Immune Response Genes (immune + response_gene)

Distribution by Scientific Domains


Selected Abstracts


The MHC class,II transactivator (CIITA) mRNA stability is critical for the HLA class,II gene expression in myelomonocytic cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005
Andrea De Lerma Barbaro
Abstract The human promyelocytic U937 cells express detectable levels of MHC class,II (MHC-II) molecules. Treatment with 12-o- - tetradecanoyl phorbol 13-acetate (TPA), inducing macrophage-like differentiation, produces a dramatic decrease of MHC-II expression as result of down-modulation of the activation of immune response gene,1 (AIR-1)-encoded MHC-II transactivator (CIITA). This event is specific, as MHC class,I remains unaffected. Similar results are observed with U937 cells expressing an exogenous full-length CIITA. Molecular studies demonstrate that TPA treatment affects the stability of CIITA mRNA rather than CIITA transcription. Importantly, cis -acting elements within the distal 650,bp of the 1035-bp 3,,untranslated region (3,UTR, nucleotides 3509,4543) are associated to transcript instability. Transcription inhibitors actinomycin,D and 5,6-dichlororibofuranosyl benzimidazole, and the translation inhibitor cycloheximide significantly rescue the accumulation of CIITA mRNA in TPA-treated cells. A similar effect is also observed after treatment with staurosporine and the PKC-specific inhibitor GF109203X. The instability of CIITA mRNA produced by TPA in U937 cells is not seen in B,cells. These results demonstrate the presence of an additional level of control of MHC-II expression in the macrophage cell lineage depending upon the control of CIITA mRNA stability, most likely mediated by differentiation-induced, 3,UTR-interacting factors which require kinase activity for their destabilizing function. [source]


Peptide-induced suppression of collagen-induced arthritis in HLA,DR1 transgenic mice

ARTHRITIS & RHEUMATISM, Issue 12 2002
Linda K. Myers
Objective To identify peptides capable of altering the immune response to type II collagen (CII) in the context of HLA,DR. Methods Immunizing mice transgenic for the human HLA,DRB1*0101 immune response gene with CII elicits an arthritis (collagen-induced arthritis [CIA]) that resembles rheumatoid arthritis. We have previously identified an immunodominant determinant of CII, CII (263,270), recognized by T cells in the context of DR1. To produce synthetic peptides with the potential of disrupting the DR1-restricted immune response, synthetic analog peptides were developed that contain site-directed substitutions in critical positions. These peptides were used to treat CIA in DR1 transgenic mice. Results An analog peptide, CII (256,276, N263, D266), that inhibited T cell responses in vitro, was identified. When DR1 mice were coimmunized with CII and CII (256,276, N263, D266), the incidence and severity of arthritis were greatly reduced, as was the antibody response to CII. Moreover, CII (256,276, N263, D266) was effective in down-regulating the immune responses to CII and arthritis, even when administered 2 weeks following immunization with CII. Spleen and lymph node cells from CII-immunized mice cultured with CII (256,276, N263, D266) in vitro produced increased amounts of interleukin-4 (IL-4) compared with cells cultured with the wild-type peptide, CII (256,276). Furthermore, CII (256,276, N263, D266) was incapable of preventing arthritis in DR1 IL-4,/, mice (genetically deficient in IL-4). Conclusion These data establish that CII (256,276, N263, D266) is a potent suppressor of the DR-mediated immune response to CII. Its effect is mediated, at least in part, by IL-4. These experiments represent the first description of an analog peptide of CII recognized by T cells in the context of a human major histocompatibility complex molecule that can suppress autoimmune arthritis. [source]


Pyrosequencing and characterization of immune response genes from the American dog tick, Dermacentor variabilis (L.)

INSECT MOLECULAR BIOLOGY, Issue 5 2010
D. C. Jaworski
Abstract Ticks continue to be a threat to animal and human health, and new and novel control strategies are needed for ticks and tick-borne pathogens. The characterization of the tick,pathogen interface and the tick immune response to microbial infections is fundamental toward the formulation of new control strategies for ticks and the pathogens they transmit. Our overall hypothesis for this research is that the tick immune system manages the maintenance of pathogens. Therefore, discovery of tick immune response genes may provide targets for novel control strategies directed toward reducing vector competency and pathogen transmission. In these studies, 454 pyrosequencing, a high-throughput genomic sequencing method was used to discover tick genes expressed in response to bacterial and fungal infections. Expressed sequence tags (ESTs) were analysed from Dermacentor variabilis ticks that had been injected with bacteria (Escherichia coli, Bacillus subtilis, Micrococcus luteus) or fungi (Saccharomyces cerevisiae and Candida albicans) and ticks that were naturally infected with the intracellular bacterium, Anaplasma marginale. By this approach, ESTs were assembled into 5995 contigs. Contigs fell into the five main functional categories of metabolism, genetic information processing, environmental information processing, cellular processes and human diseases. We identified more than 30 genes that are likely to encode for proteins involved in tick immune function. We further analysed by reverse transcriptase PCR (RT-PCR) the expression of 22 of these genes in each of our bacterial or fungal treatment groups and found that seven were up-regulated. Up-regulation of these seven genes was confirmed for bacterial, but not fungal treatment by quantitative PCR (qPCR). One of these products was novel, encoding a new tick defensin. Our results clearly demonstrate the complexities of the tick immune system and mark new directions for further study and characterization of proteins that modulate microbial infections in the American dog tick. [source]


Canine diabetes mellitus: from phenotype to genotype

JOURNAL OF SMALL ANIMAL PRACTICE, Issue 1 2008
B. Catchpole
Breed differences in susceptibility to diabetes mellitus in dogs suggest an underlying genetic component to the pathogenesis of the disease. There is little evidence for an equivalent of human type 2 diabetes in dogs, and it has been proposed that canine diabetes is more comparable to the type 1 form of the disease. Certain immune response genes, particularly those encoding major histocompatibility complex molecules involved in antigen presentation, are important in determining susceptibility to human type 1 diabetes. We tested the hypothesis that canine major histocompatibility complex genes (known as the dog leucocyte antigen) are associated with diabetes in dogs. A total of 530 diabetic dogs and more than 1000 controls were typed for dog leucocyte antigen, and associations were found with three specific haplotypes. The DLA-DRB1*009/DQA1*001/DQB1*008 haplotype shows the strongest association with diabetes in the UK dog population. This haplotype is common in diabetes-prone breeds (Samoyed, cairn terrier and Tibetan terrier) but rare in diabetes-resistant breeds (boxer, German shepherd dog and golden retriever), which could explain differences in the prevalence of diabetes in these different breeds. There is evidence that the DLA-DQA1*001 allele is also associated with hypothyroidism, suggesting that this could represent a common susceptibility allele for canine immune-mediated endocrinopathies. [source]


Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis

LIVER INTERNATIONAL, Issue 7 2007
Xiao X. Huang
Abstract Background/Aims: Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Method: Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Results: Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. Conclusion: PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis. [source]


Trade-off between immune stimulation and expression of storage protein genes

ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 2 2009
Anete P. Lourenço
Abstract Proteins stored in insect hemolymph may serve as a source of amino acids and energy for metabolism and development. The expression of the main storage proteins was assessed in bacterial-challenged honey bees using real-time (RT)-PCR and Western blot. After ensuring that the immune system had been activated by measuring the ensuing expression of the innate immune response genes, defensin-1 (def-1) and prophenoloxidase (proPO), we verified the expression of four genes encoding storage proteins. The levels of vitellogenin (vg) mRNA and of the respective protein were significantly lowered in bees injected with bacteria or water only (injury). An equivalent response was observed in orally-infected bees. The levels of apolipophorin II/I (apoLp-II/I) and hexamerin (hex 70a) mRNAs did not significantly change, but levels of Hex 70a protein subunit showed a substantial decay after bacterial challenge or injury. Infection also caused a strong reduction in the levels of apoLp-III transcripts. Our findings are consistent with a down-regulation of the expression and accumulation of storage proteins as a consequence of activation of the immune system, suggesting that this phenomenon represents a strategy to redirect resources to combat injury or infection. © 2009 Wiley Periodicals, Inc. [source]