Search results for "Immune system"

Human genetic polymorphisms and risk of viral infection after solid organ transplantation.

2021

The immune system plays a key role in the host defense against viral pathogens. A signaling cascade is activated upon infection involving a variety of molecules such as pattern-recognition receptors (PRRs), interleukins or antiviral interferons. Long-term immunosuppression after solid organ transplantation (SOT) mainly abrogates adaptive T-cell-mediated responses, thus highlighting the relative contribution of innate immunity. Single-nucleotide polymorphisms (SNPs) within genes coding for PRRs or soluble mediators have been associated with differential susceptibility to viral infections among SOT recipients. A protective effect against cytomegalovirus (CMV) infection or disease has been att…

Antitumor Vaccination with Synthetic mRNA: Strategies for In Vitro and In Vivo Preclinical Studies

2012

Synthetic antigen-encoding mRNA is increasingly exploited as a tool for delivery of genetic information of complete antigens into professional antigen presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. Two strategies for mRNA-based antitumor vaccination have emerged into the clinical setting. One is transfection of autologous dendritic cells with synthetic mRNA for adoptive transfer into the patient. The other is direct injection of naked synthetic mRNA. Both methods have proven to be feasible and safe and to elicit antigen-specific immune responses. The design of novel synthetic vaccines employing synthetic mRNA requires further in-depth i…

DIFFERENT ROLE OF HUMAN HLA-DR AND -DQ MOLECULES IN XENOGENEIC TRANSPLANTATION USING TRANSGENIC MICE1

1999

Background. The role of T lymphocytes in graft rejection in xenotransplantation is still unclear. The ability of the human HLA class II molecules DR and DQ to function as xenoantigens was investigated in a murine model of skin grafting, using HLA-DR1 and -DQ6-transgenic mice. Methods, Skin from HLA-DR1- or -DQ6-transgenic mice was transplanted in control littermates. Spleen cells from donors or recipients were tested in mixed lymphocyte reaction and cytotoxic assay. Results. Skin from HLA-DR1-transgenic mice was rejected and spleen cells from rejecting mice were able to proliferate to donor cells, although no rejection was observed when the skin of HLA-DQ6-transgenic mice was engrafted in c…

313: A cDNA-based assay for donor-chimerism analysis of epidermal langerhans cells

2007

A Method of Transposon Insertion Sequencing in Comprehensively Identifying Vibrio vulnificus Genes Required for Growth in Human Serum

2021

One of the most powerful approaches to detect the loci that enable a pathogen to cause disease is the creation of a high-density transposon mutant library by transposon insertion sequencing (TIS) and the screening of the library using an adequate in vivo and/or ex vivo model of the disease. Here we describe the procedure for detection of the putative loci required for a septicemic pathogen to cause sepsis in humans by using TIS plus an ex vivo model of septicaemia: to grow the pathogen in fresh and inactivated human serum. We selected V. vulnificus because it is a highly invasive pathogen capable of spreading from an infection site to the bloodstream, causing sepsis and death in less than 2…

African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system

2019

Significance Many parasites escape the host immune system by undergoing antigenic variation, a process in which surface antigens are regularly shed and replaced by new ones. Trypanosoma brucei employs multiple sophisticated molecular mechanisms to ensure the expression of a homogeneous VSG coat. We generated a mutant parasite that expresses multiple distinct VSGs and studied the consequences of having a multi-VSG coat during an infection. We showed that expression of multiple VSGs makes the parasites more vulnerable to the immune response, which can now control the trypanosomes from the onset of the infection, allowing most mice to survive. In the future, trypanosome infections may be treat…

Mycobacterium tuberculosis Immune Response in Patients With Immune-Mediated Inflammatory Disease

2021

Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have an intrinsic higher probability to develop active-tuberculosis (TB) compared to the general population. The risk ranges from 2.0 to 8.9 in RA patients not receiving therapies. According to the WHO, the RA prevalence varies between 0.3% and 1% and is more common in women and in developed countries. Therefore, the identification and treatment of TB infection (TBI) in this fragile population is important to propose the TB preventive therapy. We aimed to study the M. tuberculosis (Mtb) specific T-cell response to find immune biomarkers of Mtb burden or Mtb clearance in patients with different TB …

Biology of gama delta T Cells in Tuberculosis and Malaria

2002

Tuberculosis and malaria remain the leading causes of mortality among human infectious diseases in the world. It is estimated that 3 to 5 million people die from tuberculosis and malaria each year. Although it is traditionally believed that CD4 and CD8 alphabeta T lymphocytes are mandatory for protective immune responses against Mycobacterium tuberculosis and Plasmodium falciparum (the ethiologic agents of tuberculosis and the most severe form of malaria, respectively), there is still incomplete understanding of the mechanisms of immune protection and of the causes of its failure in the affected patients. Several studies in humans and animal models have suggested that Vgamma9/Vdelta2 T cell…

Mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events

2015

Background Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB. Methods Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calc…

Plasmacytoid dendritic cells are inefficient in activation of human regulatory T cells

2011

BACKGROUND: Dendritic cells (DC) play a key role in initiation and regulation of immune responses. Plasmacytoid DC (pDC), a small subset of DC, characterized as type-I interferon producing cells, are critically involved in anti-viral immune responses, but also mediate tolerance by induction of regulatory T cells (Treg). In this study, we compared the capacity of human pDC and conventional DC (cDC) to modulate T cell activity in presence of Foxp3(+) Treg. PRINCIPAL FINDINGS: In coculture of T effector cells (Teff) and Treg, activated cDC overcome Treg anergy, abrogate their suppressive function and induce Teff proliferation. In contrast, pDC do not break Treg anergy but induce Teff prolifera…