Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model

PubMed Central

Guttormsen, Hilde-Kari; Wetzler, Lee M.; Finberg, Robert W.; Kasper, Dennis L.

1998-01-01

We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules. PMID:9573085

Antigens in tea-beverage prime human Vγ2Vδ2 T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses

PubMed Central

Kamath, Arati B.; Wang, Lisheng; Das, Hiranmoy; Li, Lin; Reinhold, Vernon N.; Bukowski, Jack F.

2003-01-01

Human γδ T cells mediate innate immunity to microbes via T cell receptor-dependent recognition of unprocessed antigens with conserved molecular patterns. These nonpeptide alkylamine antigens are shared by tumor cells, bacteria, parasites, and fungi but also by edible plant products such as tea, apples, mushrooms, and wine. Here we show that priming of γδ T cells with alkylamine antigens in vitro results in a memory response to these antigens. Such priming results also in a nonmemory response to whole bacteria and to lipopolysaccharide, characterized by IL-12-dependent secretion of IFN-γ by γδ T cells and by γδ T cell proliferation. Drinking tea, which contains l-theanine, a precursor of the nonpeptide antigen ethylamine, primed peripheral blood γδ T cells to mediate a memory response on reexposure to ethylamine and to secrete IFN-γ in response to bacteria. This unique combination of innate immune response and immunologic memory shows that γδ T cells can function as a bridge between innate and acquired immunity. In addition, these data provide an explanation for the health benefits of tea. PMID:12719524

Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine.

PubMed

Snape, Matthew D; Maclennan, Jenny M; Lockhart, Stephen; English, Mike; Yu, Ly-Mee; Moxon, Richard E; Pollard, Andrew J

2009-02-01

Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.

Lymphatic-targeted cationic liposomes: a robust vaccine adjuvant for promoting long-term immunological memory.

PubMed

Wang, Ce; Liu, Peng; Zhuang, Yan; Li, Ping; Jiang, Boling; Pan, Hong; Liu, Lanlan; Cai, Lintao; Ma, Yifan

2014-09-22

Although retaining antigens at the injection site (the so-called "depot effect") is an important strategy for vaccine development, increasing evidence showed that lymphatic-targeted vaccine delivery with liposomes could be a promising approach for improving vaccine efficacy. However, it remains unclear whether antigen depot or lymphatic targeting would benefit long-term immunological memory, a major determinant of vaccine efficacy. In the present study, OVA antigen was encapsulated with DOTAP cationic liposomes (LP) or DOTAP-PEG-mannose liposomes (LP-Man) to generate depot or lymphatic-targeted liposome vaccines, respectively. The result of in vivo imaging showed that LP mostly accumulated near the injection site, whereas LP-Man not only effectively accumulated in draining lymph nodes (LNs) and the spleen, but also enhanced the uptake by resident antigen-presenting cells. Although LP vaccines with depot effect induced anti-OVA IgG more potently than LP-Man vaccines did on day 40 after priming, they failed to mount an effective B-cell memory response upon OVA re-challenge after three months. In contrast, lymphatic-targeted LP-Man vaccines elicited sustained antibody production and robust recall responses three months after priming, suggesting lymphatic targeting rather than antigen depot promoted the establishment of long-term memory responses. The enhanced long-term immunological memory by LP-Man was attributed to vigorous germinal center responses as well as increased Tfh cells and central memory CD4(+) T cells in the secondary lymphoid organs. Hence, lymphatic-targeted vaccine delivery with LP-Man could be an effective strategy to promote long-lasting immunological memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stroma: the forgotten cells of innate immune memory.

PubMed

Crowley, Thomas; Buckley, Christopher D; Clark, Andrew R

2018-05-05

All organisms are constantly exposed to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. Whilst the innate immune system is the front line of response to each stimulant, it has been traditionally considered to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure. This concept of "innate immune memory" has been known for nearly a century, and is accepted amongst myeloid biologists. In recent years, other innate immune cells, such as natural killer cells, have been shown to display memory, suggesting innate immune memory is a trait common to several cell types. Over the last thirty years, evidence has slowly accumulated in favour of not only haematopoietic cells, but also stromal cells, being imbued with memory following inflammatory episodes. A recent publication showing this also to be true in epithelial cells suggests innate immune memory to be widespread, if underappreciated, in non-haematopoietic cells. In this review, we will examine the evidence supporting the existence of innate immune memory in stromal cells. We will also discuss the ramifications of memory in long-lived tissue-resident cells. Finally, we will pose questions we feel to be important in the understanding of these forgotten cells in the field of innate memory. This article is protected by copyright. All rights reserved. © 2018 British Society for Immunology.

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

PubMed

Guirola, María; Urquiza, Dioslaida; Alvarez, Anabel; Cannan-Haden, Leonardo; Caballero, Evelin; Guillén, Gerardo

2006-03-01

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.

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

PubMed

Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

2015-10-01

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of a booster dose of capsular group C meningococcal glycoconjugate vaccine to demonstrate immunologic memory in children primed with one or two vaccine doses in infancy.

PubMed

Pace, David; Khatami, Ameneh; Attard-Montalto, Simon; Voysey, Merryn; Finn, Adam; Faust, Saul N; Heath, Paul T; Borrow, Ray; Snape, Matthew D; Pollard, Andrew J

2016-12-07

Use of a polysaccharide vaccine challenge to demonstrate immunologic memory after priming with capsular group C meningococcal conjugate vaccines (MenCC) risks induction of immunologic hyporesponsiveness. For this reason, MenCC vaccines are now used as probes of immunologic memory, however, no studies have demonstrated their ability to distinguish primed from unprimed children. This study was part of a randomised controlled trial investigating the immunogenicity of a booster dose of the combined Haemophilus influenzae type b and MenC-tetanus toxoid vaccine (Hib-MenC-TT) in infants receiving reduced dose MenCC vaccine priming schedules (one MenC-CRM/MenC-TT or two MenC-CRM vaccine doses) compared with an unprimed group. Antibody kinetics were studied in a subset of 269 children by measuring changes in the MenC serum bactericidal antibody, using rabbit complement, (MenC rSBA) titres and MenC specific IgG memory B-cells before and at 6 and 28days following the 12month booster vaccination. At 6days after the 12monthMenCC vaccine, the rise in MenC rSBA titres and MenC specific IgG memory B-cells of the primed groups were significantly higher than the infant MenCC naïve group. Participants primed with one MenC-TT dose had the highest increase in MenC rSBA titres compared with all other groups. The MenC rSBA titres at the 28th compared with the 6th day after boosting was significantly higher in those primed with a single MenC-TT/MenC-CRM vaccine in infancy compared with those who were not primed or who were primed with two doses of the MenC-CRM vaccine. Immunologic memory can be demonstrated by a MenCC booster vaccination but is affected by the type and number of MenCC doses used for infant priming. The MenC rSBA responses can be used to demonstrate successful immunologic priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory

PubMed Central

Díaz-Montero, C Marcela; Naga, Osama; Zidan, Abdel-Aziz A; Salem, Mohamed L; Pallin, Maria; Parmigiani, Anita; Walker, Gail; Wieder, Eric; Komanduri, Krishna; Cole, David J; Montero, Alberto J; Lichtenheld, Mathias G

2011-01-01

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8+ T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory. PMID:21915391

Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8+ T cells.

PubMed

Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D; Dyring-Andersen, Beatrice; Agerbeck, Christina; Nielsen, Morten M; Poulsen, Steen S; Woetmann, Anders; Ødum, Niels; Thomsen, Allan R; Geisler, Carsten; Bonefeld, Charlotte M

2017-04-01

Skin-resident memory T (T RM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore, the mechanisms whereby T RM cells induce rapid recall responses need further investigation. To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. To address these questions, we analysed responses to contact allergens in mice and humans sensitized to 2,4-dinitrofluorobenzene and nickel, respectively. Challenge responses in both mice and humans were dramatically increased at sites previously exposed to allergens as compared with previously unexposed sites. Importantly, the magnitude of the challenge response correlated with the epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)-γ-producing T RM cells. Moreover, IL-17A and IFN-γ enhanced allergen-induced IL-1β production in keratinocytes. We show that sensitization with contact allergens induces a strong, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8 + T RM cells. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alba, Martha P.; Suarez, Carlos F.; Universidad del Rosario, Bogotá D. C.

Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPII{sub L} 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche{sup −} rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. Thismore » data, in association with previously-described p3 and p7 apolar residues having gauche{sup +} orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory. - Highlights: • Stereo-electronic and topochemical rules associated with FPLLI immunological memory. • Presence of very high long-lasting antibody titres against Plasmodium falciparum Spz. • Protective memory induction associated with a binding capacity to HLA-DRβ1*. • gauche{sup −} rotamer orientation in p8 polar residue is related to is related to immunological memory.« less

Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in premature infants.

PubMed

Collins, Clare L; Ruggeberg, Jens U; Balfour, Gail; Tighe, Helen; Archer, Marion; Bowen-Morris, Jane; Diggle, Linda; Borrow, Ray; Balmer, Paul; Buttery, Jim P; Moxon, E Richard; Pollard, Andrew J; Heath, Paul T

2005-11-01

Protein-polysaccharide conjugate vaccines against Neisseria meningitidis serogroup C were introduced into the U.K. routine immunization schedule in 1999. This study is the first to describe both persistence of antibody and evidence for induction of immune memory using meningococcal C conjugate (MCC) vaccine in preterm infants. Immunogenicity and induction of immunologic memory by as MCC vaccine was assessed in premature infants; 62 preterm and 60 term controls received MCC at the accelerated schedule (2, 3 and 4 months of age). A meningococcal C polysaccharide challenge was administered at 12 months of age. Both groups achieved similar protective titers after primary immunization that then waned significantly by 1 year of age. Postchallenge serum bactericidal activity was significantly lower in preterm infants (P = 0.03); 73% of preterm versus 88% of term controls achieved a 4-fold rise in serum bactericidal activity (P = 0.07). MCC vaccine is immunogenic and primes for immunologic memory in preterm infants. The decreased memory responses in these preterm infants in conjunction with waning clinical efficacy data for all U.K. infants suggest a role for a routine booster dose of vaccine in all infants receiving MCC, especially those born preterm.

Associations between immunological function and memory recall in healthy adults.

