In Situ

Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. The immune system plays an important role in the reduction of parasite load, but may also contribute to the development of lesions observed during the chronic phase of the disease. We analyzed cytokines produced by inflammatory heart cells in 21 autopsy samples obtained from patients with Chagas' disease divided according to the presence or absence of heart failure (HF). Left ventricular sections were analyzed by immunohistochemistry using antibodies against human IL-4, IFN-γ, TGF-β, TNF-α, and NOS2. In situ mRNA expression was quantified by a Low Density Array. The number of IFN-γ-positive cells was significantly higher than IL-4 positive cells. TNF-α, TGF-β and NOS2 were detected in 65%, 62% and 94% of samples respectively. There was an association between TNF-α-producing cells and the presence of HF. Subjects with HF presented higher levels of STAT4 mRNA, whereas FoxP3 and STAT6 levels were similar in the two groups. A Th1 cytokine pattern predominated in the cardiac inflammatory cell infiltrate of Chagas’ disease patients associated with HF. High degree of fibrosis was associated with low NOS2 expression. These results support the idea that Th1 immune responses are involved in heart lesions of Chagas' disease patients

Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma

A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets) microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor).Relata-se caso de metástases hematogênicas disseminadas e síndrome de Trousseau em mulher branca de 40 anos, portadora de câncer gástrico, apresentando hematoma subdural, equimoses, epistaxes, hemorragia gástrica e metrorragia. Inicialmente submetida à drenagem do hematoma, foi tratada sem sucesso com transfusões de plaquetas, hemácias e plasma crioprecipitado, além de antibióticos. O estudo de necropsia revelou adenocarcinoma gástrico com células em anel de sinete invadindo a serosa, com maciça coagulação intravascular disseminada e embolismo neoplásico sistêmico. Microtrombos hialinos (constituídos de fibrina e plaquetas) antigos e recentes, além de êmbolos tumorais, foram observados na medula óssea, meninges, fígado, pulmões, rins, linfonodos, adrenais, tireóide, coração, pâncreas e ovários (tumor de Krukenberg)

Lingual salivary gland hypertrophy and decreased acinar density in chagasic patients without megaesophagus

Although the salivary glands present several functions, there are few studies evaluating these glands in Chagas disease (CD). This study aimed to compare the percentage of collagen, the presence of inflammation, the density of chimase and tryptase mast cells, the area and density of lingual salivary gland acini in autopsied individuals with and without (CD). We analyzed 400 autopsy reports performed in a tertiary public hospital from 1999 to 2015 and selected all the cases in which tongue fragments were collected (27 cases), 12 with chronic CD without megaesophagus (CH) and 15 without CD (non-chagasic - NC). The histological sections of the tongue were stained by Picrosirius red for collagen evaluation and Hematoxylin-eosin for morphometric evaluation of salivary gland acini and inflammation. Anti-chimase and anti-tryptase antibodies were used for the immunohistochemical evaluation of mast cells. The chagasic patients presented higher volume and lower density of salivary glands acini. There was no difference in the collagen percentage, inflammation and density of mast cell chymase and tryptase between the groups. Although we did not observe a significant difference between the groups regarding the collagen percentage, inflammatory process and mast cell density, our results suggest that even without megaesophagus, chagasic patients present hypertrophy of the lingual salivary glands and lower acinar density probably due to mechanisms independent of the esophagus-glandular stimulus

High Levels of Interleukin-1 in Patients with Endemic Pemphigus Foliaceus

Endemic pemphigus foliaceus (EPF) is an autoimmune disease characterized by blister formation with a loss of cohesion and infiltration of inflammatory cells. We observed that supernatants of peripheral blood mononuclear cells from patients produced significantly more interleukin-1β (IL-1β) than those from stimulated healthy controls. Furthermore, a Th2 bias was observed in EPF patients when the IL-5/gamma interferon ratio was analyzed. These results indicate that cells from pemphigus patients react with a vigorous proinflammatory response

