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Results for “Receptors, Pattern Recognition”

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At least 847 records · Page 47Linked to original sources
PubMed2003

Antigens in tea-beverage prime human Vgamma 2Vdelta 2 T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses.

Human gammadelta T cells mediate innate immunity to microbes via T cell receptor-dependent recognition of unprocessed antigens with conserved molecular patterns. These nonpeptide alkylamine antigens are shared by tumor cells, bacteria, parasites, and fungi but also by edible plant products such as tea, apples, mushrooms, and wine. Here we show that priming of gammadelta T cells with alkylamine antigens in vitro results in a memory response to these antigens. Such priming results also in a nonmemory response to whole bacteria and to lipopolysaccharide, characterized by IL-12-dependent secretion of IFN-gamma by gammadelta T cells and by gammadelta T cell proliferation. Drinking tea, which contains l-theanine, a precursor of the nonpeptide antigen ethylamine, primed peripheral blood gammadelta T cells to mediate a memory response on reexposure to ethylamine and to secrete IFN-gamma in response to bacteria. This unique combination of innate immune response and immunologic memory shows that gammadelta T cells can function as a bridge between innate and acquired immunity. In addition, these data provide an explanation for the health benefits of tea.

Anti-Bacterial Agents↗
PubMed2003

Selective induction of matrix metalloproteinases by Borrelia burgdorferi via toll-like receptor 2 in monocytes.

Regulation of secretion of matrix metalloproteinase (MMP) underlies the basis of numerous physiological and pathological processes in multicellular organisms. The Toll receptor family, which is conserved from Drosophila species to humans, mediates pattern recognition of a diversity of ligands involved in morphogenesis and innate immunity. Here, we show that secretion of MMP-9 is selectively induced through Toll-like receptor (TLR) 2 in human and murine monocytic cells stimulated with Borrelia burgdorferi. Secretion of MMP-1 was shown to be stimulated through a pathway other than TLR2, under identical conditions. Analysis of nuclear extracts indicated that activator protein (AP)-1 was reduced in TLR2-neutralized monocytic cells, suggesting that AP-1 plays a role in the transcriptional activation of MMP-9 through TLR2. The specific induction of MMP-9 through TLR2 provides direct evidence of a new role for this ancient receptor family in regulating secretion of MMPs and demonstrates evolutionary convergence between invertebrate morphogenesis and the vertebrate innate immune system.

Animals↗
PubMed2002

Increased BDNF and trk-B mRNA expression in cortical and limbic regions following formation of a social recognition memory.

Brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine receptor kinase (trk-B), play important roles in neural plasticity, long-term potentiation and memory formation. Sheep form a selective recognition memory for their lambs within 2 h of birth. Initially, this memory is exclusively based on olfactory cues; however, as it consolidates over a 12-h recognition period it extends to incorporate visual cues. We investigated whether changes in BDNF and trk-B mRNA expression occurred in both olfactory and visual processing systems at 4.5 h postpartum, 2-3 h after the behavioural manifestations of an olfactory recognition memory were found. Animals that formed a recognition memory showed increased BDNF mRNA expression in the inferior part of the temporal cortex, subfield CA1 of the hippocampus, the diagonal band, basolateral amygdala and the anterior cingulate, medial frontal, entorhinal and pyriform cortices. No increases were observed in either the olfactory bulbs or the dentate gyrus. Expression of trk-B mRNA was significantly increased only in the medial temporal, entorhinal and pyriform cortices. These findings demonstrate that by 2-3 h following the initial formation of olfactory recognition memory there are BDNF/trk-B-mediated plasticity changes in brain areas involved in the consolidation of olfactory memory (the pyriform and entorhinal cortices). However, similar changes also occur in areas of the brain involved in visual memory, face and object recognition (the temporal cortex, entorhinal cortex, hippocampal subfield CA1 and basolateral amygdala), and in areas of the brain with integrative and attentional functions (the medial frontal and anterior cingulate cortices and diagonal band). This suggests that reorganization of neural circuits underlying the visual recognition of lambs or the integration of olfactory/visual information is occurring even at this time even though accurate behavioural recognition at this stage can only be made using olfactory cues.

