Oxford open immunology最新文献

{"title":"Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review.","authors":"Felix Clemens Richter, Aljawharah Alrubayyi, Alicia Teijeira Crespo, Sarah Hulin-Curtis","doi":"10.1093/oxfimm/iqab001","DOIUrl":"10.1093/oxfimm/iqab001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab001"},"PeriodicalIF":0.0,"publicationDate":"2021-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cell phenotypes in COVID-19 - a living review.","authors":"Stephanie J Hanna,&nbsp;Amy S Codd,&nbsp;Ester Gea-Mallorqui,&nbsp;D Oliver Scourfield,&nbsp;Felix C Richter,&nbsp;Kristin Ladell,&nbsp;Mariana Borsa,&nbsp;Ewoud B Compeer,&nbsp;Owen R Moon,&nbsp;Sarah A E Galloway,&nbsp;Sandra Dimonte,&nbsp;Lorenzo Capitani,&nbsp;Freya R Shepherd,&nbsp;Joseph D Wilson,&nbsp;Lion F K Uhl,&nbsp;Awen M Gallimore,&nbsp;Anita Milicic","doi":"10.1093/oxfimm/iqaa007","DOIUrl":"https://doi.org/10.1093/oxfimm/iqaa007","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqaa007"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/oxfimm/iqaa007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10761297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in understanding the formation and fate of B-cell memory in response to immunization or infection.","authors":"Liam Kealy,&nbsp;Kim L Good-Jacobson","doi":"10.1093/oxfimm/iqab018","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab018","url":null,"abstract":"<p><p>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 <i>in vitro</i> and <i>in silico</i>. 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.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab018"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-follicular helper cells in malaria infection and roles in antibody induction.","authors":"Megan S F Soon,&nbsp;Mayimuna Nalubega,&nbsp;Michelle J Boyle","doi":"10.1093/oxfimm/iqab008","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab008","url":null,"abstract":"<p><p>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 <i>Plasmodium</i> 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.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab008"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/oxfimm/iqab008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TB or not to be: what specificities and impact do antibodies have during tuberculosis?","authors":"Clemens Hermann,&nbsp;Carolyn G King","doi":"10.1093/oxfimm/iqab015","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab015","url":null,"abstract":"<p><p>Tuberculosis, an infectious disease caused by <i>Mycobacterium tuberculosis</i> (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 <i>in vitro</i> and <i>in vivo</i>. 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.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab015"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10790207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of antibody responses against self and foreign antigens by Tfr cells: implications for vaccine development.","authors":"Afonso P Basto,&nbsp;Luis Graca","doi":"10.1093/oxfimm/iqab012","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab012","url":null,"abstract":"<p><p>The production of antibodies can constitute a powerful protective mechanism against infection, but antibodies can also participate in autoimmunity and allergic responses. Recent advances in the understanding of the regulation of germinal centres (GC), the sites where B cells acquire the ability to produce high-affinity antibodies, offered new prospects for the modulation of antibody production in autoimmunity and vaccination. The process of B cell affinity maturation and isotype switching requires signals from T follicular helper (Tfh) cells. In addition, Foxp3⁺ T follicular regulatory (Tfr) cells represent the regulatory counterpart of Tfh in the GC reaction. Tfr cells were identified one decade ago and since then it has become clear their role in controlling the emergence of autoreactive B cell clones following infection and immunization. At the same time, Tfr cells are essential for fine-tuning important features of the humoral response directed to foreign antigens that are critical in vaccination. However, this regulation is complex and several aspects of Tfr cell biology are yet to be disclosed. Here, we review the current knowledge about the regulation of antibody responses against self and foreign antigens by Tfr cells and its implications for the future rational design of safer and more effective vaccines.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab012"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10790206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Call for emergency action to limit global temperature increases, restore biodiversity and protect health: Wealthy nations must do much more, much faster.","authors":"Lukoye Atwoli,&nbsp;Abdullah H Baqui,&nbsp;Thomas Benfield,&nbsp;Raffaella Bosurgi,&nbsp;Fiona Godlee,&nbsp;Stephen Hancocks,&nbsp;Richard Horton,&nbsp;Laurie Laybourn-Langton,&nbsp;Carlos Augusto Monteiro,&nbsp;Ian Norman,&nbsp;Kirsten Patrick,&nbsp;Nigel Praities,&nbsp;Marcel G M Olde Rikkert,&nbsp;Eric J Rubin,&nbsp;Peush Sahni,&nbsp;Richard Smith,&nbsp;Nick Talley,&nbsp;Sue Turale,&nbsp;Damián Vázquez","doi":"10.1093/oxfimm/iqab017","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab017","url":null,"abstract":"> Wealthy nations must do much more, much faster.