Antigen presentation,autoantibody production,and therapeutic targets in autoimmune liver disease

The liver is an important immunological organ that controls systemic tolerance. The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance. Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment, which is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes. In response to pathogens or autoantigens, tolerance is disrupted by unknown mechanisms. Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties. The presentation of microbial and endogenous lipid-, metabolite- and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance. Perturbation of this balance results in autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Although the exact etiologies of these autoimmune liver diseases are unknown, it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids, as well as alterations in bile acid composition, may result in changes in effector cell activation and polarization and may reduce or impair protective anti-inflammatory regulatory T and B cell responses. Additionally, the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different (non) immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance. Here, we summarize emerging aspects of antigen presentation, autoantibody production, and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.     

Frühkindliche Karies

Der Freie Zahnarzt -     

Polystyrene Brushes on Fully Deuterated Organic Nanoparticles by Surface‐Initiated Nitroxide‐Mediated Radical Polymerization

The synthesis of polystyrene (PS) brushes on fully deuterated PS nanoparticles by surface‐initiated nitroxide‐mediated radical polymerization (SI‐NMRP) is reported. Due to the high demand of deuterated monomers, an efficient deuteration procedure of suitable and readily available precursors is developed. SI‐NMRP of styrene is improved regarding reaction control, grafting density, and conversion. Insights into the scaling behavior and conformational features of surface‐attached PS chains on deuterated particles are investigated by using dynamic light scattering measurements, proving that polymer brushes are formed. The particles with surface‐attached initiator are shown to be uniform spherical core‐shell particles by small‐angle neutron scattering measurements.

     

Development of the German Speech Intelligibility Index for the treatment of oral cancer patients

ObjectivesThis study aimed at 1) adapting the well-established Speech Handicap Index (SHI) to German, 2) testing the suitability of the instrument for assessing speech-related quality of life, 3) comparing it to the German Voice-Handicap-Index (VHI), in order to support treatment of oral cancer patients who experience posttreatment speech difficulties that affect their quality of life.Material and methodsParticipants completed a web-based survey that employed a 2 (experienced problem: speech/articulation-related vs. voice-related) x 2 (SHI vs. VHI) between-subject experimental design, enabling it to distinguish between the experiences of voice and intelligibility impairments, and to determine the discriminatory ability of the two instruments.ResultsThe German SHI reliably assessed speech intelligibility and articulation-related Quality of life. While voice impairments were equally well assessed by both, VHI: M 2.48, SD 0.65; SHI: M 2.52, SD 0.63; only the latter appropriately registered intelligibility handicap in speech impairments (VHI: M 2.05, SD 0.70; SHI: 2.68, SD 0.73). The responsivity of the SHI in capturing the experienced handicap was significantly greater in the speech/articulation-impairment condition (p = .001).ConclusionThe German SHI is a reliable and responsive measure for speech intelligibility and articulation-related quality of life that should be chosen in preference to the VHI.     

Inhibition of apoptosis by the intrinsic but not the extrinsic apoptotic pathway in myocardial ischemia-reperfusion

SummaryThe detailed molecular mechanisms following activation of apoptosis in ischemia-reperfusion injury are unknown. This study using different transgenic mouse models provided first evidence that apoptosis in myocardial ischemia-reperfusion injury is rather linked to the mitochondrial pathway than to death receptor pathway.IntroductionThere is a wealth of evidence for activation of apoptosis in ischemia-reperfusion injury. However, the understanding of detailed molecular mechanism is lacking.MethodsThe extent of myocardial infarction after ligation of the left anterior descending artery in mice carrying different transgenes for inhibition of either the intrinsic or the extrinsic or a combination of both apoptotic cascades was evaluated. The extent of myocardial damage was assessed by echocardiographic determination of left ventricular (LV) ejection fraction, LV hemodynamics, troponin T, and histology. The rate of apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 staining.ResultsHighest perioperative rate of death was observed in the dominant-negative form of a truncated Fas-associated death domain (FADD-DN) group. Infarction size by 2,3,5-triphenyltetrazolium chloride (TTC) staining was smaller in the Bcl-2, but not in the other groups as compared to wild-type mice. This was accompanied by lower troponin T values in Bcl-2 transgenic mice as compared to the all other groups. Troponin T correlated well with macroscopic extent of myocardial infarction by TTC staining. A lower decline of LV ejection fraction was seen in the Bcl-2 as compared to wild-type or FADD-DN mice. A smaller number of TUNEL- and caspase-3-positive myocyte nuclei were observed in the Bcl-2 and FADD-DN group as compared to wild-type mice.ConclusionsWe provide first evidence for protective effects on the myocardium in a transgenic mouse model of myocardial ischemia-reperfusion due to inhibition of the Bcl-2, but not the FADD pathway despite that reduced apoptotic cells were observed in both groups as compared to wild-type mice.