Mesenchymal Stem Cells Induce an Immunosuppressive Microenvironment in Pituitary Tumors.

CONTEXT: The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown. OBJECTIVE: Herein we report the presence of MSCs in 2 adrenocorticotropin (ACTH)-secreting PTs causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF), and 2 nontumoral pituitary glands (MS). METHODS: We have analyzed the transcriptomic profiles by RNA sequencing and compared MSCs in terms of their immunosuppressive effects against lymphoid T-cell and macrophage populations by means of cocultures and flow cytometry. RESULTS: Our transcriptomic analysis revealed molecular differences between MSCs derived from nontumoral pituitaries and MSCs derived from PTs. Two distinct subpopulations of MSC emerged: one displaying immunosuppressive properties and the other with increased proproliferative capabilities, regardless of their origin. MSCs derived from ACTH- and nonfunctioning PTs, but not those derived from nontumoral glands, significantly inhibited the proliferation of activated T cells, favored the generation of regulatory T cells, and promoted M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony-stimulating factor (M-CSF) and interleukin-10. Importantly, MSC derived from ACTH-PTs showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors. CONCLUSION: This study demonstrates the presence of at least 2 MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSCs may have important implications in PT growth.

Effects of tumor derived exosomes on T cells markers expression / Efeitos de exossomos derivados de tumor na expressão de marcadores de células T

Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas ­ os verdadeiros representantes das células-mãe ­ modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Effects of tumor derived exosomes on T cells markers expression

Abstract Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN- expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Resumo Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas os verdadeiros representantes das células-mãe modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN- em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Respuesta inmune e inmunosupresión en pacientes con ventilación mecánica por infección por SARS-CoV-2 / Immune response and immune suppression in patients with mechanical ventilation secondary to SARS-CoV-2 infection / Resposta imune e imunossupressão em pacientes com ventilação mecânica devido à infecção por SARS-CoV-2

Resumen Introducción: La pandemia por SARS-CoV-2 ha inspirado intriga sobre la respuesta inmune a dicho virus, especialmente en pacientes graves con síndrome de dificultad respiratoria aguda (SDRA). Este estudio describe el comportamiento de la respuesta inmune, la inmunosupresión y sus desenlaces en los pacientes con ventilación mecánica (VM). Material y métodos: Cohorte prospectiva. Del 23 de marzo al 31 de diciembre de 2020 se recolectó información basal, parámetros ventilatorios, gasométricos y estudios de laboratorio de todos los pacientes mayores de 18 años que recibieron VM por COVID-19 con registros hasta el día 15 de VM. Se dividieron los grupos en pacientes vivos a los 90 días y defunciones. Resultados: Registramos 218 pacientes, con mortalidad de 23%. En el día 1 de VM, los pacientes no presentaron diferencias en conteos celulares o reactantes de fase aguda, excepto dímero D de 1,020 (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. En el análisis de regresión lineal de efectos mixtos se observaron diferencias cronológicas estadísticamente significativas en leucocitos y proteína C reactiva (PCR) concordante con la elevación de la presión de distensión alveolar (PDalv). No se encontró asociación con mortalidad en el uso de tocilizumab 2.20 (0.279-17.358) y corticosteroides 0.54 (0.229-1.273) en riesgos proporcionales de Cox al día 1 de VM. Durante los 15 días de VM los pacientes que fallecieron recibieron dosis más altas de corticosteroides, dosis mayores de 150 mg/día equivalente a prednisona se asocian a mortalidad. Conclusiones: Existe evolución cronológica similar en elevación de PCR, leucocitos y elevación de la PDalv, las cuales se explican por la disminución de la distensibilidad pulmonar estática (Cstat) y la presión positiva al final de la espiración total (PEEP total). El uso de tocilizumab no tuvo asociación con la mortalidad y dosis equivalentes a prednisona entre 100-150 mg/día se asocian a mejores resultados.

