CONTENTS
- When Antibodies are Antigens.
Felix Milgrom
Review
- How Endothelial Cell Organo-Specificity Mediates Circulating Cell Homing
Claudine Kieda (Centre de Biophysique Moléculaire, 45071 Orléans CEDEX 2, France)Abstract. Normal and transformed cells are homing from the circulation into tissues in a very selective way thanks to highly complex molecular mechanisms that govern cell-to-cell interactions and drive the homing of circulating cells to be achieved properly. Because this is characterised by a resulting high selectivity, it constitutes a template for targeted drug-, gene- or cell-therapy strategies. Designing a mimetic-based therapy requires the identification of the responsible selective molecules but also, their mechanisms of action and interactions with their ligands, together with their biological modulation and regulation. This homing/invasion event happens to be decisive at the level of the endothelium that lines the vessel walls. Since cell-to-cell interactions mean a double recognition process, this review will illustrate the part played by the endothelial cells (EC) and their adhesion molecules: the protein as well as the glycan part point of view, the chronology and environmental modulation of EC adhesion molecules expression. These characteristics should provide keys to understand the resulting overall specificity of cell localisation. Taking into account the cytokine microenvironment, it was recently documented a fundamental role for locally secreted chemokines which act through their restricted presentation by endothelial cells. As such, chemokines contribute to illustrate the concept of endothelial organo-specificity which is approached here uncovering the role of glycoconjugates signalling as the hallmark of refined cellular recognitions and discussed, in the context of potential drug design against site-directed diseases as metastases, inflammatory leukocytes recruitment, tumour/inflammation-induced angiogenesis…
Keywords: adhesion; chemokines; endothelial cell; lectins/glycoconjugates.
- Suppressors of Cytokine Signaling Proteins in Innate and Adaptive Immune Responses
Alexander Dalpke and Klaus Heeg (Institute of Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany)Abstract. Suppressors of cytokine signaling (SOCS) proteins have been identified as important mediators of negative regulatory circuits within cytokine receptor signaling. They are induced upon stimulation by an increasing set of cytokines as well as further immunological stimuli and are capable to inhibit Janus-kinases and signal transducer and activator of transcription signaling. Inhibition is mediated by interfering directly with signal transduction at the receptor as well as targeting of associated molecules for proteosomal degradation. Targeted gene deletion approaches have revealed the importance of SOCS mediated termination of cytokine signaling during normal cellular activation. In addition to their function as classical feedback inhibitors SOCS proteins display a broad panel of inhibitory activity thereby mediating cross-talk modulation between different stimuli. The consequences for regulation of innate and adaptive immune responses are thus obvious. Finally, there are emerging data showing involvement of SOCS proteins in various immune diseases. Modulating SOCS activity could be a promising new approach for molecular therapeutic strategies.
Keywords: cytokine receptor signaling, immune system, inhibition, suppressors of cytokine signaling (SOCS)
- From Inflammation to Sickness: Historical Perspective
Barbara Plytycz1 and Rolf Seljelid2 (1Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, R. Ingardena 6, 30-060Kraków, Poland, 2 Institute of Medical Biology, University of Tromso, Norway)Abstract. The concept of four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, extended later by functio laesa (redness and swelling with heat and pain, extended later by loss of function). The contemporary understanding of this process we owe to nineteen-century milestone discoveries by Rudof Virchow, Julius Cohnheim, and Elie Metchnikoff. In twentieth century, the development of potent technological tools allowed the rapid expansion of knowledge of cells and mediators of inflammatory processes, and molecular mechanisms of their interactions. It turned out that some mediators of inflammation have both local and distant targets, among them the liver (responding by production of several acute phase reactants) and neurohormonal centres. In the last decades it has become clear that the immune system shares mediators and their receptors with the neurohormonal system of the body; thus they form a common homeostatic entity. Such an integrative view, introduced by J.Edwin Blalock, when combined with Hans Selye’s concept of stress, led to the contemporary understanding of sickness behaviour, defined by Robert Dantzer as a highly organised strategy of the organism to fight infections and to respond to other environmental stressors.
Keywords: local inflammatory response; acute phase response; sickness behaviour; immune-neuroendocrine network.