Animals↗
PubMed2005

Tandem machine learning for the identification of genes regulated by transcription factors.

BACKGROUND: The identification of promoter regions that are regulated by a given transcription factor has traditionally relied upon the identification and distributions of binding sites recognized by the factor. In this study, we have developed a tandem machine learning approach for the identification of regulatory target genes based on these parameters and on the corresponding binding site information contents that measure the affinities of the factor for these cognate elements. RESULTS: This method has been validated using models of DNA binding sites recognized by the xenobiotic-sensitive nuclear receptor, PXR/RXRalpha, for target genes within the human genome. An information theory-based weight matrix was first derived and refined from known PXR/RXRalpha binding sites. The promoter region of candidate genes was scanned with the weight matrix. A novel information density-based clustering algorithm was then used to identify clusters of information rich sites. Finally, transformed data representing metrics of location, strength and clustering of binding sites were used for classification of promoter regions using an ensemble approach involving neural networks, decision trees and Naïve Bayesian classification. The method was evaluated on a set of 24 known target genes and 288 genes known not to be regulated by PXR/RXRalpha. We report an average accuracy (proportion of correctly classified promoter regions) of 71%, sensitivity of 73%, and specificity of 70%, based on multiple cross-validation and the leave-one-out strategy. The performance on a test set of 13 genes showed that 10 were correctly classified. CONCLUSION: We have developed a machine learning approach for the successful detection of gene targets for transcription factors with high accuracy. The method has been validated for the transcription factor PXR/RXRalpha and has the potential to be extended to other transcription factors.

Algorithms↗
PubMed2003

Immunologic regulation of toll-like receptors in gut epithelium.

PURPOSE OF REVIEW: In response to the presence of pathogens in the environment, the innate immune system has evolved to provide a rapid defense against microbes. This response involves the recognition of molecular patterns present in diverse microbes by a series of receptors termed toll-like receptors. The focus of this article is the regulation of toll-like receptor signaling in the intestinal epithelium. The intestinal epithelium is continually exposed to a high concentration of diverse bacteria. In spite of the density of commensal bacteria, the normal intestine is not inflamed. Idiopathic inflammatory bowel disease in humans and animals is characterized by aberrant host-microbial interactions. RECENT FINDINGS: Several studies demonstrate that intestinal epithelial cells are poorly responsive to microbial products. The reason for this hyporesponsiveness is decreased or polarized expression of toll-like receptor molecules. Inflammatory cytokines upregulate expression of toll-like receptors. SUMMARY: The intestinal epithelium has evolved under the pressure of the microbiota to mute a response to commensal bacteria while maintaining the ability to respond to pathogens. In inflammatory bowel disease, the loss of tolerance to the normal flora may be due in part to inappropriate toll-like receptor signaling.

Journal Article↗
PubMed1996

Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins: effect on T helper cell repertoire selection.

T helper (Th) epitopes can be included in a recombinant protein with B and CTL epitopes to create more effective immunogens. To determine whether the antigenicity of HIV Th epitopes is preserved in this altered molecular context, human Th clones specific for peptides of HIV gp120 and reverse transcriptase p66 were challenged with recombinant proteins carrying the antigenic epitopes in different sites. We found that a given epitope was recognized by a specific T cell clone only when it was inserted in a particular position of the carrier. However, the permissive position was not the same for all epitopes. Enzymatic excision from a nonpermissive context or insertion of a polyserine spacer between the epitope and the carrier restored antigenicity. Nevertheless, antigenicity was not abolished in a synthetic peptide encompassing the epitope and the neighboring residues from the nonpermissive location. These data suggest that, in this case, the primary sequence of the chimeric protein flanking the HIV peptide is not responsible for loss of antigenicity. Furthermore, constructs carrying the epitope in a given position were recognized by peptide-specific Th clones raised from some individuals, but not from others. We show that this is due neither to individual modes of processing nor to the use of distinct major histocompatibility complex MHC class II restriction elements, but rather that it is related to the fine specificity of the clones. To study the effect of epitope context on selection of T cell repertoire in a naive individual, T cell lines were generated in vitro by stimulation with different peptide constructs. This resulted in the induction of diverse clonotypes defined by the pattern of recognition of different constructs, by T cell receptor V beta gene usage and by fine epitope mapping.

