44 research outputs found
The Exocytosis of Lytic Granules Is Impaired in Vti1b- or Vamp8-Deficient CTL Leading to a Reduced Cytotoxic Activity following Antigen-Specific Activation
No full textDressel R, Elsner L, Novota P, Kanwar N, Fischer von Mollard G. The Exocytosis of Lytic Granules Is Impaired in Vti1b- or Vamp8-Deficient CTL Leading to a Reduced Cytotoxic Activity following Antigen-Specific Activation. JOURNAL OF IMMUNOLOGY. 2010;185(2):1005-1014
Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells
No full textMultipotent adult germ-line stem cells (maGSCs) and induced pluripotent stem cells (iPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, effects of the immune system on these cells have not been investigated. We have compared the susceptibility of maGSC lines to IL-2-activated natural killer (NK) cells with embryonic stem cell (ESC) lines, iPSCs, and F9 teratocarcinoma cells. The killing of pluripotent cell lines by syngeneic, allogeneic, and xenogeneic killer cells ranged between 48 and 265% in chromium release assays when compared to YAC-1 cells, which served as highly susceptible reference cells. With the exception of 2 maGSC lines, they expressed ligands for the activating NK receptor NKG2D that belong to the RAE-1 family, and killing could be inhibited by soluble NKG2D, demonstrating a functional role of these molecules. Furthermore, ligands of the activating receptor DNAM-1 were frequently expressed. The susceptibility to NK cells might constitute a common feature of pluripotent cells. It could result in rejection after transplantation, as suggested by a reduced teratoma growth after NK cell activation in vivo, but it might also offer a strategy to deplete contaminating pluripotent cells before grafting of differentiated cells.-Dressel, R., Nolte, J., Elsner, L., Novota, P., Guan, K., Streckfuss-Bomeke, K., Hasenfuss, G., Jaenisch, R., Engel, W. Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells. FASEB J. 24, 2164-2177 (2010). www.fasebj.or
Polymorphism of interleukin-18 promoter influences the onset of kidney graft function after transplantation
No full textPolymorphism of interleukin-18 promoter influences the onset of kidney graft function after transplantation
No full textAssociation of HSP70 genes with idiopathic inflammatory myopathy in a homogeneous cohort of Czech patients
No full textMHC complex is the most polymorphic, most complex and one of the most important parts of human genome which participates in the immune response. MHC in humans is known as HLA complex (human leukocyte antigen), and consists of about 224 genes (Beck et al., 1999; Robinson et al., 2000). HLA genes are well known risk factors associated with number of autoimmune diseases (Beck et al., 1999). Idiopathic inflammatory myopathy belongs to the systemic autoimmune diseases. It is a disease with clinical manifestation of chronic muscle inflammation with a destruction of muscle cells, leading to a damage of the whole muscles. Idiopathic inflammatory myopathy (IIM) includes several diagnoses - polymyositis (PM), dermatomysitis (DM), cancer associated myositis (CDM), inclusion bodies myositis (IBM), and others. Human MHC complex consists of three parts. First two of them - the MHC class I and MHC class II genes, are already well studied and published results show their associated with numbers of (mostly immune system mediated) diseases. The third part of MHC is located between class I and II antigens and covers an area of about 150 genes. It is also called "non Class I/II" antigens (Beck et al., 1999; Carole et al., 1988; Lie, Thorsby, 2005). My work was focused on three MHC-located genes, which are known to be..
