RESUMO
Object recognition and visual categorization are typically swift and seemingly effortless tasks that involve numerous underlying processes. In our investigation, we utilized a picture naming task to explore the processing of rarely encountered objects (visual hapaxes) in comparison to common objects. Our aim was to determine the stage at which these rare objects are classified as unnamable. Contrary to our expectations and in contrast to some prior research on event-related potentials (ERPs) with novel and atypical objects, no differences between conditions were observed in the late time windows corresponding to the P300 or N400 components. However, distinctive patterns between hapaxes and common objects surfaced in three early time windows, corresponding to the posterior N1 and P2 waves, as well as a widespread N2 wave. According to the ERP data, the differentiation between hapaxes and common objects occurs within the first 380 ms of the processing line, involving only limited and indirect top-down influence.
Assuntos
Eletroencefalografia , Potenciais Evocados , Reconhecimento Visual de Modelos , Estimulação Luminosa , Tempo de Reação , Humanos , Masculino , Feminino , Estimulação Luminosa/métodos , Reconhecimento Visual de Modelos/fisiologia , Adulto , Adulto Jovem , Potenciais Evocados/fisiologia , Tempo de Reação/fisiologia , Mapeamento Encefálico , Potenciais Evocados Visuais/fisiologia , Análise de Variância , AdolescenteRESUMO
BACKGROUND: This study aimed to compare the P3 component between patients who have migraines with aura and healthy subjects, and to compare different subtypes of migraine with aura relative to the complexity of migraine aura. METHODS: Average Migraine Aura Complexity Score was calculated for each MwA patient. Visual oddball paradigm was used to elicit the P3 component. P3 amplitudes and latencies elicited from frequent and rare stimuli, as well as from difference wave, were compared with healthy subjects. Subsequently, subtypes of migraine with aura were compared and Average Migraine Aura Complexity Score was used to explore the connection between features of the P3 and complexity of migraine with aura. RESULTS: 37 patients who have migraine with aura (16 with simple aura and 21 with complex aura) patients and 28 healthy subjects were studied. Patients who have migraine with aura had significantly prolonged latencies compared to healthy subjects (411 ± 39 ms vs 372 ± 34 ms, p < 0.001) relative to a rare condition. Patients who have complex aura significantly differs from patients who have simple aura (427 ± 34 ms vs 389 ± 35 ms, p = 0.004) and healthy subjects (372 ± 34 ms, p < 0.001) relative to P3 latency in a rare condition and the patients who have complex aura significantly differs from healthy subjects (442 ± 37 ms vs 394 ± 33 ms, p < 0.001) relative to P3 latency in difference wave. P3 latency from rare condition positively correlated with the Average Migraine Aura Complexity Score (p < 0.001). CONCLUSIONS: Visual oddball paradigm, particularly rare stimuli, could serve as a potential new tool for deep profiling of different clinical complexities among patients who have migraine with aura. Also, the present pattern of P3 components provided new evidence for the cognitive dysfunctions in patients who have migraine with aura.
Assuntos
Epilepsia , Transtornos de Enxaqueca , Enxaqueca com Aura , Biomarcadores , Potenciais Evocados , Humanos , Enxaqueca com Aura/diagnósticoRESUMO
Given the complexity of ERP recording and processing pipeline, the resulting variability of methodological options, and the potential for these decisions to influence study outcomes, it is important to understand how ERP studies are conducted in practice and to what extent researchers are transparent about their data collection and analysis procedures. The review gives an overview of methodology reporting in a sample of 132 ERP papers, published between January 1980 - June 2018 in journals included in two large databases: Web of Science and PubMed. Because ERP methodology partly depends on the study design, we focused on a well-established component (the N400) in the most commonly assessed population (healthy neurotypical adults), in one of its most common modalities (visual images). The review provides insights into 73 properties of study design, data pre-processing, measurement, statistics, visualization of results, and references to supplemental information across studies within the same subfield. For each of the examined methodological decisions, the degree of consistency, clarity of reporting and deviations from the guidelines for best practice were examined. Overall, the results show that each study had a unique approach to ERP data recording, processing and analysis, and that at least some details were missing from all papers. In the review, we highlight the most common reporting omissions and deviations from established recommendations, as well as areas in which there was the least consistency. Additionally, we provide guidance for a priori selection of the N400 measurement window and electrode locations based on the results of previous studies.