Abstract Introduction: The SARS-CoV-2 pandemic has inspired interest in the immune response to the virus, especially in severe patients with acute respiratory distress syndrome (ARDS). The study describes the behaviour of the immune response, immune suppression, and their results in patients under mechanical ventilation (MV). Material and methods: Prospective cohort. From March 23rd to December 31st, 2020, we recollected basal information, MV parameters, blood gas analysis and laboratory studies of all the patients over 18 years who received MV secondary to COVID-19. We registered 15 continuous days of MV. We divided the groups in patients alive at day 60 and deaths. Results: We included 218 patients with a mortality of 23%. In day 1 of MV, the patients didn't have any differences in cell counts or acute phase reactants, except for D Dimer (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. In mixed effects linear regressions, we found statistically significant chronological differences in C reactive protein (CPR) and leucocyte count, concordant with the elevation of the driving pressure (DP). In the Cox regression we found no association with tocilizumab and corticosteroids with mortality on day 1 of MV. Patients who died received higher doses of corticosteroids throughout the 15 days of MV, with doses equivalent to prednisone over 150 mg/day are associated with mortality. Conclusions: There is a similar chronological behaviour in the elevation of acute phase reactants and the elevation con DP with no elevation of Vt, which can be explained by the drop of total PEEP and Cstat. There was no association with the use of tocilizumab and mortality, and a dose of 100-150 mg/día of equivalent of prednisone was associated with better results.

Resumo Introdução: A pandemia de SARS-CoV-2 inspirou intrigas sobre a resposta imune ao referido vírus, especialmente em pacientes gravemente doentes com síndrome do desconforto respiratório do adulto (SDRA). Este estudo descreve o comportamento da resposta imune, imunossupressão e seus desfechos em pacientes em ventilação mecânica (VM). Material e métodos: Coorte prospectiva. De 23 de março a 31 de dezembro de 2020, foram coletadas informações basais, parâmetros ventilatórios e gasométricos e estudos laboratoriais de todos os pacientes maiores de 18 anos que receberam VM para COVID-19 com registros até o dia 15 de VM. Os grupos foram divididos em pacientes vivos em 90 dias e óbitos. Resultados: Registramos 218 pacientes, com mortalidade de 23%. No dia 1 de VM, os pacientes não apresentaram diferenças na contagem de células ou reagentes de fase aguda, exceto dimero D 1020 (705-1711) vs 1328 (940-2340) ng/dL p = 0.035. Na análise de regressão linear dos efeitos mistos, observam-se diferenças cronológicas estatisticamente significativas nos leucócitos e na proteína C reativa (PCR), consistentes com o aumento da pressão de distensão alveolar (PDalv). Não foi encontrada associação com mortalidade no uso de tocilizumab 2.20 (0.279-17.358) e corticoide 0.54 (0.229-1.273) nos riscos proporcionais de COX no 1o dia de VM. Durante os 15 dias de VM, os pacientes que foram a óbito receberam doses maiores de corticosteróides, doses a partir de 150 mg/dia equivalentes a prednisona estão associadas à mortalidade. Conclusões: Há evolução cronológica semelhante em PCR e leucócitos elevados e PDalv elevados, explicados pela diminuição da complacência pulmonar estática (Cstat) e da pressão positiva ao final da expiração total (PEEPtotal). O uso de tocilizumab não foi associado à mortalidade e doses equivalentes à prednisona entre 100-150 mg/dia estão associadas a melhores resultados.

CD4+ and CD8+ T lymphocyte counts and ratio in cats with chronic gingivostomatitis and naturally infected with feline immunodeficiency virus: a preliminary study / Razão e contagem de linfócitos T CD4+ e linfócitos T CD8+ em gatos com gengivoestomatite crônica e infectados naturalmente pelo vírus da imunodeficiência felina: estudo preliminar

