Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Disseminaded coccidiodomycosis presentig as acute respiratory distress syndrome in a liver postrasplant recipient / Síndrome de dificultad respiratoria aguda (SDRA) como prensentacion de Coccidiodomicosis diseminada en un paciente receptor de trasplante hepatico ortotópico

Abstract Acute respiratory distress syndrome (ARDS) is a respiratory process of acute onset, showing on X rays as bilateral pulmonary infiltrates and severe respiratory failure, Coccidiodomycosis is a unusual cause of acute respiratory distress syndrome, the incidence of coccidiomycosis in a solid organ trasplant recipientes ranges from 1.4% a 6.9%, inadecuancy of cellular inmunity is a well established risk factor for development of coccididomcosis, less than 1% of patients develop disseminaded infecction and carrying high mortality, the case that we are presenting add to the small list of reports documenting the ocasionally acute and agressive nature of the disseminated clinical form of coccidiodomycosis.

Resumen El síndrome de dificultad respiratoria aguda (SDRA) es un proceso respiratorio de inicio agudo, que se manifiesta en las radiografías como infiltrados pulmonares bilaterales, clinicamente como insuficiencia respiratoria grave, la coccidiodomicosis es una causa inusual de síndrome de dificultad respiratoria aguda, la incidencia de coccidiomicosis en receptores de trasplante de órgano sólido varía desde 1.4% a 6.9%, una inadecuada inmunidad celular es un factor de riesgo bien establecido para el desarrollo de coccidomicosis, menos del 1% de los pacientes desarrollan enfermedad diseminada y alta mortalidad, el caso que presentamos se suma a la pequeña lista de informes que documentan la naturaleza ocasionalmente aguda y agresiva de la forma clínica diseminada de coccidiodomicosis.

Experimental studies using OMV in a new platform of SARS-CoV-2 vaccines

Although COVID-19 vaccines have recently been approved for emergency use, search for new vaccines are still urgent, since the access of the countries, especially the poorest, to the vaccines, has shown to be slower than the necessary to rapidly control the pandemic. We proposed a novel platform for vaccine using recombinant receptor binding domain (rRBD) from Sars-Cov-2 spike protein and Neisseria meningitidis outer membrane vesicles (OMVs). The antigen preparation produced a humoral and cellular immune response. Taken together our findings suggest a good immunostimulatory patter in response to immunization with rRBD plus N. meningitidis OMV.

Las células dendríticas plasmacitoides evocan la respuesta efectora de los linfocitos T citotóxicos específicos para Salmonella / The plasmacytoid dendritic cells evoke Salmonella-specific CTL effector response

Resumen Introducción. La función inmunológica de las células dendríticas plasmacitoides durante las infecciones bacterianas, como la de Salmonella spp., es poco conocida. En ese contexto, se analizó su función efectora para presentar antígenos de Salmonella Typhimurium ante linfocitos T citotóxicos. Objetivo. Analizar la respuesta de los linfocitos T citotóxicos específicos para Salmonella evocada por las células dendríticas plasmacitoides. Materiales y métodos. Se usaron células dendríticas plasmacitoides marcadas con éster de succinimidil-carboxifluoresceína, pulsadas con el epítopo de Salmonella OmpC73 Kb- restringido o infectadas con S. Typhimurium como blanco en ensayos de citotoxicidad. Resultados. La lisis específica tuvo significación estadística usando células dendríticas plasmacitoides positivas pulsadas con OmpC73 en todas las relaciones de células efectoras y blanco (E:B) (p≤0,05); en cuanto a las células dendríticas plasmacitoides positivas para S. Typhimurium, solo se observó significación estadística en la relación de 1:100 (p≤0,05) usando las células efectoras OmpC73. Conclusión. Las células dendríticas plasmacitoides pueden evocar la respuesta de los linfocitos T citotóxicos durante la infección con S. Typhimurium.