Assuntos
Eletroencefalografia , Potenciais Evocados , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Projetos de PesquisaRESUMO
BACKGROUND: This study aimed to examine the N400 effect and event-related potentials (ERPs) elicited from congruent and incongruent stimuli in patients who have migraines with aura (MwA). METHODS: A total of 33 MwA patients and 20 healthy controls (HCs) were studied. They were balanced in age (35.12 ± 8.94 vs 34.70 ± 9.59 years, p = 0.872) and sex (69.7 vs 75.0% females, p = 0.761). ERPs were measured in response to both stimuli, where pictures were preceded with an object name that either matched or mismatched with the object. Averaged amplitudes, peaks, peak latencies, difference waves and topography were compared between MwA and HCs. RESULTS: MwA patients had significantly lower averaged amplitudes at the Fz and F4 sites during incongruent stimuli, as well as reduced peaks at the C3 and Pz sites. Topography showed a more widespread N400 effect over scalp relative to HCs. The difference ERP waveforms did not differ in the N400 effect between groups, but the P600 effect was significantly stronger in the HCs group relative to the MwA group at the Pz (6.52 ± 2.57 vs. 3.50 ± 3.15, p = 0.001) and P4 (5.86 ± 2.79 vs. 3.95 ± 3.64, p = 0.040) sites. CONCLUSIONS: Picture-word matching tasks could serve as a potential new method for the investigation of semantic processing in MwA patients.
Assuntos
Epilepsia , Enxaqueca com Aura , Adulto , Eletroencefalografia , Potenciais Evocados , Feminino , Humanos , Masculino , SemânticaRESUMO
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been linked with the development of systemic lupus erythematosus (SLE). Thus far, molecular mimicry has been implicated as the principal mechanism that explains this association. In this study, we characterise a potential alternative process whereby HCMV contributes to SLE. In a cohort of SLE patients, we show a significant association between HCMV infection and SLE through a human antibody response that targets UL44. UL44 is an obligate nuclear-resident, non-structural viral protein vital for HCMV DNA replication. The intracellular nature of this viral protein complicates its targeting by the humoral response - the mechanism remains unresolved. To characterise this response, we present a thorough molecular analysis of the first human monoclonal antibody specific for UL44 derived from a HCMV seropositive donor. This human antibody immunoprecipitates UL44 from HCMV-infected cells together with known nuclear-resident SLE autoantigens - namely, nucleolin, dsDNA and ku70. We also show that UL44 is redistributed to the cell surface during virus-induced apoptosis as part of a complex with these autoantigens. This phenomenon represents a potential mechanism for the bystander presentation of SLE autoantigens to the humoral arm of our immune system under circumstances that favour a break in peripheral tolerance.
Assuntos
Anticorpos Monoclonais/sangue , Autoantígenos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Proteínas de Ligação a DNA/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Proteínas Virais/imunologia , Linhagem Celular , Proteínas de Ligação a DNA/química , Humanos , Autoantígeno Ku/imunologia , Lúpus Eritematoso Sistêmico/virologia , Microscopia Eletrônica de Varredura , Modelos Moleculares , Mimetismo Molecular , Fosfoproteínas/imunologia , Conformação Proteica , Proteínas de Ligação a RNA/imunologia , Regulação para Cima , Proteínas Virais/química , NucleolinaAssuntos
Alérgenos/imunologia , Anticorpos Monoclonais/genética , Anticorpos Neutralizantes/genética , Asma/terapia , Hipersensibilidade/terapia , Epitopos Imunodominantes/imunologia , Imunoglobulina G/genética , Engenharia de Proteínas/métodos , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Asma/imunologia , Células Cultivadas , Humanos , Hipersensibilidade/imunologia , Imunização , Imunoglobulina E/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ácaros/imunologia , Modelos Moleculares , Biblioteca de PeptídeosRESUMO
OBJECTIVES: Type 1 interferons (IFN-1) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-1 on mixed cell populations. We aimed to define modules of IFN-1-associated genes in purified leucocyte populations and use these as a basis for a detailed comparative analysis. METHODS: CD4+ and CD8+ T cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers and gene expression then determined by microarray. Modules of IFN-1-associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed. RESULTS: 1150 of 1288 IFN-1-associated genes were specific to myeloid subsets, compared with 11 genes unique to T cells. IFN-1 genes were more highly expressed in myeloid subsets compared with T cells. A subset of neutrophil samples from healthy volunteers (HV) and conditions not classically associated with IFN-1 signatures displayed increased IFN-1 gene expression, whereas upregulation of IFN-1-associated genes in T cells was restricted to SLE. CONCLUSIONS: Given the broad upregulation of IFN-1 genes in neutrophils including in some HV, investigators reporting IFN-1 signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-1-mediated pathology. Instead, specific upregulation of IFN-1-associated genes in T cells may be a useful biomarker and a further mechanism by which elevated IFN-1 contributes to autoimmunity in SLE.
