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1

Allergen-specific T lymphocytes as targets for specific immunotherapy: striking at the roots of type I allergy

100%
Bohle B.
|
|
issue 4
233-242
EN
In the past decades allergic diseases have tremendously increased and hypersensitivity reactions now represent a growing health concern in industrialized countries. Despite various effective therapeutic options for the treatment of allergic diseases, only specific immunotherapy (SIT) has been shown to have effects on the underlying immunological mechanisms, namely functional changes at the level of T helper lymphocytes (Th). It was found that allergen-specific CD4+ Th2 lymphocytes play a key role in the pathophysiology of atopic diseases. During successful SIT, the Th2-dominated immune response is modified towards a Th1 response, leading to a decline in allergen-specific IgE levels in the long term. In order to improve the efficacy and safety of SIT, novel approaches were developed targeting allergen-specific Th2 lymphocytes since specific inactivation or modulation towards Th1 cells could interfere with the disease process. In view of this aspect, this review will basically focus on two new promising approaches to improve SIT: 1) the use of hypoallergenic proteins characterized by reduced IgE-binding capacities but retained T lymphocyte-activating properties and 2) oligodeoxynucleotides containing CpG motifs as an example of adjuvants which foster Th1 immune responses. Both approaches promise to be capable of adjusting the pathological Th2 immune response.
2

Application of DNA microarray technology in studies of human allergy

100%
Woronowicz W. W., Sikorski M. M.
Biotechnologia
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2008
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issue 4
115-130
EN
Allergy is a complex genetic disorder contributing numerous genes, especially involved in Th2 immunity and IgE synthesis. Additional, environmental factors like: allergens exposure, cigarette smoke, pollutants, infectious agents and many others, have influence in allergy development. With DNA microarray technology it is possible to search for genes expression profiles of all interacting genes in pararel and learn more about the mechanism of allergy. These research include genes expression profiling of different model organisms (human, mice, monkey) and cell cultures.
3

Positive and negative regulatory mechanisms in high-affinity IgE receptor-mediated mast cell activation

100%
Roth K., Chen W.-M., Lin T.-J.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 6
385-399
EN
Mast cells are important effector cells in allergic inflammatory reactions. The aggregation of the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells initiates a complex cascade of signaling events that ultimately leads to the release of various mediators involved in allergic inflammation and anaphylactic reactions. The release of these mediators is tightly controlled by signaling pathways that are propagated through the cell by specific phosphorylation and dephosphorylation events. These events are controlled by protein kinases and protein phosphatases which either positively or negatively regulate the propagation of the signal through the cell. This review summarizes the role of both positive and negative regulators of Fc?RI-induced mast cell activation.
4

Low molecular weight protein tyrosine phosphatase and human disease: in search of biochemical mechanisms

88%
Bottini N., Bottini E., Gloria-Bottini F., Mustelin T.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
|
issue 2
95-104
EN
A major challenge in the post-genomic era is to identify the physiological function of genes and elucidate the molecular basis for human disease. Genetic polymorphisms offer a convenient aveune for these efforts by providing evidence for the involvement of a given gene in human pathophysiology. Here we review the current evidence linking the low molecular weight protein tyrosine phosphatase (LMPTP) to several common diseases, including allergy, asthma, obesity, myocardial hypertrophy, and Alzheimer's disease. Based on the know effects of the genetic polymorphisms on the alternative mRNA splicing and enzyme levels of LMPTP, we discuss the possible molecular mechanisms of LMPTP involvement in these diseases.
5

Suppression of mast cell activation by glucocorticoid

88%
Yoshikawa H., Tasaka K.
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|
vol. 48
|
issue 5
487-496
EN
Mast cells play a critical role in allergic diseases. When mast cells are activated by cross-linking of their high affinity IgE receptors by the antigen and IgE antibodies, release of chemical mediators is followed by secretion of multiple cytokines. We report that IL-3-dependent mucosal-type mast cells undergo apoptosis when IL-3 is withdrawn. In addition, cross-linking of high affinityIgE receptors prevents apoptosis of mast cells by paractine mechanisms, producing IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). However, the secretion of endogenous growth factors are not enough for cell survival, whereas IL-4 induces cell aggregation by expressing adhesion molecules such as leukocyte function-associated antigen 1 (LFA-1), and makes it reactive to endogenous growth factors by contact cell to cell interaction. On the other hand, dexamethazone down-regulates the expression of intracellular adhesion molecule 1 (ICAM-1) and IL-4 in activated mast cells, by which the self-aggregation of mast cells is inhibited and poptosis is induced. Thus, glucocorticoids suppress mast cell survival by inhibiting IL-4 production and expression of adhesion molecules.
6

