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Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells.
Assuntos
Asma , Hipersensibilidade , Células T Matadoras Naturais , Humanos , Hipersensibilidade/terapia , Citocinas , ImunoterapiaRESUMO
Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.
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Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated ß-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host's susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review.
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Infecções Bacterianas , Imunossenescência , Humanos , Heterocromatina , Senescência Celular , BiomarcadoresRESUMO
Background: Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen that causes gastrointestinal infections, ranging from acute diarrhea and dysentery to life-threatening diseases such as Hemolytic Uremic Syndrome. Currently, a vaccine to prevent STEC infection is an unmet medical need. Results: We developed a chimeric protein-based vaccine targeting seven virulence factors of STEC, including the Stx2B subunit, Tir, Intimin, EspA, Cah, OmpT, and AggA proteins. Immunization of mice with this vaccine candidate elicited significant humoral and cellular immune responses against STEC. High levels of specific IgG antibodies were found in the serum and feces of immunized mice. However, specific IgA antibodies were not detected in either serum or feces. Furthermore, a significantly higher percentage of antigen-specific CD4+ T cells producing IFN-γ, IL-4, and IL-17 was observed in the spleens of immunized mice. Notably, the immunized mice showed decreased shedding of STEC O157:H7 and STEC O91:H21 strains and were protected against weight loss during experimental infection. Additionally, infection with the STEC O91:H21 strain resulted in kidney damage in control unimmunized mice; however, the extent of damage was slightly lower in immunized mice. Our findings suggest that IgG antibodies induced by this vaccine candidate may have a role in inhibiting bacterial adhesion and complement-mediated killing. Conclusion: This study provides evidence that IgG responses are involved in the host defense against STEC. However, our results do not rule out that other classes of antibodies also participate in the protection against this pathogen. Additional work is needed to improve the protection conferred by our vaccine candidate and to elucidate the relevant immune responses that lead to complete protection against this pathogen.
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Infecções por Escherichia coli , Escherichia coli Shiga Toxigênica , Vacinas , Animais , Camundongos , Imunoglobulina G , Formação de Anticorpos , Proteínas Recombinantes de FusãoRESUMO
Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.
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COVID-19 , SARS-CoV-2 , Adolescente , Humanos , Criança , Pré-Escolar , Anticorpos Neutralizantes , Vacinas de Produtos Inativados , Anticorpos AntiviraisRESUMO
BACKGROUND: The chagra is the agroforestry system adapted to the characteristics of the Amazon region. Recently, there has been a reported loss of biodiversity and traditional knowledge associated with the chagras. This paper characterizes the cultivators, exploring knowledge and expressed value perception in the context of the Amazonian chagra of an indigenous community; also, this prioritizes species, under the optics of commercial opportunity. METHODS: A semi-structured instrument was applied to 14 volunteers, asking about marketing preferences and use values of the species; later, a floristic inventory and prioritization workshop was developed. RESULTS: Sixty-two percent of the participants were 50 years or older at the time of the interview. Open conversations showed that traditional knowledge is a matter of practice; and is maintained mainly by the older "grandfathers". Thirty-eight species, belonging to 28 different families, were reported, showing considerable diversity. Seventy-nine percent of the participants consider the Leticia market and sales to tourists as the main marketing scenarios. CONCLUSIONS: The Ziora-Amena community centralizes the handling of chagras in the community's older adults, who transmit their traditional knowledge to new generations through oral tradition. Indicators of preference, use, and abundance highlight the food species. The perception of the trade stakeholder encourages research and development of endemic species, with health properties or ingredients for industry, which represent an opportunity of high added value for the region.
