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The role of T cells in IgG production; thymus-dependent antigens induce B cell memory in the absence of T cells.

B cell memory was shown to develop in congenitally athymic (nu/nu) mice after injection with small amounts of thymus-dependent antigens, in particular heterologous serum proteins, such as fown gamma-globulin (FGG) or DNP-bovine-serum albumin (DNP-BSA). Large doses of proteins (10 mg) tended to produce a specific B cell unresponsiveness, although there was still some evidence of B cell priming. The antigen did not have to be in a multivalent form to interact with B cell so as to induce immunologic memory or tolerance. In contrast to the induction of B cell memory, the production of IgG antibody in this system was found to be strongly T cell dependent. Thymus-independent antigens like LPS or POL with pronounced adjuvant effects on IgG production in normal or surgically thymectomized mice, could not replace T cells in allowing an IgG response against thymus-dependent antigens in congenitally athymic mice. However, the action of T cells once activated is likely to be non-antigen-specific, since it was shown that supernatants of antigen-activated-syngeneic T cells stimulated IgG production in cultures of primed B cell populations non-antigen-specifically.

Animals↗

Stress-induced effects on cell-mediated innate and adaptive memory components of the murine immune response to herpes simplex virus infection.

Using a murine model, we have previously shown that restraint stress is able to suppress the development of herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTL) and natural killer (NK) cell activity in the popliteal lymph nodes following local footpad infection. These studies of the primary cell-mediated immune response to HSV infection have been extended to examine the effects of a similar stressor on the development of HSV-specific memory CTL (CTLm) following local and systemic HSV infection. In addition, the effect of stress on HSV-specific CTLm localization and proliferation in the popliteal lymph node following reexposure to HSV was investigated. Lastly, the ability to stimulate HSV-specific CTLm to the lytic phenotype under conditions of restraint stress was examined. Restraint stress did not inhibit the generation of HSV-specific CTLm. However, restraint stress inhibited the ability to activate CTLm to the lytic phenotype. In HSV seropositive mice (primed prior to stress), restraint stress prevented the in vivo activation and/or migration of HSV-specific CTLm in the popliteal lymph nodes. These findings demonstrate that activation of HSV-specific immunological memory can be inhibited by physiological changes associated with stress. Such immune inhibition may provide a possible mechanism for the development of recrudescent herpetic disease.

Animals↗

[Immune reaction to tetanus in the elderly: what is the duration of vaccine protection?].

Infectious diseases represent one of the most frequent causes of morbidity and mortality in the elderly. Little information is yet available on the state of immunization against well-known antigens such as tetanus toxoid (TT) in old age. It was, therefore, the aim of this study to analyze antibody titres and peripheral blood mononuclear cell (PBMC) reactivity to TT in healthy SENIEUR compatible young (< 30 years, n = 25) and old (> 65 years, n = 32) blood donors. TT-specific antibodies were measured by the ELISA technique; PBMC proliferation was assessed by 3H-thymidine incorporation analysis. In the young group TT antibody titres were detectable in all but two individuals, whereas 60% of the old persons had no detectable TT antibodies. This seemed partly to be due to a shortened immunological memory in old age, since 32% of the aged persons without TT antibodies had been vaccinated within the past 10 years, 21% even 3 to 6 years prior to investigation. TT antibody concentrations were normal in aged individuals vaccinated within the past two years. Peripheral blood lymphocytes from all but two persons without antibody titres did not proliferate when stimulated with TT in vitro, indicating that no memory T cells were available to reinduce an efficient immune response. Our results suggest that the tetanus vaccination strategy practised in Austria does not guarantee full protection in the elderly.

Adult↗

Studies of the adjuvant-independent antibody response to immunotargeting. Target structure dependence, isotype distribution, and induction of long term memory.