Abstract Introduction: The immunological role of plasmacytoid dendritic cells (pDC) in bacterial infections such as Salmonella has been poorly documented. Therefore, we analyzed the effector function of these cells by presenting cytotoxic T lymphocytes (CTL) with Salmonella Typhimurium antigens. Objective: To analyze the Salmonella-specific CTL response evoked by pDCs. Materials and methods: We used plasmacytoid dendritic cells stained with carboxyfluorescein succinimidyl ester (CFSE) and pulsed with OmpC73, Salmonella Kb- restricted epitopes or S. Typhimurium as targets for cytotoxicity assays. Results: Specific lysis was shown to be statistically significant in pDC + OmpC73 for all effector:target ratios (p≤0.05). For pDC + S. Typhimurium, statistical significance was only observed at a 1:100 ratio (p≤0.05) using OmpC73. Conclusion: Plasmacytoid dendritic cells evoke CTL response during S. Typhimurium infection.

Mecanismos efetores da resposta imune na infecção por Bordetella pertussis / Immune response effector mechanisms to Bordetella pertussis infection

A coqueluche é uma doença infecciosa aguda, transmissível, com predileção pelo trato respiratório, caracterizada por paroxismos de tosse seca e considerada uma importante causa de morbidade e mortalidade infantil. A resposta imunológica humoral e celular do hospedeiro promove a contenção da infecção, pois essas respostas se caracterizam como importantes linhas de defesa durante a infecção e colonização da bactéria. Dessa forma, esta revisão bibliográfica procurou descrever os mecanismos mais eficazes de resposta imune contra Bordetella pertussis e abordar os mecanismos de evasão utilizados pelo patógeno.

Pertussis is a transmissible infectious disease with a predilection for the respiratory tract characterized by paroxysms of dry cough. It is considered an important cause of child morbidity and mortality. The humoral and cellular immune responses of the host promote the containment of the infection, and these responses are characterized as important lines of defense during infection and colonization of the bacterium. Thus, this literature review sought to describe the most effective immune response mechanisms against Bordetella pertussis and to address the avoidance mechanisms used by the pathogen.

Subsets of T lymphocytes in the lesional skin of pityriasis rosea

Abstract: Background: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. Objective: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. Methods: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. Results: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. Conclusion: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.

Β-Glucan of candida albicans cell wall extract inhibits salmonella typhimurium colonization by potentiating cellular immunity (cd8 + and cd4 + t cells)

Abstract INTRODUCTION: Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. METHODS: Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). RESULTS: Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. CONCLUSIONS The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant / Avaliação da potência terapêutica da vacina de DNA do papilomavírus humano-16 E7 isolada e com interleucina-18 como adjuvante genético

AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days. RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred. CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo.

OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18. MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3.1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias. RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001). A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15). CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in vivo.

Immune response and biochemistry of calves immunized with rMSP1a ( Anaplasma marginale) using carbon nanotubes as carrier molecules / Resposta imunológica e bioquímica de bezerros imunizados com rMSP1 a (Anaplasma marginale) utilizando nanotubos de carbono como moléculas carreadoras

Abstract Vaccination against Anaplasma marginale has been considered an important control strategy for bovine anaplasmosis. Recently, mice immunized with rMSP1 a linked to carbon nanotubes (MWNT) showed significant immune responses, generating a new possibility for use of an inactivated vaccine. The objective of this study was to investigate the cellular and humoral responses in calves immunized with MWNT+rMSP1a , associated with inactivated vaccine of A. marginale produced in vitro, and evaluate the toxic effects of the MWNT on renal and hepatic function. rMSP1a was covalently linked to MWNT. Inactivated vaccine (AmUFMG2) was produced by cultivating A. marginale in IDE8 cells. Twenty-four Holstein calves were divided (four groups) and immunized subcutaneously with PBS and non-carboxylated MWNT (control, G1), AmUFMG2 (G2), MWNT+rMSP1a (G3), and AmUFMG2 with MWNT+rMSP1a (G4). Blood samples were collected for total leukocyte counts, biochemical profiling and evaluation of the cellular and humoral response. Immunization with MWNT+rMSP1a induced increase in the total number of leukocytes, NK cells, in the lymphocyte populations and higher levels of antibodies compared to calves immunized only with AmUFMG2. Furthermore, MWNT did not induce changes in the biochemical profile. These data indicate that MWNT+rMSP1a were able to induce the immune responses more efficiently than AmUFMG2 alone, without generating toxicity.

