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[Rate of development of immunologic memory and features of the secondary immune response in mice of high and low-reacting strains].

Immunological memory to sheep red blood cells developed in mice of strain CBA, DBA/2, and hybrids (CBAXXC57BL/6) F1 24 hours after the administration of a low dose of the antigen, and in C57BL/6 mice -- in 48 hours. The level of the secondary immune response in CBA, C57BL/6, and hybrid F1 mice was much greater than in the DBA/2 mice. The maximal production of the antibody-forming cells in the spleen of CBA mice occurred after twofold administration of low antigen doses. In contrast to this, repeated administration of a high antigen dose is required to obtain a marked immune response in adoptive transfer of spleen cells of the C57BL/6 strain.

Animals↗

The influence of T cells on the initiation and expression of immunological memory.

Nude and normal CBA mice have been used in adoptive transfer experiments to analyse the development of immunological memory. The development of B-cell memory to xenogeneic erythrocyte antigens is to a very large degree dependent on the presence of T cells, with IgG memory being somewhat more dependent than IgM memory. In this system, the expression of B memory, that is the transformation of memory cells to antibody-secreting cells under the inductive influence of antigen, is largely dependent on the presence of T cells. Primed (educated) T cells can have an antigen-specific potentiating effect on unprimed B cells in the presence of antigen.

Animals↗

Tooth allografts fail to stimulate immunologic memory in mice.

Tooth transplants should not preclude future transplants in the recipient. In this study teeth failed to stimulate immunologic memory in weakly disparate mice. The teeth did carry transplantation antigens and were rejected after second-set skin grafts. The teeth probably enhanced their own survival through some immunoregulatory mechanism.

Animals↗

Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic children.

BACKGROUND: Recent findings suggest that a hallmark of the atopic phenotype is reduced capacity to respond to vaccine antigens, as well as to environmental allergens, during infancy. This deficiency, which is most marked for the cytokine IFN-gamma, appears transient but can result in a long-lasting imbalance within T helper cell (T(H)) memory responses to allergens. Indirect evidence suggests that parallel effects may occur within immunologic memory responses against vaccine antigens in atopic children. OBJECTIVE: Our purpose was to compare vaccine antigen-specific T(H) memory responses in atopic and nonatopic children. METHODS: We analyzed specific serum IgG and cytokine responses to pertactin and tetanus antigens as well as to mitogen (PHA) and house dust mite (HDM) allergen in 25 HDM-sensitized atopic and 25 nonatopic 6-year-old children who were vaccinated and boosted with diphtheria-tetanus-pertussis (DTP) vaccine. RESULTS: PBMCs from the atopic subjects produced higher levels of T(H)1 and T(H)2 cytokines to HDM allergen and PHA. Vaccine antibody titers were normal in the atopic subjects; vaccine-specific T(H)2 responses were rarely detectable, yet T(H)1 (IFN-gamma) responses, in particular against tetanus, were frequent and higher in the atopic subjects (121.5 [SE 64.3] vs 8.0 [3.5] pg/mL culture fluid, P =.04). Corresponding pertactin responses were comparable in both groups. CONCLUSIONS: At the completion of the full primer-booster DTP vaccination regimen, levels of vaccine-specific immunity in atopic 6-year-old children are at least equivalent to their nonatopic counterparts, indicating that the transient atopy-associated deficiency in T(H)1 function in childhood can be successfully overcome by appropriate vaccination and boosting regimens.

Antibody Formation↗

Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state.

Traditionally, emphasis has been placed on the roles of Th cells in generating and amplifying both cellular and humoral memory responses. Little is known about the potential contributions of B cell subsets to immunological memory. Resting memory B cells have generally been regarded as poor APC, attributed in part to the relative paucity of costimulatory molecules identified on their surface. We describe a novel subpopulation of human memory B cells that express CD80 in their resting state, are poised to secrete particularly large amounts of class switched Igs, and can efficiently present Ag to and activate T cells. This functionally distinct B cell subset may represent an important mechanism by which quiescent human B cells can initiate and propagate rapid and vigorous immune memory responses. Finally, these studies extend recent observations in the murine system and highlight the phenotypic and functional diversity that exists within the human B cell memory compartment.

Antigen Presentation↗

Immunologic memory responses induced in BALB/c mice by cross-linked outer membrane extracts of four Salmonella serotypes.