Immunoconjugates composed of avidin linked to biotinylated antibodies specific for different surface determinants on cells of the immune system were evaluated for their ability to induce adjuvant-independent anti-avidin IgG responses in mice. Previously, we demonstrated that allele-specific murine anti-class II MHC-avidin immunoconjugates were immunogenic in mice bearing the appropriate haplotype. Herein we report the immunotargeting potential of heterologous anti-class II MHC antibodies specific for framework determinants, and extend the range of effective targets to include certain non-MHC structures present on APC (e.g., 33D1 on dendritic cells, 14.8 on B cells, and CD45--the leukocyte common antigen). However, antibodies with other specificities (e.g., leukocyte integrins and some macrophage markers) were not effective targeting vehicles. Surprisingly, immunoconjugates specific for CD3 and CD4 were immunogenic. The isotype distribution of the anti-avidin antibody response induced in mice by immunotargeting to class II MHC or 33D1 was similar to that induced by immunization with Ag emulsified in complete Freund's adjuvant. Most of the antibody induced was IgG1 (65-75%), but a significant proportion was IgG2a (20-30%). We also demonstrate that immunotargeting is able to prime for long-term immunologic memory in mice.

Animals↗

Natural killer T cells are required for the development of a superantigen-driven T helper type 2 immune response in mice.

We show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced a powerful immune response with a T helper type 2 (Th2) pattern, as judged by the isotype and cytokine profile, with the production of large amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of SEB-specific IgE and increased production of interleukin-4 by spleen cells. These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3+ or Vbeta8+ T cells or NK1.1+ cells. In vivo depletion of NK1.1+ cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary immune responses. Additionally, purified NK1.1+ T cells were able to perform SEB-specific helper B-cell actions in vitro and in vivo. These results suggest that NK1.1+ T cells are required for the full development of humoral immunological memory, whilst making neonatal tolerance to SEB unachievable.

Adoptive Transfer↗

Immunization with Haemophilus influenzae type b-CRM(197) conjugate vaccine elicits a mixed Th1 and Th2 CD(4+) T cell cytokine response that correlates with the isotype of antipolysaccharide antibody.

Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) induces protective antibodies but is T independent and poorly immunogenic in infants. Conjugate vaccines of Hib PS linked to proteins, such as CRM(197), increase the PS antibody titer and elicit immunologic memory. To define the conjugate-induced memory T cell response, 19 adults were immunized with Hib-CRM(197), and antibody titers, carrier protein-specific CD4(+) T cell proliferation, and cytokine production were measured. Hib-CRM(197) induced PS and CRM(197) antibodies, vigorous T cell recall responses, and production of cytokines, including interleukin (IL)-2, IL-5, IL-10, and interferon-gamma. There was marked variability in PS antibody titer, despite consistent CRM(197)-specific recall responsiveness, which correlated with peak IgM and IgA PS antibody titers. Correlations were also found between IL-2 and IL-5 and IgA PS antibody levels. Hib-CRM(197) induced a rapid increase in CRM(197)-specific memory T cells and mixed Th1/Th2 cytokines, which may regulate the isotype and quantity of PS antibody.

Adult↗

Genetic immunization with Ehrlichia ruminantium GroEL and GroES homologues.

Ehrlichia ruminantium GroEL and GroES genes were amplified from E. ruminantium Welgevonden genomic DNA and were cloned into genetic vaccine and Salmonella expression vectors. These constructs were used to inoculate Balb/c and C57BL/6J mice. Both GroEL and GroES induced low levels of protection in Balb/c and C57BL/6J mice immunized with the Salmonella expression vectors. None of the mice inoculated with the genetic vaccine survived. Immunological memory was also tested in these mice and a correlation between splenocyte proliferation and the survival rate was observed.

Animals↗

[Anti-influenzal antibodies inducing an immune response to the influenza virus].

The injection of anti-influenza antibodies into rabbits induces a specific immune response, including the production of anti-idiotypic antibodies and then the production of immune complexes and anti-influenza antibodies. The injection of antibodies induces the development of immunological memory; as a result, the animals are primed to respond to the injection of influenza vaccine.