Resumo Vacinação contra Anaplasma marginale tem sido considerada uma importante estratégia de controle da anaplasmose bovina. Recentemente, camundongos imunizados com rMSP1a funcionalizada à nanotubos de carbono (MWNT) apresentaram resposta imune significante, gerando nova possibilidade para o uso da vacina inativada. O objetivo desse estudo foi investigar a resposta celular e humoral em bezerros imunizados com MWNT+rMSP1a, associado com a vacina inativada de A. marginale produzida in vitro, e avaliar os efeitos tóxicos dos MWNT nas funções hepática e renal. rMSP1 a foi ligada covalentemente aos MWNT. Vacina inativada (AmUFMG2) foi produzida através do cultivo de A. marginale em células IDE8. Vinte e quatro bezerros Holandeses foram divididos (quatro grupos) e imunizados subcutaneamente com: PBS e MWNT não-carboxilados (controle, G1), AmUFMG2 (G2), MWNT+rMSP1 a (G3), e AmUFMG2 com MWNT+rMSP1a (G4). Amostras de sangue foram coletadas para contagem de leucócitos, perfil bioquímico e avaliação da resposta celular e humoral. Imunização com MWNT+rMSP1a induziu aumento dos leucócitos totais, células NK, na população de linfócitos e altos níveis de anticorpos comparado com animais imunizados apenas com AmUFMG2. Além disso, MWNT não induziu alterações no perfil bioquímico. Esses dados indicam que MWNT+rMSP1a foram capazes de induzir eficientemente a resposta imune comparado com AmUFMG2 sozinho, sem gerar toxicidade.

Non-polarized cytokine profile of a long-term non-progressor HIV infected patient

ABSTRACT The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles.

Alteraciones leucocitarias por exposición a perclorato de amonio en ratones de la cepa ICR / Leucocitary changes by ammonium perchlorate in ICR mice strain / Alterações leucocitárias por exposição a perclorato de amônio em camundongos da linhagem ICR

El presente trabajo tuvo como objetivo identificar alteraciones en el recuento de leucocitos en sangre periférica, generadas por la exposición a perclorato de amonio, en ratones de la cepa ICR, evaluando diferentes concentraciones de exposición y diferenciando dichas alteraciones en machos y hembras. Se realizó mediante un trabajo de diseño analítico tipo experimental. Se utilizaron 60 ratones de la cepa ICR, 30 machos y 30 hembras de los cuales 50 fueron expuestos a perclorato de amonio. La manipulación se llevó a cabo de acuerdo con lo establecido en la resolución 008430 de 1993, artículo 87 del Ministerio de Salud de la República de Colombia. Un 70% de los ratones hembra y un 83% de los ratones macho expuestos a perclorato de amonio presentaron alteraciones en el recuento celular de la línea blanca. Los machos presentaron mayor alteración leucocitaria, en especial linfocitopenia. Por otro lado, el peso en los ratones expuestos disminuyó considerablemente hacia la tercera semana de administración de perclorato de amonio, lo cual podría indicar que esta sustancia tóxica genera un estado de inmunosupresión. Se evidenció leucopenia, específicamente neutropenia, neutrofilia y linfocitopenia como principales alteraciones en el recuento de leucocitos en ratones de la cepa ICR, expuestos a perclorato de amonio.