The dynamic and complex role of mast cells in allergic disease

88%
Kulka N., Befus A. D.
Archivum Immunologiae et Therapiae Experimentalis
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2003
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vol. 51
|
issue 2
111-120
EN
Mast cells (MC) are found widely distributed in tissues and contribute to regulation of inflammatory responses and ongoing modulation of the tissues. Although MC are important in a variety of processes including innate immunity, their role in allergic disease has received increasing attention in the past decade. MC are located throughout the human body and upon allergen exposure they are stimulated via the IgE receptor (FceRI) to release several proinflammatory mediators such as tumor necrosis factor (TNF), reactive oxygen species such as nitric oxide (NO), proteases, and lipid-derived mediators. However, we now recognize that MC can be activated by a variety of mechanisms and that mediator release is a consequence of several intra- and extracellular signals. Some of these mechanisms, such as Fc receptor aggregation and proteinase activated receptor (PAR)-mediated activation facilitate and augment local inflammatory responses. Other mechanisms, such as interferon gamma (IFN-gamma) induction of nitric oxide (NO) may inhibit MC function and downregulate inflammatory responses. Increased understanding of these complex pathways has encouraged the development of therapies for allergic inflammation that target specific MC functions and mediators. Some novel strategies include oligonucleotides that induce or inhibit the production of specific mediators. Such approaches may yield useful therapies for allergic individuals in the near future.
7

Phage display as a tool for rapid cloning of allergenic proteins

88%
Appenzeller U., Blaser K., Crameri R.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
|
issue 1
19-26
EN
Allergic diseases represent an immune disorder associated with the production of immunoglobulin E (IgE) against normally innocuous antigens (allergens). Almost 20% of the population in industrialised countries suffer from Type I allergic symptoms like allergic rhinitis, conjunctivitis, urticaria or asthma. Although the mechanisms responsible for these allergic reactions are quite well understood, knowledge about the repertoire of molecules able to elicit Type I symptoms is still limited. To clone and characterise entire allergen repertoires from complex allergenic sources in a fast and efficient way, new technologies are required. The phage surface display of cDNA libraries described here has proven to be a versatile cloning system to selectively isolate allergens physically linked to their genetic information. The screening of cDNA libraries displayed on phage surface with immobilised serum IgE from allergic patients reduces the time required for the selection of candidate clones to a few weeks. Robot assisted high throughput screening of enriched library provides a fast and cost-effective way to isolate complete allergen repertoires. The biotechnological production of recombinant allergens derived from these sequences bear a high potential for the improvement of the diagnosis of allergic diseases.
8

Specific allergen induced motility of peripheral blood mononuclear cells and polymorphonuclear leukocytes in insect sting allergy

88%
Zak-Nejmark T., Malolepszy J., Jutel M., Nittner-Marszalska M.
|
|
vol. 40
|
issue 2
107-111
EN
The motility of perpheral blood mononuclear cells (MNC) and polymorphoxnuclear (PMN) leukocytes form normal and bee venom allergic subjects was investigated by a modified Boyden micropore filter method. The study comprised MNC locomotion in bee venom and gradients and PMN locomotion in bee venom and fMLP gradients. We demonstrated statistically significant increase in MNC and PMN motility towards bee venom in allergic patients group. This effect disappeared after the preincubation of MNC with anti-human IgE antiboidies. We observed no such effect in PMN leukocytes. Increased MNC motility in histamine gradient was observed only in control subjects group. Similarily significant increase in PMN locomotion towards fMLP was found in both allergic and control subjects. The results here demonstrated suggest that a specific allergen might be a chemoattractant for peripheral blood MNC and PMN leukocytes from atopics and could be capable to induce non-infectious inflammatory reactions as a result of its interaction with these sensitive cells.
9

Effects of Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) larvae on the degranulation of dermal mast cells in mice; an electron microscopic study

88%
Kalender Y., Kalender S., Uzunhisarcikli M., Ogutcu A., Acikgoz F.
Folia Biologica
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2004
|
vol. 52
|
issue 1-2
13-17
EN
The pine caterpillar Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) is found in pine woods. Hairs of the T. pityocampa caterpillar cause a cutaneous reaction in humans and animals. Mast cells are responsible for allergic reactions in mammals. In this study male swiss albino mice were divided into two groups: 5 mice in the control group and 25 mice in the experimental group. The dorsal skin of mice was shaved. The mice in the experimental group and T. pityocampa larvae (fifth instar, approximately n=100) were put in the same cage. Dermal mast cells of mice exposed to T. pityocampa were examined with a transmission electron microscope and compared to the control group 1, 3, 6, 12 and 24 hours after exposure. Dermal mast cell degranulation in mice was observed 12 and 24 hours after exposure.
10

Recent advances in understanding how interleukin 13 signals are involved in the pathogenesis of bronchial asthma

