Different Aspects Of Immune Function Research Articles

Abstract 1343: SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC

Abstract We sought to assess the role of single nucleotide polymorphisms (SNPs) in genes of the alternative NF-KB pathway, important in regulating different aspects of immune functions in colorectal cancer (CRC). The study comprised DNA samples from 418 patients with CRC and 299 age-matched healthy individuals. Genotyping was performed with real time PCR followed by high resolution melt curve analysis for the following SNPs: CD40 rs1883832 (C/T), BAFFR rs7290134 (A/G), LTβR rs10849448 (A/G). Genotypes of random samples were confirmed by sequencing. Genotype frequencies differed between CRC and healthy individuals for CD40 rs1883832 and LTβR rs10849448 (p = 0.001 and p = 0.016, respectively) but were similar for BAFFR rs7290134. The LTβR rs10849448 G allele was more frequent in CRC patients compared to healthy controls and increased risk for CRC by 61% (p = 0.024). Moreover, the G allele was found more frequently in stage D patients compared to stages A and C while the A allele was more prevalent in stage B patients (p = 0.007). Additionally, most patients with grade III tumors were G allele carriers whereas the majority of grade I tumors were AA homozygotes (p = 0.019). The CD40 rs1883832 T allele was less frequent in CRC patients and reduced risk for CRC by 71% (p = 0.027). The CD40 rs1883832 SNP proved to be a prognostic factor for PFS with the CC individuals displaying a longer PFS compared to T carriers (p = 0.045). The BAFFR rs7290134 SNP was independent of all clinical parameters evaluated. Primary site was independent of genotypes for all three SNPs. SNPs within genes of receptors of the NF-KB alternative pathway, CD40 rs1883832 and LTβR rs10849448, influence PFS and risk for CRC development. Additionally, particular genotypes correlated with stage and grade. Citation Format: Anna Antonacopoulou, Anastasia Kottorou, Angelos Koutras, Foteinos-Ioannis Dimitrakopoulos, Thomas Makatsoris, Haralabos P. Kalofonos. SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1343.

Sex and life history shape the strength of cellular and humoral immune responses in a wing dimorphic cricket

Immune function is a complex collection of responses that often trade-off with one another and with other life history traits, because of the high costs of mounting and maintaining immune responses. Animals, even those from the same populations, may emphasize different aspects of immune function depending on their habitat and phenotype. For example, host population density mediates the threat from density-dependent parasites. Animals at high densities may emphasize fast-acting humoral responses, while those at low densities may favor slower, but more specific, cellular responses. However, these predictions may be dependent on other life history traits, like sex, which is associated with variation in many immune responses. We used wing dimorphic Gryllus firmus crickets to test humoral responses, measured by lysozyme and phenoloxidase activities, and cellular immune responses, measured by encapsulation, between morphs and sex. We found that both morphs and sexes differed in aspects of immune function. Long wing morphs had stronger encapsulation responses than short winged morphs. Additionally, females exhibited higher PO activity than males, and by contrast, males had higher lysozyme activity than females. Our study suggests that G. firmus morphs prioritize different immune responses that may reflect a balancing between the costs of immunity and differing pathogen threats. Male and female crickets exhibit differences in humoral immune responses that may reflect their different life history demands.

The alternative NF-κB pathway in colorectal cancer: From genetic polymorphisms through mRNA to protein levels.

e15619Background: In colorectal cancer (CRC), there is scarce information regarding the alternative NF-κB pathway which regulates different aspects of immune functions. Methods: Formalin-fixed para...

