IgA vasculitis
AbstractIgA vasculitis (IgAV) is an inflammation of small vessels caused by perivascular deposition of IgA and activation of neutrophils. It may present as systemic vasculitis (IgAV - Henoch-Sch önlein purpura) or as a variant restricted to the skin (skin-limited IgAV), while IgA nephropathy presents a variant restricted to the kidneys. Systemic IgAV affects children more frequently than adults (150 to 200 for 1; incidence 1 in 1 million/year). In the latter, disease more often leads to ch ronic renal disease. The dominant clinical features include round or oval and retiform palpable purpura predominantly on the lower leg...
Source: Seminars in Immunopathology - June 25, 2021 Category: Pathology Source Type: research
Eosinophils and helminth infection: protective or pathogenic?
AbstractSince the earliest descriptions of this enigmatic cell, eosinophils have been implicated in both protective and pathogenic immune responses to helminth infection. Nevertheless, despite substantial data from in vitro studies, human infections, and animal models, their precise role in helminth infection remains incompletely understood. This is due to a number of factors, including the heterogeneity of the many parasites included in the designation “helminth,” the complexity and redundancy in the host immune response to helminths, and the pleiotropic functions of eosinophils themselves. This review examines the co...
Source: Seminars in Immunopathology - June 24, 2021 Category: Pathology Source Type: research
Complement in metabolic disease: metaflammation and a two-edged sword
AbstractWe are currently experiencing an enduring global epidemic of obesity and diabetes. It is now understood that chronic low-grade tissue inflammation plays an important role in metabolic disease, brought upon by increased uptake of a so-called Western diet, and a more sedentary lifestyle. Many evolutionarily conserved links exist between metabolism and the immune system, and an imbalance in this system induced by chronic over-nutrition has been termed ‘metaflammation’. The complement system is an important and evolutionarily ancient part of innate immunity, but recent work has revealed that complement not only is ...
Source: Seminars in Immunopathology - June 22, 2021 Category: Pathology Source Type: research
The contact system in liver injury
AbstractCoagulation is controlled by a delicate balance of prothrombotic and antithrombotic mechanisms, to prevent both excessive blood loss from injured vessels and pathologic thrombosis. The liver plays a pivotal role in hemostasis through the synthesis of plasma coagulation factors and their inhibitors that, in addition to thrombosis and hemostasis, orchestrates an array of inflammatory responses. As a result, impaired liver function has been linked with both hypercoagulability and bleeding disorders due to a pathologic balance of pro- and anticoagulant plasma factors. At sites of vascular injury, thrombus propagation t...
Source: Seminars in Immunopathology - June 14, 2021 Category: Pathology Source Type: research
Eosinophils in skin diseases
AbstractEosinophil infiltration is a common finding in a broad spectrum of skin diseases, despite the fact that the skin is devoid of eosinophils under physiologic conditions. Although cutaneous eosinophilia is reactive, cytokine-mediated in most cases, diseases with an intrinsic mutation-mediated clonal expansion of eosinophils can also manifest on the skin. As eosinophils are involved in host defense, regulate immune responses, generate pruritus, induce remodeling and fibrosis, and can cause tissue damage, they have the capacity to actively contribute to the pathogenesis of diseases. Recent research provided deeper insig...
Source: Seminars in Immunopathology - June 7, 2021 Category: Pathology Source Type: research
Eosinophilic esophagitis —established facts and new horizons
AbstractDespite dramatic advances in our understanding of the pathogenesis and course of disease in the relatively short timeframe since the discovery and first description of eosinophilic esophagitis (EoE) less than three decades ago, many open questions remain to be elucidated. For instance, we will need to better characterize atypical clinical presentations of EoE and other forms of esophageal inflammatory conditions with often similar clinical presentations, nut fulfilling current diagnostic criteria for EoE and to determine their significance and interrelationship with genuine EoE. In addition, the interrelationship o...
