Immunologic research
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Immunologic research · Mar 2013
COPD is associated with production of autoantibodies to a broad spectrum of self-antigens, correlative with disease phenotype.
The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly appreciated. In this study, we identified serum autoantibody reactivities associated with chronic bronchitis or emphysema, as well as systemic autoimmunity and associated lung disease. Using autoantigen array analysis, we demonstrated that COPD patients produce autoantibodies reactive to a broad spectrum of self-antigens. ⋯ Strikingly, the autoantibody reactivities observed in emphysema were increased over those detected in rheumatoid arthritis patients, and included similar reactivities to those associated with lupus. These findings raise the possibility that autoantibody profiles may be used to determine COPD risk, as well as provide a diagnostic and prognostic tool. They shed light on the heterogeneity of autoantibody reactivities associated with COPD phenotype and could be of use in the personalization of medical treatment, including determining and monitoring therapeutic interventions.
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Immunologic research · Dec 2009
ReviewThe platelet as an immune cell-CD40 ligand and transfusion immunomodulation.
The discovery that platelets possess cell membrane, cytoplasmic, and secreted forms of the co-stimulatory molecule CD40 ligand (CD40L, also known as CD154) has led to a revolution in the view of this anucleate, differentiated cell fragment, previously thought only to be involved in blood clotting (hemostasis). During the last decade, it has become clear that platelets function in innate and adaptive immunity and possess pro-inflammatory, as well as pro-thrombotic properties. They interact not only with other platelets and endothelial cells, but also with lymphocytes, dendritic cells, and structural cells such as fibroblasts. ⋯ Each year millions of platelet transfusions are given to patients that contain large amounts of sCD40L. sCD40L in the supernatant of stored platelets can induce cytokines, chemokines, and lipid mediators by activating CD40 bearing cells. Increased levels of sCD40L in transfused blood are associated with transfusion-related acute lung injury, a potentially fatal complication, as well as more common, milder transfusion reactions such as fever and rigors. These effects come under the rubric of transfusion immunomodulation, which postulates that transfusion recipient biology, particularly immune function, is dramatically altered by transfusion of stored allogeneic blood.
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Interleukin-1 receptor-associated kinase-4 (IRAK-4), a member of the IRAK family, plays an essential role in Toll-like receptor- and IL-1 receptor-mediated signaling. We briefly review inherited human IRAK-4 deficiency, a recently described primary immunodeficiency leading to recurrent, invasive, pyogenic bacteria infection, and invasive pneumococcal disease in particular.
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Despite intensive ongoing research efforts, the mortality of patients with sepsis remains unacceptably high. Clinical trials emerging from promising results in animal models have mostly failed to deliver sufficient treatment strategies so far. Many studies investigating the underlying mechanisms of sepsis have focused on deterioration of the humoral and cellular components of the immune system. ⋯ So far, not much is known about the effects of a dysregulated immune system as seen in sepsis on parenchymal cells of end organs. Studies on the interaction of the complement system and kidney as well as liver cells resulted in interesting yet still inconclusive data. In this review, we provide new insights into mechanisms during sepsis based on recent findings.
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Immunologic research · Jan 2006
ReviewDeciphering the complexity of acute inflammation using mathematical models.
Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. ⋯ The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.