Immunologie der Tuberkulose

Zusammenfassung: Die Infektion mit M.tuberculosis (Mtb) ist nach wie vor weit verbreitete, aber nur bei bestimmten Menschen wird aus der primären Infektion eine Erkrankung. Nur Patienten mit einer Immunschwäche oder einer reduzierten Immunität erkranken. Das sind pro Jahr weltweit ca. 8-10Mio. Menschen. Ein gutes Verständnis der Mtb-Immunität ist wichtig, wenn man Mtb verhindern, Immunmodulatoren für bestimmte Krankheiten einsetzen oder neue Impfstoffe auf der Grundlage des durch die Entschlüsselung der Genomstruktur von Mtb gewonnenen Wissens entwickeln wil

Suppression of alcohol-induced hypertension by dexamethasone

BACKGROUND. Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS. To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS. The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS. Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events

Fat-free mass change to weightchange ratio during refeeding following lungtransplantation

Abstract. : Malnutrition occurs frequently prior to lung transplantation (LTR), but patients gain weight after LTR. The study aimed to determine the ratio changes of fat-free mass (ΔFFM): changes of body weight (ΔBW) during refeeding. A total of 37 LTR patients were measured for weight and FFM and body fat by bioimpedance analysis at 1 month post-LTR, then annually for 3 years. Linear regressions determined the ratio ΔFFM:ΔBW during refeeding. ΔFFM was: year- 1=1.822+0.389* ΔBW, r 2=0.397; yr-2=0.611+0.246* ΔBW, r 2=0.441; yr-3=-0.17+0.208 * ΔBW, r 2=0.319. Refeeding during year-1 in thin subjects resulted in a ratio ΔFFM:ΔBW of 0.389, whereas the change in ratio ΔFFM:ΔBW during year- 2 and 3 was 0.246 and 0.208, respectively. Refeeding resulted in a larger ratio ΔFFM:ΔBW in thin subjects versus normal and overweight subjects. Thus, refeeding in underweight LTR patients is geared to normalizing depleted FFM, whereas later FFM gains were similar to FFM gains in normal and overweight subject

Prevalence of low fat-free massindex and high and very high body fat mass index following lungtransplantation

Abstract. : The aim of this study was to determine the prevalence of low fat-free mass index (FFMI) and high and very high body fat mass index (BFMI) after lung transplantation (LTR). A total of 37 LTR patients were assessed prior to and at 1 month, 1 year and 2 years for FFM and compared to 37 matched volunteers (VOL). FFM was calculated by the Geneva equation and normalized for height (kg/m2). Subjects were classified as FFMI "low”, ≤17.4 in men and ≤15.0 in women; BFMI ”high”, 5.2-8.1 in men and 8.3-11.7 in women; or "very high” >8.2 kg/m2 in men and >11.8 kg/m2 in women. In 23 M/14 F, body mass index (BMI) was 22.3±4.4 and 20.1±4.9 kg/m2, respectively. The prevalence of low FFMI was 80% at 1 month and 33% at 2 years after LTR. Prevalence of very high BFMI increased and was higher in patients than VOL after LTR. The prevalence of low FFMI was high prior to and remained important 2 years after LTR, whereas BFMI was lower prior to and higher 2 years after LT

Inhaled nitric oxide for high-altitude pulmonary edema

BACKGROUND. Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. When administered by inhalation, nitric oxide, an endothelium-derived relaxing factor, attenuates the pulmonary vasoconstriction produced by short-term hypoxia. METHODS. We studied the effects of inhaled nitric oxide on pulmonary-artery pressure and arterial oxygenation in 18 mountaineers prone to high-altitude pulmonary edema and 18 mountaineers resistant to this condition in a high altitude laboratory (altitude, 4559 m). We also obtained lung-perfusion scans before and during nitric oxide inhalation to gain further insight into the mechanism of action of nitric oxide. RESULTS. In the high-altitude laboratory, subjects prone to high-altitude pulmonary edema had more pronounced pulmonary hypertension and hypoxemia than subjects resistant to high-altitude pulmonary edema. Arterial oxygen saturation was inversely related to the severity of pulmonary hypertension (r=-0.50, P=0.002). In subjects prone to high-altitude pulmonary edema, the inhalation of nitric oxide (40 ppm for 15 minutes) produced a decrease in mean (+/-SD) systolic pulmonary-artery pressure that was three times larger than the decrease in subjects resistant to such edema (25.9+/-8.9 vs. 8.7+/-4.8 mm Hg, P<0.001). Inhaled nitric oxide improved arterial oxygenation in the 10 subjects who had radiographic evidence of pulmonary edema (arterial oxygen saturation increased from 67+/-10 to 73+/-12 percent, P=0.047), whereas it worsened oxygenation in subjects resistant to high-altitude pulmonary edema. The nitric oxide-induced improvement in arterial oxygenation in subjects with high-altitude pulmonary edema was accompanied by a shift in blood flow in the lung away from edematous segments and toward nonedematous segments. CONCLUSIONS. The inhalation of nitric oxide improves arterial oxygenation in high-altitude pulmonary edema, and this beneficial effect may be related to its favorable action on the distribution of blood flow in the lungs. A defect in nitric nitric oxide synthesis may contribute to high-altitude pulmonary edema

Combined Use of Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses Is a Powerful Diagnostic Tool of Active Tuberculosis.

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infection

Combined Use of Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses Is a Powerful Diagnostic Tool of Active Tuberculosis

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infectio

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach