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To investigate the role of lung lymphocytes (LL) in the local defense mechanisms, we studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using S. pneumoniae type 3 as target. In parallel, natural killer (NK) activity against YAC-1 tumor cells was investigated. Lung cells obtained by enzymatic digestion were found to exert detectable NA and NK activities, which were further increased after purification of LL (greater than 90% lymphocytes) by carbonyl iron and magnet treatment. Depletion experiments with antibodies and complement indicated that the effector cell of NA activity was a Thy 1.2+, L3T4+, aGM1+ lymphocyte, whereas the effector of NK activity was found to have a Thy 1.2-, aGM1+ phenotype. Preincubation of LL with anti-IgA antibodies, but not with anti-IgG, completely inhibited NA activity, suggesting that it was mediated by preexisting IgA bound to the LL surface. Furthermore, purified IgA from S107 plasmacytoma with specificity for phosphorylcholine, a component of the outer wall of S. pneumoniae, was able to enhance the antibacterial activity of LL and to restore their activity after treatment with anti-IgA. In addition, S107 antibodies were found to specifically induce antibacterial activity against S. pneumoniae in resident alveolar macrophages (AM) and peritoneal exudate cells, which did not express NA activity. We conclude that mouse LL include a subset of IgA-bearing lymphocytes with the phenotype of helper-T cells, which are able to exert NA activity against pneumococcus through an IgA-driven mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.

The synthetic peptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, could potently enhance the primary and secondary response of mice immunized with SRBC, measured as the number of specific antibody-secreting cells in the spleen. This adjuvant activity was dose-dependent, being maximal when the nonapeptide was administered intraperitoneally (i.p.) or subcutaneously (s.c.) at 100 mg/kg or orally (p.os) at 33 mg/kg, reaching levels comparable to those attained by 20 ng/kg of hu rIL-1 beta given i.p. or s.c. A dose-dependent enhancement of the primary response to SRBC was also observed when IL-1 beta or its peptide fragment were injected intravenously (i.v.) together with the antigen, with a maximum activity at 10 micrograms/kg for the 163-171 peptide and 100 pg/kg for hu rIL-1 beta. Thus, the in vivo immunostimulatory activity of hu IL-1 beta depended on the administration route as follows: i.v. much greater than s.c. = i.p. much greater than p.os. Conversely, the adjuvant effect of the 163-171 peptide was: i.v. much greater than p.os greater than s.c. = i.p.

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.