Outer membrane proteins (OMP), extracted from Salmonella enteritidis, S anatum, S typhimurium, and S infantis, were cross-linked to form a large immunogen (4-OMP-lipopolysaccharide [LPS]). Vaccinations with 4-OMP-LPS dissolved in phosphate-buffered saline solution and 4-OMP-LPS emulsified with muramyl dipeptide were capable of eliciting specific and sustained primary IgM and IgG responses in BALB/c mice, as well as inducing immunologic memory for 130 days. In addition to 4-OMP-LPS-specific responses, substantial IgM and IgG responses specific for each live homologous organism were detected over the 130-day trial. In comparison with vaccination with 4-OMP-LPS dissolved in phosphate-buffered saline solution, responses specific for the antigen or the homologous Salmonella were not markedly increased in mice vaccinated with 4-OMP-LPS emulsified with muramyl dipeptide. Seemingly, cross-linked OMP, without the inclusion of muramyl dipeptide, may have potential as vaccine components and may induce immunologic memory.

Animals↗

Antibody persistence and immunological memory at age 4 years after meningococcal group C conjugate vaccination in children in the United kingdom.

Antibody persistence and immunological priming for 2 formulations of a meningococcal group C (menC) conjugate (MCC) vaccine (containing 2 or 10 microg of menC polysaccharide) administered at 2, 3, and 4 months of age was investigated by boosting vaccine recipients at age 13-16 months or 4 years with 10 microg of unconjugated menC polysaccharide. At age 4 years, geometric mean titers (GMTs) and concentrations of menC-specific immunoglobulin G and serum bactericidal antibody (SBA) had decreased to prevaccination levels. Geometric mean avidity indices increased after the primary vaccination until age 13-16 months and then remained constant until age 4 years. One month after boosting at age 4 years, menC immunoglobulin G and SBA levels increased significantly. The postbooster SBA GMT for the 2-microg vaccination (2181.2; 95% confidence interval [CI], 975.9-4875.1) was 2-fold higher than that for the 10-microg vaccination (931.6; 95% CI, 338.0-2568.1). This is the first demonstration of immunological memory at 4 years of age in children receiving MCC vaccine on the United Kingdom's 2/3/4-month immunization schedule.

Antibodies, Bacterial↗

Induction of immunological memory in mice by RNA extract.

RNA extract isolated from spleens of mice immunized with lipopolysaccharide from E. coli induced an immunological memory in normal mice. Application of small amounts of corresponding antigen provoked a specific secondary immune response in RNA primed mice.

Animals↗

Immune response to glutaraldehyde-treated cells. I. Dissociation of immunological memory and antibody production.

Glutaraldehyde (GA)-treated sheep red blood cells (SRBC) or H-2-allogeneic spleen cells (SC), induced immunological memory with absent or markedly reduced primary antibody production. In contrast, a normal secondary response was obtained when GA-SRBC or GA-SC were given to mice primed with the corresponding untreated antigens. The secondary response of mice primed and boosted with GA-treated cells was relatively high with GA-SRBC, and negative or very low with GA-SC. Morphological studies of the fate of intraperitoneally injected cells showed that endocytosed GA-SRBC persisted much longer in peritoneal macrophages than untreated SRBC. Simultaneous challenge of mice with untreated and GA-treated SRBC revealed that phagocytosis and digestion of both types of cells in the same macrophage proceeded independently of each other. The primary response of mice receiving both SRBC and GA-SRBC was entirely similar to the response when SRBC alone was given.

Aldehydes↗

Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines.

The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.

Bacterial Outer Membrane Proteins↗

Long-term immunological memory against viruses.

This review addresses a novel facet of human T cell biology that constitutes a fundamental problem for long-term maintenance of immunological memory against viruses. The finite proliferative capacity of human T lymphocytes is sufficiently great to accommodate the waves of clonal expansion associated with primary and even secondary immune responses. However, long-term memory to viruses that establish latency and to repeatedly encountered viruses such as influenza may be severely impaired by "replicative senescence", a genetically programmed process affecting most somatic cell types of human origin. Consistent with this idea, memory CD8+ T cells with hallmarks of replicative senescence have been identified in vivo. Such cells may contribute to compromised viral immunity and response to vaccines, and furthermore, their very presence may negatively influence homeostatic mechanisms that control the size of the memory T cell pool in elderly persons.

Aging↗

Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs.

Secondary lymphoid organs (SLOs) promote primary immune responses by recruiting naive lymphocytes and activated APCs. However, their role in the persistence or responsiveness of memory lymphocytes is unclear. We tested whether memory cells were maintained and could respond to challenge in the absence of SLOs. We found that influenza-specific CD8 cells in the lung acquired a memory phenotype, underwent homeostatic proliferation, recirculated through nonlymphoid tissues, and responded to and cleared a challenge infection in the complete absence of SLOs. Similarly, influenza-specific virus-neutralizing antibody was generated and maintained in the absence of SLOs. Inducible bronchus-associated lymphoid tissue (iBALT) was also formed in the lungs of previously infected mice and may provide a niche for the maintenance of memory cells at the local level. These data show that SLOs are dispensable for the maintenance of immunologic memory and directly demonstrate the utility of local tissues, such as iBALT, in secondary immune responses.

