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Immune Components (immune + component)
Selected AbstractsImmune enhancement of nitroreductase-induced cytotoxicity: Studies using a bicistronic adenovirus vectorINTERNATIONAL JOURNAL OF CANCER, Issue 1 2003Nicola K. Green Abstract The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in preclinical studies and is currently being assessed in phase I clinical trials. It is well established that there is an immune component to the bystander effect observed with other systems such as thymidine kinase and cytosine deaminase; however, such an effect has not previously been described using NR. We have preliminary data suggesting an immune bystander effect with NR to further examine these effects and their potential enhancement by cytokines, an adenoviral vector containing CMV-NR, an internal ribosome entry site (IRES) and the gene for murine GM-CSF (mGM-CSF) was constructed. The NR-GM-CSF virus was validated in 2 experimental models and demonstrated increased therapeutic efficacy in the MC26 murine colorectal tumour model. These data illustrate that the combination of suicide gene therapy using NR and CB1954 with immune stimulation via GM-CSF gives an improved response compared to either modality alone and suggests that the immune component of this response may be beneficial in combating unresectable, metastatic disease and preventing tumour recurrence. © 2002 Wiley-Liss, Inc. [source] Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia,HEPATOLOGY, Issue 4 2008Maura Dandri Analysis of hepatitis B virus (HBV) kinetics with mathematical models may disclose new aspects of HBV infection and host response mechanisms. To determine the kinetics of virion decay from the blood of patients in different phases of chronic infection, we applied mathematical modeling to real-time polymerase chain reaction assays, which enable quantification of viremia and intrahepatic HBV productivity by measuring both copy number and activity of covalently closed circular DNA (relaxed circular DNA/covalently closed circular DNA) in the liver of 80 untreated chronically active HBV carriers (38 hepatitis B e antigen [HBeAg]-positive and 42 HBeAg-negative individuals). We found that the half-life of circulating virions is very fast (median 46 and 2.5 minutes in HBeAg-positive and HBeAg-negative individuals, respectively) and strongly related to viremia, with clearance rates significantly accelerating as viral loads decrease. To investigate whether immune components can influence the kinetics of virion decay, we analyzed viral dynamics in immunodeficient urokinase-type plasminogen activator chimera mice. Virion half-life in mice (range, 44 minutes to >4 hours) was comparable to estimates determined in high viremic carriers, implying that clearance rates in these patients are mostly determined by common nonspecific mechanisms. Notably, the lack of correlation between virion half-life and viremia in mice indicated that immune components significantly accelerate virion clearance rates in individuals with low titers. Conclusion: Our analyses suggest that both host defense mechanisms and levels of circulating virions affect the kinetics of HBV decay assessed in the serum of chronic carriers. Identification of the factors affecting clearance rates will be important for future antiviral drug developments and it may give insights into the mechanisms involved in clearance of other chronic infections, such as human immunodeficiency virus and hepatitis C virus. (HEPATOLOGY 2008.) [source] Dissecting innate immunity by germline mutagenesisIMMUNOLOGY, Issue 4 2008Sophie Rutschmann Summary The innate arm of our immune system is the first line of defence against infections. In addition, it is believed to drive adaptive immune responses, which help fight pathogens and provide long-term memory. As such, the innate immune system is instrumental for protection against pathogens that would otherwise destroy their host. Although our understanding of the innate immune components involved in pathogen sensing and fighting is improving, it is still limited. This is particularly exemplified by increased documentation of innate immune deficiencies in humans that often result in high and recurrent susceptibility to infections or even death, without the genetic cause being evident. To provide further insight into the mechanisms by which pathogen sensing and eradication occur, several strategies can be used. The current review focuses on the forward genetic approaches that have been used to dissect innate immunity in the fruit fly and the mouse. For both animal models, forward genetics has been instrumental in the deciphering of innate immunity and has greatly improved our understanding of how we respond to invading pathogens. [source] Enhanced efficacy of DNA vaccination against Her-2/neu tumor antigen by genetic adjuvantsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Sun Young Chang Abstract Certain types of malignant tumors overexpress Her-2/neu, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective Her-2/neu vaccine for selective immunotherapy of these malignancies, we prepared Her-2/neu DNA plasmid encoding the transmembrane and extracellular domain (pHM) and tested the ability of this construct to induce antitumor immunity in animal models. In addition, we investigated the effects of cytokine used as a genetic adjuvant. Modulation by factors that affect T-cell function or hematopoiesis, including interleukin-12, interleukin-15, interleukin-18, interleukin-23, Eta-1, Flt3L and GM-CSF, was studied in the forms of monocistronic and bicistronic plasmid. Our results demonstrated that vaccination of pHM could induce successful antitumor immunity against Her-2/neu-expressing murine tumor cells in BALB/c mice. We also showed that the antitumor activity of pHM was augmented by coadministration and coexpression of different cytokines. Despite the similar levels of gene expression, the antitumor effects of bicistronic plasmids coexpressing Her-2/neu antigen and cytokine were improved in comparison with coadministration of separate monocistronic plasmid. In particular, coexpression