Animals↗

Long-term persistence of immunity after immunisation with Haemophilus influenzae type b conjugate vaccine.

Although Haemophilus influenzae type b (Hib) conjugate vaccines, after licensure in 1987, are now recommended for world-wide use, the duration of protective immunity afforded by them is not known. We therefore assessed the immunogenity at 9-10 years of age in 37 children who had received the first Hib conjugate, PRP-D, in infancy (the Hib-conjugate group) and were now given a dose of Hib polysaccharide (PS) as a test vaccine. The anti-Hib PS antibodies (Hib-ab) were measured before and after this test vaccination, and the values compared to those in 37 control children who had not previously received any Hib vaccine and in 13 children who had received Hib PS vaccine in infancy (the Hib-PS group). Prior to the test vaccination, the Hib-ab concentrations in the Hib-conjugate group were 3.6-fold higher than in the control group. After the test vaccination, the Hib-conjugate group had higher total Hib-ab concentrations, higher proportion of IgG and higher avidity of Hib-ab than the control or the Hib-PS group, suggesting persisting immunological memory in a Hib-c group. A mathematical model, including memory, predicted accurately the Hib-ab concentrations, which are maintained through anamnestic responses to intervening stimuli (Hib or cross-reacting bacteria).

Antibodies, Bacterial↗

Effect of a diphtheria booster vaccination in adults with a documented history of an incomplete primary series vaccination.

BACKGROUND: An incomplete series of diphtheria vaccination is frequently found in the vaccination documents of adult patients. This paper investigates the effect of a booster vaccination in adults with an incomplete series of primary vaccination. MATERIALS AND METHODS: The effect of one diphtheria booster vaccination in adults with a documented history of only two childhood vaccinations has been investigated in 21 adults. Before the vaccination and 4 to 8 weeks thereafter, blood samples were taken and analyzed with an in vitro neutralization assay. RESULTS: None of the participants had prevaccinal full protective diphtheria antitoxin levels (AT) > or = 0.1 IU/ml and four (19%) had limited serological protection (AT 0.01 to 0.1 IU/ml). After the vaccination, 14 individuals (67%) had protective LeveLs and six (29%) had limited protective levels. The risk for post-booster non-protection (AT < 0.1 IU/ml) was 7.7 times higher in comparison with a group of 170 adults with a history of at least one booster vaccination. CONCLUSION: A specific immunologic memory exists in adults with a history of only two previous diphtheria vaccinations. However, our results also indicate the need for a second booster vaccination in this group if long-term protection is to be achieved.

Adult↗

Assessing the replicative history of human T cells.

Upon encountering antigen, T cells clonally expand and differentiate into effector cells that directly or indirectly eliminate antigen-bearing pathogens. When renewed contact with the same pathogen occurs the immune response is mounted in a faster and more accurate way, a process that is referred to as immunological memory. The basis for T-cell memory is at least partially provided by an enhanced precursor frequency of antigen-specific T cells, and an increased responsiveness of primed T cells to activation signals. In contrast to B cells, which acquire mutations in the immunoglobulin genes after antigenic challenge, somatic markers are lacking that distinguish unprimed (or naive) from primed (encompassing memory and effector) T cells. Instead, differential expression of cell surface molecules on subsets of T cells and measures for replicative history can be used to obtain insight into the antigen-driven development of the T-cell compartment. Apart from fundamental issues addressing lineage relationships between naive, memory and effector T cells and the cellular basis for long-term T-cell memory, these types of studies have proved to be valuable in understanding T-cell reconstitution in situations of severe T-cell depletion, i.e., after chemotherapy, treatment with depleting CD4 monoclonal antibodies or during HIV infection.

Age Factors↗

Induction of compartmentalized B-cell responses in human tonsils.

