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Keeping on the topic of natural killer cells, Jordan Orange, MD, PhD contributes a review on immunodeficiencies associated with NK cell dysfunction [ J Allergy Clin Immunol 2013; 132(3):515-525 ].  The author provides a concise review of NK cell biology, covering their intrinsic activities of cytotoxicity, tumor surveillance, and co-stimulation and signaling.  Orange points out that NK cell deficiency [NKD] is a subset of primary immunodeficiency diseases [PID] that is difficult to diagnose and treat because of the limited clinical information and testing available.  Like other PID, the author notes that NKD patients are characterized by a susceptibility to chronic and/or severe viral infections, especially herpes viruses.  Accurate diagnosis hinges on determining that the seminal deficiency is associated with NK cells, and that NKD is not secondary to other causes. The author provides an algorithm for identifying primary NKD.  Orange discusses the current class...

This month, Deniz et al. give an overview of current knowledge about natural killer cells [NK cells] and their interface with pathways and mechanisms of adaptive immunity, with attention to allergic disease processes [ J Allergy Clin Immunol 2013; 132(3):527-535 ].  The authors cover fundamentals of NK biology, such as their surface marker characterization, IFN-γ secretion, MHC class I interactions, phenotypes, tissue prevalence, cytokine profiles, and cytotoxicity to target cells.  NK cells are characterized by their cytotoxic activity through release of perforin and granzymes that are targeted at tumor cells, virally infected cells, and IgG antibody expressing cells, cytokine and chemokine secretion and signaling of adaptive immune cells, and co-stimulatory interaction with antigen presenting cells [APC] via IL-10 and TGF-β.   Deniz et al. note that NK chemokine secretion is particularly important in the co-localization and mutual maturation of dendritic cells [DC]...

In a review this month, Greer and co-authors present interesting information on just how much our health depends on the well-being and communal balance of the microscopic symbionts in our gastrointestinal tract [ Journal of Allergy and Clinical Immunology 2013; 132(2): 253-262 ].  They begin their review noting that, until fairly recently, immunity, metabolic functions and gut physiology had been studied as separate biological systems.  In light of growing evidence that the delineation between these is arbitrary, the authors point out that systems biology has developed new methods for investigating the interactions between the intestinal microbiota and immune and metabolic outcomes. Greer et al covers two broad categories, small intestine enteropathies and obesity with metabolic syndrome.  They describe current animal models used to study immunodeficiency enteropathies, celiac disease, inflammatory bowel disease, obesity and lipid metabolism dysregulation. The authors di...

Apoptosis was previously thought to be the only mode of regulated or programmed cell death in eosinophils, as necrosis was regarded as unregulated cell death.  However, Kano et al. , have discovered that the activated eosinophils, found in abundance in asthma and allergic disease, can die by means of a type of regulated necrosis in response to Siglec-8 ligation [ J Allergy Clin Immunol 2013; 132(2): 437-445 ]. Siglec-8 is a cell-surface receptor protein that is highly and selectively expressed by human eosinophils, as well as mast cells and basophils. The authors show that Siglec-8 ligation in the presence of IL-5 triggers necrosis in activated eosinophils in a reactive oxygen species (ROS) – dependent manner. Further, they explain why IL-5 promotes cell death in this system even though it is typically a pro-survival signal.  They demonstrate that ROS switch IL-5’s function from pro-survival to cell death enhancement by augmenting ERK phosphorylation and this serves as a decis...

Highlighting the role of innate immunity in the evolution of obesity and associated metabolic disorders, Jin and Flavell deliver a concise review of mechanisms involving pattern recognition receptors that produce pathology in liver, pancreas, brain and intestinal microbiota [ J Allergy Clin Immunol 2013; 132(2):287-294 ].  The authors provide a summary of the biology of the major types of pattern recognition receptors [PRR], with emphasis on toll-like receptors [TLR] and NOD-like receptors [NLR].  They discuss briefly their activity in response to pathogen infection and endogenous injury.  Several NLRs can coalesce into multiprotein complexes called inflammasomes which have proven to be important ly involved in the development of insulin resistance.  Jin and Flavell review PRR mechanisms in five critical physiologic areas: brain, pancreatic islet, and vascular inflammation, induction of peripheral insulin resistance, and disruption of intestinal microbiota homeos...

In a new series for the Journal, “ Allergy and clinical immunology around the world ,” Paul Potter, MD, describes sublingual immunotherapy practice in South Africa, which is based on recommendations put forth by the Allergy Society of South Africa [ J Allergy Clin Immunol 2013; 132(1): 99-100 ].  Because of the long grass pollen season, approximately 8 months, seasonal rhinitis in the region is reclassified as persistent rhinitis, for which SLIT is indicated.  Potter notes that SLIT has been available for 15 years in South Africa.  European vaccines are employed for Bermuda/rye grass pollens and D. pteronyssinus/farinae for mite allergies.  Patients eligible for SLIT must be sensitive to only one allergen per the recommendations, though 80% of the patient population is allergic to multiple allergens.  The author reports that clinical trials for SLIT in South Africa have had variable outcome agreement, in spite of significant efficacy results.  A retrospecti...

While investigations of microRNAs [miRNA] and their role in transcription in disease have been growing for the last decade, more recently they have come under the scrutiny of immunologists searching for signs of miRNA dysregulation in allergic inflammation.  This month, Lu and Rothenberg review the evidence to-date and give us some very interesting news on miRNA in several atopic diseases [ J Allergy Clin Immunol 2013; 132(1): 3-13 ]. Lu and Rothenberg start with a review of the general pathophysiology of miRNAs, which effect gene transcription networks by silencing posttranscriptional gene expression of mRNA.  One miRNA can modulate multiple genes and one gene may be targeted by many miRNAs.  miRNAs are also known to modify DNA methylation and histone acetylation, as well as interact with transcription factors.  The authors comment that miRNAs have been found in exosomes in cell-free body fluids, raising the intriguing possibility of their usefulness as peripheral b...