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[Immunologic memory in the course of udder immunization for the protection of calves against Salmonella infections].

Cows were vaccinated once or twice intracisternally in order to protect calves against salmonella infections. The amount of antibodies measured in the colostrum of re-vaccinated and not re-vaccinated cows indicated that a sensitive immunological memory has been provoked by this vaccination technique. This immunological memory showed a distinct synchronism with the state of pregnancy in order to provide a maximum amount of antibodies in the colostrum.

Animals↗

Dietary fish oil impairs primary host resistance against Listeria monocytogenes more than the immunological memory response.

The primary objective of this study was to determine whether dietary (n-3) polyunsaturated fatty acids (PUFA) impair the ability of mice to generate an immunological memory response against the bacterial pathogen, Listeria monocytogenes. Weanling BALB/c female mice were fed for 28 d one of two semipurified high fat diets containing either lard or refined menhaden fish oil, rich in long-chain (n-3) PUFA. Mice were immunized with 10(4) or 10(3) colony forming units (cfu) bacteria. Thirty-five days later, these immune mice and age-matched naïve (i.e., unimmunized) mice were challenged with 10(5) cfu bacteria. Three days postchallenge, bacterial clearance was determined. Compared with lard-fed mice, naïve mice in the fish oil treatment group had higher bacterial loads in their liver and spleen (P < 0.001). When mice were immunized with 10(4) cfu bacteria before rechallenge with 10-fold more bacteria, both lard- and fish oil-fed mice had significantly lower bacterial loads in their liver and spleen (e.g., approximately 2 log(10); P < 0.001) compared with their naïve counterparts. However, when the immunization dose was reduced to 10(3) bacteria, a modest diet treatment effect was observed, such that compared with immune lard-fed mice, immune fish oil-fed mice had significantly greater bacterial loads in their liver and spleen (i.e., approximately 0.5 log(10); P < 0.01). These data demonstrate for the first time that although dietary (n-3) PUFA can significantly impair host resistance to a primary as well as a secondary L. monocytogenes infection, the impairment of the immunological memory response is much less severe.

Animals↗

[Significance of bacteremia in the development of immunological memory suppression in Shigella sonnei infection in mice].

Experiments on mice infected intraperitoneally with S. sonnei have revealed that the level of bacteriemia is directly related to the duration of the blocking of immunological memory constituting the basis of secondary humoral and cell-mediated immune response. The transfer of syngeneic splenocytes from immunized mice has demonstrated that virulent S. sonnei directly affect the immunological memory cells.

Animals↗

The dynamics of immunological memory.

Memory has long been thought of as a stable phenomenon within the immune system: once generated it lasts for a very long time. This static view of immunological memory predicts that an established population of memory cells is independent of outside influences. Recent findings, concerning the population kinetics of the peripheral pool of lymphocytes and, more directly, concerning the influence of antigen on memory cell survival, are forcing us to reassess this idea. I present here a dynamic view of immunological memory which takes into account an immune system that appears in continual flux and whose constituent cells may rely upon recurrent signals for their survival. This view of memory also makes certain predictions and these are considered.

Animals↗

[Mechanism of the suppression of the formation of immunologic memory].

An extract from splenocytes of mice immunized with sheep red blood cells contains suppressor factor (SF) that specifically inhibits the primary immune response. The system of adoptive transfer was studied for the action of the SF on the formation of immunologic memory for sheep and rat blood cells. It was established that the SF carrying a receptor for specific antigen causes nonspecific suppression of the generation of immunologic memory cells. Within the system in question radioresistant T helper cells act as suppression targets. It is suggested that the final effect of the SF lies in the inhibition of the release of transmitters promoting differentiation or proliferation of T memory cells.

Animals↗

Immunological memory against viruses.

Viral infections often result in long-term immunological memory. This article reviews the phenotypic changes seen in memory T cells and suggests a re-evaluation of the current dogma that T cell memory is maintained by persistence of antigen.

Animals↗

Evolution of immunological memory and the regulation of competition between pathogens.

Memory is a central characteristic of immune responses. It is defined as an elevated number of specific immune cells that remain after resolution of infection and can protect the host against reinfection. The evolution of immunological memory is subject to debate. The advantages of memory discussed so far include protection from reinfection, control of chronic infection, and the transfer of immune function to the next generation. Mathematical models are used to identify a new force that can drive the evolution of immunological memory: the duration of memory can regulate the degree of competition between different pathogens. While a long duration of memory provides lasting protection against reinfection, it may also allow an inferior pathogen species to persist. This can be detrimental for the host if the inferior pathogen is more virulent. On the other hand, a shorter duration of memory ensures that an inferior pathogen species is excluded. This can be beneficial for the host if the inferior pathogen is more virulent. Thus, while in the absence of pathogen diversity memory is always expected to evolve to a long duration, under specific circumstances, memory can evolve toward shorter durations in the presence of pathogen diversity.

Biological Evolution↗

Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. IV. The roles of antigen and adjuvant for induction of primary and secondary antibody responses and for development of immunological memory to bovine serum albumin.

A study was performed to clarify the roles of primary and secondary injections of antigen and adjuvant (capsular polysaccharide of Klebsiella pneumoniae, CPS-K) in induction of antibody responses and in the development of immunological memory in mice to bovine serum albumin (BSA). A primary injection of BSA alone neither induced significant primary antibody response nor increased immunological memory for a secondary antibody response but, if primary injections of BSA and CPS-K were performed simultaneously, high antibody responses were induced. Moreover, a prior injection of BSA alone or CPS-K alone decreased the level of primary antibody response and the degree of increase in memory following the subsequent injection of BSA mixed with CPS-K. In contrast, a secondary injection of BSA alone into mice once primed with a mixture of BSA and CPS-K elicited very high secondary type antibody response and increased secondarily the memory for a tertiary antibody response. Injection of CPS-K simultaneously with or shortly before or after the secondary injection of BSA did not increase the level of the secondary antibody response and the degree of the secondary increase in memory. Augmentation of the secondary antibody response was elicited by simultaneous injection of CPS-K only when the secondary response was induced inadequately by a suboptimum or supraoptimum dose of antigen.

Adjuvants, Immunologic↗

Development of immunological memory in rainbow trout (Oncorhynchus mykiss). I. An immunochemical and cellular analysis of the B cell response.

In vivo and in vitro analyses of the antibody responses of rainbow trout (Oncorhynchus mykiss) confirmed the existence of immunological memory in this species. An enhanced in vitro secondary antibody response was found to be due strictly to an expansion of the antigen-sensitive precursor pool without a concomitant increase in clone size. In contrast to the development of immunological memory in mammalian species, there was no evidence for affinity maturation during the primary or secondary response. A distinct shift in the fine specificity profiles of the antibodies, however, did occur during the generation of the secondary response. Additionally, more than a single injection of the priming antigen, TNP-KLH was required to produce an enhanced in vitro response to this T-dependent antigen. However, a second priming injection was not required to produce an enhanced secondary response to the T-independent form of antigen, TNP-LPS. These results indicate that memory in trout may be due to a simple expansion of the antigen-specific precursor pool without many of the qualitative changes in antibody or B cell function associated with the expression of memory in mammals.

Animals↗

Reactivity and persistence of local immunological memory on murine contact hypersensitivity.

In a rechallenge system examining murine contact hypersensitivity to DNFB in BALB/c mice, the reactivity to the specific antigen at the previously responded site and the persistence of an immunological memory were investigated. Flare-up reactions were induced 4 weeks after the first challenge only at the previously responded site by local or systemic administrations of minute quantities of a specific antigen. The intensity of ear swelling was dependent on the quantity of applied antigen at the time of the rechallenge. The local hypersensitivity to the specific antigen observed in the previously responded site and the regional lymph node persisted for at least 1 year. These results suggest that the sensitivity to a specific antigen at the previously responded site is intensified and the immunological memory persists for a long time. This may explain the mechanisms by which chronic contact dermatitis recurs readily at the limited site by exposure to minute quantities of causative antigens.

