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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 181 records · Page 10Linked to original sources
PubMed1985

Monocyte chemotactic responsiveness triggered by Lymphocyte-Derived Chemotactic Factor in aged donors. Definitive report.

Monocyte chemotactic responsiveness triggered by autologous Lymphocyte-Derived Chemotactic Factor (LDCF) has been evaluated in a group of aged donors. LDCF obtained from Peripheral Blood Lymphocytes (PBL) supplemented with varying numbers of monocytes from aged donors gave a lower chemotactic response when compared to young donors. Moreover, when cell suspensions were pretreated with indomethacin (INDO) before LDCF production, an enhancement of LDCF-induced chemotaxis was observed in old individuals, this implying a prostaglandin-mediated suppression on LDCF release in the elderly. This lymphokine seems to be produced by T cells and, above all, OKT8+ cells, whose frequency is lower in aging. Interestingly, LDCF obtained from OKT8+ enriched cells supplemented with autologous monocytes induced in aged donors a chemotactic activity comparable to that observed in young subjects. These data suggest that the lower frequency of OKT8+ cells in the aging may play a key role in the impairment of LDCF-mediated monocyte chemotaxis.

Adolescent↗
PubMed1984

[Characteristics of the electrophoretic mobility of blasts from acute non-lymphoid leukemias].

The behaviour of electrophoretic mobility (E.M.) of the blast cells has been investigated in 15 cases of acute non lymphoid leukemias (A.N.L.L.), (eleven cases of M1 type and four M5 type). The fast and homogeneous E.M. of M5 type in comparison with M1 has been underlined. E.M. of M1 blasts has been reported in a wide range varying from a "normal" migration (similar to that of normal neutrophils and monocytes) to a "fast" one (similar to M5 type). It is suggested that M1 leukemic forms, morphologically recognizable as the same leukemic type, are different L.A.N.L. indeed.

Acute Disease↗
PubMed1984

Non-specific immunity in aging: deficiency of monocyte and polymorphonuclear cell-mediated functions.

Peripheral blood monocytes obtained from 55 aged donors were evaluated for their chemotactic and phagocytic capacity. In the same subjects, polymorphonuclear cell-mediated functions were studied by chemotaxis, phagocytosis, nylon fiber adherence and nitroblue-tetrazolium reduction assay. Monocytes showed a normal chemotactic responsiveness to zymosan-activated serum, while the chemotactic activity induced by leukocyte-derived chemotactic factor and phagocytosis were rather depressed. A dramatic impairment of polymorphonuclear cell-mediated immune response was also observed. In fact, in spite of a normal nylon fiber adherence, chemotaxis, phagocytosis and nitroblue-tetrazolium reduction capacity were significantly depressed by the aging process. These data suggest that the deficiency of non-specific immunity may play an important role in the increased susceptibility to infections in aged donors.

Adult↗
PubMed1984

Mucosal immunoregulation: environmental lipopolysaccharide and GALT T lymphocytes regulate the IgA response.

In this review, we have emphasized: 1) bacterial lipopolysaccharide (LPS) involvement in IgA responses to orally administered thymic-dependent (TD) antigens; 2) characterization of Peyer's patch (PP) lymphoreticular cells; and 3) gastrointestinal immunization with gram negative pathogens and anti-LPS immunity to infection. Gut LPS, which interacts with PP lymphoreticular cells, is a major determinant for host responses to orally administered TD antigens. Bacteroides species are the principal microflora present in the gastrointestinal tract and our studies with phenol-water LPS extracts from Bacteroides fragilis indicate that both polysaccharide and lipid A activate lymphoreticular cells. The B. fragilis lipid A moiety, like that derived from E. coli and Salmonella LPS, induces B cell mitogenic responses in cultures from LPS responsive mice, but does not stimulate C3H/ H3J B cells. The inability of lipid A to stimulate gut-associated lymphoreticular tissue (GALT) cells of C3H/HeJ mice results in the induction of greater T helper cell activity in this tissue in response to orally administered TD antigens and ultimately results in an elevated IgA response pattern. Murine PP contain accessory cells (approximately 1% dendritic cells and 6-8% macrophages) and lymphocytes T (35-38%) and B (40-42%). Recent studies with antigen-specific T cell clones from C3H/ H3J PP have resulted in the isolation of IgA isotype-specific T helper cells (PP Th A cells). PP Th A cells are antigen-specific, bear Fc alpha receptors, and require H-2 histocompatibility with B cells for helper activity. PP Th A cells most effectively collaborate with surface IgA (sIgA)-bearing B cells (IgA committed B cells) for IgA isotype responses. Other studies have shown that PP dendritic cells and T cells form clusters when stimulated in vitro with sodium periodate and that these clusters promote polyclonal IgA responses in B cell cultures. Polyclonal IgA responses in cultures containing PP cell clusters from C3H/ H3J mice are considerably higher than those in identical cultures from LPS responsive mice. In other studies, the environmental influence on GALT B cells and their resultant commitment to IgA isotype is under investigation. CBA/N, X-linked immunodeficient (xid) mice possess an immature splenic B cell population which cannot respond to thymic-independent class-2 (TI-2) or certain TD antigens. However, GALT B cells of xid mice possess a mature Lyb-5+ B cell subpopulation capable of both TI-2 and TD responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

