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1

Mechanisms of type I interferon signaling in normal and malignant cells

100%
Li Y., Srivastava K. K., Platanias L. C.
Archivum Immunologiae et Therapiae Experimentalis
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2004
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vol. 52
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issue 3
156-163
EN
Type I interferons (IFNs) are cytokines that induce multiple biological effects on target cells, including antiviral, antiproliferative, and immunomodulatory activities. Consistent with the pleiotropic nature of these cytokines, multiple signaling pathways are activated during binding of IFNs to the type I IFN receptor. An important signaling cascade activated by type I IFNs is the Jak-Stat pathway. Activation of the Tyk-2 and Jak-1 kinases, and downstream formation of various Stat complexes, mediates IFN-dependent gene transcription for IFN-stimulated genes. In addition to the classic Jak-Stat pathway, type I IFNs activate multiple other pathways, including the insulin receptor substrate-phosphatidylinositol 3'-kinase cascade, the CBL-CrkL pathway, and mitogen-activated protein kinase pathways. There is accumulating evidence that non-Stat IFN-regulated signaling pathways play important roles in the generation of the antiproliferative effects of type I IFNs. In this review, the regulation of various signaling cascades by the type I IFN receptor is summarized and an update on recent advances in the field is provided.
2

Mechanisms regulating the development and function of natural regulatory T cells

100%
Gupta S., Shang W., Sun Z.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 2
85-102
EN
The key of the immune system is to protect the host from foreign threat posed by pathogens and from the internal threat posed by self-attacking lymphocytes. The ability to discriminate self versus non-self ensures that only 'non-self' pathogens, but not the self antigens, are attacked. Such tolerance to 'self' arises from the central tolerance mechanisms that include the deletion of thymocytes with high reactivity to self antigens and also the induction of unresponsiveness of autoreactive T cells in the periphery. Natural regulatory T cells (nTregs) directly inhibit effector T cells, and keep their proliferation in control. Apart from preventing autoimmune reactions, Tregs also contribute to peripheral immune homeostasis as evidenced by the excessive lymphocyte accumulation in peripheral lymphoid organs and intestinal inflammation in the absence of nTregs. Here we discuss the molecular aspects of the development and suppressive function of naturally occurring Tregs. Accumulating evidence shows the importance of these Tregs in autoimmunity, tumor immunity, organ transplantation, allergy, and microbial immunity.
3

Ligand-independent activity of the B cell antigen receptor in physiology and pathology

100%
Corcos D.
Archivum Immunologiae et Therapiae Experimentalis
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2007
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vol. 55
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issue 2
77-82
EN
The B cell receptor (BCR) is required for stimulation of B cells by antigen, and is also involved in the negative selection of autoreactive B cells. In the past few years, a constitutive ligand-independent signaling activity of the BCR has been demonstrated. In this paper, the various findings are summarized and their interpretation and their significance, both in pathology and in physiology discussed. The constitutive activity of the BCR may be important for tumor formation, at least in the case of heavy-chain diseases, neoplastic proliferations developed from B cells. A large body of evidence suggests that this activity could be required for B cell survival and would play a role in B cell development as a process monitoring BCR functionality. A model explaining signaling in the absence of antigen as a function of dimer formation is proposed. The putative constitutive activity of the pre-BCR is also discussed.
4

The immunological synapse

100%
Klemmensen T., Pedersen L. O., Geisler C.
Archivum Immunologiae et Therapiae Experimentalis
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2003
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vol. 51
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issue 6
377-388
EN
Induction of a proper adaptive immune response is dependent on correct transfer of informations between antigen-presenting cells (APCs) and antigen specific T cells. Defects in information transfer may result in development of diseases, e.g. immunodeficiencies and autoimmunity. A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure was termed the ?immunological synapse? (IS). Here, we review molecular aspects concerning IS formation, appearance, and cessation. In addition, proposed functions of the IS are discussed. The process of IS formation occur in a sequential manner initially causing a remarkable large-scale redistribution of a number of integral membrane- and cytosolic proteins. At the T cell/APC interface the structure comprises in its nascent stage a non-random pattern of protein distribution. The protein pattern is regulated during development of the mature IS and is finally organized into concentric rings of co-receptors and adhesive molecules surrounding the T cell antigen receptor (TCR). The relocations of proteins are influenced by passive as well as active mechanisms. Considering the IS as a device enabling cell-cell communication, clarification of its exact function is of huge general as well as therapeutic interest.
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