Vol. 53, No. 6, 2005

Gillian L Beamer and Joanne Turner, (Division of Infectious Diseases, Department of Internal Medicine, The Ohio State Univeristy, Columbus, OH 43210, USA)

Abstract: Approximately one third of the world’s population is infected with Mycobacterum tuberculosis, yet each year a small proportion of those individuals progress to an active disease state. Early identification and treatment of such individuals is essential to reduce transmission; however, genetic and immunological correlates of disease progression have not been well established in man. The murine model has been a central tool for the elucidation of protective immune mechanisms that are essential for controlling M. tuberculosis infection. Additionally, the study of inbred mice has revealed significant divergence in the susceptibility and disease progression of individual mouse strains to an infection with M. tuberculosis. The continued study of genetically disparate mouse strains has the potential to identify immune mechanisms that correlate with increasing susceptibility to tuberculosis. These mechanisms will be highly applicable to studies in man and assist in the early detection of individuals that are more vulnerable to the development of reactivation tuberculosis.

Keywords: tuberculosis; reactivation; murine; lung.

Shree K. Kurup and Chi-Chao Chan, (National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA)

Abstract: This comprehensive review discusses immunotherapeutic approaches to ocular inflammatory diseases, updates information provided in the literature, and presents clinical experiences with an emphasis on autoimmune uveitis at the National Eye Institute, United States. Current medical and surgical therapeutic approaches, including medications such as corticosteroids, anti-metabolites, alkylating agents, calcineurin and purine synthesis inhibitors, biologics as well as some anti-infectious agents, are reviewed along with new modalities and experimental approaches. Most immunosuppressive therapies have significant adverse effects. Physicians must be familiar with the pharmacology of the available drugs and aware of the philosophies behind the treatment.

Keywords: inflammation; uveitis; autoimmune diseases; immunosuppressive medications; adverse effect; therapy.

Huan Yuan Chen, Fu-Tong Liu and Ri-Yao Yang, (University of California, Davis, School of Medicine, Sacramento, CA 95817, USA)

Abstract: Galectins are a family of animal lectins with conserved carbohydrate-recognition domains for β-galactoside. Galectin-3 is the only family member that is composed of a glycine/proline-rich N-terminal repeated sequence and a C-terminal carbohydrate-binding domain. Multiple functions of galectin-3 have been reported, depending on its location. Extracelluar galectin-3 can bind to cell surface through glycosylated proteins and thereby trigger or modulate cellular responses such as mediator release or apoptosis. Intracellular galectin-3 has been reported to inhibit apoptosis, regulate the cell cycle, and participate in the nuclear splicing of pre-mRNA. Recent studies have revealed that galectin-3 is expressed in a variety of cell types in the immune system, constitutively or in response to microbial invasion. These studies implicate galectin-3 in both innate and adaptive immune responses, where it participates in the activation or differentiation of immune cells. This review summarizes the roles of galectin-3 in the immune system and discusses the possible underlying mechanisms.

Keywords: galectin; galectin-3; immunity; immune response.

Scott D. Kobayashi, Jovanka M. Voyich, Christopher Burlak and Frank R. DeLeo, (Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA)

Abstract: Polymorphonuclear leukocytes (PMNs or neutrophils) are an essential component of the human innate immune system. Circulating neutrophils are rapidly recruited to sites of infection by host- and/or pathogen-derived components, which also prime these host cells for enhanced microbicidal activity. PMNs bind and ingest microorganisms by a process known as phagocytosis, which typically triggers production of reactive oxygen species and the fusion of cytoplasmic granules with pathogen-containing vacuoles. The combination of neutrophil reactive oxygen species and granule components is highly effective in killing most bacteria and fungi. Inasmuch as PMNs are the most abundant type of leukocyte in humans and contain an arsenal of cytotoxic compounds that are non-specific, neutrophil homeostasis must be highly regulated. To that end, constitutive PMN turnover is regulated by apoptosis, a process whereby these cells shut down and are removed safely by macrophages. Notably, apoptosis is accelerated following phagocytosis of bacteria, a process that appears important for the resolution of infection and inflammation. This review provides a general overview of the role of human neutrophils in the innate host response to infection and summarizes some of the recent advances in neutrophil biology.

Keywords: neutrophil; phagocytosis; inflammation; infection; apoptosis.

Agnieszka Krawczenko¹, Claudine Kieda² and Danuta Duś¹, (¹Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland, ² Cell Recognition Group, CBM, UPR 4301 CNRS, Orléans, France)

Abstract: Interleukin (IL)-7 is a pleiotropic, non-redundant cytokine necessary for the development of B and T lymphocytes, in particular γδ T cell receptor-positive cell differentiation. The cytokine can function as a cofactor during myelopoiesis and the generation of cytotoxic T cells and natural killer cells, can activate monocytes/macrophages, and support the survival of mature T cells. A role for IL-7 in promoting the formation of Peyer’s patch anlage has also been demonstrated. IL-7 is constitutively expressed in the thymus, bone marrow stromal cells, epithelial and dendritic cells, keratinocytes, as well as in fetal and adult liver. IL-7 acts on various cells through its receptor (IL-7R), a heterodimer consisting of an α chain (CD127) that specifically binds IL-7 and a common γ_c chain (CD132) shared by other cytokine receptors. The receptor is expressed on bone marrow progenitor cells, lymphoid T and B precursors, and mature T cells. IL-7 activity towards murine endothelial cells has been recently described. The presence of IL-7R on human endothelial cells has also been demonstrated. Several therapeutic applications of recombinant IL-7 have been proposed. These have focused on the enhancement of lymphopoiesis, promotion of stem cell engraftment, and the anti-tumor activity of the cytokine.

