Review of Care Transition Records and Their Transmission Process in Nursing Facilities and Hospitals in Germany - Results of an Online Questionnaire.

A quantitative approach in the form of an online questionnaire was used to identify challenges and desires related to the Care Records Transmission Process and Care Transition Records (CTR). The questionnaire was sent to nurses, nursing assistants, and trainees working in ambulatory, acute inpatient, or long-term care settings. The survey revealed that creating CTRs is time-consuming, and the lack of standardization of CTRs makes the process even more cumbersome.

A pro-survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection.

Intracellular serpins are proposed to inactivate proteases released from lysosome-related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B-mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8 T cells.

Ectromelia virus N1L is essential for virulence but not dissemination in a classical model of mousepox.

Mousepox is caused by the orthopoxvirus ectromelia virus (ECTV), and is thought to be transmitted via skin abrasions. We studied the ECTV virulence factor N1 following subcutaneous infection of mousepox-susceptible BALB/c mice. In this model, ECTV lacking N1L gene was attenuated more than 1000-fold compared with wild-type virus and replication was profoundly reduced as early as four days after infection.

Granzyme B promotes cytotoxic lymphocyte transmigration via basement membrane remodeling.

Granzyme B (GzmB) is a protease with a well-characterized intracellular role in targeted destruction of compromised cells by cytotoxic lymphocytes. However, GzmB also cleaves extracellular matrix components, suggesting that it influences the interplay between cytotoxic lymphocytes and their environment. Here, we show that GzmB-null effector T cells and natural killer (NK) cells exhibited a cell-autonomous homing deficit in mouse models of inflammation and Ectromelia virus infection.

Cytolytic effector pathways and IFN-γ help protect against Japanese encephalitis.

Japanese encephalitis, caused by infection with the neurotropic flavivirus, Japanese encephalitis virus (JEV), is among the most important viral encephalitides in Asia. While previous studies established an essential role of Ab and type I IFN, it is still unclear if the cell-mediated immune responses, through their direct antiviral effector functions, contribute to protection against the fatal disease. We report here that mice defective in both the granule exocytosis and death receptor pathways of cytotoxicity display increased susceptibility to JEV.

The chemokine receptor CCR5, a therapeutic target for HIV/AIDS antagonists, is critical for recovery in a mouse model of Japanese encephalitis.

Japanese encephalitis is a severe central nervous system (CNS) inflammatory disease caused by the mosquito-borne flavivirus, Japanese encephalitis virus (JEV). In the current study we have investigated the immune responses against JEV in mice lacking expression of the chemokine receptor CCR5, which functions in activation and chemotaxis of leukocytes during infection. We show that CCR5 serves as a host antiviral factor against Japanese encephalitis, with CCR5 deficiency markedly increasing mortality, and viral burden in the CNS.

Gamma-irradiated influenza virus uniquely induces IFN-I mediated lymphocyte activation independent of the TLR7/MyD88 pathway.

Background: We have shown previously in mice, that infection with live viruses, including influenza/A and Semliki Forest virus (SFV), induces systemic partial activation of lymphocytes, characterized by cell surface expression of CD69 and CD86, but not CD25. This partial lymphocytes activation is mediated by type-I interferons (IFN-I). Importantly, we have shown that γ-irradiated SFV does not induce IFN-I and the associated lymphocyte activation.

In vivo elimination of MHC-I-deficient lymphocytes by activated natural killer cells is independent of granzymes A and B.

NK cells kill target cells mainly via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and induction of apoptosis is severely impaired in the absence of gzm A and B. However, their importance for in vivo cytotoxicity by cytotoxic T cells has been questioned.

The ectromelia virus SPI-2 protein causes lethal mousepox by preventing NK cell responses.

Ectromelia virus (ECTV) is a natural pathogen of mice that causes mousepox, and many of its genes have been implicated in the modulation of host immune responses. Serine protease inhibitor 2 (SPI-2) is one of these putative ECTV host response modifier proteins. SPI-2 is conserved across orthopoxviruses, but results defining its mechanism of action and in vivo function are lacking or contradictory.

TCR down-regulation boosts T-cell-mediated cytotoxicity and protection against poxvirus infections.

Cytotoxic T (Tc) cells play a key role in the defense against virus infections. Tc cells recognize infected cells via the T-cell receptor (TCR) and subsequently kill the target cells by one or more cytotoxic mechanisms. Induction of the cytotoxic mechanisms is finely tuned by the activation signals from the TCR.

Pivotal role of antibody and subsidiary contribution of CD8+ T cells to recovery from infection in a murine model of Japanese encephalitis.

The immunological correlates for recovery from primary Japanese encephalitis virus (JEV) infection in humans and experimental animals remain poorly defined. To investigate the relative importance of the adaptive immune responses, we have established a mouse model for Japanese encephalitis in which a low-dose virus inoculum was administered into the footpads of adult C57BL/6 mice. In this model, ~60% of the mice developed a fatal encephalitis and a virus burden in the central nervous system (CNS).

Evaluating vaccinia virus cytokine co-expression in TLR GKO mice.

Using Toll-like receptor (TLR) and MyD88 gene knock-out (GKO) mice the effect of TLRs and MyD88 on virus replication, interferon (IFN)-β production, natural killer (NK) cell and CD8T cell responses were assessed following ectromelia virus (ECTV) and recombinant vaccinia virus (rVV) infection. The capacity for rVVs encoding cytokines to restore immune function in MyD88(-/-) mice was clearly demonstrated. Results showed that TLR2(-/-), TLR4(-/-)and TLR7(-/-) mice survived ECTV infection whereas MyD88(-/-) and TLR9(-/-)mice, in contrast, were highly susceptible.