Administration, Cutaneous↗

Immunologic memory response induced by a meningococcal serogroup C conjugate vaccine using the P64k recombinant protein as carrier.

In this study, we used an adoptive lymphocyte transfer experiment to evaluate the ability of the P64k recombinant protein to recruit T-helper activity and induce immunologic memory response to the polysaccharide moiety in a meningococcal serogroup C conjugate vaccine. Adoptive transfer of splenocytes from mice immunized with the glycoconjugate conferred antipolysaccharide immunologic memory to naive recipient mice. The observed anamnestic immune response was characterized by more rapid kinetics, isotype switching from IgM to IgG and higher antipolysaccharide antibody titers compared with those reached in groups transferred with splenocytes from plain polysaccharide or phosphate-immunized mice. The memory response generated was also long lasting. Sera from mice transferred with cells from conjugate-immunized mice were the only protective in the infant rat passive protection assay, and also showed higher bactericidal titers. We demonstrated that priming the mice immune system with the glycoconjugate using the P64k protein as carrier induced a memory response to the polysaccharide, promoting a switch of the T-cell-independent response to a T-cell dependent one.

Adoptive Transfer↗

Induction of immunological memory in the skin. Role of local T cell retention.

Using an experimental contact sensitivity model in guinea-pigs, evidence is presented that hapten (DNCB or oxazolone) specific T lymphocytes may persist for several months in previous sites of inflammation. Immunological memory, revealed by accelerated contact skin reactions upon retesting with the hapten, was limited to the original contact skin reaction sites. This 'local skin memory' to DNCB or oxazolone could be induced in both specific and non-specific skin inflammatory reactions, provided the animals had been sensitized to the hapten not longer than 2 weeks before. In animals which had been sensitized more than 1 month earlier, local skin memory could be induced if the animals received a booster application of hapten shortly (0-2 days) before primary skin testing. From these results we conclude that recently activated T cells may enter inflammatory sites non-specifically, producing specific local immunological memory. This memory may last several months. Accumulation of hapten specific T cells at inflammatory sites may be important in retest reactivity, in flare-up reactivity and in chronic inflammation.

Animals↗

[Immunologic memory in influenza patients according to the blast transformation reaction to specific antigen].

One hundred-sixty patients with the laboratorily confirmed diagnosis of influenza were examined in the study on the capacity of T-and B-lymphocytes to retain immunological memory for influenza infection by the method of lymphocyte blast-cell transformation (LBT). The studies were carried out in the epidemic periods of influenza A2, A1, and B at various stages of the disease and convalescence. The LBT test was positive in 21--70% of tests depending on the time after the onset. Memory cells were detectable as early as by the end of the 1st week of the disease. The optimal results were found within 2--4 months after the disease. Early in the disease LBT was detected mostly in influenza A2, less frequently in influenza A1 and was practically absent in influenza B. The specificity of reaction in response to the stimulation with influenza A2 and B viruses was demonstrated. The accompanying bacterial pneumonia, a severe course of the disease, concurrent other viral infections did not prevent immunological memory formation.

Adolescent↗

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial.

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.

Antibodies, Bacterial↗

Enhanced immunological memory responses to Listeria monocytogenes in rodents, as measured by delayed-type hypersensitivity (DTH), adoptive transfer of DTH, and protective immunity, following Lactobacillus casei Shirota ingestion.

