Addition of either a lauroyl or a pentapeptide (FLLAV) hydrophobic foot to the NH2 terminus of a small, synthetic peptide allowed the peptide to hydrophobically complex to meningococcal outer membrane protein proteosomes by simple dialysis. Both conventional and LPS-hyporesponsive mice immunized with these complexes without any adjuvants developed high-titered and persistent anti-peptide IgG. Since proteosomes have been safely given to many people and since important antigenic determinants are generally hydrophilic, this system should be widely applicable to the development of peptide vaccines for human use.
In cooperation with human heat-inactivated antisera from adults immunized with group C meningococcal polysaccharide, normal human peripheral blood mononuclear cells significantly decreased the viability of group C meningococci (Mgc) in vitro. K lymphocytes (Null cells) and monocytes, (but not T or B lymphocytes) were capable of effecting antibody-dependent cell-mediated (ADC) antibacterial activity in this system. The degree to which meningococcal viability was decreased was a function of the length of the test incubation, the concentration of effector cells, and the amount of antiserum used in the assay. When specific antibodies directed against Mgc were adsorbed from the antiserum, cell-mediated antibacterial activity was abolished. ADC antibacterial activity was also abrogated by performing the assay at 4 degrees C or by heating effector cells to 46 degrees C for 15 min before the assay, Similarities between the ADC antibacterial system and previously described ADCC assays are discussed. The data suggest the K cells (as well as monocytes) may play a role in host immune defense against pathogenic bacteria.
IgA purified from the sera of patients convalescing from disseminated group C meningococcal disease induced human monocyte-mediated anti-meningococcal activity in vitro in the absence of complement. Both IgA- and IgG-dependent activity were directed against the group C meningococcal polysaccharide (Csss) capsule. The amount of IgA that was effective bound less than 1 ng of Csss. Antibacterial activity was dependent upon the length and the temperature of the test incubation and on the concentration of monocytes. The implications of this mechanism for local cell-mediated antibacterial immunity are discussed.
A B S T R A C T We have compared the abilities of immunoglobulin (Ig)G, IgM, and IgA to induce either mononuclear cell-mediated (complement-independent) or complement-mediated (cell-free) antibacterial activity against group C meningococci. In each of these assays, immunoglobulins purified from the sera of individuals immunized with meningococcal group C polysaccharide were compared with those purified from sera of patients convalescing from disseminated meningococcal disease. Our data support three conclusions. First, although nonbactericidal in cooperation with complement, IgA can induce cell-mediated antibacterial activity as well as IgG. Second, the amount of IgG required to induce cell-mediated antibacterial activity is similar to the amount required for complement-mediated killing. Third, although the amount of either postimmunization or convalescent IgM required to induce complement-mediated killing is 16-to 20-fold less than the amount of respective IgG required, IgM is inferior to IgG in its ability to induce cell-mediated antibacterial activity because in the cell-mediated system (a) postimmunization IgM is ineffective; (b) the amount of convalescent IgM required for minimal activity is eightfold more than the amount of convalescent IgG required; and (c) the maximal antibacterial index induced by convalescent IgM is 50% less than that which can be induced by IgG. These data suggest that IgG and IgA may play a greater role than IgM in mononuclear cell-mediated antibacterial host immune defense.
Antibody-dependent activity against group C meningococci mediated by human mononuclear cells or purified lymphocytes was inhibited when sera from adults immunized with group C meningococcal polysaccharide were preincubated with that polysaccharide. Likewise, activity against group A meningococci induced by heat-inactivated sera from adults immunized with group A meningococcal polysaccharide was inhibited by preincubation with that polysaccharide. Neither heterologous polysaccharide nor homologous protein or lipopolysaccharide meningococcal antigens inhibited the activity of either of these sera. The data indicate that immune specificity in this cell-mediated antibacterial system is dependent upon antibodies to the specific polysaccharide antigen with which the serum donor had been immunized.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.