The objective of this work was to identify the changes in the leukocyte counts in peripheral blood by ammonium perchlorate in ICR strain mice, evaluating the different exposure concentrations and differentiating the changes between males and females. Through an analytic experimental investigation, 60 ICR strain mice, 30 males and 30 females were used, 50 of which were exposed to ammonium perchlorate. This study was carried out by Resolution 008430/93, article 87 of Ministry of Health of Colombia. A total of 70% females and 83% males had changes in the leukocyte counts, especially lymphocytopenia in males, further, weight decreased the third week of treatment, and probably that toxic substance induces a state of immunosuppression. The main changes in the leukocyte counts in peripheral blood by ammonium perchlorate in ICR strain was leukopenia.

O objetivo deste trabalho foi identificar as alterações na contagem de leucócitos em sangue periférico, geradas pela exposição a perclorato de amônio em camundongos da linhagem ICR, avaliando diferentes concentrações de exposição e diferenciando estas alterações entre machos e fêmeas. Isto foi realizado através de um trabalho de desenho analítico tipo experimental. Foram utilizados 60 camundongos da linhagem ICR, sendo 30 machos e 30 fêmeas, dos quais 50 foram expostos ao perclorato de amônio. O manuseio foi realizado conforme a resolução 008430 de 1993, artigo 87 do Ministério da Saúde da Colômbia. 70% dos camundongos fêmea e 83% dos machos apresentaram alterações na contagem celular dos leucócitos, especialmente a linfocitopenia em machos. Além disso, o peso nos camundongos expostos diminuiu en forma considerável para a terceira semana de tratamento com perclorato de amônio, o qual poderia indicar que esta substância tóxica gera um estado de imunossupressão. Houve evidência de leucopenia, especificamente neutropenia, neutrofilia e linfocitopenia como principais alterações na contagem de leucócitos em camundongos da linhagem ICR, expostos a perclorato de amônio.

Leprosy and American cutaneous leishmaniasis coinfection

Abstract: Brazil is a country with a high prevalence of infectious diseases such as leprosy and leishmaniasis. However, coinfection of these diseases is still poorly understood. We report a case of a patient who presented with lepromatous leprosy and cutaneous-mucosal leishmaniasis at the same period. After clinical, laboratory, and histopathological diagnosis, the treatment was introduced and the patient showed important clinical improvement. He was followed in our outpatient clinic. Both pathologies play an important role in the immune system. Depending on the immune response profile of the host, diseases may present themselves in different ways. In this case, the patient showed a divergent immune response for each disease. We hypothesized that this response is specific for each pathogen.

Algunas consideraciones sobre las afecciones dermatológicas en pacientes con virus de inmunodeficiencia humana/sida / Some considerations on dermatological disorders in patients with human immunodeficiency virus/AIDS

La infección por el virus de la inmunodeficiencia humana/sida es uno de los problemas de salud pública más importante en todo el mundo. Se estima que hasta 95 por ciento de los afectados presentan manifestaciones cutáneas durante el curso de la infección, entre las cuales se encuentran las producidas por hongos. A tales efectos, se describen algunas de ellas, las cuales deben ser reconocidas por los médicos y el personal de salud a cargo del tratamiento y control de los pacientes con esta enfermedad.

Human immunodeficiency virus/AIDS infection is one of the most important public health problems worldwide. It is considered that up to 95 percent of the affected patients present cutaneous manifestations during the course of the infection, among which we can mention those caused by fungus. To such effects, some of these are described, which should be recognized by doctors and health staff in charge of the treatment and control of patients with this disease

Humoral and cellular immune response of mice challenged with Yersinia pestis antigenic preparations