RESUMO
Opalized white tuff (OWT) with 40 µm average particle size and 39.3 m(2)/g specific surface area has been introduced into polyisoprene rubber (NR). Their reinforcing effects were evaluated by comparisons with those from precipitated silica (PSi). The cure characteristic, apparent activation energy of cross-link (E(ac)) and reversion (E(ar)), and mechanical properties of a variety of composites based on these rubbers were studied. This was done using vulcanization techniques, mechanical testing, and scanning electron microscopy (SEM). The results showed that OWT can greatly improve the vulcanizing process by shortening the time of optimum cure (t(c90)) and the scorch time (t(s2)) of cross-linked rubber composites, which improves production efficiency and operational security. The rubber composites filled with 50 phr of OWT were found to have good mechanical and elastomeric properties. The tensile strengths of the NR/OWT composites are close to those of NR/PSi composites, but the tear strength and modulus are not as good as the corresponding properties of those containing precipitated silica. Morphology results revealed that the OWT is poorly dispersed in the rubber matrix. According to that, the lower interactions between OWT and polyisoprene rubber macromolecules are obtained, but similar mechanical properties of NR/OWT (100/50) rubber composites compared with NR/PSi (100/50) rubber composites are resulted.
Assuntos
Butadienos/química , Resinas Compostas/química , Hemiterpenos/química , Pentanos/química , Borracha/química , Dióxido de Silício/química , Teste de Materiais , Fenômenos MecânicosRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using a combination of immunological and biophysical techniques. Disease monitoring in the SLE cohort was undertaken with serial British Isles Lupus Assessment Group (BILAG) scoring. Correlations between specific lipid/anti-lipid responses were investigated as disease activity developed from active flares to quiescent during a follow up period. We report a significant negative correlation between anti-lipid antibodies for 24S-hydroxycholesterol, cardiolipin and phosphatidylserine with SLE disease activity. Taken together, these data suggest that lipid autoantigens represent a new family of biomarkers that can be employed to monitor disease activity plus the efficacy of therapeutic intervention in SLE.
Assuntos
Autoanticorpos/imunologia , Lipídeos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Biomarcadores/metabolismo , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoglobulina G/sangueRESUMO
Dengue virus (DENV) is the principal arthropod-borne viral pathogen afflicting human populations. While repertoires of antibodies to DENV have been linked to protection or enhanced infection, the role of T lymphocytes in these processes remains poorly defined. This study provides a comprehensive overview of CD4(+) and CD8(+) T cell epitope reactivities against the DENV 2 proteome in adult patients experiencing secondary DENV infection. Dengue virus-specific T cell responses directed against an overlapping 15mer peptide library spanning the DENV 2 proteome were analyzed ex vivo by enzyme-linked immunosorbent spot assay, and recognition of individual peptides was further characterized in specific T cell lines. Thirty novel T cell epitopes were identified, 9 of which are CD4(+) and 21 are CD8(+) T cell epitopes. We observe that whereas CD8(+) T cell epitopes preferentially target nonstructural proteins (NS3 and NS5), CD4(+) epitopes are skewed toward recognition of viral components that are also targeted by B lymphocytes (envelope, capsid, and NS1). Consistently, a large proportion of dengue virus-specific CD4(+) T cells have phenotypic characteristics of circulating follicular helper T cells (CXCR5 expression and production of interleukin-21 or gamma interferon), suggesting that they are interacting with B cells in vivo. This study shows that during a dengue virus infection, the protein targets of human CD4(+) and CD8(+) T cells are largely distinct, thus highlighting key differences in the immunodominance of DENV proteins for these two cell types. This has important implications for our understanding of how the two arms of the human adaptive immune system are differentially targeted and employed as part of our response to DENV infection.
Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Epitopos de Linfócito T/imunologia , Adulto , Proteínas do Capsídeo/imunologia , Células Cultivadas , Feminino , Humanos , Interferon gama/biossíntese , Interleucinas/biossíntese , Masculino , Pessoa de Meia-Idade , Proteoma/imunologia , RNA Helicases/imunologia , Receptores CXCR5/biossíntese , Serina Endopeptidases/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas não Estruturais Virais/imunologiaRESUMO
Antigen-activated T lymphocytes undergo an immune or tolerogeneic response in part according to the activation status of their antigen-presenting cells. However, factors controlling the activation of antigen-presenting cells are not fully understood. In this study, we demonstrate that immune tolerance after organ allotransplantation in the rat is associated with a repressed intragraft expression of several enzymes of the trans-sulfuration pathway, including cystathionine γ-lyase (CSE). The pharmacologic blockade of CSE with propargylglycine delayed heart allograft rejection and abrogated type IV hypersensitivity but did not modify antibody responses, and was associated with a selective inhibition of the TH-1 type factors T-bet, IL-12, and IFN-γ. IL-12 repression could also be induced by propargylglycine in vitro in monocytes and dendritic cells (DCs), a phenomenon not mediated by changes to nuclear factor-κ B or hydrogen sulfide but that occurred together with a modulation of intracellular cysteine content. Intracellular cysteine levels were predominantly controlled in DCs by CSE activity, together with extracellular import via the X(c)(-) transporter. Our results indicate that CSE plays a critical role in regulating IL-12 in monocytes and DCs and is down-modulated in transplant tolerance, presumably participating in the maintenance of the tolerant state.
Assuntos
Cistationina gama-Liase/metabolismo , Células Dendríticas/imunologia , Transplante de Coração/imunologia , Interleucina-12/metabolismo , Transplante de Rim/imunologia , Células Th1/imunologia , Tolerância ao Transplante/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Biomarcadores/metabolismo , Western Blotting , Cistationina/metabolismo , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/genética , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Rejeição de Enxerto/imunologia , Interferon gama/metabolismo , Interleucina-12/genética , Lipopolissacarídeos/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Tolerance is the so-called "Holy Grail" of transplantation but achieving this state is proving a major challenge, particularly in the clinical settings. This tolerance state can be induced in rodent models using a variety of maneuvers. This phenomenon is classically characterized by donor specificity (recipients accept a secondary donor-specific allograft but reject third-party allograft) as well as by the absence of chronic rejection lesion. We previously showed that administration and anti-donor anti-class II serum on the day of transplantation induce tolerance to a kidney allograft in the LEW-1W to LEW-1A strain combination. In this study, we used DNA microarrays to compare gene patterns involved in anti-donor anti-class II tolerated or untreated syngeneic kidney transplants in this strain combination. Statistical and non-statistical analyses were combined with ab initio analysis, using the recently developed leader gene approach, to shed new light on this phenomenon. Theoretical and experimental results suggest that tolerance and rejection outcome may be in large part determined by low expression variations of some genes, which can form a core gene network around specific genes such as Rac1, NFKB1, RelA, AKT1, IKBKB, BCL2, BCLX, and CHUK. Through this model, we showed that AKT1 gene, WNT pathway and NO synthesis are strictly connected to each other and may play an important role in kidney tolerance and rejection processes, with AKT1 gene being the center of this complex network of interactions.
Assuntos
Regulação da Expressão Gênica , Transplante de Rim/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Tolerância ao Transplante , Animais , Redes Reguladoras de Genes , Antígenos de Histocompatibilidade Classe II/imunologia , Modelos Animais , Óxido Nítrico/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Proteínas Wnt/metabolismoRESUMO
Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunossupressores/uso terapêutico , Linfócitos T/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoimunidade/imunologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-7/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Prognóstico , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Vasculite/tratamento farmacológico , Vasculite/imunologiaRESUMO
Chronic active antibody-mediated rejection is a form of late rejection with a poor prognosis. To identify specific markers of this, we analyzed several microarray studies in the literature and performed mRNA profiling of 65 biopsies and 165 blood samples of a large cohort of renal transplant patients with precisely characterized pathologies. Immunoproteasome beta subunit 10 was found to be specifically increased in the graft and blood samples during chronic active antibody-mediated rejection and was also significantly increased in rat cardiac allografts undergoing acute rejection as well as chronic active antibody-mediated rejection. This syndrome is characterized by chronic transplant vasculopathy associated with diffuse C4d staining and circulating donor-specific antibodies. Using this animal model, we found that administration of the proteasome inhibitor, Bortezomib, delayed acute rejection and attenuated the humoral response in both the acute phase and established state of this syndrome in a dose-dependent manner. Following treatment with this reagent, donor-specific antibodies and C4d deposition were reduced. These studies highlight the role of the proteasome in chronic rejection and identify this molecule as a marker of this syndrome.
