Modulating offspring responses: concerted effects of stress and immunogenic challenge in the parental generation

ABSTRACTThe perception, processing and response to environmental challenges involves the activation of the immuno-neuroendocrine (INE) interplay. Concerted environmental challenges might induce trade-off when resource allocation to one trait occurs at the expense of another, also producing potential transgenerational effects in the offspring. We evaluated whether concerted challenges, in the form of an immune inoculum against inactivated Salmonella enteritidis (immune challenge, ICH) and a chronic heat stress (CHS) exposure on adult Japanese quail, modulate the INE responses of the parental generation and their offspring. Adults were inoculated and later exposed to a CHS along nine consecutive days. For the last 5 days of the CHS, eggs were collected for incubation. Chicks were identified according to their parental treatments and remained undisturbed. Induced inflammatory response, heterophil/lymphocyte (H/L) ratio and specific humoral response against sheep red blood cells (SRBC) were evaluated in both generations. Regardless of the ICH, stressed adults showed a reduced inflammatory response and an elevated H/L ratio compared with controls. In offspring, the inflammatory response was elevated and the specific SRBC antibody titres were diminished in those chicks prenatally exposed to CHS, regardless of the ICH. No differences were found in the H/L ratio of the offspring. Together, our results suggest that CHS exposure influences the INE interplay of adult quail, establishing trade-offs within their immune system. Moreover, CHS not only affected parental INE responses but also modulated their offspring INE responses, probably affecting their potential to respond to future challenges. The adaptability of the developmental programming of offspring would depend on the environment encountered.

Prognostic Value of Circulating IGFBP2 and Related Autoantibodies in Children with Metastatic Rhabdomyosarcomas

Insulin-like growth factor-binding protein 2 (IGFBP2) is a tumor-associated protein measurable in patients’ biopsies and blood samples. Increased IGFBP2 expression correlates with tumor severity in rhabdomyosarcoma (RMS). Thus, we examined the plasmatic IGFBP2 levels in 114 RMS patients and 15 healthy controls by ELISA assay in order to evaluate its value as a plasma biomarker for RMS. Additionally, we looked for the presence of a humoral response against IGBFP2 protein measurable by the production of anti-IGFBP2 autoantibodies. We demonstrated that both circulating IGFBP2 protein and autoantibodies were significantly higher in RMS patients with respect to controls and their combination showed a better discriminative capacity. IGFBP2 protein identified metastatic patients with worse event-free survival, whereas both IGFBP2 and anti-IGFBP2 antibodies negatively correlated with overall survival. Our study suggests that IGFBP2 and anti-IGFBP2 antibodies are useful for diagnostic and prognostic purposes, mainly as independent negative prognostic markers in metastatic patients. This is the first study that reports a specific humoral response in RMS plasma samples and proves the value of blood-based biomarkers in improving risk assessment and outcome of metastatic RMS patients.

Evaluation of the Immunoprotective Potential of Recombinant Paraflagellar Rod Proteins of Trypanosoma evansi in Mice

Trypanosomosis, caused by Trypanosoma evansi, is an economically significant disease of livestock. Systematic antigenic variation by the parasite has undermined prospects for the development of a protective vaccine that targets the immunodominant surface antigens, encouraging exploration of alternatives. The paraflagellar rod (PFR), constituent proteins of the flagellum, are prominent non-variable vaccine candidates for T. evansi owing to their strategic location. Two major PFR constituent proteins, PFR1 (1770bp) and PFR2 (1800bp), were expressed using Escherichia coli. Swiss albino mice were immunized with the purified recombinant TePFR1 (89KDa) and TePFR2 (88KDa) proteins, as well as with the mix of the combined proteins at equimolar concentrations, and subsequently challenged with virulent T. evansi. The PFR-specific humoral response was assessed by ELISA. Cytometric bead-based assay was used to measure the cytokine response and flow cytometry for quantification of the cytokines. The recombinant TePFR proteins induced specific humoral responses in mice, including IgG1 followed by IgG2a and IgG2b. A balanced cytokine response induced by rTePFR 1 and 2 protein vaccination associated with extended survival and improved control of parasitemia following lethal challenge. The observation confirms the immunoprophylactic potential of the covert antigens of T. evansi.

Features of the specific humoral response and cytokine regulation in whooping cough in children

In the article there is presented the comparative analysis of the character of the specific humoral response to pertussis in dependence on the age, terms of the disease and vaccination history in 279 patients, among which 114 patients were under 1 and 165 patients - over 1 year of the age. In the study of the level of the production of antibodies of different isotypes in unvaccinated patients of different age in dependence on the terms of medical examination it has been revealed that in the patients under the age of 1 year there was typical the low production of all the classes of antibodies in any time of the disease, especially IgM. It has been shown that in babies aged from 0 to 3 and from 4 to 6 months old the production level of these immunoglobulins in examination at the early stages of the disease was established to be considerably lower than in the patients at the age from 7 to 12 months, and was equal to 1,1 ± 0,4 and 1,5 ± 0,1 U/ml versus 9,1 ± 3,8 U/ml correspondingly, (p

Red-Eared Slider Turtles Lack Response to Immunization with Keyhole Limpet Hemocyanin but Have High Levels of Natural Antibodies

While the specific humoral response of reptiles is slow and does not typically increase in titer or binding affinity upon secondary immunization, reptiles produce polyreactive natural antibodies (NAbs) that have low binding affinity and are produced in the absence of antigen stimulation. Given the poor specific response, NAbs may be an important protective resource in reptiles. In order to investigate the relative contributions of natural and specific antibodies, we immunized turtles with the novel antigen keyhole limpet hemocyanin (KLH). We did not detect an increase in antibody titers. However, preimmunization titers to KLH, as well as to a series of other novel antigens, were high in the turtles, indicating a strong NAb response. Interestingly, we found an age-associated increase in NAb titers in adults. Overall, our data suggest that reptiles may use NAbs as part of a strong innate immune response rather than relying on slower specific humoral responses.