Vol. 46, No. 3, 1998

CONTENTS

Mini-Review

  • Carcinoembryonic Antigen as an Adhesion Molecule
    ANNA KROP-WĄTOREK and ELWIRA LISOWSKA

    Abstract. Carcinoembryonic antigen (CEA), one of the most widely studied tumor markers, shows homotypic (CEA-CEA) intercellular adhesion and heterotypic adhesion to other members of CEA family, receptors on Kupffer cells, macrophages, microorganisms, and lectins. This review is focused on those adhesive properties of CEA which may pertain to the role of CEA in tumor progression.

    Keywords: carcinoembryonic antigen; cell adhesion; tumor progression; immunoglobulin superfamily.family.

  • MHC Molecules and Lymphocytes: Evolutionary Perspective
    BARBARA PŁYTYCZ and ROLF SELJELID

    Abstract. The classical polymorphic MHC molecules of class I or class II bind peptides derived from the processed cytosolic or endosomal antigens and export them to the cell surface for presentation to the T cell receptors (TcR) of CD8 or CD4 T lymphoeytes, respectively. The classical MHC molecules are unstable when peptides are not bound. The MHC-peptide-TcR interactions constitute a molecular basis of thymic selection of the major streams of a b and gd T lymphocytes. The monomorphic MHC class I-like molecules (class Ib) bind peculiar peptides or nonpeptide antigens or can keep proper conformation even without antigenic peptides. They are recognized by the specialized subsets of nonconventional lymphocytes, mainly extrathymic g d T or natural killer (NK) T lymphocytes. The most unorthodox T lymphoeytes can see antigens directly without the participation of MHC or MHC-like molecules or can see MHC-like molecules not loaded with peptides. The conventional B2 lymphocytes are indirectly dependent on MHC-peptide-TcR interactions as they can bind the epitopes of native antigens via Ig surface receptors, to be activated they must present the processed antigens via the MHC class II molecules to the Th2 lymphocytes. In contrast, the B1 lymphocytes can be activated directly without cooperation with T cells via MHC molecules. It seems that both MHC molecules and lymphocyte antigen receptors arose by the expansion of Ig-superfamily genes at the early steps of vertebrate phylogeny. The nonconventional T lymphocytes (gd T cells and NK T lymphoeytes) and Bl cells which support innate immunity at the body surfaces or cavities as well as the MHC-like molecules might appear earlier, creating a proper microenvironment for development of the conventional T and B2 subsets of lymphocytes.

    Keywords: MHC molecules; MHC-like molecules; B2 lymphocytes; B1 lymphocytes; a b T cells; g d T cells; NK T lymphocytes; phylogeny of immunity.

  • Cytokines in Inflammatory Bowel Disease
    ZBIGNIEW KMIEĆ

    Abstract. Inflammatory bowel disease (IBD) denotes chronic inflammatory disorders of gastrointestinal tract of unknown etiology that comprises 2 major groups: ulcerative colitis (UC) and Crohn’s disease (CD). Disregulation of the intestinal immune system both at humoral and cellular level constitutes an important element in the multifactorial pathogenesis of IBD. The expression of pro-inflammatory cytokines, most notably IL-1, IL-6, TNF-( and chemokines (IL-8, ENA-78, MCP-1, RANTES) in intestinal mucosa from IBD patients is markedly enhanced, however, it is not always accompanied by increases in cytokines’ serum levels. In IBD also significant changes occur in the tissue expression of immunoregulatory cytokines: increased levels of IL-2 mRNA and IFN-( mRNA, and decreased expression of IL-4 were found in affected intestinal mucosa. Chronic intestinal lesions of patients with Crohn’s disease are associated with a Th1 type cytokine profile. The clinical effectiveness of anti-TNF-( antibodies and of IL-10 has been demonstrated in steroid-refractory Crohn’s disease patients. The data demonstrating the role of cytokines in the pathogenesis of IBD should be carefully analyzed because of limitations imposed by the patient- and sample-related parameters. Further investigations will clarify the significance of the impairments in cytokine network for the initiation and progression of the IBD.

    Keywords: inflammatory bowel disease; cytokines; interleukins; anti-TNF-( therapy).NF-( therapy).

  • Immunoregulatory Role of Soluble HLA Molecules: a New Skin for an Old Subject?
    FRANCESCO PUPPO, MASSIMO GHIO, PAOLA CONTINI, SABRINA BRENCI, DONATELLA BIGNARDI, GILBERTO FILACI, MARCO SCUDELETTI and FRANCESCO INDIVERI

    Abstract. The available evidence suggests that measurement of the level of total sHLA-1 antigens and of donor-derived and recipient-derived allospecificities as well as the characterization of their variants in recipient’s serum may provide useful information to differentiate graft rejections from infections in allograft recipients. Moreover, a significant progress has been made in our understanding of the functional properties of sHLA-I antigens in serum and of their potential role in the modulation of immune responses. If these preliminary results will be confirmed, then sHLA-I antigens are likely to become important reagents to monitor and treat graft recipients.