PubMed

Wang, Grace Y; Taylor, Tamasin; Sumich, Alexander; Merien, Fabrice; Borotkanics, Robert; Wrapson, Wendy; Krägeloh, Chris; Siegert, Richard J

2017-12-01

Studies in clinical and aging populations support associations between immunological function, cognition and mood, although these are not always in line with animal models. Moreover, very little is known about the relationship between immunological measures and cognition in healthy young adults. The present study tested associations between the state of immune system and memory recall in a group of relatively healthy adults. Immediate and delayed memory recall was assessed in 30 participants using the computerised cognitive battery. CD4, CD8 and CD69 subpopulations of lymphocytes, Interleukin-6 (IL-6) and cortisol were assessed with blood assays. Correlation analysis showed significant negative relationships between CD4 and the short and long delay memory measures. IL-6 showed a significant positive correlation with long-delay recall. Generalized linear models found associations between differences in all recall challenges and CD4. A multivariate generalized linear model including CD4 and IL-6 exhibited a stronger association. Results highlight the interactions between CD4 and IL-6 in relation to memory function. Further study is necessary to determine the underlying mechanisms of the associations between the state of immune system and cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Induction of long term mucosal immunological memory in humans by an oral inactivated multivalent enterotoxigenic Escherichia coli vaccine.

PubMed

Lundgren, Anna; Jertborn, Marianne; Svennerholm, Ann-Mari

2016-06-08

We have evaluated the capacity of an oral multivalent enterotoxigenic Escherichia coli (ETEC) vaccine (MEV) to induce mucosal immunological memory. MEV consists of four inactivated E. coli strains over-expressing the major colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the LTB-related toxoid LCTBA. Memory responses were analyzed by comparing the magnitudes and kinetics of intestine-derived antibody-secreting cell responses to a single dose of MEV in three groups of adult Swedish volunteers (n=16-19 subjects per group) in a Phase I trial: non-immunized controls (I) and subjects who in a previous Phase I trial 13-23 months earlier had received two biweekly doses of MEV (II) or MEV+double mutant LT (dmLT) adjuvant (III). Responses against CFs and LTB were analyzed in antibodies in lymphocyte secretions (ALS) of blood mononuclear cells collected before (day 0) and 4/5 and 7 days after immunization. Specific circulating memory B cells present at the time of the single dose vaccination were also studied to determine if such cells may reflect mucosal memory. Considerably higher and significantly more frequent IgA ALS responses against all CFs and LTB were induced by the single vaccine dose in the previously immunized than in non-immunized volunteers. Furthermore, peak IgA ALS responses against all antigens were observed on days 4/5 in most of the previously immunized subjects whereas only a few previously non-vaccinated individuals responded before day 7. Priming with adjuvant did not influence memory responses. Circulating vaccine specific IgA memory B cells were not detected, whereas anti-toxin IgG memory B cells were identified 13-23 months after priming vaccination. We conclude that MEV induces functional mucosal immunological memory which remains at least 1-2 years. Furthermore, our results support that analysis of antibody-secreting cell responses after booster vaccination may be a useful approach to evaluate longstanding mucosal immunological memory in humans. ISRCTN27096290. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Memory-like Responses of Natural Killer Cells

PubMed Central

Cooper, Megan A.; Yokoyama, Wayne M.

2010-01-01

Summary Natural killer (NK) cells are lymphocytes with the capacity to produce cytokines and kill target cells upon activation. NK cells have long been categorized as members of the innate immune system and as such have been thought to follow the ‘rules’ of innate immunity, including the principle that they have no immunologic memory, a property thought to be strictly limited to adaptive immunity. However, recent studies have suggested that NK cells have the capacity to alter their behavior based on prior activation. This property is analogous to adaptive immune memory; however, some NK cell memory-like functions are not strictly antigen-dependent and can be demonstrated following cytokine stimulation. Here we discuss the recent evidence that NK cells can exhibit properties of immunologic memory, focusing on the ability of cytokines to non-specifically induce memory-like NK cells with enhanced responses to restimulation. PMID:20536571

Memory T cells maintain protracted protection against malaria.

PubMed

Krzych, Urszula; Zarling, Stasya; Pichugin, Alexander

2014-10-01

Immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. Adequately maintained memory T and B cell pools assure a fast, effective and specific response against re-infections. However, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, Plasmodium spp., the causative agents of malaria. For example, memory responses to Plasmodium antigens amongst residents of malaria endemic areas appear to be either inadequately developed or maintained, because persons who survive episodes of childhood malaria remain vulnerable to intermittent malaria infections. By contrast, multiple exposures of humans and laboratory rodents to radiation-attenuated Plasmodium sporozoites (γ-spz) induce sterile and long-lasting protection against experimental sporozoite challenge. Multifactorial immune mechanisms maintain this protracted and sterile protection. While the presence of memory CD4 T cell subsets has been associated with lasting protection in humans exposed to multiple bites from Anopheles mosquitoes infected with attenuated Plasmodium falciparum, memory CD8 T cells maintain protection induced with Plasmodium yoelii and Plasmodium berghei γ-spz in murine models. In this review, we discuss our observations that show memory CD8 T cells specific for antigens expressed by P. berghei liver stage parasites as an indispensable component for the maintenance of protracted protective immunity against experimental malaria infection; moreover, the provision of an Ag-depot assures a quick recall of memory T cells as IFN-γ-producing effector CD8 T cells and IL-4- producing CD4 T cells that collaborate with B cells for an effective antibody response. Published by Elsevier B.V.

Acquired immunologic tolerance: with particular reference to transplantation

PubMed Central

Starzl, Thomas E.

2009-01-01

The first unequivocally successful bone marrow cell transplantation in humans was recorded in 1968 by the University of Minnesota team of Robert A. Good (Gatti et al. Lancet 2: 1366–1369, 1968). This achievement was a direct extension of mouse models of acquired immunologic tolerance that were established 15 years earlier. In contrast, organ (i.e. kidney) transplantation was accomplished precociously in humans (in 1959) before demonstrating its feasibility in any experimental model and in the absence of a defensible immunologic rationale. Due to the striking differences between the outcomes with the two kinds of procedure, the mechanisms of organ engraftment were long thought to differ from the leukocyte chimerism-associated ones of bone marrow transplantation. This and other concepts of alloengraftment and acquired tolerance have changed over time. Current concepts and their clinical implications can be understood and discussed best from the perspective provided by the life and times of Bob Good. PMID:17917005

Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.

PubMed

Yong, Pierre L; Orange, Jordan S; Sullivan, Kathleen E

2010-08-01

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.

TLR agonists are highly effective at eliciting functional memory CTLs of effector memory phenotype in peptide immunization

USDA-ARS?s Scientific Manuscript database

Given the importance of memory cytotoxic T lymphocytes (CTLs) in eliminating altered self-cells, including virus-infected and tumor cells, devising effective vaccination strategies for generating memory CTLs is a priority in the field of immunology. Herein, we elaborate upon a novel boosting approac...

Immunological characteristics and response to lipopolysaccharide of mouse lines selectively bred with natural and acquired immunities.

PubMed

Narahara, Hiroki; Sakai, Eri; Katayama, Masafumi; Ohtomo, Yukiko; Yamamoto, Kanako; Takemoto, Miki; Aso, Hisashi; Ohwada, Shyuichi; Mohri, Yasuaki; Nishimori, Katsuhiko; Isogai, Emiko; Yamaguchi, Takahiro; Fukuda, Tomokazu

2012-05-01

Genetic improvement of resistance to infectious diseases is a challenging goal in animal breeding. Infection resistance involves multiple immunological characteristics, including natural and acquired immunity. In the present study, we developed an experimental model based on genetic selection, to improve immunological phenotypes. We selectively established three mouse lines based on phagocytic activity, antibody production and the combination of these two phenotypes. We analyzed the immunological characteristics of these lines using a lipopolysaccharide (LPS), which is one of the main components of Gram-negative bacteria. An intense immunological reaction was induced in each of the three mouse lines. Severe loss of body weight and liver damage were observed, and a high level of cytokine messenger RNA was detected in the liver tissue. The mouse line established using a combination of the two selection standards showed unique characteristics relative to the mouse lines selected on the basis of a single phenotype. Our results indicate that genetic selection and breeding is effective, even for immunological phenotypes with a relatively low heritability. Thus, it may be possible to improve resistance to infectious diseases by means of genetic selection. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

Establishment of anti-tumor memory in humans using in vitro-educated CD8+ T cells

PubMed Central

Butler, Marcus O.; Friedlander, Philip; Milstein, Matthew I.; Mooney, Mary M.; Metzler, Genita; Murray, Andrew P.; Tanaka, Makito; Berezovskaya, Alla; Imataki, Osamu; Drury, Linda; Brennan, Lisa; Flavin, Marisa; Neuberg, Donna; Stevenson, Kristen; Lawrence, Donald; Hodi, F. Stephen; Velazquez, Elsa F.; Jaklitsch, Michael T.; Russell, Sara E.; Mihm, Martin; Nadler, Lee M.; Hirano, Naoto

2013-01-01

While advanced stage melanoma patients have a median survival of less than a year, adoptive T cell therapy can induce durable clinical responses in some patients. Successful adoptive T cell therapy to treat cancer requires engraftment of anti-tumor T lymphocytes that not only retain specificity and function in vivo but also display an intrinsic capacity to survive. To date, adoptively transferred anti-tumor CD8+ T lymphocytes (CTL) have had limited life spans unless the host has been manipulated. To generate CTL that possess an intrinsic capacity to persist in vivo, we developed a human artificial antigen presenting cell system that can educate anti-tumor CTL to acquire both a central memory and effector memory phenotype as well as the capacity to survive in culture for prolonged periods of time. In the present report, we examined whether anti-tumor CTL generated using this system could function and persist in patients. Here, we showed that MART1-specific CTL, educated and expanded using our artificial antigen presenting cell system, could survive for prolonged periods in advanced stage melanoma patients without previous conditioning or cytokine treatment. Moreover, these CTL trafficked to the tumor, mediated biological and clinical responses, and established anti-tumor immunologic memory. Therefore, this approach may broaden the availability of adoptive cell therapy to patients both alone and in combination with other therapeutic modalities. PMID:21525398

In situ vaccine, immunological memory and cancer cure.

