CONTENTS
Review
- Three-Dimensional Structures of MHC Class I-Peptide Complexes: Implications for Peptide Recognition
KARINA PERSSON and GUNTER SCHNEIDERAbstract. Over the last decade, the number of crystal structures of major histocompatibility complex (MHC) class I-peptide complexes has increased rapidly. These studies have provided unique and fascinating insights into the structural basis of MHC-peptide interactions and the specificity of peptide recognition by MHC class I molecules.
Keywords: MHC class I; peptide binding; protein crystallography.
- A Burgeoning Family of Biological Mediators: Chemokines and Chemokine Receptors
YINGYING LE1, WANGHUA GONG2, WEIPING SHEN1, BAOQUN LI2, NANCY M. DUNLOP1 and JI MING WANG1Abstract. Chemokines are a superfamily of pro-inflammatory polypeptide cytokines that selectively attract and activate different cell types. Most of its members are small proteins that exhibit conserved cysteines in specific positions. Chemokines activate cells through their binding to shared or unique cell surface receptors which belong to the seven-transmembrane (STM), G-protein-coupled receptors (GPCRs). The large number of chemokines and chemokine receptors are indicative of the importance of these molecules in a variety of pathophysiological conditions.
Keywords: chemokines; G protein-coupled receptor; leukocytes.
- Listeria monocytogenes as an Alternative Vaccine Vector for HIV
MARIELENA MATA and YVONNE PATERSONAbstract. The necessity for an HIV vaccine and a brief review of current strategies towards this aim are given here to set into context contemporary studies towards exploiting the bacterium Listeria monocytogenes as an HIV vaccine vector. The cell biology and immunology of this unusual intracellular organism are also reviewed, in addition to its application to introducing viral antigens, including HIV antigens, to the immune system.
Keywords: HIV vaccine; Listeria monocytogenes; vaccine vector.
- Beyond a Structural Component: Sphingolipids in Immunology
EVA E. PRIESCHL and THOMAS BAUMRUKERAbstract. Two major classes of lipids paricipating in signaling cascades in immune cells are known today. One comprises glycerol-based lipids with diacylglycerol as its most prominent member that mediates the activation of classical and novel protein kinase C molecules. The second group contains the sphingolipids, with the best-investigated representatives being sphingosine, sphingosine-1-phosphate, and ceramide. In the last years the latter two molecules have especially received considerable attention for their modulatory capacity in the course of an apoptotic response. Today it is clear that sphingolipids are ubiquitously distributed in all eukaryotic cells, especially in cellular membranes, where they were previously thought to fulfil an exclusively structural role. Recent findings, however, have demonstrated functions beyond this. Sphingolipid specific G-protein coupled receptors were identified and their role as intracellular second messengers has been further elucidated. In addition, glycosphingolipids, in particular, are enriched in certain membrane compartments, known as detergent resistant membranes. These serve as entry sites for several receptor-mediated signaling events by stabilizing receptor/kinase interactions, suggesting an involvement in the initiation of signaling cascades. Altogether, these findings have led to new insights into both the role of these lipids in signaling as well as the underlying pathology of several diseases with imbalances in the sphingolipid metabolism. The development of these disorders has mainly been attributed to the toxic potential of lysosphingolipids up to now. In addition, attempts have been made to develop compounds and drugs containing the sphingolipid backbone for influencing diseases associated with unwanted cell activation (e. g, cancer, inflammatory processes). These novel findings and developments are reviewed in the following.
Keywords: cell signaling; detergent resistant membranes; intracellular second messengers; sphingolipids.
- Cytokine-Producing T Cell Subsets in Human Leishmaniasis
KARE KEMPAbstract. Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokines leads to subclinical or mild infections. In mice, an infection leads to a polarisation of either Th1 or Th2 Leishmania antigen specific cells. In contrast, both Th1 and Th2 Leishmania antigen specific cells can be identified in humans cured from L. donovani infections. Theoretically, Th1 cells and Th2 cells mutually down-regulate each other. However, the presence of antigen specific regulatory T cell subsets may provide an environment that allows the presence of both Th1 and Th2 cells.
Keywords: human leishmaniasis; cytokines; T cells.
- Current Status and Future Perspectives of DNA Vaccine Delivery by Attenuated Intracellular Bacteria
GUIDO DIETRICHAbstract. Vaccination by intradermal or intramuscular injection of antigen-encoding plasmid-DNA elicits strong cellular and humoral immune responses. Professional antigen presenting cells (APC) seem to induce these responses, making it, therefore, desirable to deliver the plasmid molecules directly to these cells. The exploitation of attenuated intracellular bacteria as DNA delivery vehicles makes the direct targeting of DNA vaccine vectors to professional APC feasible.
