Annales d'immunologie最新文献

An inflammatory reaction induced in mice by a subcutaneous injection of magnesium silicate embedded in a calcium phosphate gel is followed by an increased resistance against Plasmodium berghei. The occurrence of this increased resistance against Plasmodium berghei. The occurrence of this increased resistance is related to the time elapsed between the induction of the inflammatory process and the infection. The delayed mortality is correlated with a slowed development of parasitemia. It is hypothesized that the protective effect may be related to the capacity of the inflammatory reaction to promote in mice both specific and non-specific antiparisitic immune responses.

The recent isolation, by recombinant DNA techniques, of cloned probes for mouse and human class I major transplantation antigens has initiated the molecular analysis of the corresponding genes. Mouse genes belong to a relatively large multigene family, whose members share extensive structural homologies. Sequence analyses suggest that some genes could have a mosaic structure. This feature might help us to understand one of the distinctive traits of these antigens: their large antigenic polymorphism.

The different types of cell population in organotypic cultures of spleen from chicken immunized with Salmonella paratyphi B were enumerated. The kinetics of immunoglobulin and of antiflagellar antibody synthesis followed the cellular variations observed. Two phases were generally observed: one was characterized by a considerable decrease in small and medium-sized lymphocytes by a lytic process and the appearance, by transformation and/or multiplication, of a large population of hyperactive macrophages. The IgM and IgG synthesized between the 2nd and 9th days only partially consisted of antiflagellar antibodies; some were synthesized probably by large basophilic cells and others by the few plasma cells which were observed, generally isolated on the prints. The second phase, from the 11th to the 21st day, manifested a narrower antibody specificity in that all the IgG, the only immunoglobulin synthesized during this period, might be entirely absorbed by the antigen and corresponded to the proliferation of a new lymphoreticular population. A close cellular cooperation seemed to occur at this stage between these two types of population, the macrophages appearing to stimulate lymphopoiesis. Colonies of plasma cells, characteristic of this phase, appeared from the 13th day. These two phases were separated around the 9th day be a brief period of cellular depression. Although the transformations, the contacts and the islets observed among the lympho-reticular populations indicated their plasticity and their capacity for change during the reaction, it must be noted that there was no in vitro example of antibody synthesis occurring without the simultaneous presence of lymphocytes, macrophages and pyroninophile cells.

The enhancement of the response of T cells to concanavalin A (ConA) and phtyohaemagglutinin (PHA) by macrophages has been shown in most species, whereas the accessory role of B cells has been only described in studies using human or rabbit lymphocytes. In rabbit, the accessory activity is confined to a subpopulation of B lymphocytes: the majority of B cells have sedimentation velocity of 2.5 to 4 mm/h, whereas the maximum of the accessory activity is found among the B cells, sedimenting with a velocity of 3.5 to 8 mm/h; B cells sedimenting between 1 and 3.5 mm/h have only a very weak accessory activity. Splenic adherent and/or phagocytic spleen cells may contribute additional augmentation of the response of T cells to ConA, since other macrophages (peritoneal and alveolar) are able to increase the ConA response to spleen T cells.

An immunogenic complex was obtained from Salmonella typhi by the bacterial acetone powder method. This complex induced in mice a high degree of protection against a challenge with the virulent Salmonella. This immunogenic complex was fractionated at least into 19 fractions when chromatographied on a DEAE-cellulose column. By SDS-polyacrylamide gel electrophoresis, 25 protein bands were observed. Eleven DEAE-cellulose fractions were tested in order to know their immunogenicity. Mice were inoculated with 10 micrograms of protein of each fraction. Seven days after, the mice received a booster. Thirty days after the first inoculation, the animals were challenged with S. typhi resuspended in chondroitin-sulphate at 13%, by the intraperitoneal route. Appropriate control mice were included; 30 min before the challenge, mice had been inoculated with 850 microgram of lead acetate by the intravenous route. The immunogenic complex protected 100% of mice; six of its fractions were good immunogens; one of them, the fraction 4, was shown to contain at least 3 proteins by electrophoresis assay. This fraction induced in mice a high degree of protection against the challenge by the virulent Salmonella. Finally, a ribonucleoprotein purified from this fraction was highly immunogenic to mice against the challenge by 10 LD50 of S. typhi (1 LD50 was equivalent to 2 X 10(6) CFU).

