Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52.604
Filtrar
1.
Sci Rep ; 10(1): 16219, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004978

RESUMO

COVID-19 pandemic has resulted in 16,114,449 cases with 646,641 deaths from the 217 countries, or territories as on July 27th 2020. Due to multifaceted issues and challenges in the implementation of the safety and preventive measures, inconsistent coordination between societies-governments and most importantly lack of specific vaccine to SARS-CoV-2, the spread of the virus that initially emerged at Wuhan is still uprising after taking a heavy toll on human life. In the present study, we mapped immunogenic epitopes present on the four structural proteins of SARS-CoV-2 and we designed a multi-epitope peptide based vaccine that, demonstrated a high immunogenic response with a vast application on world's human population. On codon optimization and in-silico cloning, we found that candidate vaccine showed high expression in E. coli and immune simulation resulted in inducing a high level of both B-cell and T-cell mediated immunity. The results predicted that exposure of vaccine by administrating three injections significantly subsidized the antigen growth in the system. The proposed candidate vaccine found promising by yielding desired results and hence, should be validated by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.


Assuntos
Epitopos/imunologia , Simulação de Acoplamento Molecular , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia , Complexo Antígeno-Anticorpo/química , Complexo Antígeno-Anticorpo/imunologia , Antígenos Virais/imunologia , Linfócitos B/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos/química , Antígenos HLA/química , Antígenos HLA/imunologia , Humanos , Imunogenicidade da Vacina , Proteínas do Nucleocapsídeo/química , Proteínas do Nucleocapsídeo/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Receptores Toll-Like/imunologia , Vacinas de Subunidades/química , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/imunologia , Vacinas Virais/química
3.
Int J Mol Med ; 46(4): 1266-1273, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945352

RESUMO

The outbreak of the 2019 coronavirus disease (named, COVID­19), caused by the novel SARS­CoV­2 virus, represents a worldwide severe threat to public health. It is of the utmost importance to characterize the immune responses against the SARS­CoV­2 and the mechanisms of hyperinflammation, in order to design better therapeutic strategies for COVID­19. In the present study, a transcriptomic analysis was performed to profile the immune signatures in lung and the bronchoalveolar lavage fluid samples from COVID­19 patients and controls. Our data concordantly revealed increased humoral responses to infection. The elucidation of the host responses to SARS­CoV­2 infection may further improve our understanding of COVID­19 pathogenesis and suggest better therapeutic strategies.


Assuntos
Linfócitos B/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Ativação Linfocitária , Pneumonia Viral/imunologia , Transcriptoma , Linfócitos B/metabolismo , Betacoronavirus/fisiologia , Líquido da Lavagem Broncoalveolar , Infecções por Coronavirus/genética , Bases de Dados Factuais , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Pandemias , Pneumonia Viral/genética
4.
Medicine (Baltimore) ; 99(36): e20993, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32898991

RESUMO

Radiotherapy (RT) can affect the immune function of patients with cancer. The purpose of this study was to investigate the effect of RT on lymphocyte and its subsets in patients with esophageal cancer (EC).All patients received RT with a mean dose of 5369 cGy (gray). Blood parameters were measured in 31 patients on 3 occasions (before, at the end of radiotherapy, and at 3 months follow-up). The whole blood count and lymphocyte subsets were measured and correlated with short time efficiency and radiation dose parameters.White blood count (WBC) and lymphocyte count (ALC) were greatly decreased at the end of radiotherapy, and the percentages of CD3+, CD3+CD8+ T cells were significantly increased, on the other hand, a decrease in the CD4/CD8 ratio was observed. The percentages of CD3-CD16/56+NK cells and CD19+ B cell were decreased at the end of RT compared with prior RT. The percentages of CD3+ T cells before RT and the WBC and ALC count after RT can be used as prognostic indicators for survival. The PTV dose can cause significant changes in lymphocytes count after RT. CD3+T cells after RT were significantly correlated with mean heart dose and heart V50.Our study identified that RT causes changes in lymphocyte subsets, and these changes may indicate differences in immune function between individuals. Radiotherapy plan should be designed to minimize normal tissue dose to reduce the impact on WBC and lymphocytes.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Subpopulações de Linfócitos/imunologia , Idoso , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Estudos Retrospectivos
5.
Sci Rep ; 10(1): 15838, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985562

RESUMO

The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4+ T cell, CD8+ T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4+ cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Fenômenos do Sistema Imunológico/fisiologia , Pneumonia Viral/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Cell ; 183(1): 143-157.e13, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877699

RESUMO

Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.