We have investigated the effect of orally administered Lactobacillus casei Shirota (L. casei) on immunological memory, as measured by delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR). The studies were performed in animal models in which the animals were rendered immune by a primary Listeria monocytogenes infection. It was shown that orally administered viable L. casei, and not heat-killed L. casei, enhanced significantly the antigen-specific DTH at 24 and 48 h in Wistar rats, Brown Norway rats, and BALB/c mice in a time- and dose-dependent fashion. L. casei had to be administered at least 3 days prior to the DTH assay at a daily dose of 10(9) CFU in order to induce significant effects. Long-term administration of 10(9) CFU of viable L. casei resulted in enhanced ACR, as demonstrated by reduced L. monocytogenes counts in the spleen and liver and diminished serum alanine aminotransferase activity after reinfection. Enhancement of cell-mediated immunological immune responses by L. casei was further established in an adoptive transfer study. Naïve recipient BALB/c mice, which were infused with nonadherent, immunized spleen cells from L. casei-fed donor BALB/c mice, showed significantly enhanced DTH responses at 24 and 48 h compared to recipient mice which received spleen cells from control donor mice. In conclusion, orally administered L. casei enhanced cell-mediated immunological memory responses. The effects relied on lactobacillus dose and viability as well as timing of supplementation and, further, appeared to be independent of host species or genetic background.

Administration, Oral↗

Hepatitis E virus DNA vaccine elicits immunologic memory in mice.

Injection of an expression vector pJHEV containing hepatitis E virus (HEV) structural protein open reading frame 2 gene generates a strong antibody response in BALB/c mice that can bind to and agglutinate HEV. In this study, we tested for immunologic memory in immunized mice whose current levels of IgG to HEV were low or undetectable despite 3 doses of HEV DNA vaccine 18 months earlier. Mice previously vaccinated with vector alone were controls. All mice were administered a dose of HEV DNA vaccine to simulate an infectious challenge with HEV. The endpoint was IgG to HEV determined by ELISA. Ten days after the vaccine dose, 5 of 9 mice previously immunized with HEV DNA vaccine had a slight increase in IgG to HEV. By 40 days after the vaccine dose, the level of IgG to HEV had increased dramatically in all 9 mice (108-fold increase in geometric mean titer). In contrast, no control mice became seropositive. These results indicate that mice vaccinated with 3 doses of HEV DNA vaccine retain immunologic memory. In response to a small antigenic challenge delivered as DNA, possibly less than delivered by a human infective dose of virus, mice with memory were able to generate high levels of antibody in less time than the usual incubation period of hepatitis E. We speculate that this type of response could protect a human from overt disease.

Animals↗

Quantitative studies of the adoptive immunological memory in mice. II. Linear transmission of cellular memory.

A calibrated cell transfer system allows detection of the anamnestic response to albumin without interference from the host's immune machinery; it was used to study the immunological memory of mouse spleen cell populations. The secondary antibody-forming capacity of the transferred cells was measured by challenging them at periods up to 6 months after transfer. The peak levels attained show a declining pattern in two phases: during the first month with a half-life of 15 days; thereafter, with a half-life of 100 days. The corresponding half-lives of the cellular memory are 26 and 190 days. In the light of these and of radioinactivation data, immunological memory is defined as the persistence of a specifically determined stem cell line, along which the information necessary to give rise to an antibody-forming cell population is transmitted from mother to daughter cells.

Animals↗

The induction of immunologic memory after vaccination with Haemophilus influenzae type b conjugate and acellular pertussis-containing diphtheria, tetanus, and pertussis vaccine combination.

The significance of reduced antibody responses to the Haemophilus influenzae type b (Hib) component of acellular pertussis-containing combination vaccines (DTaP-Hib) is unclear. A DTaP-Hib vaccine evaluated in infants vaccinated at ages 2, 3, and 4 months showed reduced anti-Hib polysaccharide IgG (geometric mean concentration [GMC], 1.23 microgram/mL; 57%, >1.0 microgram/mL). Polyribitolribosyl phosphate (PRP) and Hib conjugate (PRP-T) vaccine given as a booster during the second year of life was evaluated for the presence of immunological memory. After boosting, most children achieved anti-PRP IgG >1.0 microgram/mL, although the GMC was higher with PRP-T (88.5 microgram/mL) than with PRP vaccine (7.86 microgram/mL, P<.001). The GMC of the PRP group was higher than anticipated for naive PRP recipients of the same age. PRP-specific IgG avidity was significantly higher after boosting than after priming, providing further evidence for the generation of memory. Despite reduced immunogenicity, DTaP-Hib combination vaccines appear to prime for immunologic memory.

Antibodies, Bacterial↗