1,721,104 research outputs found
Unsolved mysteries of intestinal M cells
No full textM cells are highly specialised cells present within the epithelium overlying organised lymphoid follicles of the small and large intestine. They play a central role in the initiation of mucosal immune responses by transporting antigens and microorganisms to the underlying lymphoid tissue. In this way the mucosal immune system encounters the limitless variety of antigens that enter the body through the gut mucosa and reacts by mounting specific mucosal and systemic immune responses.
Despite the role of M cells in mucosal defence many basic aspects of their biology, the most controversial being their origin within the follicle associated epithelium (FAE), still remain the subjects of debate. Recently, new information on the complex interactions of luminal microorganisms, mucosal immune system, and epithelial cells, that are instrumental in the induction of this cell phenotype, have become available. Here, the most novel data and hypotheses on M cell genesis and function in the gut are reviewed and discussed
Age-associated changes of the intestinal epithelial barrier: Local and systemic implications
No full textIn the past few years, increasing evidence has suggested that alterations of the epithelial barrier of the GI tract are linked to both local and systemic disorders of various natures. However, in spite of the numerous debilitating health problems that might stem from it, very little attention has been given to how ageing affects this critical structure. Here, the most recent data on the age-associated modifications of some of the physical and immunological features of intestinal epithelial barrier are discussed along with potential strategies to restore its function and improve the quality of life of the elderly, an ever increasing demographic segment of our society
Antibody protection in aging: Influence of idiotypic repertoire and antibody binding activity to a bacterial antigen
No full textPrevious studies demonstrated that the anti-phosphorylcholine (PC) antibodies produced by aged BALB/c (18-22 months old) mice are structurally different and less protective against infection with Streptococcus pneumoniae than those produced by young (3-4 months old) syngeneic mice. However, PC antibody from aged animals had a different idiotypic repertoire and, at the same time, showed a diminished antibody binding activity to pneumococci compared to ''young'' antibody. To determine the cause of the reduced protective activity of the ''aged'' antibody, experiments of passive protection were performed using anti-PC monoclonal antibody (mAb) from either young and aged BALB/c or young syngeneic mice that were neonatally injected with an equimolar mixture of two monoclonal antibodies specific for two distinct idiotopes of the T15 idiotype (Id) family. At young/adult age, the mice neonatally injected with anti-Id antibody were still able to respond to PC, but the idiotypic repertoire was characterized by the absence of the dominant T15 idiotype. The two groups of mAb generated had a similar affinity to PC and binding activity to pneumococci but were totally diverse in regard to both their idiotypic repertoire and V-H/V-L gene utilization. Experiments of passive protection allowed us to determine the influence of the idiotypic repertoire and antibody binding activity to pneumococci on the reduced antibody protective efficiency in aging. Young recipients (BALB/c) were injected ip with a dose of anti-PC mAb from young, either T15Id(+) or T15Id(-), and aged donors (20 mu g/recipient) and 2 hr later the groups of mice were challenged with 10(3) CFU of S. pneumoniae WU-2. Both groups of ''young'' antibody afforded a similar degree of protection, regardless of the idiotypic repertoire, always higher than that of PC antibody from aged mice. These experiments suggested that the decline of binding activity, and not the switch in the idiotypic repertoire, may be responsible for the reduced anti-pneumococcal activity of the anti-PC antibody on aging
Antibody Response in Aged C57BL/6 Mice: T Helper Cells are Responsible for the Decline of the Primary Antibody Response to a Bacterial Antigen in Aging
No full textT cells in agein
In vivo and in vitro study of the primary and secondary antibody response to a bacterial antigen in aged mice
No full textOne of the most important manifestations of aging in both humans and laboratory animals is a gradual decline in immune effectiveness. However, it is not clear as to how general is this decline. We here report that aged BALB/c mice showed no decline in the magnitude of the in vivo primary antibody response to phosphorylcholine (PC), an immunodominant epitope of the Streptococcus pneumoniae R36a (Pn). Often it appeared that aged mice responded better than young syngeneic mice. In contrast, the secondary antibody response had a different profile, with aged mice showing a marked decrease in PC-specific antibody. Further in vitro studies were conducted in order to determine the cause of the decline of the secondary antibody response in aging. We noted that B cells from young and aged donors, either primed or twice immunized with the antigen, when cultured without T cells and in the presence of antigen did not display any significant difference in their antibody response to PC. However, L3T4 cells from aged BALB/c mice, previously immunized twice with Pn, failed to augment the in vitro B cell response as compared to L3T4 cells from young mice. Moreover, we found that Lyt 2 cells from young and aged mice had no regulatory effects on the anti-PC response in vitro. Further in vivo experiments demonstrated that alteration of the idiotypic network may not be related to a decline in the secondary antibody response since two injections of the antigen are unable to elicit an anti-idiotypic antibody response in either young or aged mice. These data demonstrate that the decline of the anti-PC response after a secondary challenge with Pn is linked to defects in the T cell compartmen