The capacity of tonsillar and nasal mucosal lymphoid tissues to serve as induction sites of local and/or distant B-cell responses in humans has been examined. The frequencies of vaccine-specific antibody-secreting cells (ASC) in cell suspensions from palatine tonsils (PT) and adenoids were determined after local (intra-tonsillar [i.t.]) and regional (intranasal [i.n.]) immunizations as well as peroral and parenteral immunizations with cholera and tetanus toxoids. While peroral and parenteral immunizations evoked negligible ASC responses in PT, i.t. vaccination induced a substantial ASC response which consisted of immunoglobulin G (IgG) and IgA ASC. Responses were highly restricted to immunized tonsils. Primary immunization in one PT followed by a second immunization of both PT evoked a larger ASC response in the primed tonsil. The latter ASC response was associated with higher frequencies of ASC precursors in primed tonsils. Furthermore, two i.n. immunizations induced only modest ASC responses in PT, although such immunizations evoked high ASC responses in adenoids. However, both i.t. and i.n. routes of immunization induced specific peripheral blood ASC responses, suggesting that a fraction of B cells activated in tonsils or in nasal mucosa may enter the circulation and disseminate to distant organs. These blood ASC responses preceded increases in both IgA and IgG antibody titers in nasal washes and serum samples. However, vaccine-specific ASC were not detected in duodenal cell suspensions from volunteers who had received i.t. or i.n. immunizations. Collectively, these results indicate that tonsils can serve as expression sites of locally induced antibody responses and support the development of immunological memory. Furthermore, tonsils may serve as powerful inductive sites for immune responses expressed in the upper aerodigestive tract.

Adenoids↗

Development of long-term tolerance versus sensitisation to environmental allergens during the perinatal period.

Evidence is steadily accumulating which indicates that the patterns of T cell reactivity against the environmental antigens that determine the allergen responder phenotype in adulthood are, in many cases, established during infancy. The underlying regulatory processes which determine the nature of long-term immunological memory against these antigens appear to involve a combination of classical high zone and low zone tolerance mechanisms. It appears likely that these T cell responses are initiated before birth via the transplacental transfer of low levels of allergen to which mothers are exposed during pregnancy.

Allergens↗

Are follicular dendritic cells really good for nothing?

Follicular dendritic cells (FDCs), which reside in the primary B-cell follicles and germinal centres of lymphoid tissues, can sequester antigen in the form of immune complexes and are thought to be pivotal to the germinal-centre reaction and the maintenance of immunological memory. But, many recent studies question the importance of FDCs and their bound immune complexes in B-cell responses. This article asks whether we can truly rule out a requirement for these cells in host defence.

Animals↗

Naive and memory T cells in hypertrophied adenoids in children according to age.

The anatomic location of the adenoid implies that this organ is the first site of contact with inhaled antigens. Depending on the expression of different isoforms of the CD45 molecules, T cells can be divided into naive (CD45RA(+)) and memory (CD45R0(+)) cells, the latter representing T cells that have already been exposed to antigens. The purpose of this study was to analyse the lymphoid cells' subsets in adenoids and relate the findings to the age. The analysed material was adenoid tissue removed on the grounds of hypertrophy from 22 children. The patients were divided into two groups: up to 5 and above 5 years of age. The analyses of the lymphocytes subpopulations in the adenoid were performed in an EPICX XL (Coulter) flow cytometry. The results are expressed as the percentage of positively labeled cells (CD4(+), CD8(+), CD4(+)/CDB(+), CD4(+)CD45RA(+), CD8(+)CD45RA(+), CD4(+)CD45R0(+), CD8(+)CD45R0(+)). The percentage of CD4(+)/CD45R0(+) in children up to 5 years of age was significantly lower than in older children. We found the positive regression between age and the percentage of CD4(+) cells was CD45R0(+) (r=0.64). There were no statistically significant differences between study subgroups for the other parameters. The positive regression for CD4(+)/CD45R0(+) cells and age may result from increased stimulation by bacterial, viral and other antigens. Our results indicate that the adenoid have an important role in the development of an immunological memory among younger children.