This study aimed to evaluate the CD4+ and CD8+ T lymphocytes counts and CD4+: CD8+ ratio in a colony of cats with chronic gingivostomatitis (CGS). We used forty domestic short-haired cats inhabiting the same colony. Ten cats with CGS were immunodeficiency virus-positive (group IV), and ten with CGS were immunodeficiency virus-negative (group III). As a control, twenty cats without CGS were used: ten cats were immunodeficiency virus-positive (group II) and ten cats were immunodeficiency virus-negative (group I). We employed flow cytometry to count CD4+ and CD8+ T lymphocytes. In cats infected with the immunodeficiency virus, the presence of CD4+ lymphocytes were lower both for animals with and without CGS. Conversely, not immunodeficiency virus-infected cats with CGS had a higher amount of CD4+ when compared to seronegative animals without CGS. The counts of CD8+ T lymphocytes showed no significant difference among cats with CGS, whether infected with immunodeficiency virus or not. The CD4+: CD8+ ratio was only different for group III, which was higher than any other group. No difference was observed for total lymphocyte number and CD8+ among groups. By contrast, mean CD4+ levels were different, with cats from groups III and IV showing higher levels than those from groups I and II. The flow cytometry could be a useful tool for the diagnosis and prognosis of cats with CGS infected by the immunodeficiency virus.

Este estudo teve como objetivo avaliar a contagem e a razão de linfócitos T CD4+ e CD8+ em uma colônia de gatos com gengivoestomatite crônica (CGS). Foram analisados quarenta gatos domésticos que habitavam a mesma colônia. Dez gatos com CGS foram positivos para o vírus da imunodeficiência (grupo IV), e dez com CGS foram negativos para o vírus da imunodeficiência (grupo III). Como controle, vinte gatos sem CGS foram usados: dez gatos foram positivos para o vírus da imunodeficiência (grupo II) e dez gatos foram negativos para o vírus da imunodeficiência (grupo I). Empregou-se a citometria de fluxo para contagem de linfócitos T CD4+ e CD8+. Nos gatos infectados pelo vírus da imunodeficiência, a presença de linfócitos CD4+ foi menor tanto para os animais com e sem CGS. Por outro lado, gatos não infectados e com CGS apresentaram maior quantidade de linfócitos CD4+ quando comparados a animais soronegativos sem CGS. A contagem de linfócito T CD8+ não mostrou diferença significativa entre gatos com CGS, infectados ou não com o vírus da imunodeficiência. A razão CD4+:CD8+ foi diferente apenas para o grupo III, que foi maior do que qualquer outro grupo. Não foi observada diferença para o número total de linfócitos e CD8+ entre os grupos. Em contraste, os níveis médios de CD4+ foram diferentes, com os gatos dos grupos III e IV apresentando níveis mais elevados do que os dos grupos I e II. A citometria de fluxo pode ser uma ferramenta útil para o diagnóstico e prognóstico de gatos com CGS infectados pelo vírus da imunodeficiência.

Annexin A1 as a Regulator of Immune Response in Cancer.

Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N-terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.

Immunosuppression by UVB radiation exacerbates Leishmania mexicana skin lesions in mice.

Cutaneous leishmaniasis is the most common form of leishmaniasis in humans. The disease is caused by several species, such as Leishmania mexicana, a protozoa parasite. Several major risk factors are associated with this disease, including poverty, poor housing, inadequate domestic hygiene, malnutrition, mobility, and occupational exposure. Solar radiation (UVB) has not been considered a risk factor because there is no scientific evidence demonstrating a correlation with increased susceptibility to cutaneous leishmaniasis. In this study, the shaved skin of the back of C57BL/6 mice was irradiated with 24.2 mJ/cm2 of UVB. A delayed-type hypersensitivity (DTH) reaction was used to assess UV-induced immune suppression. Skin lesions were quantitated, and parasite burden and the presence of anti-Leishmania mexicana antibodies in serum and germinal centers in draining lymph nodes were determined. We found an increased in the lesion size and parasitic load in UVB-irradiated mice compared to the WT mice and B lymphocyte activation in draining lymph nodes and increased IgG1 production. Our results show an important role of UVB-induced suppression in cutaneous leishmaniasis through local production of IL-10 and systemic IgG1antibodies. This is the first study that demonstrates the effects of UVB radiation on cutaneous leishmaniasis by Leishmania mexicana.