Keywords: DNA vaccines; delivery; attenuated intracellular bacteria.
- Prospects for Development of New Antimycobacterial Drugs, with Special Reference to a New Benzoxazinorifamycin, KRM-1648
HARUAKI TOMIOKAAbstract. In this article, I have thoroughly reviewed the status of development of new antimycobacterial drugs, in particular, rifamycin derivatives (rifabutin, rifapentine, and a new benzoxazinorifamycin, KRM-1648), fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, moxifloxacin, and others), new macrolides (clarithromycin, azithromycin, roxithromycin), and others. In this review, I have mainly described the in vitro and in vivo activities of these drugs against Mycobacterium tuberculosis and atypical mycobacteria, especially Mycobacterium avium complex. In addition, therapeutic efficacy of these drugs in cases of clinical treatment of mycobacterial infections have also been briefly mentioned.
Keywords: mycobacterial infection; Mycobacterium tuberculosis; Mycobacterium avium complex; rifamycin; fluoroquinolones; new macrolides.
- Immune Phenomena in Echinoderms
ZDZISŁAW GLIŃSKI and JAN JAROSZAbstract. Advances in biochemistry and molecular biology have made it possible to identify a number of mechanisms active in the immune phenomena of echinoderms. It is obvious that echinoderms have the ability to distinguish between different foreign objects (pathologically changed tissues, microorganisms, parasites, grafts) and to express variable effector mechanisms which are elicited specifically and repeatably after a variety of non-self challenges. The molecular and biochemical basis for the expression of these variable defense mechanisms and the specific signals which elicit one type of effector mechanism are not, however, yet well known. The high capacity of coelomocytes to phagocytose, entrap and encapsulate invading microorganisms is a valid immune cell-mediated mechanism of echinoderms. The entrapped bacteria, discharged cellular materials and disintegrating granular cells are compacted and provoke the cellular encapsulation reaction. Moreover, humoral-based reactions form an integral part of the echinoderm defense system against microbial invaders. Factors such as lysozyme, perforins (hemolysins) vitellogenin and lectins are normal constituents of hemolymph, while cytokines are synthesized by echinoderms in response to infection.
Keywords: echinoderm immunity; defense molecules; effector cells; amebocyte immune reactions; cell-free immune factors.
Clinical Immunology
- Circulating Immune Complexes in Advanced Hodgkin’s Disease: Qualitative Analysis and Prognostic Significance
ZORAN TOMASEVIĆ and SVETISLAV JELIĆAbstract. The level of circulating immune complexes (CIC) may be a reflection of the underlying malignancy and appears to be related to the stage of disease, tumor burden and prognosis. Prognostic factors at diagnosis, clinical response, survival and CIC were analyzed in 89 patients with Hodgkin’s disease. All patients were newly diagnosed, in advanced stage and treated with MOPP regimen. The median follow-up was 41 months. CIC were estimated by the polyethylene glycol precipitation test. The median age was 40 years and 52% were under the age of 45. Nodular sclerosis and mixed cellularity were the most common histologies, 36 and 35% respectively. “B” symptoms were present in 65%, bulky disease in 29% and bone marrow involvement in 4% of the total. The erythrocyte sedimentation rate (ESR) was over 30 in 72% of patients and 27% had one or two extranodal localizations. Complete remission (CR) was obtained in 69 patients (77%). The only factor influencing the CR rate was the number of extranodal localizations (p<0.05). The ten-year relapse-free survival (RFS) and overall survival (OS) were 63 and 83%, respectively. RFS was adversely influenced by lymphocyte depletion histology (p=0. 009) and by performance status over 1 (p=0. 003). Elevated CIC levels were detected in 58% of the total. Patients with ESR over 30 had significantly higher values of CIC (p<0. 05). Qualitative analysis of the CIC showed high levels of positivity to immunoglobulin G and M. C-reactive protein (CRP) was identified in 42% of all samples. CRP is an acute phase protein which shows conformational similarity to the immunoglobulin molecule. There were no significant correlations between levels of CIC and the other prognostic factors. Survival was not influenced by the CIC level.
Keywords: Hodgkin’s disease; immune complexes; prognostic factors.
