The mucosal immune system in IgA nephropathy

Summary: IgA nephropathy is a clinically and histologically defined syndrome of unknown aetiology, which may have various causes in different parts of the world. Immunologically it is characterized by deposition of IgA1, probably polymeric IgA, in the mesangium and is frequently associated with IgG, C3 and components of the alternative pathway of the complement cascade. the disease can go into complete remission in children, but in adults it usually has a progressive course, characterized by the appearance of proteinuria and hypertension and loss of glomerular filtration rate (GFR). Histologically the development of glomerulosclerosis and tubulo-interstitial changes correlate with a clinical progressive course. the mucosal immune system is characterized by high plasma IgAl antibody responses after parenteral immunization with viral or bacterial vaccines. However, following nasal challenge with a bacterial neoantigen, IgA nephropathy patients appear to have a defective mucosal immune response in their nasal washes, in their bone marrow and in their plasma IgA1 antibody levels.     

High-dose UV-B radiation alters human dendritic cell costimulatory activity but does not allow dendritic cells to tolerize T lymphocytes to alloantigen in vitro

Human blood dendritic cells require UV-B radiation (290 to 320 nm) in excess of 1,000 J/m2 to inhibit their stimulation of primary T-cell responses to alloantigen by 60% to 70% or more. The effect is twofold to threefold greater in the allogeneic mixed leukocyte reaction (MLR) than in polyclonal mitogenesis using comparable numbers of dendritic cells and doses of UV-B radiation. UV-B radiation does not significantly alter dendritic cell viability at the doses administered. Dendritic cell expression of important costimulatory ligands, eg, B7/BB1 and ICAM-1/CD54, is reduced in proportion to the dose of UV-B light administered. UV-B irradiated dendritic cells nevertheless initiate stable contacts with primary alloreactive T lymphocytes that are sufficient to prime T-cell responsiveness to interleukin-2 (IL-2). Subsequent proliferation is severely abrogated without supplemental lymphokine, while T-cell alloreactivity is preserved in a secondary response, irrespective of primary exposure to UV-B irradiated dendritic cells.     

Kinematics of the knee at high flexion angles: an in vitro investigation.

Restoration of knee function after total knee, meniscus, or cruciate ligament surgery requires an understanding of knee behavior throughout the entire range of knee motion. However, little data are available regarding knee kinematics and kinetics at flexion angles greater than 120 degrees (high flexion). In this study, 13 cadaveric human knee specimens were tested using an in vitro robotic experimental setup. Tibial anteroposterior translation and internal-external rotation were measured along the passive path and under simulated muscle loading from full extension to 150 degrees of flexion. Anterior tibial translation was observed in the unloaded passive path throughout, with a peak of 31.2+/-13.2 mm at 150 degrees. Internal tibial rotation increased with flexion to 150 degrees on the passive path to a maximum of 11.1+/-6.7 degrees. The simulated muscle loads affected tibial translation and rotation between full extension and 120 degrees of knee flexion. Interestingly, at high flexion, the application of muscle loads had little effect on tibial translation and rotation when compared to values at 120 degrees. The kinematic behavior of the knee at 150 degrees was markedly different from that measured at other flexion angles. Muscle loads appear to play a minimal role in influencing tibial translation and rotation at maximal flexion. The results imply that the knee is highly constrained at high flexion, which could be due in part to compression of the posterior soft tissues (posterior capsule, menisci, muscle, fat, and skin) between the tibia and the femur.     

Age-related changes in perception of support surface inclination during quiet stance

The ability to detect that a support surface is level, based upon individual concept of verticality and normal ankle angle during quiet stance, was studied in 11 elderly and 11 young subjects. In response to initial displacement of the tilt platform within a ± 4° range, subjects returned their support surface to level using a hand-held control switch. All sensory inputs regarding the actual platform position were available except direct visual feedback. The task was performed both with eyes open and eyes closed, with both feet on the platform. Elderly subjects exhibited a positive 0.9° shift of the subjective level compared with absolute level, in contrast to young subjects whose subjective level differed from absolute level by not more than 0.25°. There were no significant within-group differences between the eyes open and eyes closed conditions; however, positive shift of the subjective level persisted in the elderly group. The observed shift might be related to a compensatory strategy for overcoming the age-related decline in postural stability in old adults.     

Lymphokine-activated killer cell generation and recovery. Comparison of an automated cell processing device and a manual procedure

This report describes the separation or processing of leukapheresis-derived peripheral blood mononuclear cells, their culture in the presence of interleukin-2 (IL-2) to generate lymphokine-activated killer (LAK) cells, and the harvest of LAK cells using the Du Pont SteriCell processor and culture containers. The report compares this automated closed system to the standard National Cancer Institute (NCI) manual protocols. Lymphocytes (approximately 2.0 x 10(10)) were harvested on the Cobe 2997 blood cell separator for each set of experiments. A set of experiments using automated Ficoll-Isopaque (FI) separation and a set of experiments using an automated wash for platelet reduction were compared to the respective manual methods. SteriCell culture containers were compared to roller bottles, and automated harvest was compared to manual harvest. The cytolytic activity of LAK cells was assayed against that of Daudi cells in a standard 51Cr release assay. The cytolytic activity of LAK cells prepared by a manual method and by the automated SteriCell method are equivalent. The manual and SteriCell FI separation procedures were substantially equivalent. The SteriCell harvest method gave higher recoveries than the manual harvest method (p = 0.04 and p = 0.07), but the overall recovery of LAK cells was not significantly different. Differential counts on the products were similar. Platelet reduction by the SteriCell automated wash procedure was greater than that by the manual procedure (p = 0.05). The SteriCell system represents an acceptable alternative to the manual methods for LAK cell generation and recovery.     

Multiple antigen challenge produces pulmonary eosinophilia but not pulmonary hyperresponsiveness in actively sensitized guinea pigs.

Exposure of actively sensitized boosted guinea pigs to aerosolized antigen, 3 times on alternate days, produced pulmonary eosinophilia but not pulmonary hyperresponsiveness to methacholine Cl measured 3 days after the last antigen challenge. These data suggest that the presence of large numbers of eosinophils in the airways and tissues of the lungs is not sufficient to produce nonspecific pulmonary hyperresponsiveness. These data also suggest that actively sensitized and boosted guinea pigs respond differently to repeated antigen exposure than do asthmatics or wild caught allergic cynomolgus monkeys.