Oxford open immunology最新文献

{"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":"Lymphoid stromal cells-more than just a highway to humoral immunity.","authors":"Isabella Cinti,&nbsp;Alice E Denton","doi":"10.1093/oxfimm/iqab011","DOIUrl":"https://doi.org/10.1093/oxfimm/iqab011","url":null,"abstract":"<p><p>The generation of high-affinity long-lived antibody responses is dependent on the differentiation of plasma cells and memory B cells, which are themselves the product of the germinal centre (GC) response. The GC forms in secondary lymphoid organs in response to antigenic stimulation and is dependent on the coordinated interactions between many types of leucocytes. These leucocytes are brought together on an interconnected network of specialized lymphoid stromal cells, which provide physical and chemical guidance to immune cells that are essential for the GC response. In this review we will highlight recent advancements in lymphoid stromal cell immunobiology and their role in regulating the GC, and discuss the contribution of lymphoid stromal cells to age-associated immunosenescence.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab011"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546950","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}

{"title":"Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology.","authors":"Patrícia R S Rodrigues, Aljawharah Alrubayyi, Ellie Pring, Valentina M T Bart, Ruth Jones, Clarissa Coveney, Fangfang Lu, Michael Tellier, Shayda Maleki-Toyserkani, Felix C Richter, D Oliver Scourfield, Ester Gea-Mallorquí, Luke C Davies","doi":"10.1093/oxfimm/iqaa005","DOIUrl":"10.1093/oxfimm/iqaa005","url":null,"abstract":"<p><p>The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa005"},"PeriodicalIF":0.0,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10770918","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":"A new immunology forum for a new age of immunology.","authors":"Daniel M Altmann","doi":"10.1093/oxfimm/iqaa002","DOIUrl":"https://doi.org/10.1093/oxfimm/iqaa002","url":null,"abstract":"","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa002"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/oxfimm/iqaa002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10780700","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":"Adaptive immunity to SARS-CoV-2.","authors":"Daniel M Altmann","doi":"10.1093/oxfimm/iqaa003","DOIUrl":"10.1093/oxfimm/iqaa003","url":null,"abstract":"<p><p>The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 exposed individuals mount an antibody response within around 2-weeks and spike antigen-binding responses correlate well with functional virus neutralization. A minority makes little detectable antibody, generally those with either very mild/asymptomatic disease or those with severe/lethal infection. However, in general, antibody titre correlates with viral load and duration of exposure. There is evidence for cross-reactivity with the other human coronaviruses, though the functional impact of this is as yet unclear. Therapeutic use of neutralizing monoclonal antibodies offers potential for clinical use. While there is evidence for neutralizing antibody as a correlate of protection, some cases indicate the potential for full recovery in the absence of antibody. Studies of T-cell immunity following acute infection show CD4 and CD8 responses to epitopes across diverse viral antigens, possible cross-reactivity with epitopes from the common cold human coronaviruses and large-scale activation. However, in severe cases, there is evidence for T-cell lymphopaenia as well as expression of exhaustion markers. Analysis of serum biomarkers of disease severity implicates a hyperinflammatory contribution to pathogenesis, though this has not been mechanistically delineated beyond a likely role of raised IL-6, considered a therapeutic target. Despite rapid progress, there remain pressing unknowns. It seems likely that immune memory to SARS-CoV-2 may be relatively short lived, but this will need longitudinal investigation. Also, this is a disease of highly variable presentation and time course, with some progressing to protracted, chronic symptoms, which are not understood. The contribution of immunopathological mechanisms to tissue damage, whether in the lung, kidney, heart or blood vessels, is unclear. The immunology underlying the differential susceptibility between the very young and the very old is unresolved, a question with ramifications for vaccine roll-out. The greatest challenge relates to rapid generation, testing and manufacture of vaccines that are immunogenic, protective (at least from symptomatic disease) and safe-a challenge that looks achievable.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa003"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10770917","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":"Cholesterol-modifying drugs in COVID-19.","authors":"Nathalie M Schmidt, Peter A C Wing, Jane A McKeating, Mala K Maini","doi":"10.1093/oxfimm/iqaa001","DOIUrl":"10.1093/oxfimm/iqaa001","url":null,"abstract":"<p><p>Infection with severe acute respiratory syndrom coronavirus 2 (SARS-CoV-2) is more likely to lead to poor outcomes in the elderly and those with cardiovascular disease, obesity or metabolic syndrome. Here, we consider mechanisms by which dyslipidaemia and the use of cholesterol-modifying drugs could influence the virus-host relationship. Cholesterol is essential for the assembly, replication and infectivity of enveloped virus particles; we highlight several cholesterol-modifying drugs with the potential to alter the SARS-CoV-2 life cycle that could be tested in <i>in vitro</i> and <i>in vivo</i> models. Although cholesterol is an essential component of immune cell membranes, excess levels can dysregulate protective immunity and promote exaggerated pulmonary and systemic inflammatory responses. Statins block the production of multiple sterols, oxysterols and isoprenoids, resulting in a pleiotropic range of context-dependent effects on virus infectivity, immunity and inflammation. We highlight antiviral, immunomodulatory and anti-inflammatory effects of cholesterol-modifying drugs that merit further consideration in the management of SARS-CoV-2 infection.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"1 1","pages":"iqaa001"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9230131","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}