Research progress of tumor microenvironment and tumor-associated macrophages.

Cancer is a health issue causing utmost concern and continuing to be one of the leading causes of mortality worldwide. Effective tumor eradication methods that will improve the prognosis and prolong human life are an important topic in modern medicine. Increasing amounts of evidence indicate that the tumor microenvironment plays a significant role in tumor development and migration. Macrophages are important immune cells that commonly infiltrate the tumor microenvironment. Several studies found that macrophages play different roles in the process of cancer development. This article focuses on the tumor microenvironment and the generation, classification, and function of tumor-associated macrophages as well as their significance for tumor immunotherapy and other aspects, it summarizes nearly 10 years of tumor microenvironment and tumor-associated macrophage research, providing a novel insight for tumor immunotherapy.

In Vitro and In Vivo Characterization of a Typical and a High Pathogenic Bovine Viral Diarrhea Virus Type II Strains.

Non-cytopathic (ncp) type 2 bovine viral diarrhea virus (BVDV-2) is widely prevalent in Argentina causing high mortality rates in cattle herds. In this study, we characterized an Argentinean ncp BVDV-2 field isolate (98-124) compared to a high-virulence reference strain (NY-93), using in silico analysis, in vitro assays, and in vivo infections of colostrum-deprived calves (CDC) to compare pathogenic characters and virulence. In vitro infection of bovine peripheral blood mononuclear cells (PBMC) with BVDV 98-124 induced necrosis shortly after infection while NY-93 strain increased the apoptotic rate in infected cells. Experimental infection of CDC (n = 4 each) with these strains caused an enteric syndrome. High pyrexia was detected in both groups. Viremia and shedding were more prolonged in the CDC infected with the NY-93 strain. In addition, NY-93 infection elicited a severe lymphopenia that lasted for 14 days, whereas 98-124 strain reduced the leukocyte counts for 5 days. All infected animals had a diminished lymphoproliferation activity in response to a mitogen. Neutralizing and anti-NS3 antibodies were detected 3 weeks after infection in all infected calves. Virulence was associated with a more severe clinical score, prolonged immune-suppression, and a greater window for transmission. Studies of apoptosis/necrosis performed after in vitro PBMC infection also revealed differences between both strains that might be correlated to the in vivo pathogenesis. Our results identified 98-124 as a low-virulence strain.

Daily very low UV dose exposure enhances adaptive immunity, compared with a single high-dose exposure. Consequences for the control of a skin infection.

Ultraviolet radiation (UVr) promotes several well-known molecular changes, which may ultimately impact on health. Some of these effects are detrimental, like inflammation, carcinogenesis and immunosuppression. On the other hand, UVr also promotes vitamin D synthesis and other beneficial effects. We recently demonstrated that exposure to very low doses of UVr on four consecutive days [repetitive low UVd (rlUVd)] does not promote an inflammatory state, nor the recruitment of neutrophils or lymphocytes, as the exposure to a single high UV dose (shUVd) does. Moreover, rlUVd reinforce the epithelium by increasing antimicrobial peptides transcription and epidermal thickness. The aim of this study was to evaluate the adaptive immune response after shUVd and rlUVd, determining T-cell and B-cell responses. Finally, we challenged animals exposed to both irradiation procedures with Staphylococcus aureus to study the overall effects of both innate and adaptive immunity during a cutaneous infection. We observed, as expected, a marked suppression of T-cell and B-cell responses after exposure to an shUVd but a novel and significant increase in both specific responses after exposure to rlUVd. However, the control of the cutaneous S. aureus infection was defective in this last group, suggesting that responses against pathogens cannot be ruled out from isolated stimuli.

Respiratory Tract Infection Caused by Fonsecaea monophora After Kidney Transplantation.

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.