ABSTRACT Objectives: The plague, which is an infectious disease caused by Yersinia pestis, still threatens many populations in several countries. The worldwide increase in human plague cases and the potential use of the bacteria as a biological weapon reinforce the need to study the immunity that is induced by potential vaccine candidates. To determine the immunogenicity of antigenic preparations based on the F1 protein and the total extract from Y. pestis, we assessed the role of these antigens in inducing an immune response. Methods: The immunogenicity of antigenic preparations based on the Y. pestis (YP) total extract and the Y. pestis fraction 1 capsular antigen protein (F1) was determined in Swiss-Webster mice immunized with 40 µg or 20 µg for each preparation. Immunophenotyping was performed by flow cytometry. Results: Animals immunized with the YP total extract did not elicit detectable anti-F1 antibodies (Ab) in the hemaglutination/inhibition (HA/HI) test. Animals immunized with 40 µg or 20 µg of the F1 protein produced anti-F1 Abs, with titres ranging from 1/16 to 1/8132. The average of CD3+-CD4+ and CD3+-CD8+ T cells did not differ significantly between the groups. Neither YP total extract nor F1 protein induced a significant expression of IFN-γ and IL-10 in CD4+ T lymphocytes. In addition, F1 failed to induce IFN-γ expression in CD8+ T cells, unlike the YP total extract. Conclusion: The results showed that F1 protein is not an immunogenic T cell antigen, although the YP total extract (40 µg dose) favoured CD8+ T cell-mediated cellular immunity.

Immunotherapy and gene therapy as novel treatments for cancer / Inmunoterapia y terapia génica como nuevos tratamientos contra el cáncer

Abstract The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is an anti-CTLA-4 antibody which demonstrated good results when administered to patients with melanoma. Gene therapy has also shown promising results in clinical trials. Particularly, Herpes simplex virus (HSV)-mediated delivery of the HSV thymidine kinase (TK) gene to tumor cells in combination with ganciclovir (GCV) may provide an effective suicide gene therapy for destruction of glioblastomas, prostate tumors and other neoplasias by recruiting tumor-infiltrating lymphocytes into the tumor. The development of new treatment strategies or combination of available innovative therapies to improve cell cytotoxic T lymphocytes trafficking into the tumor mass and the production of inhibitory molecules blocking tumor tissue immune-tolerance are crucial to improve the efficacy of cancer therapy.

Resumen El sistema inmune interactúa íntimamente con los tumores durante el proceso del desarrollo de la enfermedad y su progresión a metástasis. Esta compleja comunicación entre el sistema inmune y las células tumorales puede prevenir o promover el crecimiento del tumor. Los nuevos enfoques terapéuticos que aprovechan los mecanismos inmunológicos, ya sea por el bloqueo de señales inhibitorias o por la activación directa de células efectoras, han mostrado resultados prometedores. El bloqueo de puntos de control inmunológicos (immune-checkpoints) con anticuerpos monoclonales dirigidos contra receptores que normalmente inhiben el sistema inmune, como CTLA-4 o PD-1, ha resultado ser un tratamiento exitoso para pacientes con melanoma avanzado. El fármaco ipilimumab es un anticuerpo anti-CTLA-4 que ha demostrado buenos resultados terapéuticos en pacientes con melanoma. Por otro lado, la terapia génica también ha mostrado resultados prometedores en ensayos clínicos. En especial, la administración de la enzima timidina quinasa del virus Herpes simplex (HSV-TK) en combinación con el fármaco ganciclovir (GCV) ha mostrado ser una terapia suicida muy efectiva para la destrucción de diferentes neoplasias incluyendo glioblastomas y tumores prostáticos, por un mecanismo que involucra el reclutamiento de linfocitos infiltrantes de tumor. Es importante la búsqueda de nuevas estrategias o la combinación de terapias innovadoras, con el fin de involucrar tanto la atracción de linfocitos citotóxicos así como el empleo de moléculas que inhiban la inmunotolerancia del tejido tumoral para mejorar la eficiencia de los tratamientos contra el cáncer.

