Tolling for autoimmunity-prime time for 7

The reason certain self-antigens are consistently targeted by autoantibodies may be because they are self-adjuvants. Two papers in this issue of Immunity provide important insights into the contribution of Toll-like receptors in systemic autoimmune disease (Berland et al., 2006; Christensen et al., 2006).     

Receptor editing for better or for worse

Receptor editing has emerged from its original identification as a minor secondary mechanism of B cell tolerance to be considered as a dominant mechanism by which autoreactive immature B cells are rendered tolerant. Clonal deletion, previously regarded as the major mechanism of central B cell tolerance, has been shown by recent studies to operate secondarily and only when receptor editing is unable to provide a non-autoreactive specificity. Receptor editing has also been shown to operate during the development of wild-type B lymphocytes, and ongoing investigations demonstrate the influence of particular signaling molecules in the induction and/or inhibition of receptor editing. Together, these studies begin to map the signaling pathways that regulate receptor editing in autoreactive and non-autoreactive immature B cells.     

Prospects for peptide-based immunotherapy for dog allergy

PURPOSE OF REVIEW: Tolerance to ubiquitous environmental substances, allergens, can be accomplished with specific immunotherapy. Conducting therapy with allergen peptides helps to avoid immediate allergic reactions. Dogs are a source of important indoor allergens, which necessitates the development of effective modes of therapy against the allergy they cause. RECENT FINDINGS: The human T-cell epitopes of the major dog allergen Can f 1 were determined recently. They were found to be distributed in seven epitope regions along the molecule. For the peptide immunotherapy of dog allergy, using a pool of seven peptides, one from each of the epitope regions of Can f 1, seems at present to be the best approach. As Can f 1 is not as immunodominant as the main allergens of some other mammals, it remains to be seen whether peptides from other dog allergens should be included in the pool. SUMMARY: The use of a pool of seven peptides from the T-cell epitope regions of Can f 1 is likely to be feasible for treating dog allergy in a great majority of Caucasian populations. In the future, patient-tailored preparations of variants of the T-cell epitope-containing peptides may offer a way to enhance the efficacy of peptide-based immunotherapy.     

Materials for phantoms for terahertz pulsed imaging

Phantoms are commonly used in medical imaging for quality assurance, calibration, research and teaching. They may include test patterns or simulations of organs, but in either case a tissue substitute medium is an important component of the phantom. The aim of this work was to identify materials suitable for use as tissue substitutes for the relatively new medical imaging modality terahertz pulsed imaging. Samples of different concentrations of the candidate materials TX151 and napthol green dye were prepared, and measurements made of the frequency-dependent absorption coefficient (0.5 to 1.5 THz) and refractive index (0.5 to 1.0 THz). These results were compared qualitatively with measurements made in a similar way on samples of excised human tissue (skin, adipose tissue and striated muscle). Both materials would be suitable for phantoms where the dominant mechanism to be simulated is absorption (approximately 100 cm(-1) at 1 THz) and where simulation of the strength of reflections from boundaries is not important; for example, test patterns for spatial resolution measurements. Only TX151 had a frequency-dependent refractive index close to that of tissue, and could therefore be used to simulate the layered structure of skin, the complexity of microvasculature or to investigate frequency-dependent interference effects that have been noted in terahertz images.     

Design methodology for aids for the disabled

Although many aids for the disabled appear to be quite simple, their design is subject to many difficulties. These problems arise because of the intimate relationship between the equipment and the human body. Equipment design is therefore affected by many biological variables that are difficult to define at the beginning of the design exercise and many will not even be obvious until a device is tried out with a user. Standard design methodologies rely on all the variables being defined in a thorough specification at the start of the design process and therefore often lead to ineffective devices or very long development programmes. An alternative methodology is presented which overcomes the problems by separating the user interface aspects of the design from the supporting features. The user interface aspects are then allowed to evolve in conjunction with tests with potential users and finally integrated with the supporting features once a satisfactory solution has been found. Much more effective devices result with much shorter development effort.     

Prospects for a Vaccine for Clostridium difficile

Clostridium difficile diarrhoea and colitis is a new disease that is attributable to broad spectrum antibiotic therapy. During the past 2 decades C. difficile has become one of the most common nosocomial pathogens in the developed world. As changing demographics create an increasingly elderly population and the use of broad spectrum antimicrobials continues to expand, C. difficile is likely to become increasingly problematic. Disease caused by this organism is caused by the inflammatory actions of its 2 toxins, A and B, on the intestinal mucosa. Human antibody responses to these toxins are common in the general population and in patients with C. difficile-associated disease. There is substantial, albeit inconclusive, evidence to indicate that antitoxin antibodies provide protection against severe, prolonged or recurrent C. difficile diarrhoea. Immunity induced by oral or parenteral passive administration of antibody is protective in animal models of C. difficile infection. In humans, intravenous passive immunisation with pooled human immunoglobulin has been successful in the treatment of recurrent and severe C. difficile colitis. Human trials of oral passive immunotherapy with bovine immunoglobulin therapy are in progress. Formalin-inactivated culture filtrate from toxigenic C. difficile, as well as purified and inactivated toxins, have been used to successfully immunise animals. Similar preparations are under investigation as possible human vaccines. Antibiotic therapy is effective in treating most individual patients with C. difficile diarrhoea, but has proven ineffective in reducing the overall incidence of nosocomial infection. Active immunisation is probably the most promising approach to long term control of this difficult iatrogenic disease.     

Criteria for EASO-collaborating centres for obesity management

Obesity is recognised as a global epidemic and the most prevalent metabolic disease world-wide. Specialised obesity services, however, are not widely available in Europe, and obesity care can vary enormously across European regions. The European Association for the Study of Obesity (EASO, www.easo.org) has developed these criteria to form a pan-European network of accredited EASO-Collaborating Centres for Obesity Management (EASO-COMs) in accordance with accepted European and academic guidelines. This network will include university, public and private clinics and will ensure that the obese and overweight patient is managed by a holistic team of specialists and receives comprehensive state-ofthe-art clinical care. Furthermore, the participating centres, under the umbrella of EASO, will work closely for quality control, data collection, and analysis as well as for education and research for the advancement of obesity care and obesity science.