- The Dynamic and Complex Role of Mast Cells in Allergic Disease
Marianna Kulka and A. Dean Befus (Pulmonary Research Group, 550A HMRC, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada)Abstract. 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.
Keywords: mast cells; allergy; IgE; proteases; cytokines.
- NK T Cell-NK Cell Cross-Talk: Reciprocal Interaction and Activation?
Johnna Wesley and Laurent Brossay (Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA)Abstract. Initiation and propagation of the immune response is the result of a series of coordinated cellular and biochemical interactions that lead to the activation of multiple cell types. It is now clear that an optimal immune response requires a precise and rapid communication between different cell subsets. This phenomenon, referred to as cross-talk, is believed to be an essential component of the immune response that provides necessary inflammatory mediators and cytolytic activity for controlling infections and diseases. An example of an effective cooperation between different cell types has been recently illustrated by the finding that specific activation of CD1 restricted natural killer T cells (NK T) can quickly lead to the activation of other subsets of cells such as natural killer (NK) and CD8 T cells.
Keywords: T cells cross-talk, NK cells, NK T cells, NK activation.
Immunogenetic
- Distribution of HLA-C Alleles Determined by PCR-SSP in Population of Low Silesia
Magdalena Prussak, Maria Mańczak, Bogusława Pochroń, Izabela Nowak and Piotr Kuśnierczyk (Laboratory of Immunogenetics, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland)Abstract. We typed 100 unrelated healthy Poles from Low Silesia region for HLA-C using low resolution PCR-SSP and compared observed allele frequencies with data published for other human populations. Poles appeared to be most similar to Germans and Englishmen, and were more distant from French, Catalans and Basques and dissimilar to non-Caucasoids from Equatorial Guinea and Japan. It would be interesting to HLA-C-type other Slavian and non-Slavian people from Middle and Eastern Europe for comparison.
Keywords: HLA-C, allele distribution, PCR-SSP typing, Low Silesian Polish population.
Infectious Immunology
- Serological Differentiation of H. pylori CagA(+) and CagA(-) Infections
Magdalena Chmiela1, Monika Wiśniewska1, Leokadia Bąk-Romaniszyn2, Tomasz Rechciński3, Izabela Płaneta-Małecka2, Władysław Bielański4, Stanisław J. Konturek4, Małgorzata Płonka4, Magdalena Klink5 and Wiesława Rudnicka1 (1Department of Immunology and Infectious Biology, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland, 2Mother and Child Health Center, Rzgowska 281/289, 93-338 Łódź, Poland, 3Dr W. Biegański’s Hospital, Medical University, Kniaziewicza 1/5, 91-347 Łódź, Poland, 4Department of Physiology, Medical Academy, Jagiellonian University, Grzegórzecka 16, 31-532 Kraków, Poland, 5Microbiology and Virology Centre, Polish Academy of Sciences, Lodowa 106, 93-232 Łódź, Poland)
Abstract. Many of H. pylori strains causing gastroduodenal diseases have a cagA gene encoding CagA protein, a virulence factor of these bacteria. Anti-CagA antibodies produced by majority of people infected with CagA(+) strains can indicate such infection. In this study the efficacy of three immunoenzymatic tests: immunoblot (Milenia ID Blot H. pylori IgG, DPC Biermann GmbH, Germany) (MB) and ELISA, conducted with a recombinant immunodominant fragment of CagA (rCagA) and full length CagA molecule (flCagA), in detecting CagA(+) and CagA(-) infections, was compared. The 13C urea breath test (13C-UBT) was used for establishing H. pylori status. The serum samples from 157 individuals were used for serodiagnosis. The H. pylori CagA(+) infection was detected in H. pylori infected individuals with similar frequency by MB (64%) and flCagA-ELISA (60%) and little less frequently by rCagA-ELISA (53%). There was a high coincidence between the negative results of these three tests for H. pylori uninfected individuals with no anti-CagA IgG in the serum (96-100%). The results show that rCagA-ELISA and especially flCagA-ELISA are easy, inexpensive and useful noninvasive assays for discrimination of CagA(+) and CagA(-) H. pylori infections in the subjects examined by urea breath test.
Keywords: Helicobacter pylori, CagA, serodiagnosis.