Search

The article informs on idea of ​​the "Missing Self" hypothesis as per which the immune system should be able to recognize foreign human cells, and mentions the natural killer cells (NK) with their receptors of the KIR protein family recognize this missing self and thus initiate an immune reaction.

Zinc is known to be greatly involved in the regulation of immune functions. Pharmacological zinc supplementation, leading to serum zinc concentrations of more than 0.025 mM, has often been suggested to improve immune responses. However, the exact influence of elevated zinc level on immune functions has not yet been investigated. We found that zinc level selectively enhances cytokine Suction by lipopolysaccharidc (LPS) in a concentration-dependent fashion: as little as 0.0125 mM supplemental zinc led to nearly 50% elevated interleukin-1β (IL-1β) levels both in polymorphonuclear cells (PBMC) and whole-blood cultures. The secretion of interferon-γ (IFN-γ) could be increased more than 10-fold by 0.1 mM zinc. This could not be observed during stimulation with phytohaemagglutin (PHA). In contrast, zinc levels concentration-dependently down-regulated monocyte activation caused by the superantigens, staphylococcal enterotoxins A and E (SEA, SEE, more than 90% down-regulation by 0.1 mM zinc), the Mycoplasma anthritidis-derived superantigen (MAS), but not toxic shock syndrome toxin-1 (TSST-1), while T-cell response remained unaffected. This was not the result of chemical degradation of the superantigens. We assume that zinc concentration regulates interactions between SEA, SEE and MAS, but not TSST- 1 and their major histocompatibility complex (MHC) class II-binding sites. Our data demonstrate that zinc levels control the secretion of IFN-γ and monokines after both LPS and superantigen challenge within a clinically relevant range of concentrations. This reveals new perspectives and indications for zinc supplementation and also indicates potential risks of therapeutic application of zinc. [ABSTRACT FROM AUTHOR]

Investigates the distribution of polymorphisms of HLA class-II and tumor necrosis factor molecules in patients with inflammatory bowel disease (IBD) in Estonia. Description of IBD; Use of reverse hybridization principle and sequence specific primers for HLA genotyping.

Due to the extensive polymorphism of the major histocompatibility complex (MHC), only limited progress has been made in high-resolution MHC sequencing, one of the initial requirements to elucidate the molecular immunopathology of several hundred MHC-associated diseases. We present an approach for sequencing the entire MHC with ≈ 1200 specific capture primers. Using target sites known to be highly conserved, Region-Specific Extraction (RSE, Generation Biotech) was used to target MHC segments of up to 40 kb length and enrich the contiguous 4.4 Mb MHC for sequencing. RSE uses a single primer extension-step that attaches a specific “handle” to genomic DNA target segments and firmly locks the selected DNA onto magnetic beads for capture. The captured segments extend far into both directions from any single capture point. This makes an RSE capture primer set essentially immune to changes in variable sections and avoids difficulties caused by genomic duplications, pseudo-genes, gene homologues and new sequence insertions. After RSE, unique oligonucleotide indexes were ligated to each DNA sample for parallel, paired-end 2 × 250 bp sequencing on a HiSeq2500 (Illumina). Read alignment (hg19 reference genome), local re-alignment, variant calling and annotation were performed by an in-house data analysis pipeline consisting of the CLC Genomics Workbench (Qiagen) and custom developed scripts. In our experiments, an up to 80-fold target enrichment was achieved, which provides an average coverage of about 200 across the 4.4 Mb target region. In samples with high coverage, > 90% of the target region can uniformly be sequenced with > 20× coverage. We expect that optimized target enrichment enables to sequence at least 16 samples per flow-cell with appropriate coverage for > 90% of the MHC region while maintaining the advantages of RSE in avoiding variation-dependent capture and allelic dropout. The combination of the RSE enrichment and massively parallel sequencing on HiSeq is a feasible approach for whole MHC sequencing. Further improvements in target enrichment efficiency and long-read/high-accuracy sequencing can turn it into a cost-effective and user-friendly tool in many clinical and research settings such as transplantation medicine, inflammatory or autoimmune disorders, pharmacogenomics, and many more. H. Rabenstein: Employee; Company/Organization; Center for Human Genetics and Laboratory Diagnostics. B. Bangol: Employee; Company/Organization; Center for Human Genetics and Laboratory Diagnostics. S. Linke: Employee; Company/Organization; Generation Biotech. R. Brumm: Employee; Company/Organization; Center for Human Genetics and Laboratory Diagnostics. S. Poggel: Employee; Company/Organization; Center for Human Genetics and Laboratory Diagnostics. S. Eck: Employee; Company/Organization; Center for Human Genetics and Laboratory Diagnostics. K. Ott: Employee; Company/Organization; Generation Biotech. J. Dapprich: Employee; Company/Organization; Generation Biotech. K. Hirv: Employee; Company/Organization; Center for Human Genetics and Laboratory Diagnostics. [ABSTRACT FROM AUTHOR]