Vacunación en adultos / Vaccination in adults

ResumenIntroducción:cada año, miles de adultos mueren por causa de enfermedades prevenibles mediante vacunación. Sin embargo, la aplicación de vacunas en adultos es muy baja a nivel mundial por múltiples razones, incluyendo los altos costos de implementación.Objetivos:discutir las recomendaciones nacionales e internacionales de inmunización de personas mayores de 18 años, incluyendo las poblaciones con alto riesgo de adquirir infecciones inmunoprevenibles y resumirlas en un esquema recomendado para vacunación de adultos en general, y personas con elevado nivel de riesgo.Métodos:se efectuó una revisión no sistemática de bibliografía médica y científica publicada entre 2000 y 2017, concerniente a vacunación en adultos. Así mismo, se compararon los esquemas de inmunización vigentes en América y Europa.Conclusiones:las recomendaciones para vacunación en adultos se basan principalmente en edad, condiciones médicas subyacentes, estilo de vida, inmunizaciones previas, características epidemiológicas locales y viajes. La necesidad de aplicar un esquema de vacunación adecuado a la población general y a poblaciones con factores de riesgo, representa una medida de gran importancia en un sistema de salud funcional. En este sentido, la adecuada asesoría e información provenientes del personal de salud constituyen un predictor clave en la inmunización de adultos.

AbstractIntroduction:Every year thousands of adults die from vaccine preventable disease worldwide. Nevertheless, the vaccine application rates maintain in relative low levels for multiple reason, including high costs of the implementation of vaccination programs.Objectives:Discuss national and international existing immunization schemes for adult persons, including high risk populations for the acquisition of immune preventable infections and resume this knowledge in vaccination schemes for adults in general and high risk populationMethods:A nonsystematic revision of medical and scientific literature related to adult vaccination topics from the years 2000 to 2017 was performed. As well, a comparison between actual vaccination schemes from American and European countries has been realized.Conclusion:Vaccination recommendations are based in multiple factors like age, individual medical history, lifestyle, formerly applied vaccinations, local epidemiologic criteria end traveling activity.The application of adequate vaccination scheme for both, adults in general and an adaptation for persons with elevated risk factors, represents a crucial element for effective health system. Therefore, the adequate assessing and information provided by medical personnel represents a key factor in successful vaccination and disease prevention.

Vacunación de pacientes adultos receptores de trasplante de células madre hematopoyéticas: Perspectiva de Costa Rica / Vaccination of adult patients receiving hematopoietic stem cell transplantation: Perspective of Costa Rica

In this article the present recommendations for immunization of adult patients who received hematopoietic stem cell transplantation -a common procedure in therapy of many types of hematological diseases and serious inborn defects of the immune system- are reviewed and discussed. Patients that undergo this kind of transplantation procedure exhibit, compared to the general population, an elevated susceptibility of immune-preventable infections, due to loss of the humoral and cellular protective immunity. A revaccination strategy for transplanted patients can result in a significant diminution of morbidity and mortality related to the treatment of these diseases. Few data are published about the duration and magnitude of the vaccination response in this specific population of patients. Moreover, deviation from international guidelines recommendations for post-transplant immune prophylaxis can be observed frequently, partly as a result of the absence of specific vaccines in some countries. Multiple factors as intensity of the pharmacologic immune suppression, myeloablative regimen, administration of monoclonal and polyclonal antibodies, duration of the post-transplant period or the presence of graft-versus-host disease (GVHD), can influence the immune response and establish special considerations for certain biological agents, as observed in case of living attenuated virus composed vaccines. This conditions are responsible for the fact that an optimal time point for vaccination of transplanted patients remains not clearly defined. More specific studies about the underlying immunological mechanisms during immunocompromised periods are necessary to understand better the immunogenicity and security of existing vaccines. The development of innovative vaccines as well can induce certain advances in the post-transplant therapy.

