Mast cells are innate immune cells that function as regulatory or effector cells and serve to amplify adaptive immunity. These cells also function in adaptive immunity primarily through cell surface Fc receptors that bind immunoglobulin antibodies. The dysregulation of their adaptive role makes them central players in allergy and asthma. Upon encountering an allergen (antigen), which is recognized by immunoglobulin E (IgE) antibodies bound to the high affinity IgE receptor (FcεRI) expressed on their cell surface, mast cells secrete both preformed and newly synthesized mediators of the allergic response. Blocking of these responses is an objective in therapeutic intervention of allergic diseases. Thus, understanding the mechanisms by which antigens elicit mast cell activation (via FcεRI) holds promise towards identifying therapeutic targets. Here we review the most recent advances in understanding antigen-dependent mast cell activation. Specifically, we focus on the requirements for FcεRI activation; the regulation of calcium responses; co-stimulatory signals in FcεRI-mediated mast cell activation and function; and how genetics influences mast cell signaling and responses. These recent discoveries open new avenues of investigation with therapeutic potential.
Hepatitis B virus (HBV) infection is the leading cause of severe chronic liver disease. This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America. Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection. Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America; these strains have historically circulated among the indigenous population. Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans. In contrast, genotypes F, A and D are common in acute and chronic infections among mestizos with Caucasian ancestry. Hepatocellular carcinoma is rare in Mexicans, but it has been associated with genotype F1b among Argentineans. This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America, which contrast with those reported in other regions of the world.
The distribution of HBV genotypes is associated with populations of specific geographical regions of the world. We show data from the GenBank sequence database and medical reports, which indicate that HBV genotype H (HBV/H) is mainly distributed in Mexico, whereas HBV genotype F (HBV/F) is distributed in countries from Central America. The phylogenetic analysis and historical records suggest that HBV/H has been present in Mexico even before the arrival of the Spaniards. Interestingly, occult hepatitis B is a common finding in both natives and patients with chronic liver disease in Mexico. This suggests that an immunogenic background could be important during the natural history of liver diseases. The estimated large number of HBV/H-infected patients in Mexico does not correlate with the total number of patients with chronic liver disease and cirrhosis reported in the country. This may be because of the fact that HBV infection is often masked by alcoholic liver disease, HCV coinfection and/or obesity. Here, we analyse the data concerning the distribution of HBV/F and HBV/H genotypes in Central America and Mexico. Specifically, we focus on the effect of molecular epidemiology and pathogenesis of HBV/H. These recent findings reveal new areas of study with therapeutic potential in viral liver diseases.
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