of interleukin-18 or GM-CSF with Her-2/neu increased antitumor activity in both preventive and therapeutic experiments. These findings can help in the decision concerning which of the various cytokine adjuvants should be used for the development of a Her-2/neu DNA vaccine. In addition, our results from a large panel of cytokine adjuvants in the various tumor models may provide an insight into the important immune components of antitumor immunity. © 2004 Wiley-Liss, Inc. [source] Regeneration, tissue injury and the immune responseJOURNAL OF ANATOMY, Issue 4 2006James W. Godwin Abstract The involvement of the immune system in the response to tissue injury has raised the possibility that it might influence tissue, organ or appendage regeneration following injury. One hypothesis that has been discussed is that inflammatory aspects may preclude the occurrence of regeneration, but there is also evidence for more positive roles of immune components. The vertebrate eye is an immunoprivileged site where inflammatory aspects are inhibited by several immunomodulatory mechanisms. In various newt species the ocular tissues such as the lens are regenerative and it has recently been shown that the response to local injury of the lens involves activation of antigen-presenting cells which traffic to the spleen and return to displace and engulf the lens, thereby inducing regeneration from the dorsal iris. The activation of thrombin from prothrombin in the dorsal iris is one aspect of the injury response that is important in the initiation of regeneration. The possible relationships between the immune response and the regenerative response are considered with respect to phylogenetic variation of regeneration in general, and lens regeneration in particular. [source] Repressive Coping and Blood Measures of Disease Risk: Lipids and Endocrine and Immunological Responses to a Laboratory Stressor,JOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 8 2000Steven D. Barger Relations between repressive coping and a variety of health-related variahles including insulin, lipids, catecholamines, and cellular immune components, were investigated in a laboratory study of acute stress among a sample of healthy male college students (N - 83). Compared to nonrepressors, at baseline, repressors had fewer numbers of circulating CD4 (T-helper) cells, greater numbers of natural killer (NK) cells. lower high-density lipoprotein (HDL), a higher total/HDL cholesterol ratio, and higher fasting insulin levels. In response to an acute laboratory stressor (Stroop Color Word Conflict Test). repressors demonstrated an attenuated increase in the number of circulating NK cells compared to nonrepressors. Confounds such as physical activity, age, and smoking were unrelated to the dependent measures. [source] Evolutionary origin of Venturia canescens virus-like particles ,ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2006Annette Reineke Abstract Insect host-parasitoid interactions provide fascinating examples of evolutionary adaptations in which the parasitoid employs a variety of measures and countermeasures to overcome the immune responses of its host. Maternal factors introduced by the female wasps during egg deposition play an important role in interfering with cellular and humoral components of the host's immune defence. Some of these components actively suppress host immune components and some are believed to confer protection for the developing endoparasitoid by rather passive means. The Venturia canescens/Ephestia kuehniella parasitoid-host system is unique among other systems in that the cellular defence capacity of the host remains virtually intact after parasitization. This system raises some important questions that are discussed in this mini-review: If immune protection of the egg and the emerging larva is achieved by surface properties comprising glycoproteins and virus-like particles (VLPs) produced by the female wasp, why is the prophenoloxidase activating cascade blocked in parasitized caterpillars? Another question is the evolutionary origin of these particles, given that the functional role and structural features of V. canescens VLP proteins are more related to cellular proteins than to viruses. Arch. Insect Biochem. Physiol. 61:123,133, 2006. © 2006 Wiley-Liss, Inc. [source] Comparative proteomic analysis between normal skin and keloid scarBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2010C.T. Ong Summary Background, Keloids are pathological scars and, despite numerous available treatment modalities, continue to plague physicians and patients. Objectives, Identification of molecular mediators that contribute to this fibrotic phenotype. Methods, Two-dimensional gel electrophoresis, MALDI-TOF, Mascot online database searching algorithm and Melanie 5 gel analysis software were employed for comparative proteomic analysis between normal skin (NS) and keloid scar (KS) tissue extracts. Results, Seventy-nine protein spots corresponding to 23 and 32 differentially expressed proteins were identified in NS and KS, respectively. Isoforms of heat shock proteins, gelsolin, carbonic anhydrase and notably keratin 10 were strongly expressed in NS along with manganese superoxide dismutase, immune components, antitrypsin, prostatic binding protein and crystalline. Various classes of proteins were found either to be present or to be upregulated in keloid tissue: (i) inflammatory/differentiated keratinocyte markers: S100 proteins, peroxiredoxin I; (ii) wound healing proteins: gelsolin-like capping protein; (iii) fibrogenetic proteins: mast cell ,-tryptase, macrophage migration inhibitory factor (MIF); (iv) antifibrotic proteins: asporin; (v) tumour suppressor proteins: stratifin, galectin-1, maspin; and (vi) antiangiogenic proteins: pigment epithelium-derived factor. Significant increases in expression of asporin, stratifin, galectin-1 and MIF were observed by Western blot analysis in KS. Conclusions, This work has identified differentially expressed proteins specific to KS tissue extracts which can potentially be used as specific targets for therapeutic intervention. [source] | ||||||||||