El presente artículo revisa las recomendaciones actuales para la inmunización de pacientes adultos que han recibido trasplante de células madre hematopoyéticas, procedimiento común en la terapia de muchas patologías hematológicas y defectos congénitos del sistema inmune. Los pacientes que reciben este tipo de tratamiento son más susceptibles a infecciones inmunoprevenibles que la población general debido a la pérdida de la inmunidad protectora tanto humoral como celular con posterioridad al trasplante. De esta manera, la revacunación de los receptores de trasplante representa una estrategia importante para reducir la morbilidad y mortalidad asociadas con esas enfermedades. Sin embargo, se conoce poco sobre la duración y magnitud de la respuesta inmunológica generada por las vacunas en esta población. Además, aunque existen guías internacionales consensuadas en inmunoprofilaxis post-trasplante, frecuentemente ocurren desviaciones en las prácticas recomendadas por múltiples motivos, incluyendo la no disponibilidad de ciertas vacunas en algunos sistemas de salud. Factores como la intensidad de la inmunosupresión farmacológica, el régimen mieloablativo empleado, la administración de anticuerpos monoclonales y policlonales, la duración de la fase neutropénica en el período posterior al trasplante y la presencia de enfermedad injerto versus hospedero (graft-versus-host disease, GVHD) pueden influenciar la respuesta inmunitaria y establecer consideraciones especiales para ciertos agentes como es el caso de las vacunas compuestas por virus vivos atenuados. Estas condiciones contribuyen a que el momento oportuno de inicio de las inmunizaciones en los receptores de trasplante aún no se encuentre bien definido. Se requieren más estudios específicos acerca de los mecanismos inmunológicos subyacentes durante los estados de inmunocompromiso para entender mejor la inmunogenicidad y seguridad de las vacunas existentes en dichos contextos. El desarrollo de vacunas innovadoras puede también inducir avances en la terapia post-trasplante.

Regulatory cells induced by acute toxoplasmosis prevent the development of allergic lung inflammation.

The increased prevalence of allergies in developed countries has been attributed to a reduction of some infections. Supporting epidemiological studies, we previously showed that both acute and chronic Toxoplasma gondii infection can diminish allergic airway inflammation in BALB/c mice. The mechanisms involved when sensitization occurs during acute phase would be related to the strong Th1 response induced by the parasite. Here, we further investigated the mechanisms involved in T. gondii allergy protection in mice sensitized during acute T. gondii infection. Adoptive transference assays and ex vivo co-cultures experiments showed that not only thoracic lymph node cells from infected and sensitized mice but also from non-sensitized infected animals diminished both allergic lung inflammation and the proliferation of effector T cells from allergic mice. This ability was found to be contact-independent and correlated with high levels of CD4(+)FoxP3(+) cells. IL-10 would not be involved in allergy suppression since IL-10-deficient mice behaved similar to wild type mice. Our results extend earlier work and show that, in addition to immune deviation, acute T. gondii infection can suppress allergic airway inflammation through immune suppression.

Acute effects of resistance exercise and intermittent intense aerobic exercise on blood cell count and oxidative stress in trained middle-aged women

The aim of this study was to compare the effect of an intermittent intense aerobic exercise session and a resistance exercise session on blood cell counts and oxidative stress parameters in middle-aged women. Thirty-four women were selected and divided into three groups: RE group (performing 60 min of resistance exercises, N = 12), spinning group (performing 60 min of spinning, N = 12), and control group (not exercising regularly, N = 10). In both exercise groups, lymphocytes and monocytes decreased after 1-h recuperation (post-exercise) compared to immediately after exercise (P < 0.05). Immediately after exercise, in both exercised groups, a significant increase in TBARS (from 16.5 ± 2 to 25 ± 2 for the spinning group and from 18.6 ± 1 to 28.2 ± 3 nmol MDA/mL serum for the RE group) and protein carbonyl (from 1.0 ± 0.3 to 1.6 ± 0.2 for the spinning group and from 0.9 ± 0.2 to 1.5 ± 0.2 nmol/mg protein for the RE group) was observed (P < 0.05). A decrease in antioxidant activities (non-protein sulfhydryl, superoxide dismutase, catalase) was also demonstrated with a negative correlation between damage markers and antioxidant body defenses (P < 0.05). These results indicate that an acute bout of intermittent or anaerobic exercise induces immune suppression and increases the production of reactive oxygen species, causing oxidative stress in middle-aged and trained women. Furthermore, we demonstrated that trained women show improved antioxidant capacity and lower oxidative damage than sedentary ones, demonstrating the benefits of chronic regular physical activity.

