Immunological reviews
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Inflammasomes are multi-protein complexes that sense microbial molecules and endogenous danger signals in intracellular compartments. Inflammasome assembly results in caspase-1 activation, which in turn drives maturation and secretion of the pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, and induces pyroptosis to eliminate the infectious agent. The importance of inflammasomes in regulating immune responses was recognized with the discovery of polymorphisms in genes encoding inflammasome components and their linkage to aberrant production of IL-1β and IL-18 in autoimmune and hereditary periodic fevers syndromes. We review the current knowledge on the role of inflammasomes in regulating innate and adaptive immune responses with an emphasis on the role of these immune complexes in autoinflammatory disorders and autoimmune diseases such as colitis, type I diabetes, multiple sclerosis and vitiligo.
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Immunological reviews · Jul 2011
ReviewThe genetics of asthma and allergic disease: a 21st century perspective.
Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. ⋯ These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits.
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Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization) and those who wheeze with human rhinoviruses (HRV) are at especially high risk for asthma. ⋯ These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus-allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma.
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Immunological reviews · Jul 2011
ReviewThe sentinel role of the airway epithelium in asthma pathogenesis.
The adoption of the concept that asthma is primarily a disease most frequently associated with elaboration of T-helper 2 (Th2)-type inflammation has led to the widely held concept that its origins, exacerbation, and persistence are allergen driven. Taking aside the asthma that is expressed in non-allergic individuals leaves the great proportion of asthma that is associated with allergy (or atopy) and that often has its onset in early childhood. Evidence is presented that asthma is primarily an epithelial disorder and that its origin as well as its clinical manifestations have more to do with altered epithelial physical and functional barrier properties than being purely linked to allergic pathways. ⋯ This latter response initially serves a protective function but, if exaggerated, may lead to fixed airflow obstruction associated with more severe and chronic disease. Dual pathways in the origins, persistence, and progression of asthma help explain why anti-inflammatory treatments fail to influence the natural history of asthma in childhood and only partially does so in chronic severe disease. Positioning the airway epithelium as fundamental to the origins and persistence of asthma provides a rationale for pursuit of therapeutics that increase the resistance of the airways to environmental insults rather than concentrating all effort on suppressing inflammation.
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The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. ⋯ Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access.