CONTENTS
Review
- Immunotherapy of Cancer through Targeting of the p53 Tumor Antigen
Sander Zwaveling1, 2, Sjoerd H. Van der Burg1, Anand G. Menon, Cornelis J. M. Melief1 and Rienk Offringa1 (1Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, Tumor Immunology Group and 2Department of Surgery, Albinusdreef 2, 2333 ZA Leiden, The Netherlands)Abstract. The expression of the p53 tumor suppressor protein is frequently increased in a great variety of human cancers, making this antigen an attractive candidate for targeting therapeutic T cell immunity. However, potential complications as a result of immunological tolerance or auto-immune pathology must be taken into account when exploiting this ubiquitously expressed auto-antigen for immunotherapy of cancer.
Keywords: cancer immunotherapy; p53 tumor antigen.
- Lymphocytes Distribution and Intrahepatic Compartmentalization during HCV Infection: a Main Role of MHC-Unrestricted T Cells
Chiara Agrati, Carla Nisii, Alessandra Oliva, Gianpiero D’Offizi, Carla Montesano, Leopoldo Paolo Pucillo and Fabrizio Poccia (National Institute for Infectious Diseases „L. Spallanzani”, Rome, Italy)Abstract. Hepatitis-C virus (HCV) infection induces an acute and chronic liver inflammation through an immune mediated pathway that may lead to cirrhosis and liver failure. Indeed, HCV-related hepatitis is characterized by a dramatic lymphocyte infiltrate in the liver which is mainly composed by HCV non-specific cells. Several data indicated that IFN-gamma secretion by intrahepatic lymphocytes (IHL) may drive non specific cell homing to the liver inducing IP-10 production. An interesting hallmark of these IHL is the recruitment of lymphocytes associated with mechanism of innate immunity such as NK, NKT and gamma delta T lymphocytes. CD81 triggering on NK cell surface by the HCV envelope glycoprotein E2 was recently shown to inhibit NK cell function in the liver of HCV-infected persons resulting in a possible mechanism contributing to the lack of virus clearance and to the establishment of chronic infection. In contrast, intrahepatic NKT cells restricted to Cd1d molecules expressed on the hepatocyte surface may contribute to a large extent to the liver damage. Finally, an increased frequency of T cell expressing the gamma delta TCR was observed in HCV-infected liver and recent observations indicate that intrahepatic gamma delta T cell activation could be directly induced by the HCV/E2 particle through CD81 triggering. These cells are not HCV specific, are able to kill target cells including primary hepatocytes and their ability to produce Th1 cytokines is associated with an higher degree of liver disease. Altogether, CD1d/NKT and/or E2/CD81 interactions may play a major role in the establishment of HCV immunopathogenesis. In absence of virus clearance, the chemokine-driven recruitment of lymphocytes with an innate cytotoxic behavior in the liver of HCV infected patients may boost itself leading to the necroinflammatory and fibrotic liver disease.
Keywords: hepatitis C, liver, intrahepatic lymphocytes, NK cells, NKT cells, NT cells, gamma delta T lymphocytes, HLA, CD1, CD81, E2.
- Immunotherapy in the Management of Sepsis
Janusz Piotr Sikora (Department of Pediatric Propedeutics, Institute of Pediatrics, Medical University of Łódź, Sporna 36/50, 91-738 Łódź, Poland)Abstract. The work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so called ‘respiratory burst’ of neutrophils and antioxidant mechanisms of the host are also discussed. The work has focused on possible approaches to the management of sepsis connected with immunotherapy. Neutralisation of endotoxin lypopolysaccharide (LPS), anti-TNF-alpha therapy with monoclonal antibodies or pentoxifylline (PTXF) as well as soluble recombinant cytokine agonists and antagonists used in clinical trials were taken into consideration. Besides, cytokine manipulation therapy, anti-adhesion techniques or glicocorticoides and antioxidant barrier interference were also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts aggressive examination of the immune system, aimed at affecting its function.
Keywords: sepsis, cytokines, reactive oxygen species, monoclonal antibodies, cytokine agonists and antagonists, immunotherapy.
- The Role of TGF-Beta Signaling in the Pathogenesis of Fibrosis in Scleroderma
Hironobu Ihn (Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan)Abstract. Excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that transforming growth factor (TGF)-b is a key mediator of tissue fibrosis as a consequence of ECM accumulation in pathologic states such as systemic sclerosis. TGF-b regulates diverse biological activities including cell growth, cell death or apoptosis, cell differentiation, and extracellular matrix (ECM) synthesis. TGF-b is known to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. This review focuses on the possible role of TGF-b in the pathogenesis of fibrosis in SSc.
Keywords: TGF-beta; fibrosis; systemic sclerosis; signal transduction.