Animals↗

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and long term immunologic memory.

The highlighted article by B. Paige Lawrence and Beth Vorderstrasse addresses an oft forgotten aspect of immunotoxicity, the effects of environmental toxins on immunologic memory. Here, the authors take a step towards filling that information gap by evaluating the effects of a prototypic environmental toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on memory responses to a real-world pathogen, influenza A virus, presented to an animal model in a physiologically relevant manner. Multiple outcomes are evaluated, the vast majority of which suggest important and long-term TCDD-induced changes in the immune system after both primary and secondary exposure to this pathogen. The implications of these studies with regard to the immuno-competence of TCDD-exposed individuals are far reaching.

Animals↗

Maintenance of long-term immunological memory by low avidity IgM-secreting cells in bone marrow after mucosal immunizations with cholera toxin adjuvant.

To understand the mechanisms involved in maintaining long-term immunological memory following mucosal immunizations, we determined the quality of serum hapten-specific immunoglobulins (Ig) and localized Ig-secreting cells (SC) of various isotypes in acute, persistent/resting memory and effector memory phases following oral versus intra-muscular (IM) immunizations. In the acute phase, both oral and IM immunizations induced high avidity Ig. However, in the persistent/resting memory phase, oral immunizations induced low avidity Ig while IM immunizations induced high avidity Ig. Following oral immunizations, in the persistent/resting memory phase, hapten-specific IgM titers in serum and IgM-SC in bone marrow (BM) dominated the immune response, suggesting an important role for IgM in the maintenance of memory.

Adjuvants, Immunologic↗

The role of germinal centres in the generation of immunological memory.

Germinal centres are areas of B lymphocytes proliferation that appear in primary lymphoid follicles after immunization. The results summarized here implicate these structures in the establishment of immunological memory for antibody production. It appears that after primary immunization antigen-antibody-complement complexes become trapped on the membrane of specialized dendritic cells in lymphoid follicles, and these complexes provide the stimulus for germinal centre formation. In support of this, immunization with preformed antigen-antibody complexes, rather than with antigen, leads to the earlier appearance of germinal centres and memory cells, and also accelerates the selective triggering of precursors capable of producing high affinity antibodies.

Animals↗

[Action of different cell types in influenza antibody production. 5. Keeping the immunologic memory to influenza virus A serotype by B- and T-lymphocytes].

The authors present data on the cooperation of the B- and T-lymphocytes in secondary immunological response to the antigens of influenza virus of serological type A. Cells of the spleen, bone marrow and the thymus in various combinations from the intact and immunized animals were transplanted to sublethally irradiated recipients; influenza virus was administered at the same time. Immunological memory to the virus antigens of serological type A proved to be preserved both by the B- and T-lymphocytes. Both in the primary and in the secondary response B-lymphocytes served as the precursors of cells-producers of antibodies.

Animals↗

The effect of dexamethasone on immunological memory to tetanus toxoid in sheep.

One of two groups of sheep was immunosuppressed with the glucocorticoid, dexamethasone, at the time of the first but not of the second of two booster vaccinations with tetanus toxoid given at an interval of 28 days. Treatment with dexamethasone decisively reduced the anti-tetanus antibody response to the first booster vaccination and affected both IgM and IgG1 antibody. However, antibody titres increased after the second booster vaccination in the treated sheep and were similar in size to those in the untreated sheep which rose in stepwise fashion after each booster vaccination. The differences in response imply that processes involved in displaying an anamnestic response and recalling previously established memory are sensitive to glucocorticoids. Accordingly, they can be separated from the glucocorticoid-resistant processes that lead to the expansion of immunological memory following multiple exposures to an antigen.

Animals↗

Induction of immunologic memory by a lipopolysaccharide-protein complex isolated from Fusobacterium necrophorum: cellular response.

The ability of a lipopolysaccharide protein (LPS-P) complex extracted from Fusobacterium necrophorum to establish immunologic memory in BALB/c mice splenocytes was demonstrated. The LPS-P molecule differed from the phenol water-extracted LPS because it contained approximately 12% protein. Initial experiments showed that primary and secondary spleen plaque-forming cell (PFC) responses to IV or IM injections of LPS-P were highly dose-dependent. Suitable primary doses stimulated significant (P less than 0.05) amounts of direct and direct + indirect PFC by postinoculation day (PID) 14 and primed the mice for an enhanced secondary response to small booster injections. When mice were inoculated with a suitable primary IM dose of aluminum hydroxide-precipitated LPS-P, significant amounts of direct and direct + indirect PFC were detectable through PID 120. Moreover, significant enhancement of these values was attained with an IV booster injection at PID 105. Primary IV inoculation with LPS-P produced similar results, although the primary response was not as persistent.

Animals↗