Assuntos
Infecções por Coronavirus/imunologia , Centro Germinativo/imunologia , Pneumonia Viral/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Centro Germinativo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Baço/imunologia , Baço/patologia , Fator de Necrose Tumoral alfa/metabolismo
7.
PLoS Pathog ; 16(9): e1008853, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886726

RESUMO

HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants' samples was sequenced close to transmission (median 21 days post infection, IQR 18-41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to probe effective immune responses against TF.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Efeito Fundador , Infecções por HIV , HIV-1/fisiologia , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana , Doença Aguda , Adolescente , Adulto , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Viremia/genética , Viremia/imunologia , Viremia/patologia , Replicação Viral/genética , Replicação Viral/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
8.
Cell Mol Immunol ; 17(10): 1095-1097, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32895485
11.
Eur J Immunol ; 50(9): 1283-1294, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32910469

RESUMO

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM- plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.


Assuntos
Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Isotipos de Imunoglobulinas/sangue , Pulmão/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/classificação , Linfócitos B/virologia , Betacoronavirus/imunologia , Proteína C-Reativa/imunologia , Estudos de Casos e Controles , Proliferação de Células , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Estudos Transversais , Citocinas/genética , Citocinas/imunologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Humanos , Imunidade Humoral , Memória Imunológica , Pulmão/patologia , Pulmão/virologia , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Cultura Primária de Células , Índice de Gravidade de Doença , Análise de Sobrevida
12.
PLoS One ; 15(9): e0235183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956421

RESUMO

Members of the broad complex, tram track, bric-a-brac and zinc finger (BTB-ZF) family of transcription factors, such as BCL-6, ZBTB20, and ZBTB32, regulate antigen-specific B cell differentiation, plasma cell longevity, and the duration of antibody production. We found that ZBTB38, a different member of the BTB-ZF family that binds methylated DNA at CpG motifs, is highly expressed by germinal center B cells and plasma cells. To define the functional role of ZBTB38 in B cell responses, we generated mice conditionally deficient in this transcription factor. Germinal center B cells lacking ZBTB38 dysregulated very few genes relative to wild-type and heterozygous littermate controls. Accordingly, mice with hematopoietic-specific deletion of Zbtb38 showed normal germinal center B cell numbers and antibody responses following immunization with hapten-protein conjugates. Memory B cells from these animals functioned normally in secondary recall responses. Despite expression of ZBTB38 in hematopoietic stem cells, progenitors and mature myeloid and lymphoid lineages were also present in normal numbers in mutant mice. These data demonstrate that ZBTB38 is dispensable for hematopoiesis and antibody responses. These conditional knockout mice may instead be useful in defining the functional importance of ZBTB38 in other cell types and contexts.


Assuntos
Formação de Anticorpos , Linfócitos B/imunologia , Proteínas Repressoras/imunologia , Animais , Linfócitos B/citologia , Deleção de Genes , Expressão Gênica , Hematopoese , Imunização , Camundongos , Camundongos Knockout , Proteínas Repressoras/genética
13.
mBio ; 11(5)2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978311

RESUMO

The high susceptibility of humans to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and peripheral blood mononuclear cells (PBMCs) from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBC levels. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG, and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 were higher in convalescent subjects than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.IMPORTANCE The recent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key issues are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and postinfection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study results also suggest that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.


