Annales d'immunologie最新文献

In this study, 3 groups of 15 rabbits each were sensitized with killed Mycobacterium tuberculosis, M. kansasii or M. avium bacteria. The sensitization was performed through the footpad. Eighteen days after sensitization, cellular immunity of the rabbits was tested with total homologous and heterologous antigens by direct and indirect migration inhibition tests using spleen macrophages. The bacteria were sonicated and centrifuged at 100,000 g for 1 h. The supernatant was used as the cytoplasmic antigen. Assayed by indirect migration, the migration index (MI) for homologous antigens was highly specific compared to heterologous antigens (MI of 0,60-0,65 compared to 0,79-0,96). The patterns obtained for rabbits sensitized with M. tuberculosis or M. kansasii when assayed by direct migration in the presence of homologous antigens (MI of 0,58 and 0,61, respectively) were similar. M. avium gave a distinct pattern. The results obtained indicate that crossed activity with heterologous antigens would be due to the presence of common components in the total antigens of the mycobacteria in question. On the other hand, the lower specificity of the direct test would result from the role played by humoral factors and antibodies, which might influence simultaneously migration of the target macrophages.

The C3 amplification convertase of human complement, C3b, Bb, is assembled on biological surfaces by the interaction of the alternative pathway proteins B, D and P with cell-bound C3b. Convertase formation is modulated by the action of the regulatory proteins H and I. On activating surfaces of the alternative pathway, C3b, Bb is relatively resistant to regulation by H. In contrast, non-activating surfaces exhibit surface characteristics such as high content in membrane-associated sialic acid or heparin-related material which increase the interaction of H with cell-bound C3b. Thus, finely tuned molecular interactions allow the alternative pathway to function as a major recognition and effector system for natural defence.

A collection of bacterial plasmids has been constructed carrying cDNA inserts corresponding to mouse liver C3. Eight overlapping cDNA fragments cover 4 700 out of the 5,100 +/- 200 nucleotides of the mRNA including its 3'-end. By partial DNA sequencing it has been found that the beta-chain is encoded in the 5'-half of the mRNA and must thus be located in the amino-terminal portion of the precursor polypeptide pro C3. From DNA sequences it is predicted that the amino-terminus of mouse C3-beta coincides in 12/15 residues with the known amino-acid sequence of guinea-pig C3 beta and in 9/10 residues with that of human C3 beta. A gene bank has been constructed from mouse DNA, from which four C3 genomic clones have been isolated. Two of them carry direct neighbouring fragments of 14- and 18-kilobase pairs of DNA, and contain one entire C3 gene (24-kilobase pairs). The 3'- and 5'-ends of the gene have been mapped. The DNA sequence at the 5'-end predicts that the initial translation product of the C3-mRNA is a prepro C3 molecule which carries at its amino-terminus a signal peptide of 24 amino-acids of typical composition. Human C3 genomic clones have been isolated and used to map the human C3 gene on a chromosome.

The study of antibody-dependent cellular cytoxicity mechanisms in human and experimental schistosomiasis has revealed the particular role of immune complexes in triggering phagocytic cell activation. IgE complexes or aggregates were demonstrated to bind to specific receptors on rat macrophages as well as on human or baboon macrophages, leading to the killing of the parasite target. In the eosinophil-dependent cytotoxicity mechanisms, IgE complexes have been shown to exert a regulatory effect on eosinophil activation in vitro and in vivo and on the ability of this cell population to kill parasites. The various observations reported in this review suggest that the characteristics of the Fc receptors, the composition and antigen-antibody ratio of immune complexes might be essential factors in the regulation of the immune response against parasites.

Genetic deficiencies of complement proteins are now more often recognized and analysed more precisely because the structure of the different complement proteins is better known. Partial defects may be detected in some components by the combined utilization of titration techniques, polymorphism studies and linkage analyses. The partial deficiency in C4 seems to be the most frequent protein deficiency in the human. The complement markers on the short arm of the sixth chromosome in man (BF, C2, C4A and C4B) are located in close proximity to the HLA-D/DR region. The combined study of the complement and HLA markers will probably allow the fine structure of the HLA region to be better defined. The association of some diseases with HLA types will probably also be better specified by the definition of associations not only with HLA-B or HLA-D types but also with the BF, C2 and C4 types.

C1 activation can be triggered by immune complexes and various effectors such as extrinsic proteases, bacterial or viral membranes, polyanions and polysaccharides. The basic mechanism of activation involves a limited proteolytic cleavage of C1r, with the generation of a proteolytic activity. Highly purified proenzymic C1r was obtained in high yield from human plasma by an indirect affinity chromatography step. Activation of isolated C1r in a fluid phase proceeded according to two distinct coexisting mechanisms: 1) an autocatalytic intradimer activation mediated by the pro-site of non-activated C1r; 2) an autocatalytic interdimer proteolysis triggered by nascent activated C1r formed in the course of the first reaction. DFP and C1-inhibitor did not have any effect on the first mechanism but were able to block the second mechanism. C1 activation is discussed in the light of recent results obtained by others from electron microscopy, and a tentative model is proposed.

The treatment by Corynebacterium parvum induced an increase of peritoneal cell number in conventional mice but no modifications in germ-free mice. Against YC8 tumoral target cells, cytostatic properties of peritoneal cells were of the same intensity in conventional and germ-free after C. parvum treatment. Against K.BALB cells, C. parvum treatment induced an increase of cytostatic properties from 9 to 93% in conventional mice and from 51 to 84% in germ-free mice. Cytotoxic properties were increased by C. parvum in conventional mice but were unchanged in germ-free mice. The bacterial flora could play a role in the cytotoxic and cytostatic properties of peritoneal cells in conventional mice.