Source: Seminars in Immunopathology - June 7, 2021 Category: Pathology Source Type: research
Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity
AbstractEosinophils and their mediators play a crucial role in various reactive states such as bacterial and viral infections, chronic inflammatory disorders, and certain hematologic malignancies. Depending on the underlying pathology, molecular defect(s), and the cytokine- and mediator-cascades involved, peripheral blood and tissue hypereosinophilia (HE) may develop and may lead to organ dysfunction or even organ damage which usually leads to the diagnosis of a HE syndrome (HES). In some of these patients, the etiology and impact of HE remain unclear. These patients are diagnosed with idiopathic HE. In other patients, HES...
Source: Seminars in Immunopathology - June 1, 2021 Category: Pathology Source Type: research
Intestinal eosinophils, homeostasis and response to bacterial intrusion
AbstractEosinophils are traditionally considered as end-stage effector cells involved in the pathogenesis of Th2 immune-mediated disorders as well as in the protection against parasite infection. However, this restricted view has recently been challenged by a series of studies revealing the highly plastic nature of these cells and implication in various homeostatic processes. Large numbers of eosinophils reside in the lamina propria of the gastrointestinal tract, at the front line of host defence, where they contribute to maintain the intestinal epithelial barrier function in the face of inflammation-associated epithelial ...
Source: Seminars in Immunopathology - June 1, 2021 Category: Pathology Source Type: research
Intestinal eosinophils: multifaceted roles in tissue homeostasis and disease
AbstractIntestinal eosinophils are largely considered to be one of the central immune effector cells during helminth infection and disorders such as eosinophilic oesophagitis and food allergies. Given the abundance of these cells present in the gastrointestinal tract at homeostasis, emerging studies now reveal novel roles for eosinophils in the development and regulation of immunity, and during tissue repair. In addition, the identification of distinct eosinophil subsets indicates that we must consider the heterogeneity of these cells and how they differentially participate in mucosal immunity at steady state and during di...
Source: Seminars in Immunopathology - June 1, 2021 Category: Pathology Source Type: research
Lessons learned from targeting eosinophils in human disease
AbstractEosinophils are a minor subset of the granulocyte lineage distinguished by their unique morphology, phenotype, cytoplasmic contents, and function. Evolutionarily, these are ancient cells whose existence has been conserved within vertebrates for millions of years, suggesting that their contribution to innate immunity and other pathologic and homeostatic responses are important to the host. Knowledge regarding the role of eosinophils in health and disease took a leap forward in 2004 with the creation of mouse strains deficient in eosinophils. This advance was paralleled in humans using pharmacology, namely, with the ...
Source: Seminars in Immunopathology - June 1, 2021 Category: Pathology Source Type: research
Regulation of eosinophil functions by autophagy
AbstractEosinophils are granule-containing leukocytes which develop in the bone marrow. For many years, eosinophils have been recognized as cytotoxic effector cells, but recent studies suggest that they perform additional immunomodulatory and homeostatic functions. Autophagy is a conserved intracellular process which preserves cellular homeostasis. Autophagy defects have been linked to the pathogenesis of many human disorders. Evidence for abnormal regulation of autophagy, including decreased or increased expression of autophagy-related (ATG) proteins, has been reported in several eosinophilic inflammatory disorders, such ...
Source: Seminars in Immunopathology - June 1, 2021 Category: Pathology Source Type: research
The aryl hydrocarbon receptor in liver inflammation
AbstractThe aryl hydrocarbon receptor (AHR) is a ubiquitously expressed ligand-activated transcription factor with multifaceted physiological functions. In the immune system, AHR has been unequivocally identified as a key regulatory factor that can integrate environmental, dietary, or microbial signals into innate and adaptive immune responses. Correspondingly, AHR activity seems to be most important at barrier organs, such as the gut, skin, and lung. The liver is likewise prominently exposed to gut-derived dietary or microbial AHR ligands and, moreover, generates plenty of AHR ligands itself. Yet, surprisingly little is k...
Source: Seminars in Immunopathology - June 1, 2021 Category: Pathology Source Type: research