AIDS Vaccines↗
PubMed2002

Visually evoked gamma responses in the human brain are enhanced during voluntary hyperventilation.

Hypocapnia induced by hyperventilation (HV) has powerful effects on neuronal excitability and synaptic transmission. We have studied the effect of hyperventilation on the phase-locked oscillatory components of the evoked responses in the human brain. We recorded visually evoked magnetoencephalographic responses before, during, and after voluntary hyperventilation to pattern-reversal checkerboard stimuli. Gamma-band (30-45 Hz) responses phase-locked to the stimuli were generated in the occipital visual cortex. A wavelet-based time-frequency analysis revealed that the gamma responses increased during HV whereas their frequency did not change significantly. A recent in vitro study in the rat hippocampus demonstrated that the stability of spontaneous gamma activity increases during hypocapnia as a result of enhanced GABAergic transmission. To test if a similar mechanism could account for our findings, we performed simulations on a network of 100 Hodgkin-Huxley neurons connected by inhibitory synapses. We found that enhanced GABA(A) transmission, paired with enhanced excitability, can explain the increase in evoked gamma activity without changing the frequency.

Adult↗
PubMed1989

Haloperidol and cognitive shifting.

In this study haloperidol appeared to affect the performance on a selected category of cognitive tasks considered to represent shifting aptitude. A pretest--post-test design was used with two groups of subjects: 17 patients suffering from idiopathic spasmodic torticollis, and 17 controls who were matched for age and intelligence. The results are discussed in relation to previous findings on haloperidol and cognition, shifting disorder in Parkinson's disease and changes in behavioural organization found in animals with an experimentally induced dopaminergic hypoactivity.

Attention↗
PubMed1994

Visual discrimination and P300 are affected in parallel by cholinergic agents in the behaving monkey.

We studied the acute effect of cholinergic agents, scopolamine alone and scopolamine pretreatment and acetyl-L-carnitine (ALC) on visual event-related potentials (ERPs) in a monkey performing in a go/no-go visual oddball discrimination task. The same monkey was studied repeatedly for a period extending over 1.5 years. Scopolamine is known to cause cognitive impairment in primates. In the concentrations used, primary evoked potentials did not change significantly whereas P300 latency increased maximally 20-40 min following scopolamine administration. Acetyl-L-carnitine on its own increased P300 amplitude and decreased its latency. When ALC administration was preceded by scopolamine, both P300 latency and amplitude maximally increased in 25-45 min. Apparently ALC's effect on the latency and amplitude of visual P300 of the monkey is largely via muscarinic mechanisms. Our results suggest that scopolamine may provide a valuable tool to separate cognitive from primary visual processes.

Acetylcarnitine↗
PubMed2005

Genetic susceptibility to pneumonia.

The persistent mortality from community-acquired pneumonia may be explained by genetic predisposition. Specific mutations or polymorphisms in host response genes that are associated with adverse outcomes from infection can be grouped into four categories: antigen recognition, proinflammatory responses, anti-inflammatory responses, and effector mechanisms. Mannose-binding lectin polymorphisms have a more dominant role in pneumonia when compared with other pattern recognition molecules such as the toll-like receptors. The roles of TNF and lymphotoxin alpha polymorphisms remain unclear despite extensive study. IL-10 and IL-1 receptor antagonist polymorphisms have an important role in the anti-inflammatory response. Specific organ dysfunction, such as ARDS or DIC, may be related to polymorphisms in specific effector genes.