PubMed

Tsung, Kangla; Norton, Jeffrey A

2016-01-01

As surgery is able to remove primary tumors and limit metastases, the major challenge in cancer management is the prevention of post-resection recurrence and metastases. From the immune point of view, tumor resection removes the supply of tumor antigens that maintain an active concomitant antitumor immunity elicited by the primary tumor, and may also signal for deposition of immunological memory against future metastases. However, the natural course of this antitumor immunity in many cancer patients following complete tumor resection may not be favorable because protection is often lost after 1-3 years. Recent studies suggest that chemotherapy is able to activate this pre-existing antitumor immunity, and tumor resection following immune activation may lead to higher levels of immunological memory against future tumor antigens (in the form of metastases). Interleukin-12 added to chemotherapy mimics the function of a vaccine adjuvant in that it helps to enhance the antitumor immunity activated by chemotherapy and leaves a much stronger antitumor immune memory. This finding, when applied to cancer management, may help to maintain a strong and long lasting antitumor immunity following complete tumor resection, thus eliminating post-surgery recurrence and metastases.

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda.

PubMed

Ruiseñor-Escudero, Horacio; Familiar-Lopez, Itziar; Sikorskii, Alla; Jambulingam, Nikita; Nakasujja, Noelline; Opoka, Robert; Bass, Judith; Boivin, Michael

2016-04-15

To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children aged 1-6 years, participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z scores (WAZs), antiretroviral therapy status, and immunological biomarkers. In the final analysis, 111 children were included. Lower levels of CD4 CD38 T cells (P = 0.04) were associated to higher immediate and total recall scores (P = 0.04). Higher levels of CD8 HLA-DR T cells were associated with higher total recall score (P = 0.04) of the COAT. Higher CD4 CD38 HLA-DR T cells levels were associated with higher gross motor scores of the MSEL (P = 0.02). WAZ was positively correlated to visual reception, fine motor, expressive language, and composite score of the MSEL. Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4 CD38 T cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship.

Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Natural Killer Cells in Vaccination.

PubMed

Neely, Harold R; Mazo, Irina B; Gerlach, Carmen; von Andrian, Ulrich H

2017-12-18

Natural killer (NK) cells have historically been considered to be a part of the innate immune system, exerting a rapid response against pathogens and tumors in an antigen (Ag)-independent manner. However, over the past decade, evidence has accumulated suggesting that at least some NK cells display certain characteristics of adaptive immune cells. Indeed, NK cells can learn and remember encounters with a variety of Ags, including chemical haptens and viruses. Upon rechallenge, memory NK cells mount potent recall responses selectively to those Ags. This phenomenon, traditionally termed "immunological memory," has been reported in mice, nonhuman primates, and even humans and appears to be concentrated in discrete NK cell subsets. Because immunological memory protects against recurrent infections and is the central goal of active vaccination, it is crucial to define the mechanisms and consequences of NK cell memory. Here, we summarize the different kinds of memory responses that have been attributed to specific NK cell subsets and discuss the possibility to harness NK cell memory for vaccination purposes. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Thy1+ Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive Lymphocytes

PubMed Central

Gillard, Geoffrey O.; Bivas-Benita, Maytal; Hovav, Avi-Hai; Grandpre, Lauren E.; Panas, Michael W.; Seaman, Michael S.; Haynes, Barton F.; Letvin, Norman L.

2011-01-01

While immunological memory has long been considered the province of T- and B- lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1+ subset of natural killer (NK) cells. We demonstrate that immune protection against infection from a lethal dose of virus can be adoptively transferred with memory hepatic Thy1+ NK cells that were primed with live virus. Our results also indicate that, like classical immunological memory, stronger innate memory responses form in response to priming with live virus than a highly attenuated vector. These results demonstrate that a defined innate memory cell population alone can provide host protection against a lethal systemic infection through viral clearance. PMID:21829360

Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity.

PubMed

Murphy, J E; Robert, C; Kupper, T S

2000-03-01

As our primary interface with the environment, the skin is constantly subjected to injury and invasion by pathogens. The fundamental force driving the evolution of the immune system has been the need to protect the host against overwhelming infection. The ability of T and B cells to recombine antigen receptor genes during development provides an efficient, flexible, and powerful immune system with nearly unlimited specificity for antigen. The capacity to expand subsets of antigen-specific lymphocytes that become activated by environmental antigens (memory response) is termed "acquired" immunity. Immunologic memory, although a fundamental aspect of mammalian biology, is a relatively recent evolutionary event that permits organisms to live for years to decades. "Innate" immunity, mediated by genes that remain in germ line conformation and encode for proteins that recognize conserved structural patterns on microorganisms, is a much more ancient system of host defense. Defensins and other antimicrobial peptides, complement and opsonins, and endocytic receptors are all considered components of the innate immune system. None of these, however, are signal-transducing receptors. Most recently, a large family of cell surface receptors that mediate signaling through the NF-kappaB transcription factor has been identified. This family of proteins shares striking homology with plant and Drosophila genes that mediate innate immunity. In mammals, this family includes the type I interleukin-1 receptor, the interleukin-18 receptor, and a growing family of Toll-like receptors, two of which were recently identified as signal-transducing receptors for bacterial endotoxin. In this review, we discuss how interleukin-1 links the innate and acquired immune systems to provide synergistic host defense activities in skin.

Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory

PubMed Central

Torres, Alice A.; Smith, Geoffrey L.

2018-01-01

The increasing frequency of monkeypox virus infections, new outbreaks of other zoonotic orthopoxviruses and concern about the re-emergence of smallpox have prompted research into developing antiviral drugs and better vaccines against these viruses. This article considers the genetic engineering of vaccinia virus (VACV) to enhance vaccine immunogenicity and safety. The virulence, immunogenicity and protective efficacy of VACV strains engineered to lack specific immunomodulatory or host range proteins are described. The ultimate goal is to develop safer and more immunogenic VACV vaccines that induce long-lasting immunological memory. PMID:29495547

The immunological synapse: the gateway to the HIV reservoir

PubMed Central

Kulpa, Deanna A; Brehm, Jessica H; Fromentin, Rémi; Cooper, Anthony; Cooper, Colleen; Ahlers, Jeffrey; Chomont, Nicolas; Sékaly, Rafick-Pierre

2013-01-01

A major challenge in the development of a cure for human immunodeficiency virus (HIV) has been the incomplete understanding of the basic mechanisms underlying HIV persistence during antiretroviral therapy. It is now realized that the establishment of a latently infected reservoir refractory to immune system recognition has thus far hindered eradication efforts. Recent investigation into the innate immune response has shed light on signaling pathways downstream of the immunological synapse critical for T-cell activation and establishment of T-cell memory. This has led to the understanding that the cell-to-cell contacts observed in an immunological synapse that involve the CD4+ T cell and antigen-presenting cell or T-cell–T-cell interactions enhance efficient viral spread and facilitate the induction and maintenance of latency in HIV-infected memory T cells. This review focuses on recent work characterizing the immunological synapse and the signaling pathways involved in T-cell activation and gene regulation in the context of HIV persistence. PMID:23772628

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

PubMed

Sherr, David H

2004-06-01

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.

CRISPR-Cas adaptation: insights into the mechanism of action.

PubMed

Amitai, Gil; Sorek, Rotem

2016-02-01

Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

Enhancement of Immune Memory Responses to Respiratory Infection

DTIC Science & Technology

2017-08-01

Unlimited Distribution 13. SUPPLEMENTARY NOTES 14. ABSTRACT Maintenance of long - term immunological memory against pathogens is crucial for the rapid...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long - term memory B cells needed to protect against influenza...AWARD NUMBER: W81XWH-16-1-0360 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Min Chen PhD

A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory.

PubMed

Cassidy, W M; Watson, B; Ioli, V A; Williams, K; Bird, S; West, D J

2001-04-01

Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant HB vaccine, Recombivax HB (2 or 3 doses of 5 or 10 microg given over 4 or 6 months), induce protective anti-hepatitis B surface antibody [anti-HBsAb] levels (>/=10 mIU/mL) comparable to the recommended regimen (5 microg at 0 and 1, and 6 months); 2) measured early antibody response after a single dose; and 3) assessed immunologic memory after 2- and 3-dose regimens. One thousand twenty-six adolescents were randomized to 1 of 5 treatment groups (10 microg at 0 and 4 or 0 and 6 months; 5 microg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open trial. Anti-HBsAb was measured in all participants just before and 1 month after the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb response to a booster dose 2 years later was examined to assess immunologic memory in participants vaccinated with 5 microg at 0 and 6 or 0, 1, and 6 months. All regimens induced >/=10 mIU/mL of anti-HBs in >/=95% of vaccinees. Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regimens using the following: 1) 10 versus 5 microg; 2) 3 versus 2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccinees given one 10-microg dose had >/=10 mIU/mL of anti-HBsAb versus 41.6% after one 5-microg dose. Participants vaccinated with either two or three 5-microg doses retained robust immunologic memory. . The results of this study show that a 2-dose regimen of Recombivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-microg doses may be of significant benefit for vaccinees who are poorly compliant or deviate from the intended vaccination schedule.

Remembrance of immunology past: conversations with Herman Eisen.

PubMed

Eisen, Herman N; Schlesinger, Sondra

2015-01-01

Herman Eisen and Sondra Schlesinger spent several days together in September 2007 in Woods Hole, Massachusetts, talking about immunology, focusing on his remembrances of the field over the more than 60 years of his involvement. This article is an abridged version of those discussions (the full version is available on the Annual Reviews website). It is both an oral history and a written memory of some important but selected areas of immunology.

Nutritional and immunological correlates of memory and neurocognitive development among HIV infected children living in Kayunga, Uganda

PubMed Central

Horacio, Ruiseñor-Escudero; Itziar, Familiar-Lopez; Alla, Sikorskii; Nikita, Jambulingam; Noelline, Nakasujja; Robert, Opoka; Judith, Bass; Michael, Boivin

2015-01-01

Objective To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. Design This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children ages 1–6 years participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Methods Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z-scores (WAZ), antiretroviral therapy (ART) status and immunological biomarkers. Results 111 children were included in the final analysis. Lower levels of CD4+ CD38+ T-cells (p=0.04) were associated to higher Immediate and Total Recall scores (p=0.04). Higher levels of CD8+ HLA-DR+ T-cells were associated with higher Total Recall score (p=0.04) of the COAT. Higher CD4+ CD38+ HLA-DR+ T-cells levels were associated with higher Gross Motor scores of the MSEL (p=0.02). WAZ was positively correlated to Visual Reception, Fine Motor, Expressive Language and composite score of the MSEL. Conclusions Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4+ CD38+ T-cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship. PMID:26605506

Links between Immunologic Memory and Metabolic Cycling.

