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Allergic sensitization to inhaled antigens is increasingly common; however, the mechanisms remain poorly understood. Lung epithelial cells, once thought to be merely a passive barrier impeding allergen penetrance, have recently been shown to recognize allergens via expression of pattern recognition receptors (PRRs) and mount an innate immune response driven by the activation of the cytokine NF-кB. In their review, Lambrecht and Hammad discuss recent findings that describe epithelial cells as crucial in allergy inhalation outcomes ( J Allergy Clin Immunol 2014; 134(3): 499-507 ). Traditionally, allergic asthma has been characterized as a disease of the adaptive immune system, whereby lymphocytes overreact to harmless antigens and mount a type 2 immune response, subsequently causing the activation of effector cells like mast cells, basophils and eosinophils. Recently, research has been changing this view to accommodate the concept that cells of the innate immune system contribute signif...

Airway epithelial cells are an important part of the innate immune system in the lung. Not only do they establish mucociliary clearance, epithelial cells produce anti-microbial peptides, chemokines, and cytokines that recruit and activate other cell types and promote pathogen clearance. Recent studies emphasize the importance of epithelial derived cytokines in the promotion of Th2 immune responses, at least in part by conditioning local dendritic cells (DCs). Epithelial cells also from a barrier to the outside world comprised of airway surface liquids, mucus, and apical junctional complexes (AJC) that form between neighboring cells. In their recent review, Georas and Rezaee discuss why defective epithelial barrier function may be linked to Th2 polarization in asthma, and propose a rheostat model of barrier dysfunction that implicates the size of inhaled allergen particles as an important factor influencing adaptive immunity ( J Allergy Clin Immunol 2014; 134(3): 509-520 ).  Increa...

There is evidence that the presence of asthma can influence patients’ susceptibility to infections, yet research in this aspect of asthma has been limited. Additionally, there is a debate in the field with current literature tending to suggest an increased risk of infection among atopic patien t s as due to opportunistic infections secondary to airway inflammation, especially in severe atopic diseases. Other evidence suggests that such risk and its underlying immune dysfunction may be a phenotypic or clinical feature of atopic conditions. In his review, Young J. Juhn argues that improved understanding of the effects of atopic conditions on the risk of microbial infections will bring important new perspectives to clinical practice, research, and public health concerning atopic conditions [ J Allergy Clin Immunol 2014; 134(2): 247-57 ] . The review focuses on the effect of atopic conditions on the risk of infections, termed reverse causality. For example, asthma is associated with a b...

Over the past four decades, over 180 molecular defects causing primary immunodeficiencies (PIDs) have been discovered through advances in immunology and genetics. Recent studies have identified ways to solve difficult cases such as diseases with autosomal dominant inheritance, incomplete penetrance, or mutations in non-coding regions. In their review, Platt et al focus on selected causes to illustrate a spectrum of approaches for identifying causative mutations [ J Allergy Clin Immunol 2014; 134(2): 262-68 ].   They broadly classified these approaches into 3 different strategies: 1) educated guesses based on known signaling pathways essential for immune cell development and function, 2) similarity of clinical phenotypes to mouse models, and 3) unbiased genetic approaches. They also address methods of overcoming challenges in identifying molecular causes of PIDS. Since the majority of PIDs are monogenic, whole exome/genome sequencing has expedited the discovery of pathogenic mutat...

Advances in HIV vaccine development have been hampered by roadblocks associated with failure to prevent infection. In recent years, a number of basic and translational science advances have shown promise in the development for an effective vaccine. In their review, Haynes and colleagues summarize these advances along with the roadblocks that still remain, as well as the most promising approaches to successful vaccine design ( J Allergy Clin Immunol 2014, 134(1): 3-10 ).  This year, the field of HIV-vaccine research had a major disappointment in the announcement of the lack of a vaccine efficacy seen in a DNA prime, recombinant adenovirus type 5 (rAd5) boost HIV-1 vaccine trial developed by the NIH Vaccine Research Center. The vaccine was designed to test the hypothesis that high levels of CD8+ cytotoxic T cells (CTLs) could either protect against transmission or lead to control of plasma HIV-1 viral load. The second failed trial, the Merck recombinant adenovirus type 5 trail, not o...

Asthma often begins early in life and is attributed to more than just genetic factors, because the prevalence continues to rise. Epidemiological studies have indicated roles for prenatal and early childhood exposures, including exposure to diesel exhaust, however, little is known about the mechanisms involved. To elucidate this, Manners et al developed a mouse model of asthma susceptibility through prenatal exposure to diesel exhaust ( J Allergy Clin Immunol 2014; 134(1): 63-72 ) . In this model, pregnant mice were repeatedly exposed to diesel exhaust particles (DEPs). Offspring were immunized and challenged with ovalbumin (OVA) or exposed to PBS (control) then examined for features of asthma. Compared to controls, offspring that were exposed to DEP were hypersensitive to OVA, indicated by airway hyperresponsiveness, elevated serum levels of OVA-specific IgE, and elevated levels of pulmonary and systemic T-helper type 2 (Th2) and Th17 cytokines. The authors determined that natural kill...

The current and most effective treatment for asthma therapy is the use of glucocorticoids by improving the clinical features and airway inflammation associated with asthma. However, a cohort of well-defined asthma patients exists in whom high-dose glucocorticoid treatment is not only clinically ineffective, but potentially detrimental.  Several mechanisms have been proposed to contribute to glucocorticoid resistance, including vitamin D insufficiency. Nanzer et al recently published data that glucocorticoid resistant patients fail to synthesize the anti-inflammatory cytokine interleukin-10 (IL-10) in response to glucocorticoid in vitro compared to glucocorticoid sensitive patients ( J Allergy Clin Immunol 2014; 133(6): 1755-1757 ). When resistant patients ingested a form of vitamin D called calcitriol (1,25-dihydroxyvitamin D3) in combination with glucocorticoid, levels of IL-10 were restored in vivo and ex-vivo. Taken together, these data along with epidemiological evidence linkin...