Análise do envolvimento de células T reguladoras na hanseníase / Analysis of the involvement of regulatory T cells in leprosy

A hanseníase é uma doença crônica causada por Mycobacterium leprae e apresenta diversas formas clínicas. O entendimento da interação parasita-hospedeiro na hanseníase evidenciou que ocorre a persistência assintomática do patógeno, caracterizando um estado de latência. Os fatores mais importantes relacionados com a permanência do patógeno são: a patogenicidade do agente infeccioso e o perfil da resposta imune, no qual os eventos de migração celular, produção de citocinas, as células efetoras e reguladoras são extremamente relevantes. As células T reguladoras (Treg) desempenham papel central na regulação da resposta imune em infecções crônicas o que favorece a persistência do patógeno. A importância de células T reguladores na hanseníase ainda é pouco conhecida. Neste trabalho investigou-se a presença de células T reguladoras em lesões e sangue periférico de indivíduos com hanseníase. Inicialmente avaliou-se a proliferação e a produção de citocinas por células mononucleares do sangue periférico (PBMC) de pacientes com hanseníase. Os resultados evidenciaram que não há diferenças quanto à proliferação de células T e produção de IFN-γ e TNF-α por células desses pacientes, mas a produção de IL-4 e IL-5 foi detectada apenas entre os pacientes com hanseníase virchoviana. Em relação à presença de células T reguladoras, os resultados evidenciaram aumento no número de linfócitos T CD4+CD25+FoxP3+ no sangue periférico de pacientes com hanseníase virchoviana. As células T reguladoras dos pacientes com hanseníase apresentaram elevada expressão de moléculas co-inibitórias PD-1, CTLA-4, GITR e ICOS. De modo relevante, as células T CD4+CD25+ isolados de pacientes com hanseníase virchoviana apresentaram maior atividade supressora quando comparado às células isoladas de pacientes com hanseníase tuberculóide. As células T CD4+CD25+ de pacientes com hanseníase virchoviana inibiram a proliferação de PBMC alogênico e a produção de IFN-γ e TNF-α...

Leprosy is caused by Mycobacterium leprae and its clinical features depend on the host immune background. The understanding of parasite-host interactions in leprosy have highlighted asymptomatic persistence of the pathogen, which indicates that this infection becomes latent. The most important factors related to the permanence of pathogens are: the pathogenicity of the infectious agents; the profile of the immune response developed by the host whose events of cellular migration, cytokines production, and the effector and regulatory cells are extremely relevant. The regulatory T cells (Treg) seem to play a central role in the regulation of the immune response in chronic infections, which favors the persistence of the pathogen. Herein, we analyzed the relation between tuberculoid and lepromatous leprosy with the presence and function of T regulatory cells from peripheral blood mononuclear cells (PBMC) and skin lesions from these patients. First, the proliferation and cytokine production of PBMC isolated from leprosy patients were analyzed. We did not observe any difference in the proliferation ability or IFN-γ and TNF-α release; however, the production of IL-4 and IL-5 was detected only in patients with lepromatous leprosy. Furthermore, T CD4+CD25+FoxP3+ cells were detected in the PBMC of patients with leprosy and these cells from lepromatous patients showed high expression of co-inhibitory molecules such as PD-1, GITR, CTLA-4 and ICOS. T CD4+CD25+cells isolated from patients with lepromatous leprosy were significantly more suppressive than the cells obtained from tuberculoid patients. In addition, TCD4+CD25+ cells isolated from patients with lepromatous leprosy inhibited allogeneic PBMC proliferation and their production of IFN-γ and TNF-α. The results also demonstrated that IL- 10 and TGF-ß were co-expressed with CD25+ cells at the inflammatory infiltrate of skin lesions from lepromatous patients, but similar results were not detected among tuberculoid...