Cytokines↗
PubMed2000

BDNF upregulation during declarative memory formation in monkey inferior temporal cortex.

In primates, visual long-term memory of objects is presumably stored in the inferior temporal (IT) cortex. Because brain-derived neurotrophic factor (BDNF) is involved in activity-dependent neural reorganization, we tested the hypothesis that BDNF would be upregulated in IT cortex during formation of visual pair-association memory. To eliminate genetic and cognitive variations between individual animals, we used split-brain monkeys for intra-animal comparison in PCR-based mRNA quantitation. The monkeys learned a pair-association (PA) task using one hemisphere and a control visual task using the other, to balance the amount of visual input. We found that BDNF was upregulated selectively in area 36 of IT cortex during PA learning, but not in areas involved in earlier stages of visual processing. In situ hybridization showed that BDNF-expressing cells were localized in a patchlike cluster. The results suggest that BDNF contributes to reorganization of neural circuits for visual long-term memory formation in the primate.

Actins↗
PubMed2006

Characterization of monoclonal antibodies to human soluble MD-2 protein.

Toll-like receptors (TLRs) are mammalian innate immune recognition receptors that are activated by pathogen associated molecular patterns (PAMPs). TLR4 is the signaling molecule of the lipopolysaccharide (LPS) receptor complex. TLR4 associates with its adapter molecule, MD-2, which is absolutely required for LPS-induced activation of TLR4. MD-2 exists as a cell surface protein in association with TLR4 and as secreted forms consisting of MD-2 monomers and multimers. To facilitate the studies of MD-2 distribution, abundance, and function, we produced monoclonal antibodies (MAbs) to baculovirally expressed soluble MD-2 (sMD-2). Eleven MAbs were characterized by enzyme-linked immunosorbent assay (ELISA) with soluble TLR4/MD-2 complex (sTLR4/MD-2) and sMD-2, Western blotting against sMD-2 monomer and multimers, and inhibition of direct LPS binding to sMD-2. Four MAbs preferentially recognized mainly MD-2 oligomers, not monomers, as judged by Western blotting and ELISA. Anti-MD-2 MAbs useful for indirect immunofluorescent staining of cells expressing TLR4 and MD-2 were identified. One MAb that recognized all forms of MD-2 was used in an ELISA to measure sMD-2 in normal human sera as well as sera from intensive care patients with and without sepsis. Serum levels of sMD-2 were undetectable or very low in normal and in nonsepsis patients but significantly (p < 0.05) increased in sepsis patients. These MAbs should therefore be very useful new tools for studies of MD-2 expression and function in health and disease.

Animals↗
PubMed1991

Proliferative responses of T cells primed against human rhinovirus to other rhinovirus serotypes.

Lymphocytes from mice immunized with human rhinovirus (HRV) serotypes 1A or 15 proliferated in vitro in response to HRV and the activated cells were shown to be helper T (Th) cells. Lymphocytes from mice primed with HRV-1A responded to seven of eight heterologous virus serotypes, the responses to other minor cell receptor group viruses being greater than to those belonging to the major cell receptor group. A similar bias was seen with cells from mice primed with HRV-15 in that they responded preferentially to other major receptor group viruses. This pattern of cross-serotype recognition was shown to be similar in three inbred mouse strains and was not dependent upon the major histocompatibility complex haplotype. These results have revealed that there are determinants within the viral proteins of a number of serotypes of HRV that are recognized by Th cells primed against a single HRV serotype. Thus, at the level of Th cell recognition of HRV, a cross-serotype reactivity is seen which is not reflected in the B cell antibody response to virus, which is generally highly serotype-specific.