    Keywords: HLA soluble molecules; graft recipients; graft rejections.ctions.

Clinical Immunology

  • Systemic Humoral Response to Helicobacter pylori in Children and Adults
    MAGDALENA CHMIELA, MAGDALENA ŁAWNIK, EL(BIETA CZKWIANIANC, TOMASZ RECHCIŃSKI, IZABELA PŁANETA-MAŁECKA and WIESŁAWA RUDNICKA

    Abstract. In this study we compared the development of anti-H. pylori humoral response in adults and children. Two antigens: H. pylori acid glycine extract (GE) and recombinant caga were used for ELISA and Western blot. Anti-GE IgG were detected in all and anti-caga IgG in about 50% of H. pylori infected adults and children. The prevalence of anti-GE and anti-caga IgG in the sera from H.pylori-uninfected children with gastritis/gastroduodenitis was lower than in the sera from healthy adult blood donors. Serum IgA were demonstrated for 71% of H. pylori-infected adults and for a smaller proportion (about 30%) of uninfected adult patients or normal subjects. Such antibodies were detected neither for infected nor for uninfected children. There was an evident difference between the proteins of H. pylori glycine extract recognized by antibodies present in the sera from H. pylori-infected children and adults. The antigen of molecular weight over 107 kDa was recognized exclusively by the sera from 30% of H. pylori-infected adults. The 80- 107 kDa bands were recognized more frequently by the sera from adults than from children. In contrast, sera from infected children more frequently than sera from infected adults reacted with the bands of 14 kDa, 19 kDa and 26 kDa. The H. pylori antigens recognized by IgG, produced by infected children and adult patients, should be taken into consideration in the developing of tests for serodiagnosis of H. pylori infection.

    Keywords: Helicobacter pylori; patient’s age; ELISA; Western blot. Western blot.

  • Lactoferrin Effects on the in Vitro Immune Response in Critically Ill Patients
    BARBARA ADAMIK, MICHAŁ ZIMECKI, ANDRZEJ WŁASZCZYK, PAWEŁ BEREZOWICZ and ANDRZEJ KÜBLER

    Abstract. The aim of the study was to investigate whether lactoferrin can improve the immune competence of cells from patients with systemic inflammatory response syndrome (SIRS). We studied the effect of lactoferrin (LF) on the proliferative response of peripheral blood mononuclear cells (PBMC) to lipopolisaccharide (LPS) in vitro and its influence on production of 2 proinflammatory cytokines: interleukin – 6 (IL-6) and tumor necrosis factor a . (TNF-a ). Three groups of patients: septic survivors, septic nonsurvivors and multiple trauma patients, were investigated. Blood samples were taken upon admission to intensive care unit and after 2, 3 and 5 days. The proliferative response of PBMC in vitro was tested using 3-day culture with LPS. Cell proliferation/death was measured using MTT calorimetric method. The spontaneous and LPS-induced activity of TNF-a and IL-6 were measured with bioassays using indicator cell lines WEHI-164.13 and 7TD1, respectively. We demonstrated that LF inhibited the proliferative response, both spontaneous and LPS-induced, in all groups of patients. Lactoferrin alone was a good inducer of IL-6 and TNF-a production by monoclear cells in vitro. Addition of LF to the cultures of LPS-activated mononuclear cells stimulated IL-6 production, most markedly in the group of septic survivor patients (mean 1479, 1452, 1728, 1980 pg/ml on day 1, 2, 3 and 6 respectively). Lactoferrin also unregulated TNF-a production. That effect was very significant in the septic survivor patients (mean 7407, 6739, 7498 and 8509 pg/ml on day 1, 2, 3 and 5 respectively) and less pronounced in the group of trauma patients. We conclude that lactoferrin exhibited regulatory actions on the altered reactivity of PBMC from patients with sepsis and multiple injury. Lactoferrin is a good inducer of IL-6 and TNF-a production. However, in most cases of septic nonsurvivors LF could not abolish low reactivity of cells with regard to cytokine production.

    Keywords: lactoferrin; sepsis; multiple trauma; interleukin 6; tumor necrosis factor a .

