Inmunologia (Barcelona, Spain : 1987)最新文献

T-cell receptor (TCR) immunodeficiencies of humans are low-prevalence autosomal recessive diseases characterized by impaired surface TCR expression and selective T lymphopenia (milder in CD3γ, TCRα or CD247 deficiency, and severe in individuals lacking CD3δ or CD3ɛ). The congenital absence of TCR components has a differential impact on T-cell development and function depending on the affected TCR chain and on the species, with human patients being, in some cases, rather different from mouse counterparts.

The study of the immunophenotype by flow cytometry, along with molecular analyses, provides essential information for diagnosis and treatment, which is still to date the transplant of hematopoietic progenitors in severe immunodeficiency associated cases.

Vaccination is considered one of the most effective ways to control pathogens and prevent diseases in humans as well as in the veterinary field. Traditional vaccines against animal viral diseases are based on inactivated or attenuated viruses, but new subunit vaccines are gaining attention from researchers in animal vaccinology. Among these, virus-like particles (VLPs) represent one of the most appealing approaches opening up interesting frontiers in animal vaccines. VLPs are robust protein scaffolds exhibiting well-defined geometry and uniformity that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines; nevertheless, only one veterinary VLP-base vaccine is licensed. Here, we review and examine in detail the current status of VLPs as a vaccine strategy in the veterinary field, and discuss the potential advantages and challenges of this technology.

Recent studies have suggested that autophagy can act as a protective immune mechanism against Listeria monocytogenes infection. L. monocytogenes is a Gram-positive, facultative intracellular bacterium that causes invasive diseases in humans and animals, particularly in the central nervous system (CNS). Human listeriosis of the CNS can manifest in many ways, including meningitis and brain abscesses. The initial line of defence against bacterial colonisation is provided by microglia, resident phagocytes of the CNS parenchyma. Microglial cells are also well known for clearing dead and dying neural cells after injury, and therefore play a key role in infectious diseases and neurodegeneration.

Little is known about the role of the autophagy pathway in host–pathogen interactions in the brain as most in vitro studies have used macrophages or epithelial cells to study this interaction. In the present work, a quantitative real time-PCR array analysis was performed to assess autophagy-related gene expression in a brain rat ex vivo organotypic nervous system model during L. monocytogenes infection. We found that, in brief, core autophagy gene expression is not modulated by the infection, despite the presence of intense microglial phagocytic activity on the brain tissue surface that can be seen by scanning electron microscopy. We conclude that, in our model, autophagy could play a role in homeostasis in the damaged brain tissue instead of an immune-relevant pathway.

La recombinación V(D)J consiste en el ensamblaje de los segmentos génicos presentes en los genes de las cadenas variables de los receptores de antígeno para generar la diversidad del reconocimiento antigénico en linfocitos. El conocimiento de su regulación en condiciones normales es esencial para entender los casos en que este proceso se desregula, dando lugar a transformaciones leucémicas. La recombinación V(D)J se inicia por acción de una endonucleasa específica presente exclusivamente en linfocitos inmaduros. Según el «modelo de accesibilidad» propuesto hace más de 25 años, la recombinación V(D)J está regulada a través del control de la accesibilidad de esta endonucleasa a sus sitios de corte en el ADN, de acuerdo con unos programas de diferenciación celular muy definidos. En esta revisión se resumen los hallazgos descubiertos en este campo en los últimos años, tales como el importante papel que tiene la conformación génica y la posición de estos genes en el núcleo celular, así como aquellos que muy recientemente han permitido la validación definitiva del «modelo de accesibilidad».

V(D)J recombination is the assembly of gene segments at the antigen receptor loci in order to generate antigen receptor diversity in T and B lymphocytes. Detailed knowledge of how V(D)J recombination is normally regulated during lymphocyte development is essential to understand the cases of dysregulation of this process that result in leukemic transformation. V(D)J recombination is triggered by action of a specific endonuclease which is exclusively expressed in immature lymphocytes. According to the “accessibility model” proposed more than 25 years ago, DNA cleavage by this endonuclease is very strictly controlled during cell differentiation by regulating its accessibility to chromatin. This review summarizes the advances in the field over the last few years, including the important role of the genomic conformation and position of the antigen receptor loci within the nucleus, as well as those that have recently culminated with the validation of the “accessibility model” to control this process.

Introduction

The activating MICA/NKG2D interaction is involved in the response of intraepithelial lymphocytes (IELs) in coeliac disease (CD). The aim of this study was to investigate the expression of NKG2D ligands (MICA, MICB), IL-15 and NKG2D receptor in gut mucosa of CD patients, and the correlation with the severity of histological damage.

Patients and methods

Intestinal biopsies from 20 CD patients and five healthy controls were selected. All patients were positive for anti-transglutaminase 2 antibodies and for DQ2 or DQ8. Patients were divided into two groups according to their grade of mucosal impairment: ten each with mild and severe mucosal damage (MMD and SMD, respectively). The expression of proposed genes was determined at mRNA level. MICA expression was also determined by immunohistochemistry.

Results

Overexpression of MICA and MICB was observed in biopsies from coeliac patients compared to healthy controls (P < 0.001). Nevertheless, the expression was considerably higher in the group of patients with MMD (P < 0.0001) than in those with SMD. The levels of NKG2D receptor and IL-15 were also higher in patients than in controls, but no relationship with the severity of the mucosal lesion was found.

Conclusions

Our results suggest that NKG2D ligands may play an important role during the onset of the inflammatory process in the early stages of the development of coeliac disease.

Based on set theory a predictive method of LT-CD4 count was developed based on the number of white blood cells and total lymphocytes. The method was applied to 500 samples, in order to confirm the method's predictive capacity. The data triplets of WBC/ml³, lymphocytes/ml³ and CD4/μl for each patient were organized in descending order according to the number of white blood cells and separated in groups of 1.000. Triplets were organized in sets A, B, C and D, and then AUC, BUD, and their intersections were established. Finally, the elements of each group were calculated and their corresponding percentage for each group of WBC was determined.

As a result it was found that five of the nine groups of WBC showed an assertive percentage of 80.39% or above, and percentages of 92.54% and 100% were obtained for groups of values below 4.000/ml³ and 3.000/ml³, respectively. Results confirm that the method can be effectively applied in a clinical setting regardless of statistical measurements, and will reduce human and economic resources.