LPS regulation of the immune response: Bacteroides endotoxin induces mitogenic, polyclonal, and antibody responses in classical LPS responsive but not C3H/HeJ mice.

Recent studies have suggested that lipopolysaccharide (LPS) derived from gram-negative organisms such as Bacteroides, which are not members of the Enterobacteriaceae, stimulate B cells from the classic LPS-hyporesponsive C3H/HeJ mouse. In the present study, purified, phenol-water-extracted LPS from Bacteroides fragilis ATCC 25285 (B-LPS) was tested for its ability to induce in vivo and in vitro responses in classic LPS-responsive C3H/HeN, LPS-hyporesponsive C3H/HeJ, and (C3H/HeN X C3H/HeJ)F1 hybrid mice. B-LPS induced mitogenic responses in both C3H/HeN and C3H/HeJ spleen cell cultures when cells were cultured under standard conditions, i.e., 8 X 10(5) cells/well. Interestingly, when lower spleen cell numbers were tested with B-LPS, a typical responsive-nonresponsive pattern developed in which good mitogenic responses were induced by B-LPS in C3H/HeN cultures and in which low responses in C3H/HeJ spleen cell cultures were evident. In vivo immunization of mice with B-LPS resulted in high antibody responses in C3H/HeN, intermediate responses in F1, and low responses in C3H/HeJ mice. When purified splenic B cells were incubated with B-LPS, both mitogenic responses and polyclonal immunoglobulin M (IgM) synthesis occurred in C3H/HeN cultures, whereas intermediate responses were noted in F1 cultures and no response was seen in B cell cultures from C3H/HeJ mice. Furthermore, in vitro TNP-B-LPS responses were induced in C3H/HeN spleen cells or purified B cell cultures, and intermediate anti-TNP PFC responses occurred in F1 spleen cells or purified B cell cultures. The toxicity of B-LPS was tested in galactosamine-sensitized mice. The LD50 values for B-LPS in classic LPS-responsive C3H/HeN and C57BL/6J mice were 0.6 microgram and 1.1 microgram, respectively; F1 hybrid mice were approximately 15-fold more resistant, whereas C3H/HeJ mice gave an LD50 of 1650 micrograms. This study shows that phenol-water preparations of B-LPS are biologically active and induce responses in the classic LPS-responsive but not in the LPS-hyporesponsive C3H/HeJ mouse strain.

Animals↗
PubMed1984

Monoclonal antibodies to Salmonella lipopolysaccharide: anti-O-polysaccharide antibodies protect C3H mice against challenge with virulent Salmonella typhimurium.

The present investigation reports the production of monoclonal antibodies to antigenic determinants of the O-polysaccharide of Salmonella typhimurium lipopolysaccharide (LPS), and assesses the effectiveness of these antibodies in protecting C3H mice against the lethal effects of Salmonella infection. Hybridomas were generated by fusing spleen cells from (BALB/c X A/J)F1 (CAF1) mice hyperimmunized by i.v. injection with acetone-killed S. typhimurium SR-11 with X63-Ag8.653 murine myeloma cells. Hybridomas producing antibodies reactive with S. typhimurium SR-11 whole cells were subcloned, and seven of the resulting clones as well as one previously described clone were selected for use in the studies reported here. Monoclonal antibodies from these eight clones were of the IgG1 (1), IgG3 (6), or IgM (1) isotype and were specific for the O-polysaccharide region of Salmonella LPS, reacting with LPS from smooth S. typhimurium SR-11 and LT-2, but not with LPS from rough S. minnesota R60 (Ra), R345 (Rb), or R595 (Re). The effectiveness of each monoclonal antibody in protecting C3H/HeN and C3H/HeJ mice against the lethal effects of Salmonella infection was evaluated by comparing the median length of survival of groups of mice given antibody by i.p. injection before i.p. challenge with virulent S. typhimurium SR-11 to that of animals that received no antibody. Three out of eight monoclonal anti-O-polysaccharide antibodies, ST-1 (IgM), 10-5-47 (IgG3), and 10-5-6 (IgG3), provided significant (p less than 0.01) protection to C3H/HeN mice challenged with approximately 10(4) LD100 of Salmonella. Only antibodies ST-1 and 10-5-6, however, extended the median length of survival of C3H/HeJ mice beyond that of infected controls. Mouse antiserum prepared against S. typhimurium SR-11 was equally protective in C3H/HeJ mice. In an attempt to understand the contribution of antibody specificity to the relative differences in the protective capacities of the monoclonal antibodies, their reactivities with several Salmonella reference strains of different classical serotypes were examined. Although some differences in reactivity against the different strains were apparent, this approach was not adequate for defining the fine specificity of these monoclonal antibodies. The results of this study provide evidence that monoclonal antibodies with specificity to the O-polysaccharide region of Salmonella LPS can protect C3H mice against challenge with the homologous bacterial strain.

Animals↗
PubMed1984

Relationship between immune system and gram-negative bacteria. II. Natural killer cytotoxicity of Salmonella minnesota Rb 345-unbound human peripheral blood lymphocytes.

Spontaneous binding of human peripheral blood lymphocytes (PBL) to bacteria represents a promising approach for the characterization of lymphocyte subsets mediating different functions. In the light of previous findings on the high degree of spontaneous adherence of S. minnesota Rb cells to PBL, we have evaluated the natural killer (NK) cytotoxicity of PBL subpopulations that fail to bind to Rb bacteria. The S. minnesota Rb-unbound cell fraction exhibits higher levels of cytotoxic capacity, which is related to a more elevated frequency of active NK cells, as determined in an agarose-single cell cytotoxic assay. Moreover, the cytotoxic activity of the unbound fraction is additionally boosted by interferon-alpha pretreatment. The effector cells bear Fc gamma receptors that are involved in NK cell lysis, because a decrease of NK activity is observed after immune complex modulation of the receptors. Finally, these cells, which display a high percentage (approximately 70%) of typical large granular lymphocyte morphology, express HNK-1, T10, T8, and M1 antigens, and to a lesser extent T3 and T4 antigens. These data indicate a selective enrichment of NK cells in the S. minnesota Rb-unbound fraction.

Adhesiveness↗
PubMed1984

LPS regulation of the immune response: separate mechanisms for murine B cell activation by lipid A (direct) and polysaccharide (macrophage-dependent) derived from Bacteroides LPS.

Lipopolysaccharide (LPS) derived from Bacteroides fragilis has been reported to stimulate mitogenic responses in spleen cell cultures from the classical LPS-hyporesponsive C3H/HeJ mouse strain; however, we have shown that purified splenic B cells from C3H/HeJ mice are hyporesponsive to phenol-water extracted LPS from B. fragilis ATCC 25285 (B-LPS). In the present study, B-LPS and its purified lipid A and polysaccharide components were tested for their ability to induce mitogenic and polyclonal IgM synthesis in spleen cell and purified splenic B cell cultures from classical LPS-responsive and -hyporesponsive mice. Mitogenic responses to B-LPS and E. coli K235 LPS(Ph) of whole spleen cells (2 X 10(5) cells/culture) or purified B cells (5 X 10(5) cells/culture) from classical LPS-responsive mouse strains (C3H/HeN, BALB/c, C57BL/6J, C57BL/10Sn, and DBA/2), F1 mice (derived from crosses between LPS responsive and C3H/HeJ mice), and classical LPS-hyporesponsive mice (C3H/HeJ and C57BL/10ScN) were high, intermediate, and low, respectively. When a higher number of whole spleen cells (5 X 10(5) cells/well) were cultured, B-LPS induced high mitogenic responses in C3H/HeN, intermediate responses in F1, and lower but significant responses in C3H/HeJ cultures. Similar results were obtained when polyclonal IgM synthesis was assessed in cultures containing 1 X 10(6) cells/culture. In contrast, the purified lipid A component of B-LPS failed to induce mitogenic responses in either whole spleen or purified B cell cultures. The addition of purified splenic B cells from C3H/HeJ mice to C3H/HeN or C3H/HeJ splenic adherent cells resulted in mitogenic responses to B-LPS, implying that the hyporesponsiveness to B-LPS seen in whole spleen cell cultures from C3H/HeJ mice at the lower cell concentration was due to limiting numbers of M phi. When splenic B cells and M phi from either C3H/HeN or C3H/HeJ mice were incubated with the lipid A or the polysaccharide moiety of B-LPS, lipid A induced mitogenic responses only in C3H/HeN cultures, whereas the polysaccharide moiety induced similar responses in both C3H/HeN and C3H/HeJ cultures. These results suggest that Bacteroides lipid A does not stimulate B cells from the classical LPS-hyporesponsive C3H/HeJ mouse strain, whereas the polysaccharide moiety of B-LPS is biologically active and mediates B cell stimulation via M phi.

Animals↗
PubMed1984

Murine immune responses to Salmonella lipopolysaccharide: oral administration of whole bacteria to C3H/HeJ mice induces secondary anti-LPS responses, especially of the IgA isotype.

Because our past studies have shown that oral administration of thymic-dependent antigens induces higher IgA responses in lipopolysaccharide (LPS) nonresponsive C3H/HeJ mice than in syngeneic, LPS-responsive C3H/HeN animals, it was of interest to compare anti-LPS responses in these mouse strains after oral administration of particulate antigens containing LPS. C3H/HeJ and C3H/HeN mice were given smooth Salmonella typhimurium LT-2 or rough S. minnesota Rb (R345) or Re (R595) organisms by gastric intubation for 3 consecutive days/wk for 2 wk and were boosted by the i.v. route with either the same bacterial immunogen or with purified homologous LPS. Four days later, splenic anti-LPS plaque-forming cell (PFC) responses were assessed with a panel of indicator sheep erythrocytes (SRBC) coated with LPS derived from either smooth (S-LPS-SRBC) or rough (Rb-LPS-SRBC or Re-LPS-SRBC) Salmonella. In separate studies, both serum and salivary antibodies of the IgM, IgG, and IgA isotypes were determined by ELISA, with whole Salmonella cells used as the coating antigen. Oral immunization with LT-2 resulted in good IgM, IgG1 and IgA splenic anti-LPS PFC responses in C3H/HeJ mice, with the major isotype being IgA. Mice boosted i.v. with purified LPS gave five- to sixfold higher anti-S-LPS PFC responses than did mice given whole bacteria by the i.v. route. Low anti-Rb-LPS and anti-Re-LPS PFC responses were seen in both mouse strains. Enhanced immune responses in orally primed C3H/HeJ mice was not due to LPS-induced polyclonal responses, because splenic cultures from these mice gave poor mitogenic responses to LPS. A similar pattern of response was obtained when C3H/HeJ or C3H/HeN mice were given RB (R345) or Re (R595) bacteria orally and boosted i.v. with purified homologous LPS or whole cells. C3H/HeJ mice again showed higher immune responses in all isotypes than did C3H/HeN animals. Mice given Rb (R345) immunogen gave maximum responses to Rb-LPS, lower responses to Re-LPS, and no responses to S-LPS, whereas C3H/HeJ mice immunized with Re (R595) immunogen gave maximum PFC responses to Re-LPS and lower responses to Rb-LPS. Serum and salivary antibody titers closely paralleled the splenic PFC responses, and IgA antibodies were the predominant isotype observed, with higher IgA responses occurring in orally immunized C3H/HeJ mice than in C3H/HeN animals. These results clearly indicate that C3H/HeJ mice given whole Salmonella by gastric intubation elicit higher PFC and antibody responses to the three major LPS regions than do identically treated LPS-responsive C3H/HeN mice.

Administration, Oral↗
PubMed1984

In vitro effects of human lipoproteins on the immune system in healthy donors: inhibition of plaque forming cell generation and decreased frequency of NK cells.

The effects of human high density lipoproteins, low density lipoproteins and very low density lipoproteins on spontaneous plaque forming cell (PFC) generation have been evaluated in healthy donors. Additionally, natural killer (NK) cytotoxicity using either 51Cr release assay or agarose single cell system has been studied under identical experimental conditions. A significant inhibition of spontaneous PFC capacity was observed. Furthermore, lipoprotein (LP) pre-treatment led to a reduced frequency of cells mediating NK cytotoxic activity as shown by the decreased binding capacity, even if the killing function was per se not affected. Taken together, these results suggest an inhibitory role for human LP on certain immune functions, likely related to the imbalance of lymphocyte metabolic pathway.

Adult↗
PubMed1984

Relationship between immune system and gram negative bacteria. I. Spontaneous binding of smooth and rough Salmonella to human peripheral blood lymphocytes.

Over the past years many reports have emphasized that either Gram positive or Gram negative bacteria possess the ability to bind spontaneously to human peripheral blood lymphocytes (PBL). Here, bacterial binding to human PBL has been studied by using a smooth (S) Salmonella typhimurium LT-2 and two rough (R) mutants of Salmonella minnesota R 345 (Rb) and R 595 (Re), which possess specific deletions in their lipopolysaccharide (LPS) molecule. Our results provide evidence that all three bacterial strains spontaneously bind to PBL, even though Re and mostly Rb cells display the highest degree of adherence. The three major regions of LPS (O-polysaccharide chain, R core and lipid A) seem to be involved in the binding since adherence is specifically inhibited by pretreating PBL with S- or R-LPS extracted from homologous bacteria. Furthermore, using a panel of monoclonal antibodies to lymphocyte surface antigens, S- and R-Salmonella bacteria bind to T lymphocytes (preferentially T8+ cells), while few B cells are coated by bacteria. Additionally, bacterial binding is significantly reduced by trypsin pretreatment of PBL, this suggesting that proteins (or glycoproteins) of the PBL membrane are involved in the binding.

Antigens, Surface↗
PubMed1983

Humoral immune response in aged humans: suppressor effect of monocytes on spontaneous plaque forming cell generation.

In 50 old donors antibody synthesis has been detected using a protein A haemolytic plaque assay. Data provide evidence that the plaque forming cell (PFC) capacity of aged peripheral mononuclear cells (PBMC) is significantly depressed (0 . 01 greater than P greater than 0 . 001) in comparison to controls. Additionally, suppression is mediated by adherent cells, since monocyte depleted lymphocytes regain the ability of generating spontaneous plaques. The inhibitory effect of monocytes seems to be prostaglandin-dependent, since indomethacin pre-treated PBMC give rise to a normal number of plaques when compared to young mononuclear cells.

Adult↗
PubMed1982

In vitro modulation of cell-mediated immunity by prostaglandin E2. I. Enhancing-inhibitory effects on antibody-dependent cellular cytotoxicity.

The modulating effects of Prostaglandin E2, solubilized in medium, were observed in the antibody-dependent cytotoxic system. The pretreatment of effector cells with PGE2 up to 5 hours increased significantly the cytotoxic activity. The enhancement was distributed in both Non-T and T lymphocyte fractions suggesting a more pronounced activation of K cells. The effect was abrogated by pretreating lymphocyte suspensions with Indomethacin before exposure to prostaglandin. On the other hand, the addition of PGE2 during the test led to an inhibition of the cytotoxic capacity. Taken together, these results imply either a relationship between endogenously produced PGE2 and the concentration of exogenous PGE2 or the influence of PGE2 on microenvironment (i. e. exchange of calcium and magnesium through the cell membrane) during the cytolytic phenomenon.

Antibody-Dependent Cell Cytotoxicity↗