C57BL/6 are more resistant than DBA2 mice to Brucella suis 1330. This difference does not concern the blood clearance of the i.v. inoculated bacteria or the number of infective colonies in the spleen at very early stages but the splenic infection at later stages with maximal differences on day +7. The "resistance" character is inherited by F1 and back-crosses as a partially dominant character with polygenic control and a better expression of resistant factor(s) in females. This phenomenon of sex limitation is independent of male-female matings and therefore not sex-linked. Association of the "resistance" character with known genetic markers was investigated using (B6 X DB) X DB back-crosses, BALB/B, BALB/c, C3H/eb and C3H/HeJ mice. No correlation of "resistance" with Ig allotypes, the "d" coat color or the LPS genes was evidenced. On the other hand significant differences in the number of splenic colonies on day 7 were observed according to the H-2 haplotype or the "b" coat color phenotypes. These results are discussed in terms of: a) the partially common and partially independent genetic regulation of susceptibility to experimental brucellosis and antibody response to Brucella antigens; b) the possible importance of sex-dependent and MHC or chromosom 4-linked genetic factors for bacterial immunity.

The respective roles of cell surface receptors were studied in a model of cell-mediated cytotoxicity using 51Cr-labelled chicken erythrocytes as target cells and human polymorphonuclear neutrophils (PMN) as effector cells. The attachment of the targets to PMN, demonstrated by rosette formation, was achieved by PMN surface receptors for C3 or for Fc IgG. No receptors for Fc IgM could be demonstrated. Direct contact between targets and effector cells was required and no cell-free cytotoxic mediator was demonstrable in this model. Target cells bound to PMN-C3 receptors were not lysed unless a cytotoxicity inducing signal was delivered. This was provided by anti-PMN heteroantibodies, or by their F(ab')2 fragments as well. It was therefore possible to trigger the cytotoxic reaction by bypassing PMN-surface receptors for Fc IgG. When the target cells are coated with IgG antibodies, PMN receptors for Fc IgG ensure both the attachment and the triggering signal for the cytotoxic reaction. Polymorphonuclear neutrophils (PMN) have been reported to the effective killer cells in vitro under three different experimental conditions: during phagocytosis, in the presence of antibody directed against the target cells and in the presence of lectins. PMN accumulation has also been considered as a major component of the pathogenesis of many forms of immunologic tissue injuries since PMN may react with immune complexes bound to a surface which they cannot phagocytose. Under these circumstances, they release lysosomial enzymes, by a mechanism which has been called "reverse endocytosis" or "frustrated phagocytosis". Attachment of PMN to target involves cell surface receptors (Fc gamma R) for the Fc region of the IgG molecule and/or receptors (C3R) for the activated third component of complement. The binding of aggregated or antigen-complexed IgG to PMN surface Fc gamma R generates signals triggering the internalization phase of phagocytosis, the antibody-dependent cell cytotoxicity (ADCC) and the stimulation of glucose oxidation by the hexose monophosphate pathway. However, the latter metabolic activation was also reported to be triggered by the fixation of antibodies specific for PMN surface determinants. It was therefore conceivable that modifications induced at the membrane level on any structure distinct from Fc gamma R would produce metabolic changes leading to target cell destruction, provided that a close contact could be established between effector and target cells. In the present study we have investigated the respective roles of Fc gamma R, C3R and other yet undefined surface determinants of PMN in the induction of cytotoxic activity towards heterologous target cells.

The deep cortex of the node was previously shown to be composed by semi-rounded "units", each one comprising a centre and a periphery. The periphery was considered to a site of migration of lymphocytes circulating through a node and the centre a site where some of these migrating cells collect for a certain time. The present work compared the units of the nodes of germ-free and normal mice at age eight-weeks. The units differed in the two groups of animals. The main finding was that the units of mesenteric nodes of germ-free mice differed from those of the other nodes found in the same animals. Unlike in the mesenteric nodes of normal mice, the periphery of a unit was clearly demarcated from its center due to a greater lymphocyte density in the periphery. This fact fits a previous proposal that each part of the unit functions separately. Observations of the peripheral cortex and medulla of the germ-free nodes support other previous proposals on various aspects of the functioning of the organ in normal animals.

A VH region gene is generated from three gene segments, VH, D and JH, separated on the germline chromosome and rearranged during differentiation to generate an active VH gene. The sequence and length variations of the D region are an important source of the antibody diversification. To investigate their role in the antigen recognition, VH sequences of three myeloma proteins (ABE48, UPC10 and MOPC173) having different antigen specificities and whose VH segments were expected to be highly homologous have been determined: cDNA clones containing the structural gene sequences for the three proteins have been constructed. The nucleotide sequences of the three VH regions have been determined. The deduced amino-acid sequences are compared to those of four other myeloma proteins (J539, X44, X24 and T601). The seven proteins have highly homologous VH segments. The comparison points out the correlation existing between the D-region structure and the antigen-binding specificity.