Antigen-specific activation thresholds of CD8+ T cells are independent of IFN-I-mediated partial lymphocyte activation.

Type-I IFN (IFN-I) are highly pleiotropic cytokines known to modulate immune responses and play an early central role in mediating antiviral defenses. We have shown that IFN-I mediate transient up-regulation of a distinct subset of lymphocyte surface activation markers on both B and T cells in vivo independent of cognate antigen: a state referred to as 'partial lymphocyte activation'. Here we investigated in vitro the possibility that partial lymphocyte activation may serve to lower the antigen-specific activation thresholds for T cells.

Cytotoxic T cells are the predominant players providing cross-protective immunity induced by {gamma}-irradiated influenza A viruses.

We previously demonstrated that a single dose of nonadjuvanted intranasal gamma-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin.

Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations.

We have recently shown that intranasal (i.n.) administration of gamma-irradiated A/PR/8 [A/Puerto Rico/8/34 (H1N1)] protects mice against lethal avian influenza A/Vietnam/1203/2004 (H5N1) and other heterosubtypic influenza A infections.

Caspase-dependent inhibition of mousepox replication by gzmB.

Background: Ectromelia virus is a natural mouse pathogen, causing mousepox. The cytotoxic T (Tc) cell granule serine-protease, granzyme B, is important for its control, but the underlying mechanism is unknown. Using ex vivo virus immune Tc cells, we have previously shown that granzyme B is able to activate several independent pro-apoptotic pathways, including those mediated by Bid/Bak/Bax and caspases-3/-7, in target cells pulsed with Tc cell determinants.

Cutting edge: rapid and efficient in vivo cytotoxicity by cytotoxic T cells is independent of granzymes A and B.

Cytotoxic T (Tc) cells lyse target cells via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and in the absence of gzm A and B the induction of apoptosis is severely impaired. However, using in vivo Tc cell killing assays, we find that virus-immune, gzm A x B-deficient (gzmAxB(-/-)) mice are competent to eliminate adoptively transferred target cells pulsed with an immunodominant Tc cell determinant as rapidly and completely as their wild-type counterparts.

Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections.

Background: Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that gamma-ray inactivated flu virus can induce cross-reactive Tc cell responses.

Interferon type I responses in primary and secondary infections.

The mammalian host responds to a microbial infection with a rapid innate immune reaction that is dominated by type I interferon (IFN-I) release. Most cells of vertebrates can respond to microbial attack with IFN-I production, but the cell type responsible for most of the systemic IFN-I release is thought to be plasmacytoid dendritic cells (pDCs). Besides its anti-microbial and especially anti-viral properties IFN-I also exerts a regulatory role on many facets of the sequential adaptive immune response.

Exhaustion of type I interferon response following an acute viral infection.

Viral infections often cause a period of heightened susceptibility to a secondary infection but the cause of this phenomenon is unknown. We found that a primary viral infection in mice rapidly triggers an IFN-I-dependent partial activation state in the majority of B and T lymphocytes, which reverts to a resting phenotype within 5 days. When a secondary infection with an unrelated virus occurred 5 to 9 days after the primary infection, no recurrence of marked activation of lymphocytes was observed.

Type I interferons trigger systemic, partial lymphocyte activation in response to viral infection.

The vast majority of both T and B cells in mice were found to up-regulate cell surface expression of the early activation markers CD69 and CD86, but not CD25, within 24 h of infection with Semliki Forest virus. Kinetics and magnitude of activation marker expression was dependent on live virus, dose, and correlated with strain virulence. Activation marker expression declined to baseline levels over the next 96 h.

The immunomodulating properties of human respiratory syncytial virus and immunostimulating complexes containing Quillaja saponin components QH-A, QH-C and ISCOPREP703.

A successful vaccine against human RSV (HRSV) is likely to induce a Th1 or a balanced Th1/TH2 cytokine response. We tested a panel of HRSV immunostimulating complexes (ISCOMs) containing different Quillaja saponin fractions (QH-A, QH-C, and 703: a mixture of 70% QH-A and 30% QH-C) with different immunological properties for their capacity of inducing innate and acquired immune responses. The HRSV 703 ISCOMs induced the strongest innate and acquired immune responses, followed by RSV QH-C and QH-A ISCOMs.

The multidrug resistance gene mdr1a influences resistance to ectromelia virus infection by mechanisms other than conventional immunity.

P-glycoprotein (P-gp), an ATP-dependent membrane pump encoded by mdr, plays, in addition to its ability to efflux toxins, a role in the resistance to pathogens. We employed mdr1a gene knock out (mdr1a-/-) mice and ectromelia virus (EV) to elucidate the role of P-gp in resistance to EV. Mdr1a-/- mice are more susceptible to EV infection than wild type (wt) mice, showing increased mortality and morbidity.

Can we really learn from model pathogens?

Cytolytic T (Tc) lymphocytes are the first order response of the adaptive immune system in the recovery from primary viral infections. These effector cells execute their function either by direct cytotoxicity through the Fas or perforin pathway and/or by the release of cytokines that either directly or indirectly exert antiviral activity. Mice respond to infection by closely related viruses with a vigorous Tc response, which is characterized by extensive crossreactivity on target cells infected with these viruses.