A study of autologous anti-idiotypic antibody-forming cells in mice of different ages and genetic backgrounds
No full textAntibody response to phosphorylcholine, an immunodominant epitope of Streptococcus pneumoniae R36a (Pn), is characterized by a public idiotype, T15, that is expressed on a large proportion of antibody molecules produced by all mouse inbred strains. The ability of the immune system to produce an autologous antibody to T15 upon immunization with Pn vaccine was investigated using a modified ELISA plaque assay for detection of single antibody-forming cells (AFC). The limit of ELISA assay for detection of specific anti-T15 AFC is approximately 300 cells/spleen. However, our studies failed to detect any autologous anti-T15 AFC in the course of the primary antibody response to Pn vaccine in young/adult (2-4 months) BALB/c and C57BL/6 mice. Aged mice (20-22 months) also failed to develop any specific auto-anti-T15 AFC upon the primary Pn immunization, despite the fact that the anti-Pn response in these animals changes both quantitatively and qualitatively. In order to generate specific anti-T15 AFC, BALB/c mice had to be immunized repeatedly with Pn vaccine (four weekly injections) or immunized directly with T15 protein in CFA. Different results were obtained with D1.LP mice that are low responders to Pn and express lower levels of T15 Id as compared to BALB/c. Young D1.LP mice produced high numbers of auto-anti-T15 AFC of both IgM and IgG isotypes following a single immunization with Pn vaccine. The kinetics of auto-anti-T15 response in D1.LP mice was similar to that of the antigen-specific response. These results demonstrate that the ability of the immune network to produce autologous antibody to a shared Id depends on the genetic makeup of the host, and that this response may be regulated by the level of Id expression
Quality of antibody response in ageing: idiortypic repertoire and antigen affinity in the antipneumococcal antibody protection
No full textdescription of antibody structure in ageing and how age-related changes modify the efficacy of antibody response late in lf
Selenium is a source of aliment and ailment: Do we need more?
No full textBackground: Although the prevalence of Selenium (Se) deficiency is unknown, there is an anxiety that most Europeans may be deficient in this micronutrient because data show that recommended daily intakes are not achieved. Some countries have implemented an agricultural fertilization program to raise cereal selenium concentrations, thereby boosting dietary intakes. However, the relationships between dietary reference values (DRVs), Se adequacy and optimum selenoprotein activity are unknown, while the functional sequelae of inadequate Se supply remain uncharacterized.
Scope and approach: This commentary examines the benefits and disbenefits associated with Se supplementation. It highlights the inadequacy of currently used surrogate markers of Se status and an absence of clinical data to support stated benefits. The aim is therefore to stimulate debate about whether we really need more than the variable amounts we already consume
Increase of cross(auto)-reactive antibodies after immunization in aged mice: a cellular and molecular study
No full textAging in both humans and laboratory animals is often accompanied by an increase in autoreactive antibodies. Here we report that immunization with a bacterial antigen determined a marked increase of cross-reactive antibodies in aged but not in young mice. This phenomenon was observed in the aged individuals of two different mouse strains (Balb/c and C57BL/6) after a single injection of lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) that express the immunodominant epitope phosphorylcholine (PC). These data were then confirmed by the analysis of cross-reactivity of anti-PC monoclonal antibody (mAb) generated from Pn-immunized young and aged Balb/c and C57BL/6 mice. Most of the anti-PC mAb from aged mice showed a broad spectrum of cross-reactivity with a panel of self and non-self antigens, while none of the mAb from young mice did so. We also showed that a genetic shift, in the VH/VL gene repertoire of anti-PC antibody, appeared to take place in aged mice and that aged mAb displayed a decrease in antibody affinity for the free hapten PC as compared to the young ones. We interpret these data as showing that immunization at advanced age may be linked to the production of cross-reactive antibodies and that this event may be related to the increased incidence of autoantibody in the age
Autologous anti-idiotypic antibody response is regulated by the level of circulating complementary idiotype
No full textLevel of circulating anti-idiotypic antibody determines the levels of autologous anti-idiotypic response following antigen delivery in viv
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