Comparison of the immunomodulatory and epigenetic regulatory effects of natural estrogen 17-β estradiol and its synthetic analog 17α-ethinyl estradiol in NZB/WF1 mice

Abstract Concern is increasing regarding the effects of environmental exposures to different Estrogenic Endocrine Disrupting Chemicals (EEDCs) on immune system function. 17α-ethinyl estradiol (EE), a synthetic analog of natural estrogen 17-β estradiol (E2), is a primary component in oral contraceptive pills (OCP) and has been found in sewage effluents. In this study, to compare the immune and epigenetic regulatory effects of environmental E2 and EE exposure in NZB/WF1 mice, we implanted gonadal intact female NZB/WF1 mice with E2 or EE. While the effect of EE was more profound, both E2 and EE exposures caused splenomegaly, altered splenic and thymic T cell composition and activation, increased splenic neutrophil percentage, and promoted inflammatory molecules iNOS/NO and the chemokine MCP-1 in ex vivo-activated splenocytes. Impressively, we found that E2 and EE had differential effects on the induction of different inflammatory cytokines in ex vivo activated splenocytes (e.g. IFNβ and IL-1β were increased in LPS-activated splenocytes from EE-treated NZB/WF1 mice, but were decreased in LPS-activated splenocytes from E2-treated mice when compared to placebo controls). Also, in vivo EE exposure promoted, and E2 reduced, TLR9 agonist-induced IFNα production in splenocytes. We further demonstrated that E2 and EE regulated the expression of numerous immune-related genes and miRNAs in a similar manner, while EE had a stronger effect than E2 on the regulation of miRNAs expression. Moreover, we found that EE, but not E2 treatment, significantly reduced the global DNA methylation level in NZB/WF1 splenocytes. Together, our data revealed similar and also differential regulatory effects of E2 and EE on the different aspects of immune function.

The non-canonical NF-κB pathway in immunity and inflammation.

The nuclear factor-κB (NF-κB) family of transcription factors is activated by canonical and non-canonical signalling pathways, which differ in both signalling components and biological functions. Recent studies have revealed important roles for the non-canonical NF-κB pathway in regulating different aspects of immune functions. Defects in non-canonical NF-κB signalling are associated with severe immune deficiencies, whereas dysregulated activation of this pathway contributes to the pathogenesis of various autoimmune and inflammatory diseases. Here we review the signalling mechanisms and the biological function of the non-canonical NF-κB pathway. We also discuss recent progress in elucidating the molecular mechanisms regulating non-canonical NF-κB pathway activation, which may provide new opportunities for therapeutic strategies.

Ubiquitin signaling in immune responses.

Ubiquitination has emerged as a crucial mechanism that regulates signal transduction in diverse biological processes, including different aspects of immune functions. Ubiquitination regulates pattern-recognition receptor signaling that mediates both innate immune responses and dendritic cell maturation required for initiation of adaptive immune responses. Ubiquitination also regulates the development, activation, and differentiation of T cells, thereby maintaining efficient adaptive immune responses to pathogens and immunological tolerance to self-tissues. Like phosphorylation, ubiquitination is a reversible reaction tightly controlled by the opposing actions of ubiquitin ligases and deubiquitinases. Deregulated ubiquitination events are associated with immunological disorders, including autoimmune and inflammatory diseases.

Heritability of immunological characteristics in Florida Scrub-Jays (Aphelocoma coerulescens)

The degree to which immunological phenotype is under genetic control as opposed to plasticity in response to variable environmental conditions remains largely unknown in natural populations. We assessed different aspects of immune function in father–son pairs in Florida Scrub-Jays (Aphelocoma coerulescens (Bosc, 1795)), a species with high natal philopatry, to determine if the responses were heritable. Specifically, we examined heritability of the (i) heterophil to lymphocyte ratio, (ii) ability to kill the Gram-negative bacteria Escherichia coli in an in vitro challenge, and (iii) ability to kill the Gram-positive bacteria Staphylococcus aureus in an in vitro challenge. The heritability (h2) of each of the three measures described above was estimated as twice the slope of the regression (2β) from the mean value for each measure for sons on the mean value of the same measure for the father. Heritability estimates were high for all measures: heterophil to lymphocyte ratios (h2 = 1.54 ± 0.31) and E. coli (h2 = 1.84 ± 0.12) and S. aureus (h2 = 1.13 ± 0.16) killing abilities. Our results show a strong correlation between father and son immune function, as well as the influential nature of genetic inheritance and potential environmental effects associated with high natal philopatry on physiology.

Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being.

PPARs in Alveolar Macrophage Biology

PPARs, most notably PPAR-γ, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-γ and its ligands in deactivating alveolar macrophages—thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus—while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-γ responses play in specific lung diseases.

Impact of vitamin E on immune function and its clinical implications

Vitamin E is a chain-breaking antioxidant that protects membranes from free-radical damage. Evidence suggests significant impact of vitamin E on the modulation of immune functions. Results from animal and human studies indicate that vitamin E deficiency impairs both humoral and cell-mediated immune functions. Supplementation of vitamin E above the recommended levels has been shown to enhance immune functions and to be associated with increased resistance against several pathogens, especially in the aged. The current vitamin E consumption status from diets, the status of vitamin E supplement use, the effects of vitamin E on different aspects of immune functions and mechanisms of its action and the clinical significance of vitamin E supplementation will be reviewed.

Immunocompetence and testosterone-induced condition traits in male ruffs (Philomachus pugnax)

Abstract The immune system is costly to operate, so we expect allocation to this function to relate to other indices of overall phenotypic condition. In captive male ruffs (Philomachus pugnax), we examine covariation between three seasonal male characteristics induced by testosterone (neck 'ruff', facial wattles, and increases in mass/size) and cell-mediated and humoral immunity. The ruff has two genetically distinct morphs of males, 'independents' and 'satellites', which differ in mating behaviour, somewhat in body size, and possibly life history strategy. Ruff length and wattle number were significantly correlated with each other and with body size, but unrelated to mass/size. Humoral immunity was weakly correlated with size, but not with secondary male traits, or with cell-mediated immunity. We did not detect differences in humoral immunity between morphs. Cell-mediated immunity was weakly correlated with ruff length, but not with wattle number, size, or mass/size. Cell-mediated immunity decreased significantly with age. Controlling for age, independents had higher cell-mediated immunity responses than satellites. The expected relationships between two measures of immune function and other measures of condition were not always present, which suggests we need more data and/or more specific predictions about how the different aspects of immune function relate to each other and to ecological variables.

Alteration of the immune response of the common marine mussel Mytilus edulis resulting from exposure to cadmium

DAO Diseases of Aquatic Organisms Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsSpecials DAO 22:59-65 (1995) - doi:10.3354/dao022059 Alteration of the immune response of the common marine mussel Mytilus edulis resulting from exposure to cadmium Coles JA, Farley SR, Pipe RK The common marine mussel Mytilus edulis was used in laboratory-controlled experiments to investigate the effects of exposure to cadmium on immune capability. Haemolymph was extracted from mussels exposed for 7 d to 40 and 400 ug l-1 of cadmium, and assays were carried out to investigate the potential for immune response. The assays included total and differential haemocyte counts, the release of intracellular and extracellular reactive oxygen metabolites, phagocytosis, release of degradative enzymes and uptake of neutral red. Cadmium at 400 ug l-1 resulted in significantly enhanced numbers of circulating haemocytes and increased uptake of neutral red. No alteration was demonstrated in proportions of circulating haemocyte types, phagocytosis or production of reactive oxygen metabolites. The release of degradative enzymes during phagocytosis was found to be significantly suppressed at the 40 ug l-1 cadmium concentration. Assays to determine the immune function may provide a sensitive measure of the health status of an individual or population under pollutant stress. However the variability in effects produced in different aspects of immune function emphasises the need for a multi-assay approach to monitoring pollution. The observed effects on immunocompetence, at environmentally realistic levels of contaminant, support the view that a relationship exists between pollution and immunomodulation in aquatic organisms. Mussel . Immunocompetence . Haemolymph . Cadmium Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in DAO Vol. 22, No. 1. Publication date: May 04, 1995 Print ISSN:0177-5103; Online ISSN:1616-1580 Copyright © 1995 Inter-Research.