PubMed

Cottam, Matthew A; Itani, Hana A; Beasley, Arch A; Hasty, Alyssa H

2018-06-01

Treatments for metabolic diseases, such as diet and therapeutics, often provide short-term therapy for metabolic stressors, but relapse is common. Repeated bouts of exposure to, and relief from, metabolic stimuli results in a phenomenon we call "metabolic cycling." Recent human and rodent data suggest metabolic cycling promotes an exaggerated response and ultimately worsened metabolic health. This is particularly evident with cycling of body weight and hypertension. The innate and adaptive immune systems have a profound impact on development of metabolic disease, and current data suggest that immunologic memory may partially explain this association, especially in the context of metabolic cycling. In this Brief Review, we highlight recent work in this field and discuss potential immunologic mechanisms for worsened disease prognosis in individuals who experience metabolic cycling. Copyright © 2018 by The American Association of Immunologists, Inc.

Long-term antibody response and immunologic memory in children immunized with hepatitis B vaccine at birth.

PubMed

Saffar, M J; Rezai, M S

2004-12-01

Four hundred and fifty three healthy children immunized with a course of hepatitis B vaccine beginning at birth were tested at 10-11 years of age for persistence of anti-hepatitis B-S antigen antibody (anti-HBs); and responses of children without protective antibody to different doses of hepatitis B vaccine booster were evaluated. Although nearly 42% of them were not seroprotected, but most of boosted subjects (87.3%) retained robust immunologic memory and rapidly retained a protective anti-HBs antibody titer of at least 10 IU/L after booster vaccination.

Declarative memory: sleep protects new memories from interference.

PubMed

Norman, Kenneth A

2006-08-08

Interference is one of the most fundamental phenomena in memory research: acquiring new memories causes forgetting of other, related memories. A new study shows that sleep, interposed between learning episodes, can mitigate the extent to which new (post-sleep) learning interferes with recall of previously acquired knowledge.

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

PubMed Central

Santich, Brian H.; Kim, Jin Young; Posada, Jacqueline G.; Ho, Jason; Buckner, Clarisa M.; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E.; Manischewitz, Jody; King, Lisa R.; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S.; Malech, Harry L.

2012-01-01

CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells. PMID:23074274

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells.

PubMed

Moir, Susan; De Ravin, Suk See; Santich, Brian H; Kim, Jin Young; Posada, Jacqueline G; Ho, Jason; Buckner, Clarisa M; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E; Manischewitz, Jody; King, Lisa R; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S; Malech, Harry L

2012-12-06

CD27(+) memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27(+) but also IgG(+) B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG(+) B cells, the ratio of CD27(-) to CD27(+) was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27(-)IgG(+) B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27(+) counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27(-)IgG(+) B-cell compartment. Together, these findings show that, despite reduced circulating CD27(+) memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27(-) B cells.

Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure.

PubMed

McVernon, J; Johnson, P D R; Pollard, A J; Slack, M P E; Moxon, E R

2003-05-01

To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. Unmatched case-control study in the UK and Eire 1992-2001 and Victoria, Australia 1988-1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 microg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 microg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 microg/ml (2.78 to 5.15); unvaccinated GMC 1.48 microg/ml (0.90 to 2.21); p = 0.003). Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.

Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure

PubMed Central

McVernon, J; Johnson, P; Pollard, A; Slack, M; Moxon, E

2003-01-01

Aims: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. Methods: Unmatched case-control study in the UK and Eire 1992–2001 and Victoria, Australia 1988–1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. Results: Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 µg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 µg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 µg/ml (2.78 to 5.15); unvaccinated GMC 1.48 µg/ml (0.90 to 2.21); p = 0.003). Conclusions: Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear. PMID:12716702

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder.

PubMed

Magioncalda, Paola; Martino, Matteo; Tardito, Samuele; Sterlini, Bruno; Conio, Benedetta; Marozzi, Valentina; Adavastro, Giulia; Capobianco, Laura; Russo, Daniel; Parodi, Alessia; Kalli, Francesca; Nasi, Giorgia; Altosole, Tiziana; Piaggio, Niccolò; Northoff, Georg; Fenoglio, Daniela; Inglese, Matilde; Filaci, Gilberto; Amore, Mario

2018-05-01

White matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. In 60 type I BD patients - 20 in manic, 20 in depressive, 20 in euthymic phases - and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. We found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. Our data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD. Copyright © 2018 Elsevier Inc. All rights reserved.

Immunology of Yersinia pestis Infection.

PubMed

Bi, Yujing

2016-01-01

As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

IMMUNOLOGIC MEMORY CELLS OF BONE MARROW ORIGIN

PubMed Central

Miller, Harold C.; Cudkowicz, Gustavo

1972-01-01

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F1 mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process. PMID:4553850

Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression

PubMed Central

Sungalee, Stéphanie; Mamessier, Emilie; Morgado, Ester; Grégoire, Emilie; Brohawn, Philip Z.; Morehouse, Christopher A.; Jouve, Nathalie; Monvoisin, Céline; Menard, Cédric; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Eberle, Franziska C.; Chasson, Lionel; Baudimont, Fannie; Mancini, Stéphane J.; Tellier, Julie; Picquenot, Jean-Michel; Kelly, Rachel; Vineis, Paolo; Ruminy, Philippe; Chetaille, Bruno; Jaffe, Elaine S.; Schiff, Claudine; Hardwigsen, Jean; Tice, David A.; Higgs, Brandon W.; Tarte, Karin; Nadel, Bertrand; Roulland, Sandrine

2014-01-01

It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)+ memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation–induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)+ precursors and shapes the systemic presentation of FL patients. PMID:25384217

Haemophilus influenzae type B in an immunocompetent, fully vaccinated ALL survivor.

PubMed

Nevin, John; Kanter Washko, Julie; Arnold, John

2013-05-01

A 7-year-old boy with a history of recurrent acute lymphoblastic leukemia (ALL), in remission, presented to primary care clinic after 2 days of progressive right hip pain with weight-bearing activities. He was otherwise asymptomatic at the time of presentation. Blood cultures revealed Gram-negative diplococci, which prompted an MRI that was significant for a hip joint effusion and femoral head bone marrow edema. The patient had no sick contacts and no significant past medical history other than ALL. The patient had been given all recommended childhood vaccinations. Arthrocentesis and needle biopsy of the femoral neck were not diagnostic for malignancy and revealed only mild hip joint inflammation, leading to a diagnosis of osteomyelitis. The organism in the original blood culture was identified as Haemophilus influenzae type b, β-lactamase negative. Review of the patient's medical records showed a history of complete immunization to Haemophilus influenzae type b. An immunologic evaluation was made to determine if the patient retained immunity from his other vaccinations. Pathogen-specific antibody testing revealed detectable antibodies to polio but not measles, mumps, rubella, varicella-zoster virus, tetanus, diphtheria, pertussis, or hepatitis B. This loss of immunologic memory appears to be a rarely described side effect of ALL chemotherapy. There is currently no protocol to evaluate the immunologic memory of patients who underwent chemotherapy for ALL or to revaccinate them after their treatment. It is unclear whether the loss of immunologic memory is genuinely rare or is underdiagnosed because affected patients are protected by herd immunity.

From Immunologically Archaic to Neoteric Glycovaccines

PubMed Central

Cavallari, Marco; De Libero, Gennaro

2017-01-01

Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection. PMID:28134792

Kinetics of B cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites.

PubMed

Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F; Barfod, Lea; Hviid, Lars

2014-06-01

Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of "atypical" memory B cells may also contribute. In this first, to our knowledge, longitudinal study of its kind, we measured B cell subset composition, as well as PfEMP1-specific Ab levels and memory B cell frequencies, in Ghanaian women followed from early pregnancy up to 1 y after delivery. Cell phenotypes and Ag-specific B cell function were assessed three times during and after pregnancy. Levels of IgG specific for pregnancy-restricted, VAR2CSA-type PfEMP1 increased markedly during pregnancy and declined after delivery, whereas IgG levels specific for two PfEMP1 proteins not restricted to pregnancy did not. Changes in VAR2CSA-specific memory B cell frequencies showed typical primary memory induction among primigravidae and recall expansion among multigravidae, followed by contraction postpartum in all. No systematic changes in the frequencies of memory B cells specific for the two other PfEMP1 proteins were identified. The B cell subset analysis confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum-endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against this disease. Copyright © 2014 by The American Association of Immunologists, Inc.

Crew exploration vehicle (CEV) attitude control using a neural-immunology/memory network

NASA Astrophysics Data System (ADS)

Weng, Liguo; Xia, Min; Wang, Wei; Liu, Qingshan

2015-01-01

This paper addresses the problem of the crew exploration vehicle (CEV) attitude control. CEVs are NASA's next-generation human spaceflight vehicles, and they use reaction control system (RCS) jet engines for attitude adjustment, which calls for control algorithms for firing the small propulsion engines mounted on vehicles. In this work, the resultant CEV dynamics combines both actuation and attitude dynamics. Therefore, it is highly nonlinear and even coupled with significant uncertainties. To cope with this situation, a neural-immunology/memory network is proposed. It is inspired by the human memory and immune systems. The control network does not rely on precise system dynamics information. Furthermore, the overall control scheme has a simple structure and demands much less computation as compared with most existing methods, making it attractive for real-time implementation. The effectiveness of this approach is also verified via simulation.

How trait anxiety, interpretation bias and memory affect acquired fear in children learning about new animals.