Assuntos
Linfócitos B/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulina G/imunologia , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Anticorpos Antivirais/imunologia , Linfócitos B/virologia , Convalescença , Reações Cruzadas , Feminino , Voluntários Saudáveis , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Domínios e Motivos de Interação entre Proteínas , Subunidades Proteicas , Glicoproteína da Espícula de Coronavírus/química
14.
Adv Exp Med Biol ; 1255: 221-230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949403

RESUMO

Monoclonal antibodies from human sources are being increasingly recognized as valuable options in many therapeutic areas. These antibodies can show exquisite specificity and high potency while maintaining a desirable safety profile, having been matured and tolerized within human patients. However, the discovery of these antibodies presents important challenges, since the B cells encoding therapeutic antibodies can be rare in a typical blood draw and are short-lived ex vivo. Furthermore, the unique pairing of VH and VL domains in each B cell contributes to specificity and function; therefore, maintaining antibody chain pairing presents a throughput limitation. This work will review the various approaches aimed at addressing these challenges with an eye to next-generation methods for high-throughput discovery from the human B-cell repertoire.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Descoberta de Drogas , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Humanos
15.
Nat Commun ; 11(1): 3924, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764665

RESUMO

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8+ T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Monócitos/imunologia , Pneumonia Viral/imunologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Biologia Computacional , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Citocinas/sangue , Humanos , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Receptores de Interleucina-6/imunologia , Análise de Célula Única/métodos
16.
Nat Commun ; 11(1): 3971, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769993

RESUMO

Efficacy evaluation through human trials is crucial for advancing a vaccine candidate to clinics. Next-generation sequencing (NGS) can be used to quantify B cell repertoire response and trace antibody lineages during vaccination. Here, we demonstrate this application with a case study of Hecolin®, the licensed vaccine for hepatitis E virus (HEV). Four subjects are administered the vaccine following a standard three-dose schedule. Vaccine-induced antibodies exhibit a high degree of clonal diversity, recognize five conformational antigenic sites of the genotype 1 HEV p239 antigen, and cross-react with other genotypes. Unbiased repertoire sequencing is performed for seven time points over six months of vaccination, with maturation pathways characterize for a set of vaccine-induced antibodies. In addition to dynamic repertoire profiles, NGS analysis reveals differential patterns of HEV-specific antibody lineages and highlights the necessity of the long vaccine boost. Together, our study presents a quantitative strategy for vaccine evaluation in small-scale human studies.


Assuntos
Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Vírus da Hepatite E/imunologia , Vacinação , Vacinas contra Hepatite Viral/imunologia , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Especificidade de Anticorpos/imunologia , Linfócitos B/imunologia , Epitopos/imunologia , Genótipo , Vírus da Hepatite E/genética , Humanos , Fatores de Tempo , Doadores de Tecidos , Adulto Jovem
17.
Emerg Microbes Infect ; 9(1): 1988-1996, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32844713

RESUMO

ABSTRACT Pandemic SARS-CoV-2 has caused unprecedented mortalities. Vaccine is in urgent need to stop the pandemic. Despite great progresses on SARS-CoV-2 vaccine development, the efficacy of the vaccines remains to be determined. Deciphering the interactions of the viral epitopes with the elicited neutralizing antibodies in convalescent population inspires the vaccine development. In this study, we devised a peptide array composed of 20-mer overlapped peptides of spike (S), membrane (M) and envelope (E) proteins, and performed a screening with 120 COVID-19 convalescent sera and 24 non-COVID-19 sera. We identified five SARS-CoV-2-specific dominant epitopes that reacted with above 40% COVID-19 convalescent sera. Of note, two peptides non-specifically interacted with most of the non-COVID-19 sera. Neutralization assay indicated that only five sera completely blocked viral infection at the dilution of 1:200. By using a peptide-compete neutralizing assay, we found that three dominant epitopes partially competed the neutralization activity of several convalescent sera, suggesting antibodies elicited by these epitopes played an important role in neutralizing viral infection. The epitopes we identified in this study may serve as vaccine candidates to elicit neutralizing antibodies in most vaccinated people or specific antigens for SARS-CoV-2 diagnosis.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito B/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Animais , Linfócitos B/imunologia , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero , Proteínas do Envelope Viral/imunologia
18.
Ecotoxicol Environ Saf ; 202: 110912, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800247

