Langerhans Cell Migration: Not Necessarily Always at the Center of the Skin Sensitization Universe

Since their discovery in 1868, the role of Langerhans cells (LCs) in skin immunity has been researched extensively. Recent data deriving from transgenic animals that are deficient in LCs have begun to challenge the dogma that there is a universal requirement for these cells in the development of skin sensitization. This Commentary addresses relationships between LC mobilization, draining lymph node activation, and skin sensitization using immunomodulators agonistic for a family of sphingosine-1-phosphate (S1P) receptors

Impaired Langerhans cell migration in psoriasis

We have examined whether psoriasis is associated with systemic effects on epidermal Langerhans cell (LC) function and, specifically, the migration of LCs from the skin. Compared with normal skin, the frequency and morphology of epidermal LCs in uninvolved skin from patients with psoriasis was normal. However, mobilization of these cells in response to stimuli that normally induce migration (chemical allergen, tumor necrosis factor α [TNF-α], and interleukin-1β [IL-1β]) was largely absent, despite the fact that treatment with TNF-α and IL-1β was associated with comparable inflammatory reactions in patients and controls. The failure of LC migration from uninvolved skin was not attributable to altered expression of receptors for IL-1β or TNF-α that are required for mobilization, nor was there an association with induced cutaneous cytokine expression. Although a role for altered dynamics of LC migration/turnover has not been formally excluded, these data reveal a very consistent decrement of LC function in psoriasis that may play a decisive role in disease pathogenesis

Assessment of the inherent allergenic potential of proteins in mice.

There is considerable interest in the design of approaches that will permit the accurate identification and characterization of proteins that have the inherent potential to induce sensitization and cause food allergy. Among the methods used currently as part of such assessments are consideration of structural similarity to, or amino acid sequence homology with, known human allergens; whether there exists immunologic cross-reactivity with known allergens; and measurement of resistance to proteolytic digestion in a simulated gastric fluid. Although such approaches provide information that will contribute to a safety assessment, they do not--either individually or collectively--provide a direct evaluation of the ability of a novel protein to cause allergic sensitization. For this reason, work is in progress to design and evaluate suitable animal models that will provide a more holistic assessment of allergenic potential. In this laboratory, the approach we have taken has been to examine the characteristics of immune responses induced in mice following parenteral (intraperitoneal) exposure to test proteins. The basis of this method is to determine simultaneously the overall immunogenic potential of proteins [measured as a function of immunoglobulin (Ig) G antibody responses] and to compare this with their ability to provoke IgE antibody production, IgE being the antibody that effects allergic sensitization. Although this approach has not yet been evaluated fully, the results available to date suggest that it will be possible to distinguish proteins that have the inherent potential to induce allergic sensitization from those that do not. In this article we summarize progress to date in the context of the scientific background against which such methods are being developed

Анализ методов вибродиагностики металлорежущих станков

Цель работы - выработка рекомендаций по применению методов вибродиагностики металлорежущих станков в конкретной задаче. Объект исследования - методы и комплексы вибродиагностики металлорежущих станков. Предмет исследования – систематизация и обобщение методов вибродиагностики металлорежущих станков. Актуальность - отсутствие простой для реализации методики виброиспытаний. В процессе работы были рассмотрены различные методы вибродиагностики металлорежущих станков, сделаны предложения по применению методов вибродиагностики металлорежущих станков в каждой конкретной задаче, создана универсальная методика проведения вибродиагностики металлорежущих станков диагностическим комплексом "Виброрегистратор-М2".The aim of the work is to develop recommendations on the application of vibration diagnostics methods for metal-cutting machine tools in a specific task. The object of research is methods and complexes of vibration diagnostics of metal cutting machines. The subject of the study is the systematization and generalization of methods of vibration diagnostics of metal-cutting machines. Actuality is the absence of a simple vibration testing technique. In the course of the work various methods of vibration diagnostics of metal cutting machines were considered, suggestions were made on the application of vibration diagnostics methods for metal cutting machines in each specific task, a universal technique for performing vibration diagnostics of metal cutting machines with the Vibroregistrator-M2

Assessment of protein allergenicity on the basis of immune reactivity: animal models.

Because of the public concern surrounding the issue of the safety of genetically modified organisms, it is critical to have appropriate methodologies to aid investigators in identifying potential hazards associated with consumption of foods produced with these materials. A recent panel of experts convened by the Food and Agriculture Organization and World Health Organization suggested there is scientific evidence that using data from animal studies will contribute important information regarding the allergenicity of foods derived from biotechnology. This view has given further impetus to the development of suitable animal models for allergenicity assessment. This article is a review of what has been achieved and what still has to be accomplished regarding several different animal models. Progress made in the design and evaluation of models in the rat, the mouse, the dog and in swine is reviewed and discussed

Antibody-dependent destruction of neoplastic cells by cellular effectors

The in vitro cytotoxic potential of a range of antibodies reacting with surface antigens of neoplastic B- lymphocytes has been investigated in an antibody-dependent cell- mediated cytotoxicity assay (ADCC). The majority of the work has involved antibodies reacting with the surface im-munoglobulin molecules of the guinea pig leukaemic L3C cell and the human lymphoblastoid Daudi cell.Except where otherwise stated lysis was mediated by human effector cells prepared from venous blood of normal donors. There was marked variation in cytotoxic capacity from one donor to another, but much less variation among different samples from individual donors. Otherwise in both target cell systems cytotoxic capacity was shown to be dependent upon both the nature of the antibody and of the effector cell population.In the L2C target cell system, sheep antibody did not direct lysis with lym-phocytic or monocytic effectors. Mouse monoclonal antibodies of IgGl, IgG2a and IgG2b isotypes directed lysis only with monocytic effectors whilst antibodies with human, guinea pig and rabbit Fc regions directed lysis which was mediated mainly by lymphocytic effectors. Li the Daudi cell system, antibodies with sheep, human and rabbit Fc regions yielded the same lytic profiles with lymphocytic and monocytic effectors as they did in the L2C cell system, but the mouse monoclonal IgGl antibody was ineffective at directing lysis with either effector. Polymorphonuclear leukocytic effectors did not mediate lysis of LjC cells coated with any antibody but efficiently lysed Daudi cells coated with any of the antibodies at high concentrations. The modulatory capacity of antibody, that is its tendency to cause redistribution and internalization of surface antigen, was not of major importance in determining the ability to direct ADCC in either target cell system.The ADCC mediated by human lymphocytes could be enhanced by treatment of effectors with human recombinant interferon--y (sixteen hours) or interleukin-2 (three hours). The conventionally defined lymphokine-activated killer (LAK) cell population, obtained by five-day culture of blood mononuclear (lymphocytic plus monocytic) cells in interleukin-2, yielded greater ADCC than did the same effectors unstimulated. The same dependence on antibody isotype was observed as occurred with stimulated and unstimulated lymphocytic effectors.Lysis of a range of antibody-coated targets (L2C, Daudi and chick ery-throid cells) mediated by guinea pig lymphocytic effectors was also investigated because of our interest in immunotherapy in these animals. Daudiand L2C cells proved to be resistant to ADCC directed by all antibodiestested. Only the erythroid targets were susceptible. Oestrogen-treatmentof the donors, reported to augment effector cell cytotoxic potential, yieldedcells capable of inflicting a significant degree of lysis irrespective of thepresence of antibody.</p