  • Apolipoprotein E Genotypes in Sporadic Early and Late-Onset Alzheimer’s Disease
    ANNA KOWALSKA, JOLANTA FLORCZAK, DANUTA PRUCHNIK-WOLIŃSKA, ADAM KRASZEWSKI and MIECZYSŁAW WENDER

    Abstract. Recent data have demonstrated that presence of apolipoprotein E (APOE) e *4 allele is a major risk factor of Alzheimer’s disease (AD). We determined the APOE genotypes in 64 patients with sporadic probable AD and 43 non-demented aged controls selected from Poznań region and the western part of Poland using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) analysis. We confirmed a strong correlation of the APOE e *4 allele with sporadic late-onset AD. In contrast to manv previous reports we did not found an association between the APOE e *4 allele and sporadic early-onset AD.

    Keywords: Alzheimer’s disease; apolipoprotein E genotypes; association analysis.

  • Effect of General and Regional Anesthesia on Some Neutrophil Functions
    JOANNA CIEPICHAŁ and ANDRZEJ KÜBLER

    Abstract. Transient immunosuppression in patients during anesthesia and surgery may cause postoperative infections. In the immunity against pathogens the processes of non-specific defence are of special importance and engage neutrophils as the major cell type. The aim of this study was to monitor activity of neutrophils during and after surgery, applying different methods of anesthesia. The status of neutrophils was determined by evaluation of chemotactic, phagocytic and chemiluminescence (bactericidal) activities. The study included 78 patients, who underwent surgery due to pathological injury-effected changes or due to varicose veins of extremities. Blood samples for determination of the neutrophil activity were taken just before anesthesia, when the symptoms of anesthesia occurred, 15 min after starting of surgery, 24 h and 5-7 day after surgery. In majority of patients we observed neutrophilic leukoeytosis. There was a statistically significant correlation between leukoeytosis and percentage of neutrophils in the subsequent days after surgery, depending on a kind and extension of surgical intervention. In addition, we have found a decrease in chemotactic, phagocytic and bactericidal activity after all kinds of anesthesia. The decrease in the phagoeytic activity lasted longer, usually at least 24 h after surgery, whereas chemotaxis and chemiluminescence returned quickly to control levels. In the spinal anesthesia the chemiluminescence was not altered; this phenomenon could result from blockade of the sympathetic nerve system and activation of neutrophils metabolism. The brachial plexus blockade had the statistically smallest effect on the function of neutrophils. In the long-term anesthesia (longer than 2 h), particularly using halothane, we have observed depressed values of chemotaxis, phagocytosis and chemilumineseence which lasted longer than in other studied group of patients. We conclude that monitoring of the neutrophil functions is a useful form of studying immune reactions of patients to anesthesia and surgery.

    Keywords: general and regional anesthesia; surgery; neutrophils; chemotaxis; phagocytosis; chemiluminescence.iluminescence.

Various

  • Effect of Colostrinin, an Immunomodulatory Proline-Rich Polypeptide from Ovine Colostrum, on Sialidase and b -Galactosidase Activities in Murine Thymocytes
    IZABELA SOKAL, MARIA JANUSZ, HANNA MIECZNIKOWSKA, GOTFRYD KUPRYSZEWSKI and JÓZEF LISOWSKI

Abstract. Colostrinin: a proline-rich polypeptide (PRP) from ovine colostrum and its nonapeptide active fragment (NP) induce maturation and differentiation of murine thymocytes, formation of helper cells from PNAhigh thymocytes and cytotoxic T cells from PNAlow thymocytes. These processes are accompanied by changes in expression of receptors for peanut agglutinin (PNA), PNAhigh thymocytes were transformed into PNAlow cells, and vice versa. It was shown, in various laboratories, that sialyltransferases are involved in the transformation of PNAhigh thymocytes into PNAlow cells. To find out whether the expression of receptors for PNA on murine thymocytes might also be influenced by other enzymes, we decided to study the effect of PRP and NP on sialidase and b -galactosidase activities in these cells. The results obtained showed that the most of sialidase. activity of murine thymocytes is present in the plasma membrane compartments. Both thymocyte subpopulations PNAhigh and PNAlow, showed similar sialidase activity, which was not affected either by PRP or NP. In contrast to sialidases, most of b -galactosidase activity was present in the cytosol. PNAhigh thymocytes showed a higher b -galactosidase activity than PNA lowcells. Incubation of immature, PNAhigh thymocytes with PRP or NP enhanced the b -galactosidase activity in these cells. The presented results suggest that sialidases seem not to be involved in modulation of surface sialic acid content during murine thymocyte maturation. On the other hand, stimulation of activity of b -galactosidase in PNAhigh immature thymocytes by PRP and NP suggests that b -galactosidase in murine thymocytes might be involved in transformation of PNAhigh into PNAlow cells.

Keywords: proline-rich polypeptide; murine thymocytes; peanut agglutinin; sialidase; b -galactosidase.