PubMed

Field, Zoë C; Field, Andy P

2013-06-01

Cognitive models of vulnerability to anxiety propose that information processing biases such as interpretation bias play a part in the etiology and maintenance of anxiety disorders. However, at present little is known about the role of memory in information processing accounts of child anxiety. The current study investigates the relationships between interpretation biases, memory and fear responses when learning about new stimuli. Children (aged 8-11 years) were presented with ambiguous information regarding a novel animal, and their fear, interpretation bias, and memory for the information was measured. The main findings were: (1) trait anxiety and interpretation bias significantly predicted acquired fear; (2) interpretation bias did not significantly mediate the relationship between trait anxiety and acquired fear; (3) interpretation bias appeared to be a more important predictor of acquired fear than trait anxiety per se; and (4) the relationship between interpretation bias and acquired fear was not mediated by the number of negative memories but was mediated by the number of positive and false-positive memories. The findings suggest that information processing models of child anxiety need to explain the role of positive memory in the formation of fear responses.

Changes in immunological profile as a function of urbanization and lifestyle

PubMed Central

Mbow, Moustapha; de Jong, Sanne E; Meurs, Lynn; Mboup, Souleymane; Dieye, Tandakha Ndiaye; Polman, Katja; Yazdanbakhsh, Maria

2014-01-01

Differences in lifestyle and break with natural environment appear to be associated with changes in the immune system resulting in various adverse health effects. Although genetics can have a major impact on the immune system and disease susceptibility, the contribution of environmental factors is thought to be substantial. Here, we investigated the immunological profile of healthy volunteers living in a rural and an urban area of a developing African country (Senegal), and in a European country (the Netherlands). Using flow cytometry, we investigated T helper type 1 (Th1), Th2, Th17, Th22 and regulatory T cells, as well as CD4+ T-cell and B-cell activation markers, and subsets of memory T and B cells in the peripheral blood. Rural Senegalese had significantly higher frequencies of Th1, Th2 and Th22 cells, memory CD4+ T and B cells, as well as activated CD4+ T and B cells compared with urban Senegalese and urban Dutch people. Within the Senegalese population, rural paritcipants displayed significantly higher frequencies of Th2 and Th22 cells, as well as higher pro-inflammatory and T-cell activation and memory profiles compared with the urban population. The greater magnitude of immune activation and the enlarged memory pool, together with Th2 polarization, seen in rural participants from Africa, followed by urban Africans and Europeans suggest that environmental changes may define immunological footprints, which could have consequences for disease patterns in general and vaccine responses in particular. PMID:24924958

A Matter of Time: Rapid Motor Memory Stabilization in Childhood

ERIC Educational Resources Information Center

Adi-Japha, Esther; Badir, Rodayna; Dorfberger, Shoshi; Karni, Avi

2014-01-01

Are children better than adults in acquiring new skills ("how-to" knowledge) because of a difference in skill memory consolidation? Here we tested the proposal that, as opposed to adults, children's memories for newly acquired skills are immune to interference by subsequent experience. The establishment of long-term memory for a…

Booster vaccinations: can immunologic memory outpace disease pathogenesis?

PubMed

Pichichero, Michael E

2009-12-01

Almost all current vaccines work by the induction of antibodies in serum or on the mucosa to block adherence of pathogens to epithelial cells or interfere with microbial invasion of the bloodstream. However, antibody levels usually decline after vaccination to undetectable amounts if further vaccination does not occur. Persistence of vaccine-induced antibodies usually goes well beyond the time when they should have decayed to undetectable levels because of ongoing "natural" boosting or other immunologic mechanisms. The production of memory B and T cells is of clear importance, but the likelihood that a memory response will be fast enough in the absence of a protective circulating antibody level likely depends on the pace of pathogenesis of a specific organism. This concept is discussed with regard to Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis; hepatitis A and B; diphtheria, tetanus, and pertussis; polio, measles, mumps, rubella, and varicella; rotavirus; and human papilloma virus. With infectious diseases for which the pace of pathogenesis is less rapid, some individuals will contract infection before the memory response is fully activated and implemented. With infectious diseases for which the pace of pathogenesis is slow, immune memory should be sufficient to prevent disease.

Immunobiography and the Heterogeneity of Immune Responses in the Elderly: A Focus on Inflammaging and Trained Immunity

PubMed Central

Franceschi, Claudio; Salvioli, Stefano; Garagnani, Paolo; de Eguileor, Magda; Monti, Daniela; Capri, Miriam

2017-01-01

Owing to its memory and plasticity, the immune system (IS) is capable of recording all the immunological experiences and stimuli it was exposed to. The combination of type, dose, intensity, and temporal sequence of antigenic stimuli that each individual is exposed to has been named “immunobiography.” This immunological history induces a lifelong continuous adaptation of the IS, which is responsible for the capability to mount strong, weak or no response to specific antigens, thus determining the large heterogeneity of immunological responses. In the last years, it is becoming clear that memory is not solely a feature of adaptive immunity, as it has been observed that also innate immune cells are provided with a sort of memory, dubbed “trained immunity.” In this review, we discuss the main characteristics of trained immunity as a possible contributor to inflammaging within the perspective of immunobiography, with particular attention to the phenotypic changes of the cell populations known to be involved in trained immunity. In conclusion, immunobiography emerges as a pervasive and comprehensive concept that could help in understanding and interpret the individual heterogeneity of immune responses (to infections and vaccinations) that becomes particularly evident at old age and could affect immunosenescence and inflammaging. PMID:28861086

Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression

PubMed Central

Muhammad, A.K.M. Ghulam; Candolfi, Marianela; King, Gwendalyn D.; Yagiz, Kader; Foulad, David; Mineharu, Yohei; Kroeger, Kurt M.; Treuer, Katherine A.; Nichols, W. Stephen; Sanderson, Nicholas S.; Yang, Jieping; Khayznikov, Maksim; Van Rooijen, Nico; Lowenstein, Pedro R.; Castro, Maria G.

2009-01-01

Purpose Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme. Experimental Design We developed a combined treatment using an adenovirus (Ad) expressing fms-like tyrosine kinase-3 ligand (Flt3L), which induces the infiltration of immune cells into the tumor microenvironment, and an Ad expressing herpes simplex virus-1–thymidine kinase (TK), which kills proliferating tumor cells in the presence of ganciclovir. Results This treatment induced immunological memory that led to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastoma multiforme implanted intradermally. Rechallenged long-term survivors exhibited anti-glioblastoma multiforme–specific T cells and displayed specific delayed-type hypersensitivity. Using depleting antibodies, we showed that rejection of the second tumor was dependent on CD8+ T cells. Circulating anti-glioma antibodies were observed when glioblastoma multiforme cells were implanted intradermally in naïve rats or in long-term survivors. However, rats bearing intracranial glioblastoma multiforme only exhibited circulating antitumoral antibodies upon treatment with Ad-Flt3L + Ad-TK. This combined treatment induced tumor regression and release of the chromatin-binding protein high mobility group box 1 in two further intracranial glioblastoma multiforme models, that is, Fisher rats bearing intracranial 9L and F98 glioblastoma multiforme cells. Conclusions Treatment with Ad-Flt3L + Ad-TK triggered systemic anti–glioblastoma multiforme cellular and humoral immune responses, and anti–glioblastoma multiforme immunological memory. Release of the chromatin-binding protein high mobility group box 1 could be used as a noninvasive biomarker of therapeutic efficacy for glioblastoma multiforme. The robust treatment efficacy lends further support to its implementation in a phase I clinical trial. PMID:19789315

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

PubMed

Vogel, N; Kirisits, M; Michael, E; Bach, H; Hostetter, M; Boyer, K; Simpson, R; Holfels, E; Hopkins, J; Mack, D; Mets, M B; Swisher, C N; Patel, D; Roizen, N; Stein, L; Stein, M; Withers, S; Mui, E; Egwuagu, C; Remington, J; Dorfman, R; McLeod, R

1996-11-01

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Chimeric antigen receptors: driving immunology towards synthetic biology

PubMed Central

Sadelain, Michel

2017-01-01

The advent of second generation CARs and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells, is being developed for clinical use in a wide range of cancers. Immunological principles are thus finding a new purpose thanks to advances in genetic engineering, synthetic biology and cell manufacturing sciences. PMID:27372731

The contribution of epigenetic memory to immunologic memory.

PubMed

Zediak, Valerie P; Wherry, E John; Berger, Shelley L

2011-04-01

Memory T lymphocytes are distinct from antigen-inexperienced naïve T cells in that memory T cells can respond more rapidly when they re-encounter a pathogen. Work over the past decade has begun to define the epigenetic underpinnings of the transcriptional component of the memory T cell response. An emerging theme is the persistence of an active chromatin signature at relevant gene loci in resting memory T cells, even when those genes are transcriptionally inactive. This gives strength to the concept of gene poising, and has shown that memory T lymphocytes are an ideal model in which to further define various mechanisms of epigenetic poising. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quantitative evaluation of learning and memory trace in studies of mnemotropic effects of immunotropic drugs.

PubMed

Kiseleva, N M; Novoseletskaya, A V; Voevodina, Ye B; Kozlov, I G; Inozemtsev, A N

2012-12-01

Apart from restoration of disordered immunological parameters, tactivin and derinat exhibit a pronounced effect on the higher integrative functions of the brain. Experiments on Wistar rats have shown that these drugs accelerated conditioning of food and defense responses. New methods for quantitative evaluation of memory trace consolidation are proposed.

Retrosplenial cortex is required for the retrieval of remote memory for auditory cues.

PubMed

Todd, Travis P; Mehlman, Max L; Keene, Christopher S; DeAngeli, Nicole E; Bucci, David J

2016-06-01

The restrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of the RSC to recently acquired auditory fear memories. Since neocortical regions have been implicated in the permanent storage of remote memories, we examined the contribution of the RSC to remotely acquired auditory fear memories. In Experiment 1, retrieval of a remotely acquired auditory fear memory was impaired when permanent lesions (either electrolytic or neurotoxic) were made several weeks after initial conditioning. In Experiment 2, using a chemogenetic approach, we observed impairments in the retrieval of remote memory for an auditory cue when the RSC was temporarily inactivated during testing. In Experiment 3, after injection of a retrograde tracer into the RSC, we observed labeled cells in primary and secondary auditory cortices, as well as the claustrum, indicating that the RSC receives direct projections from auditory regions. Overall our results indicate the RSC has a critical role in the retrieval of remotely acquired auditory fear memories, and we suggest this is related to the quality of the memory, with less precise memories being RSC dependent. © 2016 Todd et al.; Published by Cold Spring Harbor Laboratory Press.

