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The article reports that the host biomarkers help diagnose tuberculosis (TB) state or correlates of protection against active disease and also direct the response to therapy. Topics include examines specific CD81 memory T cells can be considered both correlates of protective immunity and potential biomarkers of infectious diseases, such as TB, particularly when there is a need to distinguish active TB fromlatent TB infection.

The maturity method accounts for the effect of curing temperature on the strength development of well-cured and consolidated concrete. This paper describes an investigation of the accuracy of the maturity method to estimate the strength when different cementitious systems are used. Mortar cubes, made from Type I cement and various replacement levels of Class C fly ash, Class F fly ash, and ground-granulated blast-furnace slag, were cured at isothermal curing temperatures of 8, 23, and 40[degrees]C. The amount of long-term strength reduction, due to curing at high temperatures compared with curing at room temperature, is influenced by the type of cementitious system used in the concrete mixture. Based on the strength results of these mortar cubes and the procedure outlined in ASTM C 1074, datum temperature and activation energy values were determined for these cementitious systems. The ability of the equivalent age maturity method to accurately estimate the strength is significantly influenced by the composition of the cementitious material system. DOI: 10.1061/(ASCE)0899-1561(2007)19:12(1017) CE Database subject headings: Compression strength; Mortars; Cements; Evaluation.

Type 1 diabetes (T1D) is characterized by immune responses against several autoantigens expressed in pancreatic [beta] cells. T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can [...]

Author(s): Jeffrey C. Boyington [1]; Shawn A. Motyka [2]; Peter Schuck [3]; Andrew G. Brooks [4]; Peter D. Sun (corresponding author) [1] Natural killer (NK) cells constitute a vital part [...]

Killer cell inhibitory receptors (KIR) protect class 1 HLAs expressing target cells from natural killer (NK) cell-mediated lysis. To understand the molecular basis of this receptor-ligand recognition, we have crystallized the extracellular ligand-binding domains of KIR2DL2, a member of the Ig superfamily receptors that recognize HLA-Cw1, 3, 7, and 8 allotypes. The structure was determined in two different crystal forms, an orthorhombic P[2.sub.1][2.sub.1][2.sub.1] and a trigonal P[3.sub.2]21 space group, to resolutions of 3.0 and 2.9 [Angstrom], respectively. The overall fold of this structure, like KIR2DL1, exhibits K-type Ig topology with cis-proline residues in both domains that define [Beta]-strand switching, which sets KIR apart from the C2-type hematopoietic growth hormone receptor fold. The hinge angle of KIR2DL2 is approximately 80 [degrees], 14 [degrees] larger than that observed in KIR2DL1 despite the existence of conserved hydrophobic residues near the hinge region. There is also a 5 [degrees] difference in the observed hinge angles in two crystal forms of 2DL2, suggesting that the interdomain hinge angle is not fixed. The putative ligand-binding site is formed by residues from several variable loops with charge distribution apparently complementary to that of HLA-C. The packing of the receptors in the orthorhombic crystal form offers an intriguing model for receptor aggregation on the cell surface.

Abstract Background Glycosylation on the globular head of the hemagglutinin (HA) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. This, in turn, modulates the virulence of different viruses for mice. The role of particular oligosaccharide attachments on the HA in determining sensitivity to collectins has yet to be fully elucidated. Methods When comparing the virulence of H3N2 subtype viruses for mice we found that viruses isolated after 1980 were highly glycosylated and induced mild disease in mice. During these studies, we were surprised to find a small plaque variant of strain A/Beijing/353/89 (Beij/89) emerged following infection of mice and grew to high titres in mouse lung. In the current study we have characterized the properties of this small plaque mutant both in vitro and in vivo. Results Small plaque mutants were recovered following plaquing of lung homogenates from mice infected with influenza virus seed Beij/89. Compared to wild-type virus, small plaque mutants showed increased virulence in mice yet did not differ in their ability to infect or replicate in airway epithelial cells in vitro. Instead, small plaque variants were markedly resistant to neutralization by murine collectins, a property that correlated with the acquisition of an amino acid substitution at residue 246 on the viral HA. We present evidence that this substitution was associated with the loss of an oligosaccharide glycan from the globular head of HA. Conclusion A point mutation in the gene encoding the HA of Beij/89 was shown to ablate a glycan attachment site. This was associated with resistance to collectins and increased virulence in mice.

Abstract Background Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. Methods The anti-Gr-1 monoclonal antibody (mAb) RB6-8C5 was used to (i) identify neutrophils in the upper (nasal tissues) and lower (lung) respiratory tract of uninfected and influenza virus-infected mice, and (ii) deplete neutrophils prior to and during influenza virus infection of mice. Results Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6) mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Conclusion Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.

We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E–restricted CD8+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I–restricted CD8+ T cells but not by HLA-E–restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E–restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E– and HLA-A2–restricted Mycobacterium tuberculosis–specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte–derived macrophages associated with resistance to lysis by HLA-A2–restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E–restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E–restricted and Mycobacterium tuberculosis–specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti–PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E–restricted and Mycobacterium tuberculosis–specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab. [ABSTRACT FROM AUTHOR]