Population differences in the distribution of HLA-B27 allele in ankylosing spondylitis
No full textAnkylosing spondylitis (AS) is a chronic inflammatory disease affecting mainly the spine and the sacroiliac joints. This disorder has a genetic background and is strongly associated with HLA-B27 gene which occurs in about 90 % of patients. The prevalence of ankylosing spondylitis usually correlates with the frequency of HLA-B27. The strength of association HLA-B27 with AS varies between different populations and is also distinct for individual alleles of HLA-B27 gene. Some alleles can increase a risk of ankylosing spondylitis while others may have a protective effect. This work deals with the population differences in the occurrence of HLA-B27 alleles and their relation to development of ankylosing spondylitis. Key words: ankylosing spondylitis, HLA-B27, allele, subtype, population difference
Expression profiles of selected celiac disease candidate genes
No full textIntroduction: Celiac disease is a multifactorial autoimmune disease that is caused by a response to gluten and related proteins in genetically susceptible individuals. Genetic studies have demonstrated a high association of celiac disease with HLA genes (human leukocyte antigens) II. Class. Approximately 90-95% of the patients have a HLA-DQ2 genotype (DQA1 * 05 / DQB1 * 02), the remaining 5-10% are carriers of HLA-DQ8 (DQA1 * 03 / DQB1 * 03) or inherited only one allele of HLA-DQ2 genotype. Approximately 30% of the healthy population has this genotype and only 1% develops celiac disease. If 30% of healthy individuals have this genotype and do not develop celiac disease, this may be affected by a different level of expression in healthy and diseased individuals. Aims: The aim was to design and test a primer and probe system for QPCR that will amplify all selected HLA-DQA1 and HLA-DQB1 candidate genes at risk for celiac disease and use this system to measure the relative level of expression of risk genes in healthy donors and patients with celiac disease. Methods: The study included 10 patients with recent celiac disease and 15 healthy donors who were selected from the database of the Institute of Medical Genetics of the 3.LF UK based on their genotypes HLA-DQA1 and HLA-DQB1. Patients were first..
Genetic risk factors of system autoimmune diseases
No full textOne of the characteristics of systemic autoimmune diseases is the production of autoantibodies against self antigens. Genetic predisposition is supported by the HLA class II DQB and DRB genes, which constitute only about 40% of the risk. In the last few decades the search of other genetic risk factors noted major progress. There are many genetic risk factors that are shared by systemic disorders. These include genes such as PTPN22, STAT4, IRF5, TNFAIP3, TNFSF4, BANK1, BLK, CTLA4, genes coding for Fcγ receptors, FAS and others. Their presence suggests the existence of identical or similar mechanisms involved in the pathogenesis of autoimmune diseases. Conversely, many genetic factors predisposing to the development of the disease are specific to single system disorders. These genes often encode proteins involved in the functioning of the immune system, whether they are genes whose function has resulted in production of autoantigens (PADI4 and TREX1), or are responsible for the failure in selection of autoreactive T cells in the thymus (PTPN22), for antigen presentation to CD4+ T cells or cause the activation of autoreactive B cells (BANK1, IRF5, BLK)
Genetic study of obesity in children
No full textObesity is multifactorial dissease. Genetics factors participate in its origin of 40-70% (Barsh et al., 2000). Incidence of obesity is associated with a number of complications, which affect quality of life and abbreviate its length. It is projected in constantly younger age and its prevalence in the world grows. Even though several hundred genetics markers associated with obesity have been described, we still do not know all causes, which complicates efficiancy of treatment. Subject of this study was research of selected genes and their polymorphisms: FABP2 (rs1799883) and PLIN (rs1052700 and rs894160). The aim was to establish association between genotypes and antropometric and biochemical parameters related to obesity in group of 299 children and adolescents aged 7-18 years. Next goal was to establish whether these polymorphisms affect success of reduction therapy. SNP associations with antropometric and/or biochemical parameters were evaluated for boys and girls separately. Observed genotype frequencies between sex did not differ and they were in accordance with those explored in other populations. In rs1799883 polymorphism neither association with measured anthropometric and biochemical parameters nor effect on weight loss during reduction therapy have been found. The TT homozygote subjects of..
Role of peripheral blood monocytes and innate immunity in diabetes
No full textIntroduction: Diabetes mellitus is a polygenic disease and its development is influenced to some extent by environmental factors as well. Innate immunity triggers nonspecifically first defense reactions after penetration of the pathogen into the body, while overstimulation components of innate immunity may give rise to autoimmune diseases, including diabetes type 1. The components of innate immunity are, among others, Toll-like receptors (TLRs) belonging to a group of the structures recognizing preserved molecular structures characteristic of pathogens. Toll-like receptors are abundantly expressed by monocytes which produce prolactin (PRL) having an immunostimulatory function. To clarify the role of innate immunity in the pathogenesis of diabetes, we focused on the expression of mRNA and protein expression of TLR2 and TLR4. The expression of PRL was studied only at the level of mRNA. Monocytes were separated by flow cytometry into classical (CD14++) and nonclassical (CD14+). We monitored their percentages and the degree of expression of CD14 antigen on their surface.The operational objective of this dissertation was to optimize the stimulation of monocytes for the planned study of the function of non-pituitary prolactin in vitro and determine the appropriateness of the use of healthy donors' buffy..
