O papel das respostas imunológicas inata e adaptativa ao SARS-CoV-2: Revisão de literatura / The role of the innate and adaptative immune responses to SARS-CoV-2: Literature review

Introdução: O vírus SARS-CoV-2, causador da COVID-19, tornou- -se a representação de ameaça global ao que diz respeito à saúde pública, à medida que se espalha facilmente. A COVID-19 pode gerar desde um quadro assintomático até sinais e sintomas envolvendo os sistemas respiratório, hepático, neurológico, podendo, inclusive, levar à morte. O sistema imunológico possui papel fundamental no combate às infecções e sua atuação pode definir o quadro clínico, seja assintomático, leve, grave ou fatal. Objetivo: Descrever o papel das respostas imunológicas inata e adaptativa ao SARS-CoV-2. Metodologia: O estudo caracterizou-se por levantamento bibliográfico utilizando-se artigos científicos indexados nas bases de dados online PubMED, Medline, Scielo e Google Acadêmico, no período compreendido entre 2019 e 2020 Para a filtragem das publicações foram utilizados os seguintes descritores em português/inglês: COVID-19, SARS-CoV-2, Sistema imunológico, Resposta inata e Resposta adaptativa. Após filtragem, 42 artigos científicos foram selecionados. Resultados: O SARS-CoV-2 infecta as células do indivíduo ao reconhecer a enzima ECA2 ou a proteína CD147 e suas proteínas virais prejudicam a resposta imune à medida que diminuem a síntese de IFN1, ativam a via NF-kB, aumentam a síntese de citocinas pró-inflamatórias e aumentam a necroptose. Linfócitos T CD4+ possuem papel essencial na ativação de Linfócitos B e sua consequente síntese de anticorpos monoclonais. Linfócitos T CD8+ citotóxicos são capazes de dizimar células infectadas. Entretanto, estes eventos podem levar à resposta inflamatória exacerbada e à tempestade de citocinas, o que pode ser prejudicial nas infecções por SARS- -CoV-2, já que agravam sintomas e promovem alterações sistêmicas. Conclusão: Conhecido que Linfócitos T e B são ativados por peptídeos virais e que esta ativação promove a liberação de mediadores inflamatórios-chave e anticorpos monoclonais, e sabendo-se que a tempestade de citocinas inflamatórias pode agravar o quadro clínico do paciente infectado, faz-se necessário reconhecer a importância do sistema imunológico no combate à infecção da COVID-19.

Introduction: The SARS-CoV-2 virus, which causes COVID-19, has become the representation of global threat to public health, as it spreads easily, without efficient resources to control its spread until the present moment. COVID-19 can generate from an asymptomatic condition to signs and symptoms involving the respiratory, hepatic, neurological systems, and can even lead to death. The immune system has a fundamental role in fighting infections and its performance can define the clinical condition, either asymptomatic, mild, severe or fatal. Objective: To describe the role of innate and adaptive immune responses to SARS-CoV-2. Methodology: The study was characterized by a bibliographic survey, using scientific articles indexed in the online databases PubMED, Medline, Scielo and Google Scholar, in the period between 2019 and 2020. For filtering publications, the following descriptors were used in Portuguese/ English COVID-19, SARS-CoV-2, Immune system, Innate response and Adaptative response. After filtering, 42 scientific articles were selected. Results: SARS-CoV-2 infects the individual's cells by recognizing the ECA2 enzyme or the CD147 protein and its viral proteins impair the immune response as they decrease IFN1 synthesis, activate the NF-kB pathway, increase pro cytokine synthesis -inflammatory and increase necroptosis. CD4 + T lymphocytes play an essential role in the activation of B lymphocytes and their consequent synthesis of monoclonal antibodies. Cytotoxic CD8 + T lymphocytes are capable of decimating infected cells. However, these events can lead to an exacerbated inflammatory response and a cytokine storm, which can be harmful in SARS-CoV-2 infections, as they worsen symptoms and promote systemic changes. Conclusion: Known that T and B lymphocytes are activated by viral peptides and that this activation promotes the release of key inflammatory mediators and monoclonal antibodies, and knowing that the storm of inflammatory cytokines can worsen the clinical condition of the infected patient, it is necessary to recognize the importance of the immune system in combating the infection of COVID-19.

Comparison of inflammatory cytokine profiles in plasma of patients undergoing otorhinological surgery with propofol or isoflurane anesthesia.

OBJECTIVE AND DESIGN: The effects of anesthetics on cytokine release in patients without comorbidities who undergo minor surgery are not well defined. We compared inflammatory cytokine profiles in adult patients undergoing minimally invasive surgery who received isoflurane or propofol anesthesia. METHODS: Thirty-four patients without comorbidities undergoing minor surgery were randomly assigned to receive an inhaled anesthetic (isoflurane; n = 16) or an intravenous anesthetic (propofol; n = 18). Blood samples were drawn before premedication and anesthesia (T1), 120 min after anesthesia induction (T2), and on the first post-operative day (T3). Plasma concentrations of interleukins (IL-) 1ß, 6, 8, 10 and 12 and tumor necrosis factor (TNF)-α were measured using flow cytometry. RESULTS: The pro-inflammatory cytokine IL-6 was increased in the isoflurane group at T2 and T3 compared to T1 (P < 0.01). In the propofol group, IL-6 and IL-8 were significantly increased at T3 compared to T1. However, there were no significant differences in cytokine concentrations between the isoflurane and propofol groups. CONCLUSION: An inflammatory response occurred earlier in patients who received an inhaled agent compared with an intravenous anesthetic, but no differences in plasma cytokine profiles were evident between isoflurane and propofol anesthesia in patients without comorbidities undergoing minimally invasive surgeries.

Genotoxicity, cytotoxicity and gene expression in patients undergoing elective surgery under isoflurane anaesthesia.

There are numerous studies reporting on the effects of inhalation anaesthesia in cells of exposed individuals but not much is known about the ability of isoflurane (ISF) to induce oxidative DNA damage. However, surgery is often associated with a temporary perioperative immunological alteration, and some volatile anaesthetics seem to contribute to a transient lymphocytopenia after surgery. We conducted a study to evaluate a possible genotoxic effect, including oxidative DNA damage, and apoptosis in peripheral lymphocytes of 20 patients American Society of Anaesthesiologists physical status I undergoing minor elective surgery lasting at least 120 min, under anaesthesia with ISF. We also investigated the expression of several genes in blood cells. Blood samples were collected at three time points: before anaesthesia (T(1)), 2 h after the beginning of anaesthesia (T(2)) and on the first post-operative day (T(3)). General DNA damage and oxidised bases (Fpg and endo III-sites) in blood lymphocytes were evaluated using the comet assay. Lymphocytes were phenotyped and apoptosis was evaluated by flow cytometry. In addition, expressions of hOGG1 and XRCC1, genes involved in DNA repair, and BCL2, a gene related to apoptosis, were assessed by quantitative real-time polymerase chain reaction. Results showed no statistically significant difference in the level of DNA damage and oxidised bases among the three sampling times. Anaesthesia with ISF did not increase the percentage of cells in early or late apoptosis in cytotoxic or helper T lymphocytes. Lower hOGG1 and BCL2 expressions were detected at T(3) in comparison to the other two previous time points, and there was significantly lower expression of XRCC1 at T(3) in relation to T(2). In conclusion, the exposure to ISF did not result in genotoxicity and cytotoxicity in lymphocytes and in toxicogenomic effect in leukocytes, although DNA repair and apoptosis-related genes were down-regulated on the first post-operative day.