Adenoidectomy↗

A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults.

This study shows that two doses of a recombinant hepatitis B vaccine (10 micrograms or 20 micrograms of HBsAg per dose), administered 6 months apart to young, healthy adults, can induce an antibody (anti-HBs) response similar to that expected with the standard three-dose regimen of this vaccine given at intervals of 0, 1, and 6 months. While only 46-67% of the vaccinees displayed a protective anti-HBs titer of > or = 10 mIU ml-1 prior to the receipt of the second dose at 6 months, virtually all were primed as 97-99% of the subjects developed such a titer when tested a month after the second dose. Among vaccinees given 10 or 20 microgram doses, respectively, the secondary rise in antibody following the second dose yielded geometric mean titers (GMTs) of 1103 and 2538 mIU ml-1, respectively. The study further demonstrated that a two-dose regimen of vaccination induced strong immunologic memory for HBsAg, as a booster dose of vaccine given 2 years later resulted in a rapid and vigorous anamnestic antibody response.

Adolescent↗

Plasmodium falciparum sexual stage antigens: immunogenicity and cell-mediated responses.

Antibody and cell-mediated immune responses to the transmission-blocking target antigens of Plasmodium falciparum, Pfs 48/45, were determined in infected non-immune patients and in immune individuals from an endemic area. Characterization of the B cell epitopes with monoclonal antibodies showed that there were five regions identifiable but there could be interactions between them causing either competitive or enhancing effects. Sera from infected non-immune patients contained antibodies that would compete with one or more of the mAbs to the different epitopes. Immune responsiveness to purified Pfs 48/45 in P. falciparum-immune adults measured as lymphoproliferation, production of interferon-gamma, or as Pfs 48/45-specific antibody was very limited. This did not appear to be due to MHC class II restriction, to diversity in structure of the parasite antigens or to a failure of immunological memory. The antibody-response data were more consistent with down-regulation of immunity as a result of prolonged exposure to infection.

Adult↗

Differential effector functions of central and peripheral compartments of immune response system: characterization of immune responses in the spleen and mesenteric lymph nodes to directly injected sheep red blood cells.

When sheep red blood cells (SRBC) were injected intraperitoneally (i.p.), intravenously (i.v.), or into the Peyer's patches, definite plaque-forming cell (PFC) and rosette-forming cell (RFC) responses were induced in the spleen but not in the mesenteric lymph nodes (MLN). When SRBC were injected directly into the spleen or MLN, stronger PFC and RFC responses were induced in the spleen or MLN, respectively, than when injected i.p. or i.v. PFC response induced in MLN by injecting SRBC into MLN with or without the polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K) as an immunological adjuvant was weaker than that induced in the spleen by injecting the antigen into the spleen. Direct PFC (PFC of IgM type) and RFC responses induced in the spleen by injecting SRBC into MLN were rather stronger than those induced in the spleen by injecting the antigen into the spleen. In contrast, no significant responses were induced in MLN by injecting SRBC into the spleen, and no definite indirect PFC (PFC of IgG type) response was induced in the spleen by injecting the antigen into MLN. The levels of whole immunological memory as well as isolated B- or T-cell memory in the spleen and MLN of mice injected with SRBC directly into the spleen or MLN were determined by using an in vitro assay system. Definite amounts of either B- or T-cell memory were detected in the spleen of mice injected with SRBC directly into the spleen of MLN. Smaller amounts of memory were detected in MLN injected with SRBC directly into the spleen. Moreover, the amounts of whole memory detected in MLN were much less than compared with those of isolated T- and B-cell memories in MLN. Further experiments showed that in vitro expression of the memories preserved in MLN required supplement of glass non-adherent cells from normal spleen. Based on these results, we discussed the possible differential and collaborative functions of the central (spleen) and peripheral (MLN) immune response systems in antibody responses.

Animals↗