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Biodiversidade , Etnobotânica , Desenvolvimento Sustentável , Idoso , Agricultura , Colômbia , Produtos Agrícolas , Agricultura Florestal , Humanos , Povos Indígenas , Conhecimento , Pessoa de Meia-IdadeRESUMO
Resumen: En Uruguay las residencias médicas (RM) fueron creadas (Ley 19.301) con la finalidad de planificar, regular y llevar adelante la formación de especialistas en función de las necesidades sanitarias del país. Su ingreso se realiza a través de un concurso de oposición, abierto, con dos pruebas de evaluación, de corrección anónima. Este trabajo analiza los procesos de acceso a las RM mediante el análisis del temario, tipo de pruebas y la relación entre el plan de estudios de grado y los contenidos que se evalúan para el ingreso a la RM, integrando una encuesta de opinión entre internos y residentes. Se concursan 48 especialidades en 45 pruebas, que incluyen total de 1.302 temas a ser estudiados (media: 19,6 temas/disciplina) y muy distintos tipos de pruebas. Para los tribunales se requieren numerosos docentes de grado medio y superior durante algunos meses. La oferta bibliográfica se verificó sólo en 9 especialidades (18%) que recomiendan bibliografía para la preparación de las pruebas. La oferta total incluye 49 libros, algunos de ellos en idioma inglés. Los resultados demostraron una fuerte dicotomía entre los temas tratados en la currícula de grado y las exigencias de las pruebas de residencia, con escaso apoyo bibliográfico e institucional para la preparación de las mismas. Considerando que los postulantes son el producto recién surgido de un único plan de estudios, debería discutirse acerca de instaurar un sistema de pruebas a través de un programa consensuado e igualmente útil para el inicio de todas las disciplinas. Debe discutirse una reforma del sistema.
Abstract: In Uruguay medical residencies were created with the aim of planning, regulating and training specialists that meet the country's health requirements (Act 19.301). In order to be admitted, candidates take part in an open competition and sit for two exams that use anonymous marking. This study analyses the application process to medical residency by exploring the topics included, the kind of exams and the relationship between the studies plan and the topics that are evaluated admission to the medical residence, by means of a survey among interns and residents. 50 specializations competed, 48 exams were taken, including 1302 topics (average 19.6 topics/discipline), all of which included a great range of exams. A great number of average grade and higher gradeprofessors are required for the assessment committees during several months. Upon bibliographic review, only 9 specializations (18%) recommended bibliography to prepare for the exam. The total offer includes 49 books; a few of them in English. Results proved a great dichotomy between the topics covered in the undergraduate curricula and the demands of exams for admission to medical residency, the bibliographic and institutional support being deficient. In view of the fact that candidates are the recently result of a single studies plan, a debate should address the possibility of implementing an exams system that results from consensus and is effective for all disciplines. A system reform should also be debated.
Resumo: No Uruguai, as residências médicas (RM) (Lei 19.301) foram criadas com o objetivo de planejar, regulamentar e realizar a formação de especialistas de acordo com as necessidades de saúde do país. Sua inscrição é feita por meio de concurso aberto, com duas provas de avaliação, com correção anônima. Este trabalho analisa os processos de acesso à RM por meio da análise dos conteúdos programáticos, tipos de provas e a relação entre o currículo da graduação e os conteúdos avaliados para admissão à RM, integrando uma pesquisa de opinião entre internos e residentes. O processo de seleção inclui 50 especialidades com 48 provas, com um conteúdo programática composto por 1302 temas (média: 19,6 temas / disciplina) e tipos de provas muito diversos. Para as bancas examinadoras, é necessário contar com muitos docentes de nível intermediário e superior durantevários meses. Somente 9 especialidades (18%) recomendam bibliografia para a preparação das provas. A oferta total inclui 49 livros, alguns deles em inglês. Os resultados mostraram uma forte dicotomia entre os temas abordados no currículo de graduação e as exigências das provas para a residência, com pouco respaldo bibliográfico e institucional para sua preparação. Considerando que os candidatos são o produto recém-saído de um único plano de estudos, deve-se discutir sobre o estabelecimento de um sistema de provas por meio de um programa de consenso e igualmente útil para o início de todas as disciplinas. Deve-se debater uma reforma do sistema.
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Educação Médica , Internato e Residência , CurrículoRESUMO
Total vertebrectomy with spine shortening has been reported for the treatment of difficult cases of traumatic spine dislocation, both in acute and chronic phase. We report an exceptional case of a five-week-old T12-L1 spine dislocation in a 25-year-old female with complete paraplegia as a result of trauma in Ciudad de León (Nicaragua). In view of the time since the dislocation, we performed a complete L1 vertebrectomy in order to reduce the dorsolumbar hinge. For osteosynthesis material we had only eight screws and two Steffee plates. We therefore introduced pedicle screws at levels T11, T12, L2 and L3 on the right side and T11, T12, L3 and L4 on the left, and performed manual reduction of the spine. Steffee plates were placed and we added sublaminar wires to reinforce the osteosynthesis. Fifteen months after surgery, there has been no neurological improvement.