Analysis of colostrum IgA against bacteria involved in neonatal infections

<div><p>ABSTRACT Objective To describe e compare the specificity of IgA antibodies against bacteria extract of Klebsiella pneumoniae , Staphylococcus aureus , Escherichia coli , and Salmonella enteritidis . Methods Colostrum samples were aseptically collected in the first 12 hours after C-section delivery. The specificity of IgA against bacteria extracts was analyzed by the Western blot. Results The findings showed proteins of high molecular weight frequently detectable in the samples. S. aureus was the most frequently found bacterium in the samples (p<0.05). Approximately 93.8, 56.3, 62.5 and 60.4% of samples presented IgA reactive to S. aureus , K. pneumoniae , S. enteritidis, and E. coli, respectively. Roughly 40% of samples showed no IgA reactive to K. pneumoniae, S. enteritidis and E. coli . Conclusion Clinical evidence of the importance of breastfeeding for the immune protection of neonates was consistent with the observed immunological findings, since most samples showed IgA reactive against the species tested. The application and development of immunotherapies during pregnancy, focused on frequently detected antigens, could be an important tool to enhance the presence of IgA in colostrum.</p></div

Complexity and Controversies over the Cytokine Profiles of T Helper Cell Subpopulations in Tuberculosis

Tuberculosis (TB) is a contagious infectious disease caused by the TB-causing bacillus Mycobacterium tuberculosis and is considered a public health problem with enormous social impact. Disease progression is determined mainly by the balance between the microorganism and the host defense systems. Although the immune system controls the infection, this control does not necessarily lead to sterilization. Over recent decades, the patterns of CD4+ T cell responses have been studied with a goal of complete understanding of the immunological mechanisms involved in the maintenance of latent or active tuberculosis infection and of the clinical cure after treatment. Conflicting results have been suggested over the years, particularly in studies comparing experimental models and human disease. In recent years, in addition to Th1, Th2, and Th17 profiles, new standards of cellular immune responses, such as Th9, Th22, and IFN-γ-IL-10 double-producing Th cells, discussed here, have also been described. Additionally, many new roles and cellular sources have been described for IL-10, demonstrating a critical role for this cytokine as regulatory, rather than merely pathogenic cytokine, involved in the establishment of chronic latent infection, in the clinical cure after treatment and in keeping antibacillary effector mechanisms active to prevent immune-mediated damage

Cytokine serum levels in patients infected by human immunodeficiency virus with and without Trypanosoma cruzi coinfection Níveis séricos de citocinas em pacientes infectados pelo vírus da imunodeficiência humana com e sem coinfecção pelo Trypanosoma cruzi

This study assessed the number of CD4 T lymphocytes, the parasitemia and serum levels of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-4 and IL-10 of patients infected by human immunodeficiency virus (HIV) and human immunodeficiency virus/Chagas' disease coinfection. CD4 T lymphocytes were low in the two groups of patients, although significantly lower in patients without Chagas' disease. Serum levels of IFN-gamma, IL-4 and TNF-alpha were significantly higher in patients with HIV/Chagas' disease. IL-4/IFN-gamma ratios were higher in patients with HIV/Chagas' disease, which showed a clear balance in favor of Th2-like cytokines in this group of patients. This Th2 balance was higher in patients with detectable parasitemia. We conclude that, although immunosuppression was observed, with CD4 T lymphocytes bellow 200/µm³, these patients did not display reactivation of T. cruzi infection and that a balance favorable to Th2 was associated with the presence of parasitemia.Neste estudo foi avaliado o número de linfócitos TCD4, a parasitemia e os níveis séricos de interferon gama (IFN-gama), fator de necrose tumoral alfa (TNF-alfa), interleucina-1 (IL-1), IL-4 e IL-10 em pacientes infectados pelo vírus da imunodeficiência adquirida ou apresentavam co-infecção pelo HIV/Trypanosoma cruzi. O número de linfócitos T CD4 estava baixo nos dois grupos de pacientes, embora significativamente menor nos pacientes sem a doença de Chagas. Os níveis séricos de IFN-gama, IL-4 e TNF-alfa foram significativamente maiores nos pacientes com a co-infecção pelo HIV/Trypanosoma cruzi. A razão IL-4/IFN-gama foi maior nos pacientes com a co-infecção pelo HIV/T. cruzi, que sugere um balanço favorável para perfil Th2 nesse grupo de pacientes. Este balanço Th2 foi maior nos pacientes com parasitemia detectável. Conclui-se que, embora tenha sido observado imunossupressão, na maioria com linfócitos T CD4 abaixo de 200/µm³, esses pacientes não reativaram a infecção pelo T. cruzi e que o balanço favorável a Th2 estava associado à presença de parasitemia