Animals↗
PubMed1987

Cognitive concomitants of dopamine system stimulation in parkinsonian patients.

Verbal, visuospatial and motor functions were studied in eight Parkinsonian patients both during levodopa stimulated and unstimulated state and in eight matched, untreated, healthy controls. Profound changes in patients' motor status were accompanied by relatively selective effects on delayed verbal memory, a function which was also most impaired compared with controls. With dopaminomimetic therapy, tests of delayed verbal memory consistently improved, but did not reach control performance levels. These results could indicate a functional impairment in the mesocortical dopamine system, which can be attenuated, but not entirely corrected, by dopaminomimetic therapy.

Adult↗
PubMed1991

Tilt aftereffect reveals early visual processing deficits in Parkinson's disease and in chronic schizophrenic patients on depot neuroleptic.

Previous studies suggest that the tilt aftereffect (TAE) may be used to indicate the site of dopaminergic abnormalities in the human visual system. In this study we investigated the TAE in patients with Parkinson's disease, and in chronic schizophrenic patients receiving depot injections of neuroleptic. The results suggest that the retina may be abnormal in both groups of patients, and that schizophrenic patients may also have cortical changes. The results are discussed in terms of the clinical implications of these visual changes.

Adult↗
PubMed2001

Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition.

FGF signaling uses receptor tyrosine kinases that form high-affinity complexes with FGFs and heparan sulfate (HS) proteoglycans at the cell surface. It is hypothesized that assembly of these complexes requires simultaneous recognition of distinct sulfation patterns within the HS chain by FGF and the FGF receptor (FR), suggesting that tissue-specific HS synthesis may regulate FGF signaling. To address this, FGF-2 and FGF-4, and extracellular domain constructs of FR1-IIIc (FR1c) and FR2-IIIc (FR2c), were used to probe for tissue-specific HS in embryonic day 18 mouse embryos. Whereas FGF-2 binds HS ubiquitously, FGF-4 exhibits a restricted pattern, failing to bind HS in the heart and blood vessels and failing to activate signaling in mouse aortic endothelial cells. This suggests that FGF-4 seeks a specific HS sulfation pattern, distinct from that of FGF-2, which is not expressed in most vascular tissues. Additionally, whereas FR2c binds all FGF-4-HS complexes, FR1c fails to bind FGF-4-HS in most tissues, as well as in Raji-S1 cells expressing syndecan-1. Proliferation assays using BaF3 cells expressing either FR1c or FR2c support these results. This suggests that FGF and FR recognition of specific HS sulfation patterns is critical for the activation of FGF signaling, and that synthesis of these patterns is regulated during embryonic development.

Alkaline Phosphatase↗
PubMed2004

A Toll-like receptor in horseshoe crabs.

Non-self-recognition of invading microbes relies on the pattern-recognition of pathogen-associated molecular patterns (PAMPs) derived from microbial cell-wall components. Insects and mammals conserve a signaling pathway of the innate immune system through cell-surface receptors called Tolls and Toll-like receptors (TLRs). Bacterial lipopolysaccharides (LPSs) are an important trigger of the horseshoe crab's innate immunity to infectious microorganisms. Horseshoe crabs' granular hemocytes respond specifically to LPS stimulation, inducing the secretion of various defense molecules from the granular hemocytes. Here, we show a cDNA which we named tToll, coding for a TLR identified from hemocytes of the horseshoe crab Tachypleus tridentatus. tToll is most closely related to Drosophila Toll in both domain architecture and overall length. Human TLRs have been suggested to contain numerous PAMP-binding insertions located in the leucine-rich repeats (LRRs) of their ectodomains. However, the LRRs of tToll contained no obvious PAMP-binding insertions. Furthermore, tToll was non-specifically expressed in horseshoe crab tissues. These observations suggest that tToll does not function as an LPS receptor on granular hemocytes.

Amino Acid Sequence↗