Oxford open immunology最新文献

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological agent of Coronavirus Diseases 2019 (COVID-19), triggers an adaptive immunity in the infected host that results in the production of virus-specific antibodies and T cells. Although kinetic and quantitative aspects of antibodies have been analyzed in large patient cohorts, similar information about SARS-CoV-2-specific T cells are scarce. We summarize the available knowledge of quantitative and temporal features of the SARS-CoV-2 T-cell response in this review. Currently, most of the data are derived only from the analysis of the circulatory compartment. Despite this limitation, early appearance, multi-specificity and functionality of SARS-CoV-2-specific T cells are associated with accelerated viral clearance and with protection from severe COVID-19.

Long-Coronavirus Disease (Long-COVID) is becoming increasingly recognized due to the persistence of symptoms such as profound fatigue, neurocognitive difficulties, muscle pains and weaknesses and depression, which would last beyond 3-12 weeks following infection with SARS-CoV-2. These particular symptoms have been extensively observed and studied in the context of previous psychoneuroimmunology research. In this short commentary, we discuss how previous neuroimmunology studies could help us to better understand pathways behind the development of these prolonged symptoms. Various mechanisms, including viral neuroinvasion, glial cells activation, neurogenesis, oxidative stress have been shown to explain these symptoms in the context of other disorders. Previous neuroimmunology findings could represent helpful pointers for future research on long-COVID symptoms and suggest potential management strategies for patients suffering with long-COVID.

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.

COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a mucosal surface, mainly the lungs or the intestine, where epithelial cells can be infected with virus. Although it is clear that virus within the lungs can cause severe pathology, driven by an exaggerated immune response, infection within the intestine generally seems to cause minor or no symptoms. In this review, we compare the disease processes between the lungs and gastrointestinal tract, and what might drive these different responses. As the microbiome is a key part of mucosal barrier sites, we also consider the effect that microbial species may play on infection and the subsequent immune responses. Because of difficulties obtaining tissue samples, there are currently few studies focused on the local mucosal response rather than the systemic response, but understanding the local immune response will become increasingly important for understanding the mechanisms of disease in order to develop better treatments.

The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host's altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (Mtb), is a major cause of global morbidity and mortality. The primary barrier to the development of an effective tuberculosis vaccine is our failure to fully understand the fundamental characteristics of a protective immune response. There is an increasing evidence that mobilization of antibody and B cell responses during natural Mtb infection and vaccination play a role in host protection. Several studies have assessed the levels of Mtb-specific antibodies induced during active disease as well as the potential of monoclonal antibodies to modulate bacterial growth in vitro and in vivo. A major limitation of these studies, however, is that the specific antigens capable of eliciting humoral responses are largely unknown. As a result, information about antibody dynamics and function, which might fundamentally transform our understanding of host Mtb immunity, is missing. Importantly, Mtb infection also induces the recruitment, accumulation and colocalization of B and T cells in the lung, which are positively correlated with protection in humans and animal models of disease. These ectopic lymphoid tissues generally support local germinal center reactions for the proliferation and ongoing selection of effector and memory B cells in the mucosa. Efforts to leverage such responses for human health, however, require a more complete understanding of how antibodies and B cells contribute to the local and systemic host Mtb immunity.

Immunity to malaria is mediated by antibodies that block parasite replication to limit parasite burden and prevent disease. Cytophilic antibodies have been consistently shown to be associated with protection, and recent work has improved our understanding of the direct and Fc-mediated mechanisms of protective antibodies. Antibodies also have important roles in vaccine-mediated immunity. Antibody induction is driven by the specialized CD4⁺ T cells, T-follicular helper (Tfh) cells, which function within the germinal centre to drive B-cell activation and antibody induction. In humans, circulating Tfh cells can be identified in peripheral blood and are differentiated into subsets that appear to have pathogen/vaccination-specific roles in antibody induction. Tfh cell responses are essential for protective immunity from Plasmodium infection in murine models of malaria. Our understanding of the activation of Tfh cells during human malaria infection and the importance of different Tfh cell subsets in antibody development is still emerging. This review will discuss our current knowledge of Tfh cell activation and development in malaria, and the potential avenues and pitfalls of targeting Tfh cells to improve malaria vaccines.

Immunological memory has the potential to provide lifelong protection against recurrent infections. As such, it has been crucial to the success of vaccines. Yet, the recent pandemic has illuminated key gaps in our knowledge related to the factors influencing effective memory formation and the inability to predict the longevity of immune protection. In recent decades, researchers have acquired a number of novel and powerful tools with which to study the factors underpinning humoral memory. These tools have been used to study the B-cell fate decisions that occur within the germinal centre (GC), a site where responding B cells undergo affinity maturation and are one of the major routes for memory B cell and high-affinity long-lived plasma cell formation. The advent of single-cell sequencing technology has provided an enhanced resolution for studying fate decisions within the GC and cutting-edge techniques have enabled researchers to model this reaction with more accuracy both in vitro and in silico. Moreover, modern approaches to studying memory B cells have allowed us to gain a better appreciation for the heterogeneity and adaptability of this vital class of B cells. Together, these studies have facilitated important breakthroughs in our understanding of how these systems operate to ensure a successful immune response. In this review, we describe recent advances in the field of GC and memory B-cell biology in order to provide insight into how humoral memory is formed, as well as the potential for generating lasting immunity to novel pathogens such as severe acute respiratory syndrome coronavirus 2.