<4). After BRV inoculation, all animals became infected with a mean duration of virus shedding between 6 and 10 days. However, IC calves had significantly fewer days of diarrhea (0.8 days) compared to CD and CC calves (11 and 7 days, respectively). In both groups receiving colostrum there was a delay in the onset of diarrhea and virus shedding associated with IgG1 in feces. In serum and feces, CD and CC calves had peak anti-BRV IgM titers at 7 dpi, but IgA and IgG1 responses were significantly lower in CC calves. Antibody titers detected in serum and feces were associated with circulation of ASC of the same isotype in blood. The IC calves had only an IgM response in feces. At 21 dpi, anti-BRV ASC responses were observed in all analyzed tissues of the three groups, except bone marrow. The intestine was the main site of ASC response against BRV and highest IgA ASC numbers. There was an inverse relationship between passive IgG1 titers and magnitude of ASC responses, with fewer IgG1 ASC in CC calves and significantly lower ASC numbers of all isotypes in IC calves. Thus, passive anti-BRV IgG1 negatively affects active immune responses in a dose-dependent manner. In ileal Peyer's patches, IgM ASC predominated in calves receiving colostrum; IgG1 ASC predominated in CD calves. The presence in IC calves of IgG1 in feces in the absence of an IgG1 ASC response is consistent with the transfer of serum IgG1 back into the gut contributing to the protection of the intestinal mucosa.
Advanced unresectable squamous cell carcinoma of the skin (SCCS) is a rare condition, which is difficult to treat. Because of its rarity, few therapeutic trials are available. Moreover, SCCS often occur in elderly. Conventional treatment options for advanced SCCS are chemotherapy mainly with cisplatin-based regimens. Immunotherapy with interferon alpha and retinoids combination was also shown to be efficient. Toxicity of these treatments limits, however, their use in elderly patients and an initial work up for a global assessment is needed in order to adapt the choice. More recently, epithelial growth factor receptor (EGFR) targeted therapies have been developed and induced interesting response rates in small series of patients with unresectable SCCS. Their efficacy in SCCS must be confirmed by larger phase III trials and the identification of predictive biological factors of response is warranted. New therapeutic approaches combining EGFR inhibitors either with IGFR inhibitors, or immunomodulators or inhibitors of the PI3K/AKT/mTOR pathway are currently under evaluation in head and neck carcinomas and might represent valuable therapeutic approaches for unresectable SCCS. Moreover, there are several new molecular candidate treatment targets for unresectable SCCS including somatic NOTCH1 or NOTCH2 inactivating mutations, ALK1, which could be a good candidate for antiangiogenic therapy and matrix metallopeptidase 7, which enhances proliferation, migration, and invasion of cancer cells. Organ transplant recipients often develop SCCS and in some patients, SCCS are rapidly progressing. Management of SCCS in this subgroup of patients includes both carcinologic treatment and modification of immunosuppression. Specific treatment is generally the same as in immunocompetent patients. Switching from calcineurin inhibitors to sirolimus or reducing immunosuppression has to be considered.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.