88%
Izuhara K., Umeshita R., AkaiwaM., Shirakawa T., Deichmann K. A., Arima K., Yu B., Hamasaki N., Hopkin J. M.
|
|
vol. 48
|
issue 5
505-512
EN
The prevalence of allergic disease has dramatically increased in recent decades, especially in urban and industralized areas. Allergic disease are disorders of the immune system, the results of complex interactions among various genetic and environmetal factors. Among them, the important role of interleukin 13 (IL-13), a TH2-type cytokine, has recently emerged in the pathogenesis of bronchial asthma. Based on studies using mice, great attention has been paid to the direct effects of IL-13 on bronchial tissues. In this review, we describe recent advances in understanding the signal transduction mechanism of IL-13, the infolvement of IL-13 signal-related genes as genetic factors in the pathogenesis of bronchial asthma, and the expression of IL-13 receptor on bronchial tissues. We describe potential strategies for targeting IL-13 signals to improve allergic states.
11

Mast cells and cytokines - new insight into the participation of mast cells in inflamatory reactions

75%
Kuprys I., Kuna P.
Postępy Higieny i Medycyny Doświadczalnej
|
1996
|
vol. 50
|
issue 1
43-63
EN
Tissue mast cells are multifunctional immune cells and have been implicated in allergic and inflammatory reactions. They used to be regarded merely as a source of histamin, prostaglandins and leukotriens which mediated the symptoms of the acute allergic reaction but more recent work has indicated they are involved in many inflammatory reactions. The discavory of production and secretion of a unique array of cytokines by these cells has suggested new ways in which they could influence to the development of inflammation. Many experiments have disclosed that mast cells owning to cytokines can not only initiate but also regulate and modulate this process. With the results come the realisation that these cytokines might represent important effector molecules in a variety of pathologic and physiologic processes where mast cells involvment had been postulated but an understanding of the mechanisms remained obscure. The aim of this article is introduction the biology of mast cells and presentation the information concern production and secretion of cytokines by these cells like also influence of these biologically active molecules on inflammatory process.
12

Surfactant proteins SP-A and SP-D in human health and dis

75%
Kishore U., Lopez B. A., Kamran M. F., Saxena S., Singh M., Sarma P. U., Madan T., Chakraborty T.
Archivum Immunologiae et Therapiae Experimentalis
|
2005
|
vol. 53
|
issue 5
399-417
EN
Surfactant proteins A (SP-A) and D (SP-D) are lung surfactant-associated hydrophilic proteins which have been implicated in surfactant homeostasis and pulmonary innate immunity. They are collagen-containing C-type (calcium-dependent) lectins, called collectins, and are structurally similar to mannose-binding protein of the lectin pathway of the complement system. Being carbohydrate pattern-recognition molecules, they recognize a broad spectrum of pathogens and allergens via the lectin domain, with subsequent activation of immune cells via the collagen region, thus offering protection against infection and allergenic challenge. SP-A and SP-D have been shown to be involved in viral neutralization, clearance of bacteria, fungi, and apoptotic and necrotic cells, the down-regulation of allergic reaction, and the resolution of inflammation. Studies on single-nucleotide polymorphism, protein levels in broncho-alveolar lavage, and gene knock-out mice have clearly indicated an association between SP-A and SP-D and a range of pulmonary diseases. In addition, recent studies using murine models of allergy and infection have raised the possibility that the recombinant forms of SP-A and SP-D may have therapeutic potential in controlling pulmonary infection, inflammation, and allergies in humans.
13

Targeting Janus kinase 3 in the treatment of leukemia and inflammatory diseases

75%
Cetkovic-Cvrlje M., Uckun F. M.
Archivum Immunologiae et Therapiae Experimentalis
|
2004
|
vol. 52
|
issue 2
69-82
EN
Janus tyrosine kinases (JAKs) are cytoplasmic protein tyrosine kinases that play a crucial role in the initial steps of cytokine signaling. JAK3, a member of JAK kinase family of four (JAK1, JAK2, JAK3 and TYK2), is abundantly expressed in lymphoid cells. JAK3 has been found to initiate signaling of interleukin (IL)-2, IL-4, IL-7, IL-9, IL-13 and IL-15. Indispensable role of JAK3 in lymphocyte development and function has been revealed recently. Because of the involvement of JAK3 in T cell activation and proliferation, and the documented genetic evidence for the role of JAK3 in autoimmune or transplant -induced inflammatory disorders, the selective targeting of JAK3 in T cells may potentially be clinically beneficial in T cell-derived pathologic disorders. In this review we discuss inhibitors of JAK3 as a new class of immunomodulatory agents with immunosuppressive, anti-inflammatory, anti-allergic, and anti-leukemic properties. Preclinical data from multiple experimental model systems of autoimmune diabetes, allergy, solid organ transplantation, pancreatic islet transplantation and bone marrow transplantation are discussed in the context of the clinical need for new immunomodulatory agents with such properties.
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