Estudio en aves silvestres de canto ("Passeriformes") de las moléculas MHC y reclasificación molecular de la familia "Carduelini"

The Major Histocompatibility Complex (MHC) comprises the most polymorphic loci in animals. MHC plays an important role during the first steps of the immune response in vertebrates. In humans, MHC molecules (also named human leukocyte antigens, HLA) were initially regarded as class I or class II molecules. Each of them, presents to different T cells subsets. MHC class I molecules, are heterodimers in which the heavy chain (alpha) has three extracellular domains, two of which (alpha 1 and alpha 2) are polymorphic and conform the antigen recognition sites (ARS). The ARS is thought to be subjected to balancing selection for variability, which is the cause of the very high polymorphism of the MHC molecules. Different pathogenic epitopes would be the evolutionary force causing balancing selection. MHC class I genes have been completely sequenced (α1 and α2 protein domains) and thoroughly studied in Gallus gallus (chicken) as well as in mammals. In fact, the MHC locus was first defined in chicken, specifically in the highly consanguineous variety „Leghorn‟. It has been found that, in the case of chickens the MHC genetic region is considerably smaller than it is in mammals (remarkably shorter introns were found in chickens), and is organized quite differently. The noteworthy presence of short introns in chickens; supported the hypothesis that chicken‟s MHC represented a „minimal essential MHC‟. Until now, it has been assumed that chicken (order Galliformes) MHC was similar to all species included in the whole class Aves...

Microhemorragias cerebrales en ancianos con demencia: prevalencia, factores de riesgo e implicaciones clínicas

Las microhemorragias cerebrales (MHC) se observan con frecuencia en la resonancia magnética (RM) asociadas al envejecimiento, la enfermedad de Alzheimer (EA) y, en particular, a la enfermedad cerebrovascular (ECV). Si bien el sustrato patológico de MHC ha sido suficientemente aclarado, sigue existiendo una considerable controversia acerca de su posible papel fisiopatológico tanto en ECV, como en la EA, así como sobre sus implicaciones clínicas. Se ha propuesto recientemente que las MHC podrían desempeñar un papel fisiopatológico clave para explicar la asociación entre EA y ECV. En consecuencia, las MHC deberían transmitir peor pronóstico clínico en personas mayores con demencia. Distintos estudios realizados en las últimas dos décadas muestran resultados que asocian las MHC con el deterioro cognitivo, especialmente en relación con las funciones ejecutivas, incluso después de que se controlaron las variables fuertemente asociadas, tales como las lesiones isquémicas. Sin embargo, hay muy pocos estudios longitudinales y las áreas clínicas más allá de la cognición (por ejemplo, las capacidades funcionales, problemas de comportamiento o la mortalidad) apenas han sido investigados. Entre estas áreas ignoradas, el estudio del estado de ánimo, el comportamiento y las capacidades funcionales son de particular relevancia en pacientes ancianos con demencia avanzada...

Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.