Intestinal macromolecular transport supporting adaptive immunity

The gastrointestinal tract performs opposing functions of nutrient absorption, barrier maintenance, and the delivery of luminal substances for the appropriate induction of tolerogenic or protective adaptive immunity. The single-layer epithelium lining the gastrointestinal tract is central to each of these functions by facilitating the uptake and processing of nutrients, providing a physical and chemical barrier to potential pathogens, and delivering macromolecular substances to the immune system to initiate adaptive immune responses. Specific transport mechanisms allow nutrient uptake and the delivery of macromolecules to the immune system while maintaining the epithelial barrier. This review examines historical observations supporting macromolecular transport by the intestinal epithelium, recent insights into the transport of luminal macromolecules to promote adaptive immunity, and how this process is regulated to promote appropriate immune responses. Understanding how luminal macromolecules are delivered to the immune system and how this is regulated may provide insight into the pathophysiology of inflammatory diseases of the gastrointestinal tract and potential preventative or therapeutic strategies. Keywords: Antigen Transport, Mucosal Tolerance, Goblet Cell

Isolated lymphoid follicles are dynamic reservoirs for the induction of intestinal IgA

IgA is one of the most important molecules in the regulation of intestinal homeostasis. Peyer’s patches have been traditionally recognized as sites for the induction of intestinal IgA responses, however more recent studies demonstrate that isolated lymphoid follicles (ILFs) can perform this function as well. ILF development is dynamic, changing in response to the luminal microbial burden, suggesting that ILFs play an important role providing an expandable reservoir of compensatory IgA inductive sites. However, in situations of immune dysfunction, ILFs can over-develop in response to uncontrollable enteric flora, resulting in ILF hyperplasia. The ability of ILFs to expand and respond to help control the enteric flora makes this dynamic reservoir an important arm of IgA inductive sites in intestinal immunity

Hospital fall prevention: a systematic review of implementation, components, adherence, and effectiveness.

ObjectivesTo systematically document the implementation, components, comparators, adherence, and effectiveness of published fall prevention approaches in U.S. acute care hospitals.DesignSystematic review. Studies were identified through existing reviews, searching five electronic databases, screening reference lists, and contacting topic experts for studies published through August 2011.SettingU.S. acute care hospitals.ParticipantsStudies reporting in-hospital falls for intervention groups and concurrent (e.g., controlled trials) or historic comparators (e.g., before-after studies).InterventionFall prevention interventions.MeasurementsIncidence rate ratios (IRR, ratio of fall rate postintervention or treatment group to the fall rate preintervention or control group) and ratings of study details.ResultsFifty-nine studies met inclusion criteria. Implementation strategies were sparsely documented (17% not at all) and included staff education, establishing committees, seeking leadership support, and occasionally continuous quality improvement techniques. Most interventions (81%) included multiple components (e.g., risk assessments (often not validated), visual risk alerts, patient education, care rounds, bed-exit alarms, and postfall evaluations). Fifty-four percent did not report on fall prevention measures applied in the comparison group, and 39% neither reported fidelity data nor described adherence strategies such as regular audits and feedback to ensure completion of care processes. Only 45% of concurrent and 15% of historic control studies reported sufficient data to compare fall rates. The pooled postintervention incidence rate ratio (IRR) was 0.77 (95% confidence interval = 0.52-1.12, P = .17; eight studies; I(2) : 94%). Meta-regressions showed no systematic association between implementation intensity, intervention complexity, comparator information, or adherence levels and IRR.ConclusionPromising approaches exist, but better reporting of outcomes, implementation, adherence, intervention components, and comparison group information is necessary to establish evidence on how hospitals can successfully prevent falls

The effects of classic and variant infectious bursal disease viruses on lymphocyte populations in specific-pathogen-free White Leghorn chickens

