Schistosoma mansoni: importance of skin and pulmonary phases to concomitant immunity in albino mice

Fourteen-day-old schistosomula obtained from mice previously infected were surgically transferred to the portal vein of receptor mice. Another group of mice was infected with cercariae by transcutaneous route. After 90 days, those groups were challenged with 100 cercariae, transcutaneously, as well as a control group. Two weeks later the animals were perfused and mature and immature worms counted separately. Statistically significant differences were observed in the recovery of immature worms, when the control group was compared with those twice infected. No statistical difference was detected between the group infected transcutaneously, and that infected by worm inoculation in portal vein. Results demonstrated that suppression of skin and lung migration of the parasite does not interfere with the development of the so called concomitant immunity.

Schistosoma mansoni: acquired immunity in mice after the use of oxamniquine at the evolutive skin and pulmonary phases

Mice infected with 350 cercariae of Schistosoma mansoni (LE strain) were treated with oxamniquine, at the dose of 400 mg/kg, 24, 48, 72, and 96 h after infection. Forty days after the treatment, the animals were submitted to a challenge infection with 80 cercariae, through the abdominal and ear skins. The number of immature worms in the animal groups treated 24 and 96 h after the first infection was found to be lower than that in the control group, thus showing that the death of schisto-somes by chemotherapy, at the skin and pulmonary phases, causes an acquired resistance state.

Schistosoma mansoni: protective immunity in mice cured by chemotherapy at the chronic phase of the disease

Aiming at demonstrating a decrease of acquired immunity after chemotherapeutic cure, a group of mice was infected with 25 Schistosoma mansoni cercariae (LE strain). A part of these animals was treated with 400 mg/kg oxamniquine, at 120 days after infection. Challenge infections were carried out at 45, 90 and 170-day-intervals after treatment (185, 210 and 290 days after primoinfection, respectively). Recovery of worms at 20 days after reinfections showed that a residual immunity remains up to 90 days after treatment, and disappears at 170 days after cure. Using the ELISA method, it was possible to detect a decrease of antibody levels (total IgG) in the treated group, when antigens from different evolutive stages of S. mansoni were used. The epidemiological implications of the present results, and the possible mechanisms involved in the decrease of acquired immunity after treatment are discussed.

Cell and humoral immunity in endemic pemphigus foliaceus

A study was conducted on 16 patients with pemphigus foliaceus, ten of them with the localized form (group G1) and six with the disseminated form (group G2). These patients were submitted to full blood counts, quantitation of mononuclear cell subpopulations by monoclonal antibodies, study of blastic lymphocyte transformation, and quantitation of circulating antibodies by the indirect immunofluorescence test, in order to correlate their clinical signs and symptoms and laboratory data with their immunological profile, and to determine the relationship between circulating autoantibody titers and lesion intensity and course of lesions under treatment. Leucocytosis was observed especially in group G2. All patients showed decreased relative CD3+ and CD4+ values and a tendency to decreased relative values of the CD8+ subpopulation. Blastic lymphocyte transformation indices in the presence of phytohemagglutinin were higher in patients (group G1+G2) than in controls. The indirect immunofluorescence test was positive in 100% of G2 patients and in 80% of G1 patients. The median value for the titers was higher in group G2 than in group G1. Analysis of the results as a whole permits us to conclude that cell immunity was preserved and that there was a relationship between antibody titers detected by the direct immunofluorescence test and extent of skin lesions.

Frequency of hepatitis B immunity and occupational exposures to body fluids among brazilian medical students at a public university

In the present study the frequencies of immunity against hepatitis B (HB) and of potentially contaminating accidents among medical students of a Brazilian public university were evaluated. Of all the 400 students who should have been immunized, 303 (75.7%), 66.3% of whom were women, answered an anonymous, self-administered questionnaire. Serum anti-HBs were determined in 205 of them and titers > 10 UI/L were considered to be protective. A total of 86.8% of students had received three doses of HB vaccine. The frequency of immunity among women (96.4%) was higher (p = 0.04) than that among men (87.7%). Among those who did not have immunity, 12/13 (92.3%) had been vaccinated before entering medical school. Only 11% of the students with complete vaccination had previously verified serological response to the vaccine. A total of 23.6% reported having been somehow exposed to blood or secretions. Among final-year students, this frequency was 45.0%, being similar among men (47.8%) and women (43.2%). Of all these accidents, 57.7% were due to body fluids coming in contact with mucosa and 42.3% due to cut and puncture accidents. The results from this study show that: 1) the frequency of immunity against HB is high among the evaluated medical students, although verification of response to vaccination is not a concern for them; 2) anti-HBs titers should be verified after complete vaccination and on a regular basis, especially by men; and 3) the frequency of potentially contaminating accidents is high.