Assuntos
Transplante de Rim/imunologia , Transplante de Rim/patologia , Animais , Anticorpos , Biomarcadores , Biópsia , Complemento C4b , Feminino , Humanos , Imunoglobulinas , Masculino , Fragmentos de Peptídeos , Ratos , Ratos Endogâmicos , Doadores de TecidosRESUMO
The maintenance of immune homeostasis and the regulation of pro-inflammatory responses that underlie autoimmune pathology require a coordinated interplay between cytokines, cellular receptors and downstream signaling pathways. The family of fragment crystallizable receptors for immunoglobulin G (IgG) (Fc gammaR) represents a good example of how controlling the simultaneous triggering of activatory and/or inhibitory receptors results in a balanced immune response. Fc gammaRs play a crucial role in linking the antibody-mediated recognition of pathogens, allergens or auto-antigens to the cellular arm of the immune response. In this review, we detail how dysfunction in Fc gammaR pathways is linked to the development of the autoimmune disease, systemic lupus erythematosus.
Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Receptores de IgG/fisiologia , Animais , Formação de Anticorpos , Modelos Animais de Doenças , Humanos , Imunomodulação , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/fisiopatologia , Camundongos , Transdução de SinaisRESUMO
In rats, tolerance to MHC-incompatible renal allografts can be induced by the administration of anti-donor class II Abs on the day of transplantation. In this study we explored the mechanisms involved in the maintenance phase of this tolerance by analyzing intragraft gene expression profiles by microarray in long-term accepted kidneys. Comparison of the gene expression patterns of tolerated to syngeneic kidneys revealed 5,954 differentially expressed genes (p < 0.05). Further analysis of this gene set revealed a key role for the wingless-type (WNT) signaling pathway, one of the pivotal pathways involved in cell regulation that has not yet been implicated in transplantation. Several genes within this pathway were significantly up-regulated in the tolerated grafts, particularly matrix metalloproteinase 7 (MMP7; fold change > 40). Analysis of several other pathway-related molecules indicated that MMP7 overexpression was the result of the noncanonical WNT signaling pathway. MMP7 expression was restricted to vascular smooth muscle cells and was specific to anti-class II Ab-induced tolerance, as it was undetectable in other models of renal and heart transplant tolerance and chronic rejection induced across the same strain combination. These results suggest a novel role for noncanonical WNT signaling in maintaining kidney transplant tolerance in this model, with MMP7 being a key target. Determining the mechanisms whereby MMP7 contributes to transplant tolerance may help in the development of new strategies to improve long-term graft outcome.
Assuntos
Sobrevivência de Enxerto/genética , Antígenos de Histocompatibilidade Classe II/efeitos dos fármacos , Tolerância Imunológica , Transplante de Rim/imunologia , Metaloproteinase 7 da Matriz/fisiologia , Proteínas Wnt/fisiologia , Animais , Anticorpos/administração & dosagem , Expressão Gênica , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/imunologia , Rim/efeitos dos fármacos , Rim/imunologia , Masculino , Metaloproteinase 7 da Matriz/genética , Modelos Animais , Músculo Liso Vascular/citologia , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais , Doadores de Tecidos , Proteínas Wnt/genéticaRESUMO
Long-term allograft acceptance can be induced in the rat using a variety of maneuvers. One of the cardinal features of some models of tolerance is that once the tolerance state has been established, it can be perpetuated to naive recipients by the adoptive transfer of donor-specific regulatory cells. Such adoptive transfer studies have also addressed the capacity of T-cell subpopulations and non-T cells to transfer tolerance. However, tolerance cannot be transferred in all models. The underlying reasons for this are unclear with some studies pointing towards dose-dependent aspects and timing of expansion of T regulatory cells following tolerance transfer. Further exploration of this phenomenon will help us to understand better the mechanisms upon which allograft tolerance is based, and will provide new perspectives for further experimental studies.
Assuntos
Transplante de Coração/imunologia , Transplante de Rim/imunologia , Tolerância ao Transplante/fisiologia , Animais , Modelos Animais , Ratos , Ratos Endogâmicos , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Transplante Homólogo/imunologia , Irradiação Corporal TotalRESUMO
Competetive exclusion between Lacerta sicula and L. melisellensis characterizes the small islands of the Adriatic Sea.In 1958 and 1959 M. Radovanovié introduced Lacerta sicula or Lacerta melisellensis onto islands exclusively occupied by the other species. During the summer of 1971 follow-up observations were made on three of these islands, two of which completely lacked representatives of the introduced species. On the third island, the introduced species appears to be replacing the native form. Minor habitat differences permit coexistence, however the situation is dynamic and probably not at equilibrium. A reciprocal introduction involving the two species on the islands of Pod Kopiste and Pod Mrcaru is announced.