Seminars in immunopathology
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The SARS-CoV-2 pandemic urgently calls for the development of effective preventive tools. COVID-19 hits greatly the elder and more fragile fraction of the population boosting the evergreen issue of the vaccination of older people. The development of a vaccine against SARS-CoV-2 tailored for the elderly population faces the challenge of the poor immune responsiveness of the older population due to immunosenescence, comorbidities, and pharmacological treatments. ⋯ The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. In the ongoing effort in vaccine development, different SARS-CoV-2 vaccine candidates have been developed, tested in pre-clinical and clinical studies and are undergoing clinical testing, but only a small fraction of these are currently being tested in the older fraction of the population. Recent advances in systems biology integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly.
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Development of childhood asthma is complex with a strong interaction of genetic, epigenetic, and environmental factors. Ultimately, it is critical how the immune system of a child responds to these influences and whether effective strategies for a balanced and healthy immune maturation can be assured. Pregnancy and early childhood are particularly susceptible for exogenous influences due to the developing nature of a child's immune system. ⋯ Early in life, induction and continuous training of healthy maturation include balanced innate immunity (e.g., via innate lymphoid cells) and an equilibrium of T-cell subpopulations (e.g., via regulatory T cells) to counter-regulate potential pro-inflammatory or exuberant immune reactions. Later in childhood, rather compensatory immune mechanisms are required to modulate deviant regulation of a child's already primed immune trajectory. The specific effects of exogenous and endogenous influences on a child's maturing immune system are summarized in this review, and its importance and potential intervention for early prevention and treatment strategies are delineated.
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Abstract
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There is substantial epidemiological and mechanistic evidence that the increase in allergic disease and asthma in many parts of the world in part relates to changes in microbial exposures and diet acting via the composition and metabolic products of the intestinal microbiome. The majority of research in this field has focused on the gut microbiome during infancy, but it is increasingly clear that the maternal microbiome during pregnancy also has a key role in preventing an allergy-prone immune phenotype in the offspring. The mechanisms by which the maternal microbiome influences the developing fetal immune system include alignment between the maternal and infant regulatory immune status and transplacental passage of microbial metabolites and IgG. ⋯ However, our understanding of these pathways is at an early stage and further mechanistic studies are needed. There are also no data from human studies relating the composition and metabolic activity of the maternal microbiome during pregnancy to the offspring's immune status at birth and risk of allergic disease. Improved knowledge of these pathways may inform novel strategies for tackling the increase in allergic disorders in the modern world.
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Human coronaviruses (hCoVs) can be divided into low pathogenic and highly pathogenic coronaviruses. The low pathogenic CoVs infect the upper respiratory tract and cause mild, cold-like respiratory illness. ⋯ Recent studies in experimentally infected animal strongly suggest a crucial role for virus-induced immunopathological events in causing fatal pneumonia after hCoV infections. Here we review the current understanding of how a dysregulated immune response may cause lung immunopathology leading to deleterious clinical manifestations after pathogenic hCoV infections.