Infectious bursal disease virus (IBDV) is a pathogen that primarily infects B lymphocytes in domestic avian species. This viral infection has been associated with immunosuppression, clinical disease/mortality, and enteric malabsorption effects. The purpose of this experiment was to compare the effects of a classic (USDA-STC) and a new variant IBDV (RB-4, known to induce primarily the enteric disease) on immune cell populations in lymphoid organs. Seventeen-dayold specific-pathogen-free (SPF) White Leghorn chickens were either not infected (control) or inoculated with either USDA-STC or RB-4 IBD viral isolate. On days 3 and 5 post-inoculation (PI), lymphoid tissues were collected to prepare cell suspensions for immunofluorescent staining and cell population analysis by flow cytometry. Portions of the tissues were snap frozen for immunohistochemistry to localize various immune cells and IBD virus in the tissues. Tissue homogenates were prepared to test for IBDV by quantitative MTT assay. Both the USDA-STC and RB-4 viruses greatly altered lymphocyte populations in the spleen and bursa. At 5 d PI, bursal B cells were approximately 25% and 60% of lymphocytes in chicks infected with USDA-STC and RB-4, respectively, whereas in control birds, B cells constituted 99% of bursal lymphocytes. This reduction in the proportions of bursal B cells was associated with an infiltration of T cells. In the spleen, IBDV infection also reduced the percentage of B cells and increased the percentage of T cells. The differential effects of classic and variant IBDV infection on immune cell populations in lymphoid organs may explain the differences in clinical effects induced by these viruse

Electron Shock Waves with a Large Current Behind the Shock Front

The propagation of breakdown waves in a gas, which is primarily driven by electron gas pressure, is described by a one-dimensional, steady-state, three-component (electrons, ions, and neutral particles) fluid model. We consider the electron gas partial pressure to be much larger than that of the other species and the waves to have a shock front. Our set of equations consists of the equations of conservation of the flux of mass, momentum, and energy coupled with Poisson’s equation. This set of equations is referred to as the electron fluid dynamical equations. In this study we are considering breakdown waves propagating in the opposite direction of the electric field force on electrons (return stroke in lightning) and moving into a neutral medium. For Breakdown waves with a significant current behind the shock front, the set of electron fluid dynamical equations and also the boundary condition on electron temperature need to be modified. For a range of experimentally observed current values and also some larger current values which few experimentalists have been able to observe, we have been able to solve the set of electron fluid dynamical equations through the dynamical transition region of the wave. Some experimentalists have reported the existence of a relationship between return stroke lightning wave speed and current behind the shock front; however, some others are skeptical of the existence of such a relationship. Our solutions to the set of electron fluid dynamical equations within the dynamical transition region of the wave confirm the existence of such a relationship. We will present the method of solution of the set of electron fluid dynamical equations through the dynamical transition region of the wave and also the wave profile for electric field, electron velocity, electron temperature and electron number density, within the dynamical transition region of the wave

Characteristics of long-duration inhibitory postsynaptic potentials in rat neocortical neurons in vitro

1. The characteristics of long-duration inhibitory postsynaptic potentials (l-IPSPs) which are evoked in rat frontal neocortical neurons by local electrical stimulation were investigated with intracellular recordings from anin vitro slice preparation. 2. Stimulation with suprathreshold intensities evoked l-IPSPs with typical durations of 600–900 msec at resting membrane potential. Conductance increases of 15–60% were measured at the peak amplitude of l-IPSPs (150–250 msec poststimulus). 3. The duration of the conductance increases during l-IPSPs displayed a significant voltage dependence, decreasing as the membrance potential was depolarized and increasing with hyperpolarization. 4. The reversal potential of l-IPSPs is significantly altered by reductions in the extracellular potassium concentration. Therefore it is concluded that l-IPSPs in rat neocortical neurons are generated by the activation of a potassium conductance. 5. l-IPSPs exhibit stimulation fatigue. Stimulation with a frequency of 1 Hz produces a complete fatigue of the conductance increases during l-IPSPs after approximately 20 consecutive stimuli. Recovery from this fatigue requires minutes. 6. l-IPSPs are not blocked by bicuculline but are blocked by baclofen