Preserved antibody levels and loss of memory B cells against pneumococcus and tetanus after splenectomy: tailoring better vaccination strategies.

PubMed

Rosado, M Manuela; Gesualdo, Francesco; Marcellini, Valentina; Di Sabatino, Antonio; Corazza, Gino Roberto; Smacchia, Maria Paola; Nobili, Bruno; Baronci, Carlo; Russo, Lidia; Rossi, Francesca; Vito, Rita De; Nicolosi, Luciana; Inserra, Alessandro; Locatelli, Franco; Tozzi, Alberto E; Carsetti, Rita

2013-10-01

Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that pneumococcal conjugated vaccine administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Foxp3+ T cells inhibit antitumor immune memory modulated by mTOR inhibition.

PubMed

Wang, Yanping; Sparwasser, Tim; Figlin, Robert; Kim, Hyung L

2014-04-15

Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into naïve mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3-expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3(+) T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3(+) T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients. ©2014 AACR.

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence.

PubMed

Murray, Alexandra J; Kwon, Kyungyoon J; Farber, Donna L; Siliciano, Robert F

2016-07-15

Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus, ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4(+) T cells. In this review, we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. Copyright © 2016 by The American Association of Immunologists, Inc.

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence

PubMed Central

Murray, Alexandra J.; Kwon, Kyungyoon J.; Farber, Donna L.; Siliciano, Robert F.

2016-01-01

Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4+ T cells. Here we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. PMID:27382129

Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy.

PubMed

Abzug, Mark J; Qin, Min; Levin, Myron J; Fenton, Terence; Beeler, Judy A; Bellini, William J; Audet, Susette; Sowers, Sun Bae; Borkowsky, William; Nachman, Sharon A; Pelton, Stephen I; Rosenblatt, Howard M

2012-08-15

Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. NCT00013871 (www.clinicaltrials.gov).

Cognitive Rehabilitation of Episodic Memory Disorders: From Theory to Practice

PubMed Central

Ptak, Radek; der Linden, Martial Van; Schnider, Armin

2010-01-01

Memory disorders are among the most frequent and most debilitating cognitive impairments following acquired brain damage. Cognitive remediation strategies attempt to restore lost memory capacity, provide compensatory techniques or teach the use of external memory aids. Memory rehabilitation has strongly been influenced by memory theory, and the interaction between both has stimulated the development of techniques such as spaced retrieval, vanishing cues or errorless learning. These techniques partly rely on implicit memory and therefore enable even patients with dense amnesia to acquire new information. However, knowledge acquired in this way is often strongly domain-specific and inflexible. In addition, individual patients with amnesia respond differently to distinct interventions. The factors underlying these differences have not yet been identified. Behavioral management of memory failures therefore often relies on a careful description of environmental factors and measurement of associated behavioral disorders such as unawareness of memory failures. The current evidence suggests that patients with less severe disorders benefit from self-management techniques and mnemonics whereas rehabilitation of severely amnesic patients should focus on behavior management, the transmission of domain-specific knowledge through implicit memory processes and the compensation for memory deficits with memory aids. PMID:20700383

Profiles of HIV-infected anti-retroviral therapy naïve children from Mumbai, India.

PubMed

Paranjpe, Supriya Mayur; Sarkate, Purva Pankaj; Ingole, Nayana Avinash; Raut, Shweta Sadanand; Mehta, Preeti Rajeev

2016-11-01

This study aimed to investigate the demographic profiles of human immunodifficiency virus (HIV) infected anti-retroviral therapy (ART) naïve children in our hospital and their relations to the clinical, immunological and nutritional status. A cross-sectional study was conducted in an Integrated Counselling and Testing Center (ICTC) at a tertiary care hospital in Mumbai. ART naïve HIV positive children were enrolled in the study. The demographic profiles, clinical features, immunological (CD4%/CD4 count) and nutritional status of these children were recorded. The agreement between clinical, immunological and nutritional staging was determined using Cohen's kappa test. In 192 HIV-infected ART naive children enrolled with a median age of 9 years (range 3 months-14 years), 97.4% acquired infection through vertical transmission. The most common clinical presentation was fever (39.6 %), followed by generalized lymphadenopathy (32.3%), cough (22.4%) and diarrhoea (9.9%). Tuberculosis was seen in 22.9% of the children. The agreement was fair between clinical and immunological staging, and slight between nutritional, immunological and clinical staging. Perinatal transmission is the most common mode of acquiring HIV infection in children. The Prevention of Parent to Child Transmission (PPTCT) program should be strengthened for lowering the transmission rate by providing extended ART to mothers during pregnancy and breast-feeding. Tuberculosis remains a major concern in HIV-infected children. The poor correlation between WHO clinical and immunological staging emphasizes the importance of making CD4 facilities available in HIV prevalent areas. Malnutrition cannot be used as a surrogate marker for predicting stage or severity as it is common at all stages of HIV disease.

The Effects of Previously Acquired Knowledge on Memory for Textual Information.

ERIC Educational Resources Information Center

Byrd, Mark

1987-01-01

Presented series of biographical passages to young and older adults to examine how semantic memory store of previously acquired knowledge affects ability to retain textual information. Older adults had difficulty in delayed, but not in immediate, recognition condition. Suggests that as older adults' episodic memory deteriorated, they could not…

Exposure of FVIII in the Presence of Phosphatidyl Serine Reduces Generation of Memory B-Cells and Induces Regulatory T-Cell-Mediated Hyporesponsiveness in Hemophilia A Mice.

PubMed

Ramakrishnan, Radha; Davidowitz, Andrew; Balu-Iyer, Sathy V

2015-08-01

A major complication of replacement therapy with Factor VIII (FVIII) for hemophilia A (HA) is the development of unwanted immune responses. Previous studies showed that administration of FVIII in the presence of phosphatidyl serine (PS) reduced the development of anti-FVIII antibodies in HA mice. However, the impact of PS-mediated effects on immunological memory, such as generation of memory B-cells, is not clear. The effect of PS on memory B-cells was therefore investigated using adoptive transfer approach in FVIII(-/-) HA mice. Adoptive transfer of memory B-cells from a PS-FVIII-treated group to naïve mice followed by challenge of the recipient mice with FVIII showed a significantly reduced anti-FVIII antibody response in the recipient mice, compared with animals that received memory B-cells from free FVIII and FVIII-charge matched phosphatidyl glycerol (PG) group. The decrease in memory B-cell response is accompanied by an increase in FoxP3 expressing regulatory T-cells (Tregs). Flow cytometry studies showed that the generation of Tregs is higher in PS-treated animals as compared with FVIII and FVIII-PG treated animals. The PS-mediated hyporesponsiveness was found to be antigen-specific. The PS-FVIII immunization showed hyporesponsiveness toward FVIII rechallenge but not against ovalbumin (OVA) rechallenge, an unrelated antigen. This demonstrates that PS reduces immunologic memory of FVIII and induces antigen-specific peripheral tolerance in HA mice. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Human IgG2- and IgG4-expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age.

PubMed

de Jong, Britt G; IJspeert, Hanna; Marques, Lemelinda; van der Burg, Mirjam; van Dongen, Jacques Jm; Loos, Bruno G; van Zelm, Menno C

2017-10-01

The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass-specific antibodies was performed on purified IgG + memory B-cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream-located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27 + IgG + memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27 - IgG + memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2-expressing B cells as markers for efficient generation of memory responses.

Pharmacologic Induction of CD8+ T Cell Memory: Better Living Through Chemistry

PubMed Central

Gattinoni, Luca; Klebanoff, Christopher A.; Restifo, Nicholas P.

2011-01-01

The generation of a robust population of memory T cells is critical for effective vaccine and cell-based therapies to prevent and treat infectious diseases and cancer. A series of recent papers have established a new, cell-intrinsic approach in which small molecules target key metabolic and developmental pathways to enhance the formation and maintenance of highly functional CD8+ memory T cells. These findings raise the exciting new possibility of using small molecules, many of which are already approved for human use, for the pharmacologic induction of immunologic memory. PMID:20371454

Immune memory: the basics and how to trigger an efficient long-term immune memory.

PubMed

Beverley, P C L

2010-01-01

Immunological memory consists of expanded clones of T and B lymphocytes that show an increased rate of cell division and shortened telomeres compared with naïve cells. However, exhaustion of clones is delayed by kinetic heterogeneity within clones and altered survival and up-regulation of telomerase. Prolonged maintenance of protective B-cell immunity is T-cell dependent and requires a balance between plasma cells and memory B cells. Protective T-cell immunity also requires correct quality of T cells and that they are located appropriately. Copyright 2009 Elsevier Ltd. All rights reserved.

Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexaenoic acid-rich fish oil from 8 to 52 weeks of age.

PubMed

Zicker, Steven C; Jewell, Dennis E; Yamka, Ryan M; Milgram, Norton W

2012-09-01

To assess effects of foods fortified with docosahexaenoic acid (DHA)-rich fish oil on cognitive, memory, psychomotor, immunologic, and retinal function and other measures of development in healthy puppies. Evaluation study. 48 Beagle puppies. Puppies were assigned to 3 groups after weaning (n = 16/group) and received 1 of 3 foods (low-DHA, moderate-DHA, or high-DHA food) as their sole source of nutrition until 1 year of age. Visual discrimination learning and memory tasks, psychomotor performance tasks, and physiologic tests including blood and serum analysis, electroretinography, and dual-energy x-ray absorptiometry were performed at various time points. Anti-rabies virus antibody titers were evaluated 1, 2, 4, and 8 weeks after vaccination at 16 weeks of age. Foods had similar proximate analysis results but varied in concentration of DHA from fish oil; the high-DHA food also contained higher concentrations of vitamin E, taurine, choline, and l-carnitine than did other foods. The high-DHA group had significantly better results for reversal task learning, visual contrast discrimination, and early psychomotor performance in side-to-side navigation through an obstacle-containing maze than did the moderate-DHA and low-DHA groups. The high-DHA group had significantly higher anti-rabies antibody titers 1 and 2 weeks after vaccination than did other groups. Peak b-wave amplitudes during scotopic electroretinography were positively correlated with serum DHA concentrations at all evaluated time points. Dietary fortification with fish oils rich in DHA and possibly other nutrients implicated in neurocognitive development following weaning improved cognitive, memory, psychomotor, immunologic, and retinal functions in growing dogs.

Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system.

PubMed

Alexander, Tobias; Thiel, Andreas; Rosen, Oliver; Massenkeil, Gero; Sattler, Arne; Kohler, Siegfried; Mei, Henrik; Radtke, Hartmut; Gromnica-Ihle, Erika; Burmester, Gerd-Rüdiger; Arnold, Renate; Radbruch, Andreas; Hiepe, Falk

2009-01-01

Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE.

Sleep Shelters Verbal Memory from Different Kinds of Interference

PubMed Central

Sheth, Bhavin R.; Varghese, Reni; Truong, Thuy

2012-01-01

Study Objectives: Studies have shown that sleep shelters old verbal memories from associative interference arising from new, more recently acquired memories. Our objective is to extend the forms of interference for which sleep provides a sheltering benefit to non-associative and prospective interference, and to examine experimental conditions and memory strengths for which sleep before or after learning particularly affects verbal memory consolidation. Design: Acquiring paired word associates, retention across intervening sleep and wake, training on new, interfering word associates, and test recall of both sets. Setting: University laboratory. Participants: Healthy volunteers. Interventions: N/A. Measurements and Results: Comparing recall before and after intervening periods of sleep versus wake, we found that: (i) Sleep preferentially shields weakly encoded verbal memories from retroactive interference. (ii) Sleep immediately following learning helps shelter memory from associative and non-associative forms of retroactive interference. (iii) Sleep protects new verbal memories from prospective interference. (iv) Word associations acquired for the first time in the evening after a day spent in the wake state are encoded more strongly than word associations acquired in the morning following a night of sleep. Conclusions: The findings extend the known sleep protection from interference to non-associative as well as prospective interference, and limit the protection to weakly encoded word associations. Combined, our results suggest that sleep immediately after verbal learning isolates newly formed memory traces and renders them inaccessible, except by specific contextual cues. Memory isolation in sleep is a passive mechanism that can reasonably account for several experimental findings. Citation: Sheth BR; Varghese R; Truong T. Sleep shelters verbal memory from different kinds of interference. SLEEP 2012;35(7):985-996. PMID:22754045

The PHA Test Reflects Acquired T-Cell Mediated Immunocompetence in Birds

PubMed Central

Tella, José L.; Lemus, Jesús A.; Carrete, Martina; Blanco, Guillermo

2008-01-01

Background cological immunology requires techniques to reliably measure immunocompetence in wild vertebrates. The PHA-skin test, involving subcutaneous injection of a mitogen (phytohemagglutinin, PHA) and measurement of subsequent swelling as a surrogate of T-cell mediated immunocompetence, has been the test of choice due to its practicality and ease of use in the field. However, mechanisms involved in local immunological and inflammatory processes provoked by PHA are poorly known, and its use and interpretation as an acquired immune response is currently debated. Methodology Here, we present experimental work using a variety of parrot species, to ascertain whether PHA exposure produces larger secondary than primary responses as expected if the test reflects acquired immunocompetence. Moreover, we simultaneously quantified T-lymphocyte subsets (CD4+, CD5+ and CD8+) and plasma proteins circulating in the bloodstream, potentially involved in the immunological and inflammatory processes, through flow cytometry and electrophoresis. Principal Findings Our results showed stronger responses after a second PHA injection, independent of species, time elapsed and changes in body mass of birds between first and second injections, thus supporting the adaptive nature of this immune response. Furthermore, the concomitant changes in the plasma concentrations of T-lymphocyte subsets and globulins indicate a causal link between the activation of the T-cell mediated immune system and local tissue swelling. Conclusions/Significance These findings justify the widespread use of the PHA-skin test as a reliable evaluator of acquired T-cell mediated immunocompetence in diverse biological disciplines. Further experimental research should be aimed at evaluating the relative role of innate immunocompetence in wild conditions, where the access to dietary proteins varies more than in captivity, and to ascertain how PHA responses relate to particular host-parasite interactions. PMID:18820730

Immunologic Approaches for the Treatment of Multiple Myeloma

PubMed Central

Rasche, Leo; Weinhold, Niels; Morgan, Gareth J; van Rhee, Frits; Davies, Faith E

2017-01-01

The FDA approval of two monoclonal antibodies in 2015 has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, ‘off-target’ immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies. We also describe some of the limitations of the current strategies and speculate on the future of personalized immunotherapies for MM. PMID:28431262

Hematology and immunology studies

NASA Technical Reports Server (NTRS)

Kimzey, S. L.; Fischer, C. L.; Johnson, P. C.; Ritzmann, S. E.; Mengel, C. E.

1975-01-01

The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.

Does attitude acquisition in evaluative conditioning without explicit CS-US memory reflect implicit misattribution of affect?

PubMed

Mierop, Adrien; Hütter, Mandy; Stahl, Christoph; Corneille, Olivier

2018-02-05

Research that dissociates different types of processes within a given task using a processing tree approach suggests that attitudes may be acquired through evaluative conditioning in the absence of explicit encoding of CS-US pairings in memory. This research distinguishes explicit memory for the CS-US pairings from CS-liking acquired without encoding of CS-US pairs in explicit memory. It has been suggested that the latter effect may be due to an implicit misattribution process that is assumed to operate when US evocativeness is low. In the present research, the latter assumption was supported neither by two high-powered experiments nor by complementary meta-analytic evidence, whereas evocativeness exerted an influence on explicit memory. This pattern of findings is inconsistent with the view that CS-liking acquired without encoding of CS-US pairs in explicit memory reflects an implicit misattribution process at learning. Hence, the underlying learning process is awaiting further empirical scrutiny.

The neurobiology of the human memory.

PubMed

Fietta, Pierluigi; Fietta, Pieranna

2011-01-01

Memory can be defined as the ability to acquire, process, store, and retrieve information. Memory is indispensable for learning, adaptation, and survival of every living organism. In humans, the remembering process has acquired great flexibility and complexity, reaching close links with other mental functions, such as thinking and emotions. Changes in synaptic connectivity and interactions among multiple neural networks provide the neurobiological substrates for memory encoding, retention, and consolidation. Memory may be categorized as short-term and long-term memory (according to the storage temporal duration), as implicit and explicit memory (with respect to the consciousness of remembering), as declarative (knowing that [fact]) and procedural (knowing how [skill]) memory, or as sensory (echoic, iconic and haptil), semantic, and episodic memory (according to the various remembering domains). Significant advances have been obtained in understanding memory neurobiology, but much remains to be learned in its cognitive, psychological, and phenomenological aspects.

Immunometabolic circuits in trained immunity.

PubMed

Arts, Rob J W; Joosten, Leo A B; Netea, Mihai G

2016-10-01

The classical view that only adaptive immunity can build immunological memory has recently been challenged. Both in organisms lacking adaptive immunity as well as in mammals, the innate immune system can adapt to mount an increased resistance to reinfection, a de facto innate immune memory termed trained immunity. Recent studies have revealed that rewiring of cellular metabolism induced by different immunological signals is a crucial step for determining the epigenetic changes underlying trained immunity. Processes such as a shift of glucose metabolism from oxidative phosphorylation to aerobic glycolysis, increased glutamine metabolism and cholesterol synthesis, play a crucial role in these processes. The discovery of trained immunity opens the door for the design of novel generations of vaccines, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lessons learned at the intersection of immunology and neuroscience.

PubMed

Steinman, Lawrence

2012-04-01

Neurobiologists and immunologists study concepts often signified with identical terminology. Scientists in both fields study a structure known as the synapse, and each group analyzes a subject called memory. Is this a quirk of human language, or are there real similarities between these two physiological systems? Not only are the linguistic concepts expressed in the words "synapse" and "memory" shared between the fields, but the actual molecules of physiologic importance in one system play parallel roles in the other: complement, the major histocompatibility molecules, and even "neuro"-transmitters all have major impacts on health and on disease in both the brain and the immune system. Not only are the same molecules found in diverse roles in each system, but we have learned that there is real "hard-wired" crosstalk between nerves and lymphoid organs. This issue of the JCI highlights some of the lessons learned from experts who are working at this scintillating intersection between immunology and neuroscience.

Immunologic memory in cutaneous leishmaniasis.

PubMed

Scott, Phillip

2005-12-01

Leishmania major infections induce solid immunity to reinfection. Experimental studies in mice indicate that the CD4+ T cells responsible for this immunity include two populations: parasite-dependent T effector cells and parasite-independent central memory T (Tcm) cells. While there currently is no vaccine for leishmaniasis, the existence of a long-lived population of Tcm cells that does not require the continued presence of live parasites suggests that a vaccine that expands these cells might be efficacious.

Immunogenicity, Immunologic Memory, and Safety Following Measles Revaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

PubMed Central

Abzug, Mark J.; Qin, Min; Levin, Myron J.; Fenton, Terence; Beeler, Judy A.; Bellini, William J.; Audet, Susette; Sowers, Sun Bae; Borkowsky, William; Nachman, Sharon A.; Pelton, Stephen I.; Rosenblatt, Howard M.

2012-01-01

Background. Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)–infected children in the absence of highly active antiretroviral therapy (HAART). Methods. HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30 000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4–5 years later, and PRN antibody was measured before and 7 and 28 days later. Results. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4–5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Conclusions. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. Clinical Trials Registration: NCT00013871 (www.clinicaltrials.gov). PMID:22693229

Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory.

PubMed

Zhuang, Gui-Hua; Yan, Hong; Wang, Xue-Liang; Hwang, Lu-Yu; Wu, Qian; Wang, Li-Rong; Gao, Hai-Yan

2006-03-15

To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 microg per dose) or intradermal (2 microg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs>or=10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection (P=0.075). By the end of follow-up, a booster dose (5 microg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.

Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants.

PubMed

Knuf, Markus; Pankow-Culot, Heidemarie; Grunert, Detlef; Rapp, Michael; Panzer, Falko; Köllges, Ralph; Fanic, Aurélie; Habib, Ahsan; Borys, Dorota; Dieussaert, Ilse; Schuerman, Lode

2012-01-01

Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

The importance of antineuraminidase antibodies in resistance to influenza A and immunologic memory for their synthesis.

