Immunological mechanisms in specific immunotherapy

Specific immunotherapy (SIT) represents the only curative treatment of allergy and is, therefore, of particular interest for immunological and pharmacological research. The current understanding of immunological mechanisms underlying SIT focuses on regulatory T cells (T regs), which balance Th1 and Th2 effector functions. This ensures that allergens are recognized, but tolerated by the immune system. There is clear evidence that SIT restores the disturbed balance of T regs and effector cells in allergic patients. Current efforts are focused to improve SIT regimens to make them more applicable in atopy and asthma. The current review provides an overview on the mechanisms of SIT and possible adjuvant treatment strategies on the background of the T reg concep

rac-Dichlorido(1-{(diphenyl­phosphan­yl)[2-(diphenyl­phosphan­yl)phen­yl]meth­yl}ferrocene-κ2 P,P′)palladium(II) dimethyl sulfoxide disolvate

The racemic title compound, [FePdCl2(C5H5)(C36H29P2)]·2(CH3)2SO, features a Pd-chelating 1,3-diphosphine, which is substituted at a P-bearing asymmetric C atom by a ferrocenyl group. The PdII atom is in a distorted quadratic coordination by two P and two Cl atoms with bond lengths of 2.2414 (3) and 2.2438 (3) Å for Pd—P, and 2.3452 (3) and 2.3565 (3) Å for Pd—Cl. The conformation of the Pd complex is controlled by an intra­molecular slipped π–π stacking inter­action between a phenyl and a cyclo­penta­dienyl ring with corresponding C⋯C distances starting at 3.300 (2) Å and the distance between ring centroids being 3.674 (2) Å. The crystal structure is stabilized by C—H⋯Cl and C—H⋯O hydrogen bonds. The (CH3)2SO solvent mol­ecules are arranged in layers parallel to (101) and are linked in pairs by C—H⋯O inter­actions. One (CH3)2SO mol­ecule is orientationally disordered [occupancy ratio 0.8766 (17):0.1234 (17)] with sulfur in two positions at both sides of its C2O triangle

Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients

Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients. A high prevalence of hepatitis C virus (HCV) infection has been reported in hemodialysis patients. Main risk factors for transmission are previous blood transfusions and possibly nosocomial infections within the dialytic environment. In the present study 224 hemodialysis patients from the same department were tested for the presence of anti-HCV antibodies and HCV-RNA. The presence of anti-HCV in hemodialysis patients was correlated with a history of more than 10 blood transfusions (P = 0.001) and with a duration of hemodialysis treatment for more than 10 years (P = 0.001). The issue of possible patient-to-patient infection was addressed by sequence analysis of all HCV-RNA positive hemodialysis patients (N = 14) together with a control panel of HCV isolates from 56 unrelated non-hemodialysis patients with hepatitis C from the same geographical area. Subsequent phylogenetic analysis of nucleotide sequences obtained from the 5′-noncoding region and the nonstructural NS-5 region of the HCV genome revealed that only two hemodialysis patients were infected by a highly related HCV isolate. The remaining HCV-RNA positive hemodialysis patients including those without previous blood transfusions were all infected by phylogenetically-distant HCV isolates, providing evidence against a nosocomial transmission route. The data of the present study show that molecular epidemiological techniques are important to investigate the issue of nosocomial infection. In our hemodialysis unit patient-to-patient infection appears uncommon and draws attention towards other possible (such as, blood products such as human serum albumin, immunoglobulins) or even yet unrecognized transmission routes

Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity

Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy

SAPALDIA: Methods and participation in the cross-sectional part of the Swiss Study on Air Pollution and Lung Diseases in Adults

Summary: SAPALDIA-the Swiss Study on Air Pollution and Lung Diseases in Adults-focuses on the long term health effects of low to moderate levels of air pollutants as typically seen in different parts of Switzerland. The aim of the SAPALDIA cross-sectional study carried out in 1991 was to determine the prevalence of bronchial asthma, chronic bronchitis and allergic conditions in the adult population of Switzerland and to identify and to determine the respective importance of potentially influencing factors. These could be both personal (smoking habits, allergy status, family history, occupation) and environmental (outdoor and indoor pollution, aeroallergens, climate). A further aim of the cross-sectional study consisted in the identification of individuals susceptible to present symptoms during a two year observation period and to be included in the SAPALDIA follow-up study. This technical report represents the methodological documentation for the cross-sectional study of SAPALDIA. The instruments and the methods of standardisation are presented and discussed. The medical examination consisted of a computerised interview using a standardised questionnaire, the taking of a blood sample for serological tests, allergy skin testing, the measurement of endexpiratory CO and body height, and pulmonary function testing followed by methacholine challenge testing or bronchodilatation testing. The pattern of participation and the 9651 participants of the study, representing 59.3% of the sample, are described. Based on information on non-participants gained by telephone interviews and mailed short questionnaires, possible selection biases are quantified and discusse

Immunological mechanisms in specific immunotherapy

Specific immunotherapy (SIT) represents the only curative treatment of allergy and is, therefore, of particular interest for immunological and pharmacological research. The current understanding of immunological mechanisms underlying SIT focuses on regulatory T cells (T regs), which balance Th1 and Th2 effector functions. This ensures that allergens are recognized, but tolerated by the immune system. There is clear evidence that SIT restores the disturbed balance of T regs and effector cells in allergic patients. Current efforts are focused to improve SIT regimens to make them more applicable in atopy and asthma. The current review provides an overview on the mechanisms of SIT and possible adjuvant treatment strategies on the background of the T reg concep