As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID‐19) appears ...practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute‐phase reactants, and serum biochemistry in COVID‐19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1‐week, self‐limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM‐, IgA‐, and IgG‐type virus‐specific antibodies levels are important measurements to predict population immunity against this disease and whether cross‐reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID‐19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine‐secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute‐phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.
The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and ...high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.
Background IL-10–producing regulatory B cells suppress immune responses, and lack of these cells leads to exacerbated symptoms in mouse models of chronic inflammation, transplantation, and chronic ...infection. IgG4 is a blocking antibody isotype with anti-inflammatory potential that is induced in human high-dose antigen tolerance models. Objective We sought to characterize human inducible IL-10–secreting B regulatory 1 (BR 1) cells and to investigate their immunoregulatory capacity through suppression of cellular immune responses and production of anti-inflammatory immunoglobulins. Methods Highly purified IL-10–secreting B cells were phenotypically and functionally characterized by means of whole-genome expression analysis, flow cytometry, suppression assay, and antibody production. B cells specific for the major bee venom allergen phospholipase A2 (PLA) were isolated from beekeepers who displayed tolerance to bee venom antigens and allergic patients before and after specific immunotherapy. Results Human IL-10+ BR 1 cells expressed high surface CD25 and CD71 and low CD73 levels. Sorting of CD73− CD25+ CD71+ B cells allowed enrichment of human BR 1 cells, which produced high levels of IL-10 and potently suppressed antigen-specific CD4+ T-cell proliferation. IgG4 was selectively confined to human BR 1 cells. B cells specific for the major bee venom allergen PLA isolated from nonallergic beekeepers show increased expression of IL-10 and IgG4 . Furthermore, the frequency of IL-10+ PLA-specific B cells increased in allergic patients receiving allergen-specific immunotherapy. Conclusion Our data show the characterization of IL-10+ BR 1 cells and in vivo evidence for 2 essential features of allergen tolerance: the suppressive B cells and IgG4 -expressing B cells that are confined to IL-10+ BR 1 cells in human subjects.
Immune tolerance to both self-antigens and innocuous non–self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and ...suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion. However, IL-35 and TGF-β have also been associated with B cell–mediated immunosuppression. Several types of murine and human Breg cells have been described, such as mouse CD5+ CD1dhi B10 cells, CD21hi CD23hi CD24hi transitional stage 2–like B cells, and CD138+ plasma cells and plasmablasts. Human Breg cell types include CD27+ CD24high B10 cells, CD24hi CD38hi immature transitional B cells, and CD73− CD25+ CD71+ BR 1 cells and a subset of plasma cells. Support for the in vivo existence of allergen-specific human Breg cells comes from direct detection of their increase during the course of allergen-specific immunotherapy, as well as their increased expression in nonallergic but high-dose allergen–exposed beekeepers. Human BR 1 cells selectively upregulate IgG4 antibodies on differentiation to plasma cells. This suggests an additional immune regulatory role because of the noninflammatory and blocking antibody function of IgG4 . Taken together, Breg cells appear to be involved in mediating allergen tolerance, but many open questions remain to be answered.
The rising prevalence of allergies represents an increasing socioeconomic burden. A detailed understanding of the immunological mechanisms that underlie the development of allergic disease, as well ...as the processes that drive immune tolerance to allergens, will be instrumental in designing therapeutic strategies to treat and prevent allergic disease. Improved characterization of individual patients through the use of specific biomarkers and improved definitions of disease endotypes are paving the way for the use of targeted therapeutic approaches for personalized treatment. Allergen-specific immunotherapy and biologic therapies that target key molecules driving the Th2 response are already used in the clinic, and a wave of novel drug candidates are under development. In-depth analysis of the cells and tissues of patients treated with such targeted interventions provides a wealth of information on the mechanisms that drive allergies and tolerance to allergens. Here, we aim to deliver an overview of the current state of specific inhibitors used in the treatment of allergy, with a particular focus on asthma and atopic dermatitis, and provide insights into the roles of these molecules in immunological mechanisms of allergic disease.
The aim of this review is to provide an overview of the current knowledge on the mechanisms of allergen immunotherapy based on the recent publications and clinical trials.
PubMed literature review.
...In this review, we focus on diverse mechanisms of AIT and provide an insight into alternative routes of administration. Additionally, we review and discuss the most recent studies investigating potential biomarkers and highlight their role in clinical settings.
Successful allergen-specific immunotherapy (AIT) induces the reinstatement of tolerance toward allergens and represents a disease-modifying treatment. In the last decades, substantial progress in understanding the mechanisms of AIT has been achieved. Establishment of long-term clinical tolerance to allergens engages a complex network of interactions, modulating the functions of basophils, mast cells, allergen-specific regulatory T and B cells, and production of specific antibodies. The reduction of symptoms and clinical improvement is achieved by skewing the immune response away from allergic inflammation.
Although the complex nature of AIT mechanisms is becoming more clear, the need to discover reliable biomarkers to define patients likely to respond to the treatment is emerging.
With the worldwide spread of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, ...the SARS‐CoV‐2‐induced coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies.
Role of IgG4 in IgE-mediated allergic responses van de Veen, Willem, PhD; Akdis, Mübeccel, MD, PhD
Journal of allergy and clinical immunology,
11/2016, Volume:
138, Issue:
5
Journal Article
In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and ...treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS‐CoV‐2, and COVID‐19.
PDF
