Activation mechanisms of invariant natural killer T cells (iNKTs)

RESUMEN: Aunque se ha logrado un conocimiento amplio acerca de las células T asesinas naturales (iNKT), aún no existe consenso sobre sus mecanismos de activación. Dichas células reconocen diferentes antígenos glicolipídicos presentados por medio de la molécula CD1d, los cuales pueden ser endógenos, exógenos derivados de organismos como bacterias y sintéticos desarrollados para aplicaciones clínicas. Existe mucho interés en entender cómo estas distintas variantes glicolipídicas inducen diferentes tipos de polarización, pero ha sido muy difícil llegar a un consenso, debido a que la respuesta depende de varios factores como la naturaleza, la internalización y el procesamiento de los glicolípidos. Además, la activación de las células iNKT la determinan el tipo y estado de activación de la célula presentadora de antígeno, las moléculas coestimuladoras, los mecanismos de transactivación y la localización de los complejos CD1d-glicolípido en distintas microrregiones de la membrana plasmática, como las balsas lipídicas. Esta revisión explora la evidencia sobre los factores que afectan la activación de las células iNKT con el fin de entender su potencial inmunomodulador.ABSTRACT: A great amount of knowledge on natural killer T cells (iNKTs) is now available, but a consensus about their activation mechanisms has not been reached. These cells recognize different glycolipid antigens through the CD1d molecule. Such antigens may be endogenous, derived from bacteria (foreign) and synthetic, the latter have been developed for clinical applications. There exists much interest in understanding how these different glycolipid compounds induce different types of polarization, but it has been difficult to reach a consensus due to the fact that responses depend on different factors such as: the nature of the molecule, the internalization process and the presentation of the glycolipids. Moreover, activation of iNKT cells is determined by the type and state of the antigen presenting cell, the co-stimulatory molecules, the transactivation mechanisms and the location of the glycolipid-CD1d complexes on the plasma membrane, such as the lipid rafts. This review explores the evidence about the factors that affect activation of iNKT cells in order to understand their immune-modulatory potential

Campaña de lanzamiento de la primera colección de la marca Decko Primavé 2007

Decko es una empresa productora de ropa para hombres y mujeres de estratos 5 y 6, con línea de producción y comercialización propia a través de la red de almacenes de la marca. Partiendo de esta premisa se establece la necesidad de esta empresa para mantenerse a la vanguardia en el mercado que ha escogido como consumidor final. Se observa la necesidad de implementar una nueva estrategia de comunicación que logre el cambio que se necesita para dicho propósito, comenzando por lo más básico, como el concepto creativo, basándose en estudios de mercado y del consumidor, que le permitan a Decko, tomar mejores decisiones de mercadeo en el futuro. Analizando campañas anteriores, se obtienen herramientas para la elaboración de la nueva campaña Decko Primavé 2007, también se parte de la presentación de la empresa, su estructura, administración, proceso de producción y todo lo relacionado a las necesidades de publicidad que ella requiere. A través de encuestas directas al público seleccionado se puede analizar el cómo se percibe la campaña. Se puede decir que la campaña eligió un concepto creativo y estratégico que da un giro de lineamiento comunicacional a la marca; así mismo se tuvieron en cuenta elementos como textura, personajes reconocidos acordes al perfil y a la personalidad de la marca, diferentes encuadres fotográficos y diferentes estrategias de divulgación que están debidamente organizadas en una estrategia de medios completa que abarca las ciudades más importantes con los medios de comunicación más impactantes y acordes al targetTrabajo de grado (Publicista)-- Universidad Autónoma de Occidente, 2007PregradoPublicist

Modulation of Tumor Immunity by Soluble and Membrane-Bound Molecules at the Immunological Synapse

To circumvent pathology caused by infectious microbes and tumor growth, the host immune system must constantly clear harmful microorganisms and potentially malignant transformed cells. This task is accomplished in part by T-cells, which can directly kill infected or tumorigenic cells. A crucial event determining the recognition and elimination of detrimental cells is antigen recognition by the T cell receptor (TCR) expressed on the surface of T cells. Upon binding of the TCR to cognate peptide-MHC complexes presented on the surface of antigen presenting cells (APCs), a specialized supramolecular structure known as the immunological synapse (IS) assembles at the T cell-APC interface. Such a structure involves massive redistribution of membrane proteins, including TCR/pMHC complexes, modulatory receptor pairs, and adhesion molecules. Furthermore, assembly of the immunological synapse leads to intracellular events that modulate and define the magnitude and characteristics of the T cell response. Here, we discuss recent literature on the regulation and assembly of IS and the mechanisms evolved by tumors to modulate its function to escape T cell cytotoxicity, as well as novel strategies targeting the IS for therapy

A chimeric protein-based vaccine elicits a strong IgG antibody response and confers partial protection against Shiga toxin-producing Escherichia coli in mice

BackgroundShiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen that causes gastrointestinal infections, ranging from acute diarrhea and dysentery to life-threatening diseases such as Hemolytic Uremic Syndrome. Currently, a vaccine to prevent STEC infection is an unmet medical need.ResultsWe developed a chimeric protein-based vaccine targeting seven virulence factors of STEC, including the Stx2B subunit, Tir, Intimin, EspA, Cah, OmpT, and AggA proteins. Immunization of mice with this vaccine candidate elicited significant humoral and cellular immune responses against STEC. High levels of specific IgG antibodies were found in the serum and feces of immunized mice. However, specific IgA antibodies were not detected in either serum or feces. Furthermore, a significantly higher percentage of antigen-specific CD4+ T cells producing IFN-γ, IL-4, and IL-17 was observed in the spleens of immunized mice. Notably, the immunized mice showed decreased shedding of STEC O157:H7 and STEC O91:H21 strains and were protected against weight loss during experimental infection. Additionally, infection with the STEC O91:H21 strain resulted in kidney damage in control unimmunized mice; however, the extent of damage was slightly lower in immunized mice. Our findings suggest that IgG antibodies induced by this vaccine candidate may have a role in inhibiting bacterial adhesion and complement-mediated killing.ConclusionThis study provides evidence that IgG responses are involved in the host defense against STEC. However, our results do not rule out that other classes of antibodies also participate in the protection against this pathogen. Additional work is needed to improve the protection conferred by our vaccine candidate and to elucidate the relevant immune responses that lead to complete protection against this pathogen

Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies

Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells

Registro fotográfico de tres especies de felinos (Carnivora: Felidae) simpátricos en el Parque Nacional Machalilla, costa del Ecuador

The Machalilla National Park (PNM) located in the Tumbes-Chocó-Magdalena hotspot in western Ecuador, contains high levels of biodiversity and endemism; however, it presents a constant loss and degradation of its habitat due to anthropogenic activity. In this work, the presence of wild cats within the protected area of the PNM was determined. 60 trap cameras were located within the 56,184 ha of the PNM land area, between the months of October 2018 and February 2019. During this period, the presence of three species of wild cats was detected: ocelot (Leopardus pardalis), margay (Leopardus wiedii) and yaguarundí (Herpailurus yagouaroundi). This note presents a particular case in which the presence of the three feline species was reported coinciding in one of the trap chambersEl Parque Nacional Machalilla (PNM) ubicado en el hotspot Tumbes-Chocó-Magdalena al oeste de Ecuador, contiene altos niveles de biodiversidad y endemismo; sin embargo, presenta una constante pérdida y degradación de su hábitat debido a la actividad antrópica. En este trabajo se determinó la presencia de los felinos silvestres dentro del área protegida del PNM. Se ubicaron 60 cámaras trampa dentro de las 56. 184 ha de la zona terrestre del PNM, entre los meses de octubre 2018 y febrero de 2019. Durante este periodo se detectó la presencia de tres especies de felinos silvestres: ocelote (Leopardus pardalis), margay (Leopardus wiedii) y yaguarundí (Herpailurus yagouaroundi). En esta nota se presenta un caso en particular en el que se reportó la presencia de las tres especies de felinos coincidiendo en una de las cámaras tramp

Contribution of viral and bacterial infections to senescence and immunosenescence

Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated β-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host’s susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review

Gobierno parlamentarista frente al fracaso del sistema presidencialista en el Perú

Objetivo: Ilustrar de qué manera, el sistema de gobierno parlamentarista presenta beneficios al sistema democrático frente al fracaso del sistema presidencialista en el último periodo presidencial del Perú. Métodos: Conforme se aprecia del desarrollo e la investigación, esta es una que, por sus características, es una investigación aplicada de tipo explicativo, enfoque cuantitativo y corte transversal, de su desarrollo se aprecia que la valoración que merece el sistema parlamentarista en relación al débil sistema presidencialista. Asimismo, siendo que la población y la muestra es menor a las 100 personas entrevistados, en este caso 90, personas en ambos casos (especialista en derecho constitucional, jueces, parlamentarios, fiscales, especialistas y usuarios). Resultados: según la tabla 13 evidencia que la prueba de bondad de ajuste de Kolmogorov Smirnov, se advierte que las variables no se aproximan a una distribución normal (p<0.05). En este caso debido a que se determinarán correlaciones entre variables y dimensiones, la prueba estadística a usarse deberá ser no paramétrica: Prueba de Correlación de Spearman. Conclusión: El sistema de gobierno parlamentarista presenta beneficios al sistema democrático frente al fracaso del sistema presidencialista, por cuanto el primero, permite una mayor fortaleza y desarrollo institucional en el último periodo presidencial del PerúTesi

Contribution of dendritic cell/T cell interactions to triggering and maintaining autoimmunity

Under healthy conditions, there is a balance between tolerance to self-tissue constituents and immunity against foreign antigens. Autoimmunity diseases (AD) take place when that equilibrium is disrupted and the immune response is directed to self-antigens, leading to injury or destruction of host tissues. The mechanisms conducing to the loss of immune tolerance remain largely unknown. The recent appearance of biological therapies has contributed to significant reduction in morbidity. However, currently available therapies are associated with important side effects and work only as palliative treatments. Dendritic cells (DCs) have emerged as key players in developing and maintaining adaptive immunity due to their capacity to prime and modulate T cell function. Therefore, because DCs work as central modulators of immune tolerance, it is likely that alterations in their function can lead to the onset of autoimmune-inflammatory diseases. By modulating DC function, novel pathways in antigen-specific tolerance could be established. In this article, the possible contribution of altered DC-T cell interactions to the onset of autoimmunity are discussed. In addition, we expand on the notion that some of the functions of these cells could be relevant targets for intervening therapies aimed to restore the balance or even prevent the loss of tolerance