Implicancia de la inmunidad innata del epitelio bronquiolar en la modulación y prevención del asma / Implication of innate immunity in modulating bronchial epithelium and prevention of asthma

El asma alérgica ha incrementado su prevalencia, constituyéndose como un problema mundial de salud. Factores ambientales derivados de la vida moderna han sido vinculados a este fenómeno a través de la hipótesis de la higiene; la cual postula que la vida urbana disminuye la potenciación de la inmunidad innata, lograda a través del reconocimiento de estímulos microbianos por los receptores Toll-like (TLRs), conduciendo a la mayor prevalencia de respuestas alérgicas. Las investigaciones en asma en el último siglo han tenido como objetivo la disminución de la respuesta inmune adaptativa Th2 asociada a las alergias; sin embargo han conseguido escasos avances terapéuticos. Actualmente, es creciente el número de evidencias que implican a los componentes estructurales de la vía aérea en el inicio y progresión del asma; no obstante su rol en la prevención de la inflamación alérgica no ha sido suficientemente evaluado. Por lo tanto, el presente trabajo de Tesis Doctoral tuvo como objetivo general el estudio de la interacción de la inmunidad innata del epitelio bronquiolar y la inflamación alérgica del asma.

ABSTRACT: Recently, asthma rates have increased becoming a global health problem. The role of environmental factors in this increase, due to modern lifestyles, has been suggested by the hygiene hypothesis, which postulated that the urban hygienic conditions skip the early exposure to microbes hence that are clue to promote innate immune activation by signalling through the Toll-like receptors (TLRs) and thus preventing the allergic responses. Even though many investigations on asthma have been focused on the reduction of the allergic Th2-nflammatory response in the last century, the therapeutic advances have been scarce. Nowadays, there is increasing evidence of the involvement of the airway epithelial cells on the origin and progression of asthma. However, the role of these cells in preventing the triggering of allergic inflammation has not been evaluated. Therefore, the main objective of this thesis was to study the interaction of innate immunity of bronchiolar epithelium and allergic inflammation in asthma.

Heterotopic transplantation of glycerin-preserved trachea: effect of respiratory epithelium desquamation on acute rejection

An effective preservation method and decreased rejection are essential for tracheal transplantation in the reconstruction of large airway defects. Our objective in the present study was to evaluate the antigenic properties of glycerin-preserved tracheal segments. Sixty-one tracheal segments (2.4 to 3.1 cm) were divided into three groups: autograft (N = 21), fresh allograft (N = 18) and glycerin-preserved allograft (N = 22). Two segments from different groups were implanted into the greater omentum of dogs (N = 31). After 28 days, the segments were harvested and analyzed for mononuclear infiltration score and for the presence of respiratory epithelium. The fresh allograft group presented the highest score for mononuclear infiltration (1.78 ± 0.43, P <= 0.001) when compared to the autograft and glycerin-preserved allograft groups. In contrast to the regenerated epithelium observed in autograft segments, all fresh allografts and glycerin-preserved allografts had desquamation of the respiratory mucosa. The low antigenicity observed in glycerin segments was probably the result of denudation of the respiratory epithelium and perhaps due to the decrease of major histocompatibility complex class II antigens.

Mecanismos imunológicos da mucosa das vias aéreas superiores e fisiopatologia do anel linfático de Waldeyer: conceitos atuais / Immune mechanisms of the upper airways mucosa and pathophsiology of linphatic Waldeyer´s ring: current concepts

As vias aéreas superiores (VAS) são a principal porta de entrada do organismo. Apresentam uma ampla cobertura mucosa como barreira física aos agentes infecciosos, irritantes ambientais, etc. Há importantes mecanismos imunes específicos e inespecíficos nesta área.

Presence of circulating autoantibodies against bronchial epithelia cell in patients with nonatopic asthma

Allergic response to common environmental agents has been regarded as a main pathogenetic mechanism of bronchial asthma. However, allergic sensitization (atopy) can not be detected in a siginificant number of adult asthmatic patients. The etiology of nonatopic asthma has not yet been defined. To evaluate the possible involvement of autoimmune response against bronchial mucosa in the pathogenesis of nonatopic asthma, we performed indirect immunofluorescence staining of fresh frozen human bronchial mucosa tissue using serum samples from patients with atopic and nonatopic asthma, healthy controls, and patients with systemic lupus erythematosus. On immunostaining, circulating IgG autoantibodies against bronchial mucosa were detected in 2 (9.1%) of 22 patients with nonatopic asthma and in none of 22 patients with atopic asthma and of 22 healthy controls. IgG autoantibodies from the two patients with nonatopic asthma predominantly stained the cytoplasmic membrane of basal cells in bronchial epithelium. Serum samples from 10 patients with systemic lupus erythematosus immunostained the nucleus of epithelial cells in whole layer of bronchial epithelium. This study showed the presence of circulating IgG autoantibodies against the bronchial epithelial cell in a small portion of patients with nonatopic asthma. Further studies may be necessary to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.