Human Immune Responses (human + immune_response)

Distribution by Scientific Domains

Selected Abstracts

VacA-Associated Inhibition of T-cell Function: Reviewed and Reconsidered

HELICOBACTER, Issue 3 2006
Christian Schmees
Abstract Chronic Helicobacter pylori infection is characterized by dense infiltration of the mucosa with neutrophilic granulocytes, lymphocytes, and monocytes/macrophages. Among these different cell types, T-lymphocytes are the most intriguing and crucial cells for the elimination of the bacteria. Previous studies have elucidated possible mechanisms on how bacteria could interfere with the human immune response and claimed that especially the secreted vacuolating toxin VacA may be responsible for the chronic persistence of the bacteria. Some of these results have to be interpreted with caution and may just describe in vitro phenomena; others may reveal promising facts. [source]

Functional analysis of NsrR, a nitric oxide-sensing Rrf2 repressor in Neisseria gonorrhoeae

Vincent M. Isabella
Summary Nitric oxide (NO) has been shown to be an important component of the human immune response, and as such, it is important to understand how pathogenic organisms respond to its presence. In Neisseria gonorrhoeae, recent work has revealed that NsrR, an Rrf2-type transcriptional repressor, can sense NO and control the expression of genes responsible for NO metabolism. A highly pure extract of epitope-tagged NsrR was isolated and mass spectroscopic analysis suggested that the protein contained a [2Fe,2S] cluster. NsrR/DNA interactions were thoroughly analysed in vitro. Using EMSA analysis, NsrR::FLAG was shown to interact with predicted operators in the norB, aniA and nsrR upstream regions with a Kd of 7, 19 and 35 nM respectively. DNase I footprint analysis was performed on the upstream regions of norB and nsrR, where NsrR was shown to protect the predicted 29 bp binding sites. The presence of exogenously added NO inhibited DNA binding by NsrR. Alanine substitution of C90, C97 or C103 in NsrR abrogated repression of norB::lacZ and inhibited DNA binding, consistent with their presumed role in co-ordination of a NO-sensitive Fe,S centre required for DNA binding. [source]

Contemplating the murine test tube: lessons from natural killer cells and Cryptococcus neoformans

Kaleb J. Marr
Abstract Murine experimentation has provided many useful tools, including the ability to knockout or over-express genes and to perform experiments that are limited by ethical considerations. Over the past century, mice have imparted valuable insights into the biology of many systems, including human immunity. However, although there are many similarities between the immune response of humans and mice, there are also many differences; none is more prominent than when examining natural killer cell biology. These differences include tissue distribution, effector molecules, receptor repertoire, and cytokine responses, all of which have important implications when extrapolating the studies to the human immune responses to Cryptococcus neoformans. [source]

Association of HLA-DRB1*07 and DRB1*04 to citrus red mite (Panonychus citri) and house dust mite sensitive asthma

S.-H. Cho
Background Specific IgE responses to allergens provide useful models for evaluating the genetic factors that control human immune responses. A recent survey demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in the development of asthma in citrus farmers. Objective The aim of this study was to evaluate whether susceptibility or resistance to CRM-induced asthma was associated with HLA-DRB1 gene. Methods DNAs were extracted from two groups of unrelated Korean adults living around citrus farms: (1) Ninety-one adults with CRM-sensitive asthma; and (2) 98 exposed, healthy nonatopic controls. Genotypes of HLA-DRB1 alleles were carried out using PCR-based methods. Results Allelic frequency of HLA-DRB1*07 was higher in the CRM-sensitive asthmatics compared to the controls (17.6% vs 4.1%, Pc = 0.01). Conversely, the frequency of DRB1*04 was lower in the CRM-sensitive asthmatics compared to the controls (19.8% vs 40.8%, Pc = 0.01). No significant difference was found in the distributions of the other HLA-DRB1 gene-encoded antigens between the two groups. Conclusion HLA-DRB1 genes may be involved in the development of CRM-induced asthma. In addition, HLA-DR7 may increase, and DR4 decrease, the risk of developing the asthma in CRM-exposed adults. [source]

Efficient generation of respiratory syncytial virus (RSV)-neutralizing human MoAbs via human peripheral blood lymphocyte (hu-PBL)-SCID mice and scFv phage display libraries

H. Nguyen
RSV is one of the major causes of pneumonia and bronchiolitis in infants and young children and is associated with high mortality. RSV neutralizing human antibody (hu-Ab) is known to mediate resistance to viral infection as well as to be an effective treatment for severe lower respiratory tract RSV infection. We have previously demonstrated that human primary and secondary immune responses can be established in severe combined immunodeficient mice engrafted with human peripheral blood lymphocytes (hu-PBL-SCID). By combining this animal model with the single-chain Fv antibody (scFv) phage display library technique, we were able to investigate further its clinical potential by generating a panel of human scFvs that exhibit both high F glycoprotein (RSV-F) binding affinities (,108 M,1) and strong neutralizing activities against RSV infection in vitro. Sequencing analysis of the randomly isolated anti-RSV-F scFv clones revealed that they were derived from different VH families with mutations in the complementarity-determining region 1 (CDR1). The results suggest that: (i) RSV-F-specific human immune responses and affinity maturation can be induced in hu-PBL-SCID mice; and (ii) this approach can be applied to generate large numbers of human scFvs with therapeutic potential. Despite the fact that hu-PBL-SCID mouse and human scFv phage display library have individually been established, our approach contributes a simple and significant step toward the generalization of antigen-specific human monoclonal antibody (hu-MoAb) production and their clinical applications. [source]