Immune

Advanced metastatic melanoma is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides as the source of antigens, and rely on foreign proteins as a source of help to generate a cell-mediated immune response. This approach limits patient accrual, because currently defined, non-mutated epitopes are restricted by a small number of human leucocyte antigens. It also fails to take advantage of mutated epitopes peculiar to the patient's own tumour, and of CD4+ T lymphocytes as potential effectors of anti-tumour immunity. We therefore sought to determine whether a fully autologous DC vaccine is feasible, and of therapeutic benefit. Patients with American Joint Cancer Committee stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC, matured after culture with irradiated tumour cells. Of 19 patients enrolled into the t...

In mobile ad-hoc networks, nodes act both as terminals and information relays, and they participate in a common routing protocol, such as Dynamic Source Routing (DSR). The networks are vulnerable to routing misbehavior, due to faulty or malicious nodes. Misbehavior detection systems aim at removing this vulnerability. For this purpose, we use an Artificial Immune System (AIS), a system inspired by the human immune system (HIS). Our goal is to build a system that, like its natural counterpart, automatically learns and detects new misbehavior. In this paper we build on our previous work [1,2] and investigate the use of four concepts: (1) “virtual thymus”, a novel concept, introduced in this paper, that provides a dynamic description of normal behavior in the system; (2) “clustering”, a decision making mechanism for decreasing false positive detections (3) “danger signal”, a concept that is, according to the “danger signal theory” of the human immune system [11,12], crucial for correct final decisions making; in our case, the signal is exchanged among nodes, which makes our detection system distributed; (4) “memory detectors”, used for achieving faster secondary response of the detection system. We implement our AIS in a network simulator and test it on two types of misbehavior. We analyze the performance and show the effects of the four concepts on the detection capabilities. In summary: thanks to the virtual thymus, the AIS does not require a preliminary learning phase in which misbehavior should be absent; the use of the clustering and the danger signal is useful for achieving low false positives; the use of memory detectors significantly accelerates the secondary response of the system.

Heat-shock protein concentrations in the blood increase after exposure to a variety of stressors, including trauma and psychological stress. Although the physiological function of extracellular heat shock protein remains controversial, there is evidence that extracellular heat shock protein 72 (Hsp72) can facilitate immunologic responses. The signal(s) that mediate(s) the in vivo elevation of extracellular Hsp72 in the blood after stressor exposure remain(s) unknown. Here we report that Hsp72 increases in the circulation via an α1-adrenergic receptor-mediated signaling pathway. Activation of α1-adrenoceptors results in a rapid increase in circulating Hsp72, and blockade of α1-adrenoceptors prevents the stress-induced rise in circulating Hsp72. Furthermore, our studies exclude a role for β-adrenoceptors, glucocorticoids, and ACTH in mediating stress-induced elevations in circulating extracellular Hsp72. Understanding the signals involved in elevating extracellular Hsp72 could facilit...

Lung injury was induced by the instillation of P. aeruginosa strain PA103 directly into the left lungs of anesthetized rats. One hour after the bacterial instillation, rabbit polyclonal anti-PcrV IgG, murine monoclonal anti-PcrV IgG Mab166 or Mab166 Fab-fragments were ...

BACKGROUND: Vaccines have virtually eliminated many diseases, but public concerns about their safety could undermine future public health initiatives. OBJECTIVE: To determine Canadians' attitudes and knowledge about vaccines, particularly in view of increasing public concern about bioterrorism and the possible need for emergency immunizations after weaponized anthrax incidents and the events of September 11, 2001. METHOD: A 20-question survey based on well-researched dimensions of vaccine responsiveness was telephone-administered to a random sample of N = 1330 adult Canadians in January, 2002. RESULTS: 1057 (79.5%) completed the survey. Respondents perceived vaccines to be highly effective and demonstrated considerable support for further vaccine research. However, results also indicate a lack of knowledge about vaccines and uncertainty regarding the safety. CONCLUSIONS: Support for vaccines is broad but shallow. While Canadians hold generally positive attitudes about vaccines, ...

1. The acute phase immune response, which includes fever and sickness behaviours, carries high costs in energy and time, but enhances pathogen clearance in diverse hosts. Hypotheses based upon pathogen pressures and life-history trade-offs predict that costly immune responses will decrease in strength as latitude increases. However, whether the acute phase response shows latitudinal patterns among free-living, wild populations remains unknown.2. Here, we studied fever and sickness behaviours during the early breeding season in free-living song sparrows (Melospiza melodia) along a latitudinal gradient in southern California (CA), Washington (WA), and Alaska (AK). In 2007 and 2008, we injected males with lipopolysaccharide and assessed sickness behaviour by measuring changes in territorial aggression. In 2008, we monitored fever and sickness behaviour in CA and WA birds using a novel telemetric technique: skin-mounted radiotransmitters with temperature sensors.3. In 2007, territorial defence varied by latitude, with a lower probability of territorial response at 24 h after injection in CA, but not in WA or AK. Radiotelemetry in 2008 revealed that CA birds showed pronounced and prolonged lethargy and fever (c. 2 °C above control males throughout the night), whereas WA birds showed only moderate lethargy and fever (c. 1 °C, returning to control levels during the night).4. This study establishes radiotelemetry as a powerful method for quantifying fever and sickness behaviours in small, free-living vertebrates. Moreover, our data suggest that latitude predicts the strength of these responses. These results can provide insight into disease susceptibility and spread among wild populations.

Peripheral blood monocytes of foals (n = 7) were isolated in the first day of life and monthly thereafter up to 3 months of life. Adult horse (n = 7) monocytes were isolated and tested once for comparison. Isolated monocytes were stimulated with IL-4 and GM-CSF (to obtain ...

Juvenile hormone (JH) acts on membrane of follicle cells to induce ovarian patency for vitellogenesis, though it regulates various other physiological processes via putative intracellular receptors. This study suggests another JH membrane action by analyzing in vitro hemocyte behavior. In response to nonself, both granular cells and plasmatocytes of Spodoptera exigua can exhibit cell shape changes through spreading behaviors. Plasmatocytes were separated from total S. exigua hemocytes by Percoll gradient and exposed in vitro to an insect cytokine, plasmatocyte-spreading peptide (PSP), identified from Pseudoplusia includens. In response, the purified plasmatocytes spread in a dose-dependent manner from picomolar to micromolar concentrations. Interestingly, the PSP responses of plasmatocytes in S. exigua varied among different larval ages during fifth instar ( approximately 5 days at 25 degrees C) in a sensitivity order of late (5 days old)<early (1 day old)<mid (3 days old). Co...