Keywords: interleukin 7; interleukin-7 receptor; B cell development; T cell development; endothelium; cytokine therapy.

Elżbieta Jabłonowska¹, Henryk Tchórzewski^{2, 3}, Przemysław Lewkowicz² and Jan Kuydowicz¹, (¹Department of Infectious Diseases and Hepatology, Medical University of Łódź, Poland, ²Department of Clinical Immunology, Polish Mother’s Memorial Hospital, Research Institute, Łódź, Poland, ³Department of Pathophysiology, Medical University of Łódź, Poland)

Abstract. Introduction:
In this study, the chemiluminescence (CL) of peripheral blood polymorphonuclear leukocytes (PMNLs) and the serum total antioxidative system (TAS) were assessed in patients with chronic C hepatitis (CCH) before and after 3 and 6 months of treatment with interferon (IFN)-α and thymus factor X (TFX).

Materials and Methods:
The study included 26 patients with CCH aged between 25–63 years (mean: 42.67). Combined therapy with IFN-α 2a and a TFX preparation was applied. PMNL metabolic activity was assessed applying the whole-blood CL method. We measured CL response of neutrophils unstimulated and stimulated by opsonized zymosan, N-formyl-methionylleucyl-phenylalanine (N-fMLP), and phorbol-myristate-acetate (PMA) without and after priming with tumor necrosis factor α (10 ng/ml). The assessment of serum TAS was performed directly before the beginning of therapy with IFN-α and TFX and after 3 and 6 months of the treatment. A colorimetric method based on the reduction of the cationic radical ABTS^•+ (cation 2, 2’-azido-bis-[3-ethylobenzothiazolino-6-sulfonate]) in the presence of serum antioxidants was used.

Results:
As a result of the treatment with IFN-α and TFX, the formation of free oxygen radicals by resting (unprimed) neutrophils increased statistically significantly both without stimulation and following stimulation by fMLP and PMA. A statistically significant increase in the serum antioxidant capacity was observed, which suggests the induction of compensatory processes.

Conclusions:
Increased in vitro reactive oxygen species production by both stimulated and unstimulated peripheral blood neutrophils of patients with CCH was observed. Treatment with IFN-α and TFX resulted in a compensatory increase in serum antioxidative capacity.

Keywords: chronic hepatitis; HCV; chemiluminescence; neutrophils; free radicals.

Małgorzata Pawlikowska and Wiesław Deptuła, (Department of Microbiology and Immunology, Faculty of Natural Sciences, University of Szczecin, Poland)

Abstract. Introduction:
Studies of non-specific immunity in infection or immunization with Chlamydophila (Chl.) psittaci in static experimental models showed changes in parameters of this immunity. The aim of this study was to evaluate selected parameters of non-specific immunity in rabbits immunized with Chl. psittaci.

Materials and Methods:
The study was performed on rabbits, divided into two groups of 10 animals each. The rabbits of the first group were immunized with Chl. psittaci strain 6BC and those of the second group were control animals. Blood samples were examined 9 times every 7 days. Adherence capacity and ingestion capacity of polymorphonuclear (PMN) cells (index of ingestion, percentage of ingestive cells) were determined in the blood. The cidal capacity of PMN cells was determined by evaluating the reduction of nitroblue tetrazolium test by cytochemical (spontaneous and stimulated tests) and spectrophotometric techniques. The presence of specific antibodies in the sera was estimated by the complement-fixation technique.

Results:
Analysis of the results of all the studied parameters of non-specific immunity showed tendencies to decrease or increase. These differences appeared on days 7–14 and lasted to days 42–56 of the experiment. Positive titers of specific antibodies appeared on day 42 after immunization, i.e. 5 weeks after the first changes in the parameters of non-specific immunity.

Conclusions:
The alterations noted in the parameters of non-specific immunity may prove useful in determining the condition of a macroorganism in contact with Chl. psittaci.

Keywords: Chlamydophila psittaci; rabbit; immune indices.

Krystyna Zych , Małgorzata Siwińska and Zygmunt Sidorczyk, (Department of General Microbiology, Institute of Microbiology and Immunology, University of Łódź, Poland)

Abstract. Introduction:
Gram-negative bacteria of genus Proteus are common human intestinal and urinary tract pathogens. In the genus Proteus there are four clinically important named species: P. mirabilis, P. vulgaris, P. penneri, and P. hauseri, and three unnamed Proteus genomospecies: 4, 5, and 6. The clinical significance of P. penneri, described in 1982 as a new species, is poorly documented. The aim of this work is serological characterization and classification of a ceftriaxone-susceptible P. penneri S29 strain isolated from a 34-year-old patient with postneurosurgical meningitis. In this characterization we will also include a ceftriaxonresistant strain, P. penneri R15, isolated from the same patient after 12 days’ treatment with ceftriaxon and other antibiotics.

Materials and Methods:
Rabbit polyclonal O-antisera were obtained against these two strains and purified lipopolysaccharides (LPS) were extracted from the bacterial mass of the P. penneri S29 and R15 strains. In the serological investigations the following tests were used: enzyme immunosorbent assay (EIA), passive immunohemolysis (PIH), inhibition of these tests, absorption of rabbit O-antisera with the respective LPS, and repeated PIH, SDS/PAGE, and Western blot techniques.

Results:
The serological studies of the LPS extracted from both P. penneri strains showed the identity of both preparations of O-polysaccharides from LPS. In P. penneri S29 O-antiserum, four different types of antibodies were described and characterized.

Conclusions:
Both investigated P. penneri S29 and R15 strains were classified to the Proteus O31ab serogroup.

Keywords: Proteus penneri; lipopolysaccharide; O-serogroup; epitope; serological classification.