Strategies of the African swine fever virus to manipulate innate immunity

Dissertation presented to obtain the Ph.D degree in Biology

Structural characterization of the urea-unfolded state of Colicin Immunity Protein Im7 and Im9

Dissertação para obtenção do Grau de Mestre em Bioquímica Estrutural e Funcional

Monotherapy and combined therapy of new potential antitumor compounds: antiproliferative activities and biological targets

Review article Martins, P., Marques, M., Coito, L., Pombeiro, A.J.L., Baptista, P.V., Fernandes, A.R. 2014. Organometallic Compounds in Cancer Therapy: Past Lessons and Future Directions. Anti-cancer Agents in Medicinal Chemistry 14. PMID: 25173559

Serologic assessment of yellow fever immunity in the rural population of a yellow fever-endemic area in Central Brazil

IntroductionThe yellow fever epidemic that occurred in 1972/73 in Central Brazil surprised the majority of the population unprotected. A clinical-epidemiological survey conducted at that time in the rural area of 19 municipalities found that the highest (13.8%) number of disease cases were present in the municipality of Luziânia, State of Goiás.MethodsThirty-eight years later, a new seroepidemiological survey was conducted with the aim of assessing the degree of immune protection of the rural population of Luziânia, following the continuous attempts of public health services to obtain vaccination coverage in the region. A total of 383 volunteers, aged between 5 and 89 years and with predominant rural labor activities (75.5%), were interviewed. The presence of antibodies against the yellow fever was also investigated in these individuals, by using plaque reduction neutralization test, and correlated to information regarding residency, occupation, epidemiological data and immunity against the yellow fever virus.ResultsWe found a high (97.6%) frequency of protective titers (>1:10) of neutralizing antibodies against the yellow fever virus; the frequency of titers of 1:640 or higher was 23.2%, indicating wide immune protection against the disease in the study population. The presence of protective immunity was correlated to increasing age.ConclusionsThis study reinforces the importance of surveys to address the immune state of a population at risk for yellow fever infection and to the surveillance of actions to control the disease in endemic areas.

Understanding how dentritic cell glycans affect antitumor immune responses

RESUMO: As células dendríticas (DCs) têm a capacidade única de induzir respostas imunitárias contra as células tumorais, fagocitando antigénios tumorais e apresentando-os às células T, provocando respostas imunitárias específicas que conduzem à eliminação de células de tumorais. Por induzirem memória imunológica de longa duração, as DCs são uma estratégia atrativa para o tratamento e/ou prevenção do cancro. No entanto, os resultados terapêuticos obtidos em ensaios clínicos com DCs são escassos e pouco eficientes. O nosso grupo demonstrou que ácidos siálicos que contêm glicanos desempenham um papel funcional importante em DCs geradas ex vivo. Com o objetivo de estabelecer um modelo in vitro para avaliar a resposta anti-tumoral específica realizou-se um tratamento enzimático a DCs derivadas de monócitos (moDCs) com sialidase, enzima que cliva ácidos siálicos na superfície celular. O perfil de maturação de moDCs foi caracterizado por citometria de fluxo e expressão de citocinas. Os resultados mostram que a sialidase pode regular positivamente a expressão de moléculas co-estimuladoras na superfície de moDCs estimuladas com agonistas de Toll like receptors (TLRs). Para percebermos se o tratamento com sialidase afeta a sinalização dos TLRs foram usadas células HEK transfectadas de forma estável com TLRs 2, 4 and 7/8. Os dados mostraram que a desialilação não afeta a sinalização através estes recetores. Para investigar o impacto funcional da sialidase na capacidade de moDCs em apresentar um antigénio e ativar células T, moDCs foram tratadas, ou não, com sialidase e cultivadas com clones de células T CD8+ específicas para os péptidos derivados do antigénio tumoral gp100. Os resultados mostram que DCs HLA*02:01+ desialiladas exibem maior cross-presentation do péptido gp100280-288 às células T CD8+ específicas. Além disso o tratamento com sialidase também aumenta a capacidade de DCs de induzir a proliferação de células T CD4+. Em conjunto, os resultados indicam que moDCs com menos ácidos siálicos na superfície, têm melhor potencial imuno-estimulador, com maior capacidade de induzir respostas imunes anti-tumorais.--------------------- ABSTRACT: Dendritic cells (DCs) have a unique capacity to induce immune responses against tumor cells. They can phagocyte tumor antigens, maturate and present them to T cells, triggering antigen-specific immune responses that may lead to the elimination of tumor cells. Since they induce long-lasting immunological memory, DCs become an attractive strategy as cellular targets for vaccines in the treatment and/or prevention of cancer. However, the therapeutic results obtained in clinical trials with DCs are scarce and only few patients effectively respond to the DC vaccines. Our group has shown that sialic acid containing glycans play an important functional role in ex vivo generated DC. Here we aimed to establish an in vitro model to assess specific antitumor responses. To achieve this, an enzymatic treatment of monocyte-derived DCs (moDCs) was performed using sialidase to cleave surface sialic acids. The maturation profile of the moDCs was characterized by flow cytometry and cytokine expression. The results show that sialidase treatment can upregulate co-stimulatory molecules on surface of moDCs stimulated with Toll like receptor (TLR) agonists. To understand whether sialidase treatment affected the TLR signaling, we have used HEK cells stably transfected with TLRs 2, 4 and 7/8. The data showed that desialylation of moDCs does not affect the signaling via these receptors. To investigate the functional impact of sialidase treatment in the capacity of moDCs to present antigen and to activate antigen specific T cells, sialidase treated and untreated moDCs were co-cultured with CD8+ T cell clones specific for peptides derived from the gp100 tumor antigen. Our results show that desialylated HLA02:01+ DCs are superior in cross-presentation of the peptide to gp100280–288 specific CD8+ T cells. In addition, sialidase treatment also increased the DC capacity to induce CD4+ T cells proliferation. Together, these data indicate that moDCs with altered cell surface sialic acids, through a sialidase treatment, have a better immunostimulatory potential which could improve anti-tumor immune responses.