RESUMO

Occupational exposure to pesticides has been identified as a factor that predisposes to disorders of the immune system. Immunosuppression, autoimmunity, cancer of various organs and other diseases in people who apply these products have been reported by the studies. This study aimed to investigate the relationship between occupational exposure to pesticides and the immunological profile in 43 farmers exposed to mixtures of pesticides for at least 15 years. A control group composed of 30 individuals without a history of occupational exposure to pesticides was also evaluated. Peripheral blood samples were processed by flow cytometry and cells were labelled with an 8-color monoclonal antibody panel. Plasma cytokines were also measured. Significant increase in classical monocytes (p < 0.001) and dendritic cells (p < 0.001) in the exposed group was observed as well in total T cells (p = 0.04), central memory CD8 T cells (p = 0.02) and effector memory CD8 T cells (p = 0.01). On the other hand, the activation markers of T cells as the expression of CD57, HLA-DR, CD25 and CD28 were evaluated and no difference was found between groups. When the B cells were analyzed, a significant decrease in total B cells (p = 0.01), regulatory B cells (p < 0.001) and plasmablasts (p < 0.001) in the exposed group, compared to healthy controls, was observed. Pro-inflammatory IL-6 was significantly elevated (p = 0.04) in the plasma of farmers compared to that of controls. The constant antigenic stimulus that occurs during exposure to pesticides can favor the recruitment of dendritic cells and macrophages (APCs) presents in the skin and respiratory tract. In the secondary lymphoid organs, the CD4 T and B cells that process such antigens are possibly undergoing proliferative exhaustion, with the consequent depletion of all mature B subpopulations. The resulting drop in humoral immunity may be offset by an increase in the number of circulating CD8 T lymphocytes due to their cytotoxic action.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/toxicidade , Adulto , Poluentes Ocupacionais do Ar/análise , Linfócitos B/imunologia , Brasil , Antígenos CD28/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Fazendeiros , Feminino , Citometria de Fluxo , Antígenos HLA-DR/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Masculino , Pessoa de Meia-Idade , Praguicidas/análise , Praguicidas/metabolismo
19.
Nat Commun ; 11(1): 3989, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778653

RESUMO

Upon stimulation, B cells assume heterogeneous cell fates, with only a fraction differentiating into antibody-secreting cells (ASC). Here we investigate B cell fate programming and heterogeneity during ASC differentiation using T cell-independent models. We find that maximal ASC induction requires at least eight cell divisions in vivo, with BLIMP-1 being required for differentiation at division eight. Single cell RNA-sequencing of activated B cells and construction of differentiation trajectories reveal an early cell fate bifurcation. The ASC-destined branch requires induction of IRF4, MYC-target genes, and oxidative phosphorylation, with the loss of CD62L expression serving as a potential early marker of ASC fate commitment. Meanwhile, the non-ASC branch expresses an inflammatory signature, and maintains B cell fate programming. Finally, ASC can be further subseted based on their differential responses to ER-stress, indicating multiple development branch points. Our data thus define the cell division kinetics of B cell differentiation in vivo, and identify the molecular trajectories of B cell fate and ASC formation.


Assuntos
Células Produtoras de Anticorpos/metabolismo , Linfócitos B/imunologia , Ativação Linfocitária/fisiologia , Animais , Antígenos CD19/genética , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Imunidade , Fatores Reguladores de Interferon/metabolismo , Selectina L , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Transcriptoma
20.
Science ; 369(6503)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32732394

RESUMO

The lymphoid system is intimately involved in immunological processes. The small lymphocyte that circulates through blood into lymphoid tissues, then through the lymph and back to the blood through the thoracic duct, is able to initiate immune responses after appropriate stimulation by antigen. However, the lymphocytes found in the thymus are deficient in this ability despite the fact that the thymus plays a central role in lymphocyte production and in ensuring the normal development of immunological faculty. During embryogenesis, lymphocytes are present in the thymus before they can be identified in the circulation and in other lymphoid tissues. They become "educated" in the thymus to recognize a great diversity of peptide antigens bound to the body's own marker antigen, the major histocompatibility complex, but they are purged if they strongly react against their own self-components. Lymphocytes differentiate to become various T cell subsets and then exit through the bloodstream to populate certain areas of the lymphoid system as peripheral T lymphocytes with distinct markers and immune functions.


Assuntos
Imunoterapia , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Animais , Linfócitos B/imunologia , Diferenciação Celular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Linfoma/imunologia , Linfoma/terapia , Camundongos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Transplante de Pele , Subpopulações de Linfócitos T/citologia , Timo/citologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA