Biomedical subjects
Publications and source records attributed to L Nencioni.
We report a case of coincidental meningioma and astrocytoma in the same hemisphere. Neuroradiological examination, CT and angiography showed only one of the tumors.
Cell-mediated immune responses were assessed employing a 2-hr in vitro cytotoxicity assay against S. typhimurium. It was observed that lymphocytes from GALT as well as from peripheral lymphoid organs possessed natural antibacterial activity, whereas macrophages were devoid of this spontaneous activity. The distribution of this newly described natural activity was PPL greater than MnL greater than IEL = SpL = PBL greater than PoL; this did not correlate with the organ distribution of NK activity against YAC-1 tumor cells, which was PBL greater than SpL = IEL greater than MnL = PoL = PPL. Moreover, the phenotype of the splenic effector cell of the natural activity against S. typhimurium showed some differences from that of NK activity. In fact, both these cells were asialo GM1+, Fc-receptor+, nonadherent, and nonphagocytic, but the former was Thy-1.2- and the latter Thy-1.2+. The effector cell of the natural antibacterial activity in the Peyer's patches had the same phenotype as the splenic one. It was then observed that the antibacterial activity could be augmented by the addition of immune antibodies against S. typhimurium. This was particularly evident employing IEL, SpL, and PBL as effector cells, whereas PPL and MnL did not show any antibody-dependent antibacterial activity. Furthermore, these last two populations could not mediate ADCC against CRBC. Employing selective methods to deplete cell populations, we observed that, at least at the splenic level, there is also a cell that differs in its phenotypic characteristics from that mediating natural antibacterial activity but that plays a role in the antibody-dependent reactions. In conclusion, these results suggest that natural and antibody-dependent antibacterial mechanisms might be important in defense against S. typhimurium, particularly at the gastrointestinal level, where many bacterial infections first take place and begin to interact with the host immune system.
Mouse peritoneal macrophages (M phi) expressed enhanced tumoricidal activity upon in vitro stimulation either with the lymphokine M phi-activating factor (MAF) or with fibroblast interferon (IFN-beta). In contrast, M phi suppressive activity on lymphoproliferation was not affected by MAF pretreatment, but was drastically reduced or abolished by IFN-beta. Catalase, the enzyme involved in the destruction of hydrogen peroxide (H2O2), did significantly decrease M phi suppressive capacity but had no effect on M phi tumoricidal activity. Analysis of the phagocytosis-dependent H2O2 production by IFN-beta-treated M phi demonstrated a strong impairment of the oxygen metabolite release, which strictly paralleled the decreased M phi suppressive capacity. On the other hand, MAF did not modify H2O2 release by M phi. Studies on M phi antibacterial activity against Salmonella typhimurium, a function thought to depend upon H2O2 production, showed that exposure of M phi to IFN-beta significantly impaired their bactericidal and bacteriostatic capacity, again in close correlation with the decrease in H2O2 production. Thus, IFN-beta appears as modulating both suppressive and antibacterial capacities of M phi through reduction of their oxygen metabolism, whereas regulation of M phi anti-tumour activity is possibly controlled by different mechanisms.
Anti-hapten IgM antibody response and affinity were evaluated by haemolytic plaque inhibition assay on spleen cells from mice immunized with 2,4, dinitrophenyl (DNP)1.3-Dextran or DNP13-Dextran. Regardless of epitope density, affinity was found to mature with time after immunization and to be characterized by rapid oscillations independent of changes in anti-hapten plaque-forming cell (PFC) response and antibody secretion rate. Injection of the lower epitope density immunogen not only elicited higher PFC responses and higher affinity antibodies but also induced more pronounced affinity oscillations mainly confined to the higher affinity PFC subpopulation. Immunization of athymic nude mice with DNP1.3-Dextran elicited PFC responses comparable to those observed in similarly immunized euthymic mice. However, affinity oscillations were drastically reduced in athymic mice and the restricted variation of antibody affinity observed shortly after immunization was followed by no oscillations in any of the affinity PFC subpopulations. Athymic mice did not produce high affinity PFC which account to a large extent for the affinity oscillations observed in euthymic mice. These findings demonstrate the important role of T cells in the appearance of rapid changes in IgM antibody affinity. The generation of T-cell-dependent oscillations of high affinity antibody-producing cell subpopulations is discussed in terms of interactions among cells and soluble factors involved in regulatory circuits of the immune network.
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The in vivo immunizing potency of diphtheria toxoid and formalin-treated corss-reacting material (CRM197, a nontoxic mutant protein) was compared in guinea pigs. Major antigenic differences between the two untreated proteins were also tested in rats. The results showed that diphtheria toxoid and CRM197 were equally effective immunogens, but only if the latter was treated with formalin in the same concentration (0.7% vol/vol) was that of the toxoid. Formalin treatment rendered the antigens more resistant to enzymatic proteolysis by trypsin in vitro.
Secretory antibodies of the IgA class (sIgA) are thought to have an important role in the defence against bacteria at mucosal surfaces--the level at which the infectious agents first come into contact with the host. However, the mechanism by which sIgA exert their antibacterial activity is still a matter of debate. After the recent discovery of receptors for the Fc portion of IgA (RFc alpha) on lymphocytes, monocytes and granulocytes of human, rabbit, guinea pig and mouse origin, it has been hypothesized that IgA also mediate antibody-dependent cellular cytotoxicity (ADCC). Indeed, ADCC mediated by human leukocytes against bacteria has been demonstrated in the presence of human circulating IgA. As RFc alpha have also been shown to bind sIgA, we decided to investigate whether sIgA could mediate antibacterial ADCC when bound to lymphocytes from the murine gut-associated lymphoid tissues (GALT) which first interact with the invading bacteria. By using Shigella X16 (a hybrid strain between the enteric pathogen Shigella flexneri and Escherichia coli) as target in an in vitro assay that measures cell-mediated antibacterial responses, we found that murine lymphocytes from GALT but not from other tissues are able to exert natural antibacterial activity against Shigella X16, and that sIgA significantly and specifically increase the natural antibacterial activity of GALT lymphocytes from mice and induce antibacterial activity in cells from the spleen, but not from the thymus or popliteal lymph nodes. Thus, we now propose a new role for sIgA in protecting the host against infectious agents at the mucosal level.
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The immunostimulatory activity in vivo of the pleiotropic cytokine IL-1 beta can be retained by its nonapeptide VQGEESNDK, in position 163-171. A series of shorter and longer peptides around this position has been assayed for IL-1-like biological activity, in order to identify the structural requirements for full expression of adjuvant capacity. Elongated peptides, comprising the loop region 165-169 and up to six amino acids in the preceding beta strand or up to seven amino acids in the following beta strand, showed activity comparable or lower than that of the nonapeptide 163-171. This would indicate that the beta strand sequences are not required for optimizing the active conformation of the immunostimulatory IL-1 beta moiety. Accordingly, stabilization of the 163-171 peptide conformation by cyclization did not increase its biological activity. In contrast, the pentapeptide GEESN, corresponding the exposed loop 165-169 between two beta strands, had biological activity higher than that of the 163-171 nonapeptide and fully comparable to that of the entire IL-1 beta protein. Thus, the highly exposed fragment 165-169 within the IL-1 beta molecule may be the structure selectively responsible for the IL-1 beta immunostimulatory capacity in vivo.
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A case of permanent global amnesia resulting from a bilateral hippocampal lesion is reported, remarkable for its typical clinical picture and prolonged period of observation with repeated neuropsychological testing. No tendency toward spontaneous recovery was noted, even though extra-mnesic cognitive functions remained undamaged. No differences were observed between this amnesic syndrome and the neuropsychological picture during an acute episode of transient global amnesia.
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