Behçet's disease: review with emphasis on dermatological aspects

Abstract: Behçet's disease is a systemic vasculitis characterized by attacks of acute inflammation, which can affect almost every vascularized area of the body. There is a close correlation between the geographical distribution of HLA-B51 and its prevalence. In the etiopathogenesis there are indications of genetic susceptibility associated with environmental influence. Among the involved genes are those that encompass innate and adaptive immunities. Polymorphisms and epistatic interactions in several genes are described, as well as the presence of imbalance lineage between HLA-B51 and A (MICA). Herpes simplex and Streptococcus sanguinis may be important extrinsic factors. An increase of Th1 response and of IL-21 is observed. The production of IL-21 is positively related to Th17 cells and negatively to T-regs. The mucocutaneous manifestations are Behcet´s disease markers, and their earlier onset indicates a worse prognosis. Recurrent oral ulcers have varied sizes and arrangements, genital ulcers are recurrent, leaving scars, skin lesions are multivaried, and pathergy, although not so frequent, is important for the diagnosis. There are numerous attempts to validate indexes that can evaluate the disease activity and among them the Mucocutaneous Activity Index. This is a specific score that can help with therapeutic decisions and to reduce morbidity, but still lacks validation. The clinical manifestations of other organs are described as well as treatment options.

Papel de las células dendríticas en la infección por el virus dengue: blancos de replicación y respuesta inmune / Role of dendritic cells in infection by dengue virus: targets for replication and immune response

Dengue fever, caused by dengue virus (DENV) infection, is one of the most important diseases in the world, not only due to the high morbidity/mortality rates it causes, but also because of its great economic and social impact in tropical/subtropical countries. DENV infection has a wide range of clinical manifestations ranging from asymptomatic infection or infection with mild symptoms to severe dengue that can lead to death. At present, no etiological treatment or effective globally distributed vaccine against the four DENV serotypes exists. Despite great efforts made to understand the mechanism associated with DENV disease pathogenesis the causes leading to severe dengue presentation have not been clarified. Some hypotheses seek to give a biological and physiological explanation to the clinical manifestations that appear during the infection. Based on the evidence that after contact with dendritic cells DENV alters the functionality of these cells, this review aims to describe the most relevant findings regarding the importance of dendritic cells in the context of DENV infection and progression of the illness.

El dengue, causada por el virus dengue (DENV), es una de las enfermedades más importantes no sólo por los altos índices de morbilidad/mortalidad, sino también por su gran impacto económico y social en los países de las regiones tropicales/subtropicales. La infección por el DENV cursa por un variado rango de manifestaciones clínicas que van desde una infección asintomática o con síntomas leves, hasta el dengue grave que puede ser fatal. En la actualidad, no se dispone de un tratamiento etiológico y tampoco de una vacuna eficaz mundialmente distribuida, contra los 4 serotipos del DENV. A pesar de los grandes esfuerzos orientados a entender el mecanismo asociado con la patogénesis de la enfermedad, aún no se ha logrado esclarecer de forma definitiva las causas que conllevan a las formas graves de enfermedad. Algunas hipótesis buscan dar una explicación biológica y fisiológica a las manifestaciones clínicas que se presentan durante la infección. Dado que una de ellas sugiere que luego del contacto con las células dendríticas el DENV altera su funcionalidad, la presente revisión tiene como objetivo describir los hallazgos más relevantes referentes a la importancia de dichas células en el marco de la infección por el DENV y progresión de la enfermedad.

Roles of monocyte chemotactic protein 1 and nuclear factor-kappaB in immune response to spinal tuberculosis in a New Zealand white rabbit model

This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis.