\u0000\u0000The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (Conference of the Parties (COP)26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature and protect health.\u0000\u0000Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with COVID-19, we cannot wait for the pandemic to pass to rapidly reduce emissions.\u0000\u0000Reflecting the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory.\u0000\u0000The risks to health of increases above 1.5°C are now well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical infections, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4 \u0000\u0000Global heating is also contributing to the decline in …","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab017"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing NKT cells for vaccination.","authors":"Olivia K Burn,&nbsp;Theresa E Pankhurst,&nbsp;Gavin F Painter,&nbsp;Lisa M Connor,&nbsp;Ian F Hermans","doi":"10.1093/oxfimm/iqab013","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab013","url":null,"abstract":"<p><p>Natural killer T (NKT) cells are innate-like T cells capable of enhancing both innate and adaptive immune responses. When NKT cells are stimulated in close temporal association with co-administered antigens, strong antigen-specific immune responses can be induced, prompting the study of NKT cell agonists as novel immune adjuvants. This activity has been attributed to the capacity of activated NKT cells to act as universal helper cells, with the ability to provide molecular signals to dendritic cells and B cells that facilitate T cell and antibody responses, respectively. These signals can override the requirement for conventional CD4⁺ T cell help, so that vaccines can be designed without need to consider CD4⁺ T cell repertoire and major histocompatibility complex Class II diversity. Animal studies have highlighted some drawbacks of the approach, namely, concerns around induction of NKT cell hyporesponsiveness, which may limit vaccine boosting, and potential for toxicity. Here we highlight studies that suggest these obstacles can be overcome by targeted delivery <i>in vivo</i>. We also feature new studies that suggest activating NKT cells can help encourage differentiation of T cells into tissue-resident memory cells that play an important role in prophylaxis against infection, and may be required in cancer therapy.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab013"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medawar and the immunological paradox of pregnancy: in context.","authors":"Victoria Male","doi":"10.1093/oxfimm/iqaa006","DOIUrl":"10.1093/oxfimm/iqaa006","url":null,"abstract":"<p><p>In 1953, Peter Medawar defined 'the immunological paradox of pregnancy', whereby the semi-allogeneic foetus can survive for 9 months in its mother, while a semi-allogeneic graft would be rejected. Here, I revisit the immunological paradox of pregnancy, setting it in the context of the time in which it was proposed. I go on to examine the extent to which Medawar's ideas on the subject have stood the test of time and how they have shaped reproductive immunology.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqaa006"},"PeriodicalIF":0.0,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10790203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immunology in COVID-19-a living review. Part I: viral entry, sensing and evasion.","authors":"Clarissa Coveney, Michel Tellier, Fangfang Lu, Shayda Maleki-Toyserkani, Ruth Jones, Valentina M T Bart, Ellie Pring, Aljawharah Alrubayyi, Felix C Richter, D Oliver Scourfield, Jan Rehwinkel, Patrícia R S Rodrigues, Luke C Davies, Ester Gea-Mallorquí","doi":"10.1093/oxfimm/iqaa004","DOIUrl":"10.1093/oxfimm/iqaa004","url":null,"abstract":"<p><p>The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer a chance to treat disease, prophylactic and anti-viral treatments are still of vital importance, especially in context of the mutative ability of this group of viruses. Therefore, it is essential to elucidate the molecular mechanisms of viral entry, innate sensing and immune evasion of SARS-CoV-2, which control the triggers of the subsequent excessive inflammatory response. Viral evasion strategies directly target anti-viral immunity, counteracting host restriction factors and hijacking signalling pathways to interfere with interferon production. In Part I of this review, we examine SARS-CoV-2 viral entry and the described immune evasion mechanisms to provide a perspective on how the failure in initial viral sensing by infected cells can lead to immune dysregulation causing fatal COVID-19, discussed in Part II.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa004"},"PeriodicalIF":0.0,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10758780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}