Clinical Immunology
- A Protective Role of HLA-DR Locus in Patients with Various Clinical Types of Alopecia Areata
Grażyna Broniarczyk-Dyła1, Magdalena Prusińska-Bratoś1, Małgorzata Dubla-Berner1, Celina Arkuszewska1, Maciej Borowiec2, Marek L. Kowalski2 and Grzegorz Woszczek2 (1Department and Clinic of Dermatology and Venereology, Medical University of Łódź, Krzemieniecka 5, Łódź, Poland, 2Department of Clinical Immunology and Allergy, Medical University of Łódź, Poland)Abstract. One of genetic factors associated with the development of alopecia areata (AA) is HLA locus. The study comprised 52 patients with AA, aged 10 to 64 years. The frequences of HLA-DR B alleles in patients and controls were compared. The control group comprised 152 healthy persons. Familiar occurrence of alopecia areata was seen in 7 cases (13.5%). Significantly lower frequency of HLA-DRB1*03 was observed in patients with AA in comparison to control group. In all patients with AA alleles HLA-DRB1*15/*16 occurred more frequently than in control group, but it was not significant after correction. In the group of patients with more severe form of alopecia areata (AAT/U) there was no significant difference in HLA- DR alleles distribution.
Keywords: alopecia areata, familiar inheritance, HLA locus.
Experimental Immunology
- Lack of Relation between Serum Content of MBL, sCD14, Anti-PPD and Anti-Hsp65 IgG, and Ingestion of Mycobacterium bovis BCG Bacilli by Phagocytes
Beata Paziak-Domańska1, Agnieszka Bonar1, Magdalena Kowalewicz-Kulbat1, Magdalena Klink2, Michał Kowalski3, Jari Karhukorpi4, Ritta Karttunen5, Magdalena Jurkiewicz1, Barbara Różalska1 and Wiesława Rudnicka1 (1Department of Immunology and Infectious Biology, University of Łódź, Banacha 12, 90-237 Łódź, Poland, 2Microbiology and Virology Centre, Polish Academy of Science, Łódź, Poland, 3Health Centre for High Schools, Łódź, Poland, 4Clinical Microbiology Laboratory, University Hospital of Oulu, Finland, 5Department of Medical Microbiology, University of Oulu, Finland)Abstract. Prophylactic vaccination against tuberculosis (TB) with a live attenuated strain of Mycobacterium bovis Bacille Calmett’e-Gúerin (BCG) has been used worldwide. However, TB remains one of the most significant diseases of humans and animals. Better understanding of the mechanisms of human immunity to mycobacteria is essential for development of new vaccines and estimation of their efficacy. In this study we determined the levels of known humoral mediators of mycobacterial phagocytosis – mannose binding lectin (MBL), soluble CD14 (sCD14), antibodies of IgG class against mycobacterial purified protein derivative (PPD) and mycobacterial Hsp65 antigen, in the sera from healthy young volunteers vaccinated with BCG and presenting positive and negative Mantoux responses to PPD. Than we asked a question as to whether macrophages and polymorphonuclear leukocytes (PMNs) from the individuals with positive (TT(+)) and negative (TT(-)) tuberculin tests differ by the ability to ingest mycobacteria. Also we were looking for a relation between the intensity of mycobacterial ingestion by phagocytes in the medium with autologous sera containing different concentration of MBL, sCD14 andf anti-mycobacterial IgG. We found no significant differences between the investigated parameters for TT(+) and TT(-) volunteers. Our result suggest that ability of macrophages and PMNs to ingest mycobacteria depends on an individual intrinsic capacity of phagocytes.
Keywords: tuberculin test, macrophages, polymorphonuclear leukocytes.
Immunochemistry
- Structural and Serological Characterisation of the Lipopolysaccharide from Proteus penneri 20 and Classification of Cross-Reacting Proteus penneri Strains 10, 16, 18, 20, 32 and 45 in Proteus Serogroup O17
Zygmunt Sidorczyk1, Filip V. Toukach2, Krystyna Zych1, Nikolay P. Arbatsky2, Dominika Drzewiecka1, Andrzej Ziółkowski1, Alexander S. Shashkov2 and Yuriy A. Knirel2 (1Department of General Microbiology, Institute of Microbiology and Immunology, University of Łódź, Banacha 12/16, 90-237 Łódz, Poland, 2N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Pr. 47, Moscow 119991, Russia)
Abstract. O-specific polysaccharide (O-antigen) of the lipopolysaccharide of Proteus penneri 20 was studied using sugar analysis along with various one- and two-dimensional NMR spectroscopy techniques. The following structure of the polysaccharide was established. It has the same carbohydrate backbone structure as that described earlier for P. penneri 16, in which the positions of the O-acetyl groups have not been determined. P. penneri 20 O-antiserum showed a strong cross-reactivity with the lipopolysaccharides of P. penneri 10, 16, 18, 32, 45 and P. mirabilis O17. These data enable classifying these strains together with P. penneri 20 in one Proteus serogroup, O17.
Keywords: lipopolysaccharide, O-antigen, bacterial polysaccharide, O-acetyl group, serological classification, O-serogroup, Proteus penneri.