Estudo da resposta imune celular e humoral desencadeada por toxoplasma gondii em camundogos A/Sn imunossuprimidos / Study of cellular and humoral immune response triggered by toxoplasma gondii in immunosuppressed A / Sn mice

Toxoplasma gondii é um protozoário intracelular com alta prevalência em humanos. Em indivíduos imunocomprometidos a infecção é reativada em estados mais severos da doença, como a toxoplasmose cerebral. As vias de ação da resposta imune não estão totalmente esclarecidas, especialmente em modelos experimentais imunossuprimidos. No presente estudo, foi estabelecido um modelo experimental de toxoplasmose em animais imunossuprimidos empregando-se camundongos A/Sn fêmeas infectadas com 10 cistos da cepa ME 49 de T. gondii. O tratamento imunossupressor foi iniciado 30 dias após o inóculo parasitário e foi constituído da administração subcutânea de Ciclosporina A (CsA) ou de Dexametasona (Dex) diluída em água destilada acondicionada em bebedouros distribuídos em gaiolas. CsA e Dex induziram imunossupressão significativa (p<0.05) e subsequente reativação do parasita em animais infectados. Por meio da contagem de leucócitos, observou-se que o efeito imunossupressor da Dex foi superior à CsA. A avaliação dos padrões de resposta imune celular e humoral foi realizada com o uso de Dex, via oral, na concentração de 10 mg/L, em camundongos A/Sn fêmeas pelo período de 7 a 56 dias de tratamento. Os camundongos imunossuprimidos por Dex apresentaram redução significativa (p<0.05) na dosagem de citocinas Interleucina 5 (IL-5), Interleucina 10 (IL10), Fator de Necrose Tumoral  (TNF-) e Interferon  (IFN-). Os camundongos imunossuprimidos por Dex apresentaram níveis de anticorpos reduzidos quando analisados frente aos Antígenos Lisados de Taquizoítos (ALT), no entanto, quando analisados em relação aos Antígenos Excretados e Secretados (ESA), apresentaram aumento da concentração de anticorpos. O perfil de anticorpos e citocinas nesses animais sugeriu uma tendência da resposta celular do tipo Th2 em relação à resposta celular do tipo Th1. Os resultados indicaram que o modelo murino de imunosupressão por Dex desenvolvido no presente trabalho mostrou-se útil para a investigação da resposta imune celular e humoral frente à infecção por T. gondii e este modelo poderá ser aplicado em futuros experimentos que visem à compreensão da relação parasito-hospedeiro. (AU)

Toxoplasma gondii is an intracellular protozoan with high prevalence in humans. In immunocompromised individuals the infection is reactivated in more severe states of the disease, such as cerebral toxoplasmosis. The pathways of action of the immune response are not fully understood, especially in immunosuppressed experimental models. In the present study, an experimental model of toxoplasmosis was established in immunosuppressed animals using female A/Sn mice infected with 10 cysts of T. gondii ME49 strain. Immunosuppressive treatment was initiated 30 days after the parasitic inoculum and consisted of the subcutaneous administration of Cyclosporin A (CsA) or Dexamethasone (Dex) diluted in distilled water conditioned in cage flasks. CsA and Dex induced significant immunosuppression (p<0.05) and subsequent reactivation of the parasite in infected animals. By means of the leukocyte count, it was observed that the immunosuppressive effect of Dex was higher than CsA. The evaluation of the cellular and humoral immune response patterns was performed using oral Dex at 10 mg/L in female A/Sn mice for 7 to 56 days of treatment. Deximmunosuppressed mice showed a significant (p<0.05) reduction in the cytokines dosage of Interleukin 5 (IL-5), Interleukin 10 (IL-10), Tumor Necrosis Factor  (TNF-) and Interferon  (IFN-). Mice immunized with Dex showed reduced antibody levels when analyzed against Tachyzoite Lysed Antigens (TLA); however, when analyzed for Excreted/Secreted Antigens (ESA), they showed an increase in the concentration of antibodies. The antibody and cytokine profile in these animals suggested a trend of Th2-type cellular response over the Th1-type cellular response. The results indicated that the murine model of Dex immunosuppression developed in the present study was useful for investigating the cellular and humoral immune response to T. gondii infection and this model can be applied in future experiments aiming to understand the relationship between host and parasite. (AU)