- Lymphoid Aggregates in Gastric Biopsies: Relationship to Other Mucosal Lesions
KAZIMIERZ JAŚKIEWICZ and GRAŻYNA KOBIERSKAAbstract. The purpose of this study is to estimate the prevalence of lymphocyte aggregates (precursor of MALT lymphomas) in gastric mucosal biopsies and to associate gastric lymphoid tissue with the age of patients, Helicobacter-associated gastritis and other gastric mucosal pathology. A consecutive series of gastric mucosal samples from 150 children and 256 adults were assessed for the presence of lymphoid aggregates as well as morphological characteristics, Helicobacter pylori status, signs of gastritis, mucosal atrophy and lymphoepithelial lesions. Fifteen selected samples with prominent lymphoid aggregates and 10 controls were examined immunohistochemically for the immunoglobulins A, G, M, lymphocytes B and T, clonality of B cell population, atypical lymphocytes and Epstein-Barr virus (EBV) antigen. There was an increase of H. pylori infection and mucosal lymphoid aggregates (MALT) rates in parallel with the increasing age of patients noted in the histological assessment of the mucosal samples. A close association of lymphoid aggregates with H. pylori infection and prominent active gastritis was found, but in adults with chronic non-active, particularly atrophic gastritis this association became weaker. No morphological and immunohistochemical signs of MALT lymphoma were present. Lymphoid aggregates in children were larger, with follicles, but less numerous and tended to be located in the intermediate and deeper parts of the gastric mucosa. Immunohistochemical studies showed an increase of IgA, IgM and lymphocytes T in the deeper part of the lamina propria in H. pylori-associated gastritis and lymphocyte T accumulation in the periphery of the lymphoid follicles. No evidence of monoclonality, CD31 positive lymphocytes or EBV antigen was detected. Lymphoid aggregates are related, but not exclusively, to H. pylori infection. Their detection rates achieve a peak in young adults with H. pylori infection. Lymphocytic aggregates are also present in chronic atrophic gastritis without H. pylori infection and may relate to autoimmune inflammatory response to other factors.
Keywords: lymphoid aggregates; Helicobacter gastritis; immune response; children.
- Interleukin 1b Decreases the GSH Content and Catalase Activity in the Human Peritoneal Mesothelial Cells in Vitro
ANDRZEJ E. GRZYBOWSKIAbstract. The object of this study was to assess the effects of the inflammatory cytokine interleukin b (IL-1b) (0. 01–1. 0 ng/ml) on the activity of catalase (CAT), superoxide dismutase (SOD) and the level of glutathione (GSH), all being antioxidant mechanisms, in human peritoneal mesothelial cells (HPMC) in in vitro culture. HPMC were obtained from the omenta of nonuremic donors. The activity of the antioxidant mechanisms was studied on monolayers of HPMC, which were deprived of serum 48 h prior to experiment. The effect of the cytokine was tested in a medium with low serum concentration (0. 1%) or in a medium with 10% fetal calf serum (FCS). Activity of the antioxidant mechanisms was determined by spectrophotometry. The GSH level was decreased in mesothelial cells (MC) after 24 h of exposition to IL-1. However, after 72 h of incubation with IL-1 the GSH level increased in MC in the presence of 10% FCS, p<0.05. The activity of CAT was inhibited after 72 h exposure to IL-1. Interleukin 1 did not affect SOD activity in MC. However, when supplemented with 10% FCS, IL-1 decreased the activity of SOD after 24 and 72 h of incubation. We conclude that the activity of antioxidant mechanisms in MC is decreased by IL-1b in ways that might increase their vulnerability to the cytotoxic effect of free radicals.
Keywords: dialysis; inflammation; interleukin 1; antioxidants; catalase; superoxide.
Immunochemistry
- Identification of Blood Group A and B Antigens in Human Glycophorin
MARIA PODBIELSKA and HUBERT KROTKIEWSKI
Abstract. Glycophorin A (GPA), the major sialoglycoprotein of human erythrocyte membranes, was isolated separately from blood group A and B erythrocytes using phenol-water extraction. After purification, performed as gel filtration in the presence of SDS, two glycophorin samples GPA-A and GPA-B were run, in duplicate, in SDS-PAGE and electroblotted onto Immobilon P. After staining with 1) anti-glycophorin antibody and 2) with relevant anti-blood group (A or B) antibody it was shown that the band pattern of the samples in each duplicate was the same. GPA-A and GPA-B samples were also degraded using Carlson degradation (b-elimination in mild alkaline/strong reducing conditions) and from reaction products the fractions of O-glycans and N-glycans were isolated; they were used in hemagglutination inhibition test. It was shown that both sugar fractions derived from GPA-A did inhibit agglutination of blood group A erythrocytes by anti-A antibody, whereas oligosaccharide fractions derived from GPA-B inhibited agglutination of blood group B erythrocytes by anti-B antibody. These results, obtained using immunochemical methods, confirm the presence of blood group A and B determinants in the carbohydrate moiety of human glycophorin, derived from the blood group A or B erythrocytes, respectively.
Keywords: human glycophorin; blood group A and B antigens; protein glycosylation; O-glycans; N-glycans.