PubMed Central

Naikhin, A. N.; Tsaritsina, I. M.; Oleinikova, E. V.; Syrodoeva, L. G.; Korchanova, N. L.; Denisov, G. M.; Shvartsman YaS

1983-01-01

Eight hundred and seventy-seven sera from 360 adults aged 18-50 who were under permanent observation from October 1980 to March 1981 have been studied by haemagglutination-inhibition (HI) and erythrocyte elution-inhibition (EI) tests--a simplified method of antineuraminidase antibody titration. It was demonstrated in some subjects infected with influenza A H1N1 and H3N2 viruses that the antibody rise was to one of the surface antigens only--haemagglutinin or neuraminidase. These subjects made up 5.2-25.8% of all examinees. The protective effect of antibodies to neuraminidase was similar to that of antihaemagglutinins. Interaction of both types of antibodies was observed in protection against the disease. Data have been obtained on the influence of antineuraminidase antibodies in decreasing the severity of natural infection with influenza A. A study of heterologous immunologic responses to haemagglutinin and neuraminidase among persons immunized with live influenza A H1N1 and H3N2 vaccines and among children naturally infected with influenza A H3N2 demonstrated the presence of immunologic memory for antineuraminidase antibody synthesis. Thus, the suggestion of a common antigenic structure for neuraminidase N1 and N2 is made. PMID:6886409

[Immune system and influenza virus].

PubMed

Wierzbicka-Woś, Anna; Tokarz-Deptuła, Beata; Deptuła, Wiesław

2015-02-15

Influenza viruses are a significant cause of respiratory infections, causing 3-5 million clinical infections and 250-500 thousand deaths per year. Infections caused by the influenza virus induce a host immune response at the non-specific and specific level (defined as natural and acquired), which leads to limitation of virus replication. Moreover the elements of immunological memory are induced so that they can protect against subsequent infection by the influenza virus. However, there is still no effective way for the total elimination of this virus, and the only effective method to combat this pathogen appears to be vaccination, which through immune system activation greatly limits its spread. The present paper presents the immune reaction at different levels in response to the influenza virus after entering the body and the mechanisms of the influenza virus for avoiding reactions of the immune system, which correspond to its high variability at the molecular level. Moreover, in this paper we describe various methods of stimulating the organism's immune systems with different generations of vaccines and their effectiveness in the fight against this pathogen.

Frames of Reference in Spatial Memories Acquired From Language

ERIC Educational Resources Information Center

Mou, Weimin; Zhang, Kan; McNamara, Timothy P.

2004-01-01

Four experiments examined reference systems in spatial memories acquired from language. Participants read narratives that located 4 objects in canonical (front, back, left, right) or noncanonical (left front, right front, left back, right back) positions around them. Participants' focus of attention was first set on each of the 4 objects, and then…

Years in Cologne.

PubMed

Rajewsky, Klaus

2013-01-01

This review describes the building and scientific activity of the Immunology Department at the Institute for Genetics in Cologne, cofounded by Max Delbrück in post-World War II Germany. The protagonist, a child of Russian emigrants, became interested in antibodies as a postdoc at the Pasteur Institute in Paris and a proponent of the antigen-bridge model of T-B cell collaboration during his early time in Cologne. He was challenged by the gap between cellular immunology and molecular genetics and profited from the advances of the latter as well as postwar economic growth in Germany. The Immunology Department became a place, and little universe in itself, where young scientists from all over the world came together to study cellular and molecular mechanisms of antibody formation. This included work on normal and malignant B cells in the human, particularly the origin of Hodgkin lymphoma, but the main focus was on B cell development and homeostasis, the germinal center reaction, and immunological memory, developing recombinase-assisted and conditional gene targeting in mice as a main technical tool.

Evolution of immune systems from self/not self to danger to artificial immune systems (AIS).

PubMed

Cooper, Edwin L

2010-03-01

This review will examine the evolution of immune mechanisms by emphasizing information from animal groups exclusive of all vertebrates. There will be a focus on concepts that propelled the immune system into prominent discourse in the life sciences. The self/not self hypothesis was crucial and so was the concern for immunologic memory or anamnesia, development of cancer, autoimmunity, and clonal selection. Now we may be able to deconstruct clonal selection since it is not applicable in the sense that it is not applicable to invertebrate mechanisms. Clonal selection seems to be purely as all evidence indicates a vertebrate strategy and therefore irrelevant to invertebrates. Some views may insist that anthropocentric mammalian immunologists utilized a tool to propel: the universal innate immune system of ubiquitous and plentiful invertebrates as an essential system for vertebrates. This was advantageous for all immunology; moreover innate immunity acquired an extended raison d'être. Innate immunity should help if there would be a failure of the adaptive immune system. Still to be answered are questions concerning immunologic surveillance that includes clonal selection. We can then ask does immunologic surveillance play a role in the survival of invertebrates that most universally seem to not develop cancer of vertebrates especially mammals; invertebrates only develop benign tumor. A recent proposal concerns an alternative explanation that is all embracing. Danger hypothesis operates in striking contrast to the self/not self hypothesis. This view holds that the immune system is adapted to intervene not because self is threatened but because of the system's sense of danger. This perception occurs by means of signals other than recognition of microbial pattern recognition molecules characteristic of invertebrates. Response to danger may be another way of analyzing innate immunity that does not trigger the production of clones and therefore does not rely entirely on the self/not self model. The review will end with certain perspectives on artificial immune systems new on the scene and the product of computational immunologists. The tentative view is to question if the immune systems of invertebrates might be amenable to such an analysis? This would offer more credence to the innate system, often pushed aside thus favoring the adaptive responses.

Evolution of immune systems from self/not self to danger to artificial immune systems (AIS)

NASA Astrophysics Data System (ADS)

Cooper, Edwin L.

2010-03-01

This review will examine the evolution of immune mechanisms by emphasizing information from animal groups exclusive of all vertebrates. There will be a focus on concepts that propelled the immune system into prominent discourse in the life sciences. The self/not self hypothesis was crucial and so was the concern for immunologic memory or anamnesia, development of cancer, autoimmunity, and clonal selection. Now we may be able to deconstruct clonal selection since it is not applicable in the sense that it is not applicable to invertebrate mechanisms. Clonal selection seems to be purely as all evidence indicates a vertebrate strategy and therefore irrelevant to invertebrates. Some views may insist that anthropocentric mammalian immunologists utilized a tool to propel: the universal innate immune system of ubiquitous and plentiful invertebrates as an essential system for vertebrates. This was advantageous for all immunology; moreover innate immunity acquired an extended raison d'être. Innate immunity should help if there would be a failure of the adaptive immune system. Still to be answered are questions concerning immunologic surveillance that includes clonal selection. We can then ask does immunologic surveillance play a role in the survival of invertebrates that most universally seem to not develop cancer of vertebrates especially mammals; invertebrates only develop benign tumor. A recent proposal concerns an alternative explanation that is all embracing. Danger hypothesis operates in striking contrast to the self/not self hypothesis. This view holds that the immune system is adapted to intervene not because self is threatened but because of the system's sense of danger. This perception occurs by means of signals other than recognition of microbial pattern recognition molecules characteristic of invertebrates. Response to danger may be another way of analyzing innate immunity that does not trigger the production of clones and therefore does not rely entirely on the self/not self model. The review will end with certain perspectives on artificial immune systems new on the scene and the product of computational immunologists. The tentative view is to question if the immune systems of invertebrates might be amenable to such an analysis? This would offer more credence to the innate system, often pushed aside thus favoring the adaptive responses.

Can Interactive Working Memory Training Improve Learning?

ERIC Educational Resources Information Center

Alloway, Tracy

2012-01-01

Background: Working memory is linked to learning outcomes and there is emerging evidence that training working memory can yield gains in working memory and fluid intelligence. Aims: The aim of the present study was to investigate whether interactive working memory training would transfer to acquired cognitive skills, such as vocabulary and…

The top ten clues to understand the origin of chronic lymphocytic leukemia (CLL).

PubMed

García-Muñoz, Ricardo; Feliu, Jesús; Llorente, Luis

2015-01-01

The fundamental task of the immune system is to protect the individual from infectious organisms without serious injury to self. The essence of acquired immunity is molecular self/non self discrimination. Chronic lymphocytic leukemia is characterized by a global failure of immune system that begins with the failure of immunological tolerance mechanisms (autoimmunity) and finish with the incapacity to response to non-self antigens (immunodeficiency). Immunological tolerance mechanisms are involved in chronic lymphocytic leukemia (CLL) development. During B cell development some self-reactive B cells acquire a special BCR that recognize their own BCR. This self-autoantibody-self BCR interaction promotes survival, differentiation and proliferation of self-reactive B cells. Continuous self-autoantibody-self BCR interaction cross-linking induces an increased rate of surface BCR elimination, CD5+ expression, receptor editing and anergy. Unfortunately, some times this mechanisms increase genomic instability and promote additional genetic damage that immortalize self-reactive B cells and convert them into CLL like clones with the capability of clonal evolution and transformed CLL B cells. This review summarizes the immunological effects of continuous self-autoantibody-self BCR interaction cross-linking in the surface of self-reactive B cells and their role in CLL development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory

PubMed Central

Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn

2005-01-01

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory. PMID:16011544

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

PubMed

Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn

2005-07-01

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during tuberculosis.

PubMed

Carpenter, Stephen M; Yang, Jason D; Lee, Jinhee; Barreira-Silva, Palmira; Behar, Samuel M

2017-11-01

Immunological memory is the key biological process that makes vaccines possible. Although tuberculosis vaccines elicit protective immunity in animals, few provide durable protection. To understand why protection is transient, we evaluated the ability of memory CD4+ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naïve and memory CD4+ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. However, later during infection, memory CD4+ T cell proliferation was curtailed and no protection was observed. We show that memory CD4+ T cells are first activated in the LN and their recruitment to the lung attenuates bacterial growth. However, their interaction with Mtb-infected macrophages does not promote continued proliferation. We conclude that a lack of sustained expansion by memory-derived T cells in the lung limits the durability of their protection, linking their slower expansion with transient protection in vaccinated mice.

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection.

PubMed

Han, Seong-Ji; Glatman Zaretsky, Arielle; Andrade-Oliveira, Vinicius; Collins, Nicholas; Dzutsev, Amiran; Shaik, Jahangheer; Morais da Fonseca, Denise; Harrison, Oliver J; Tamoutounour, Samira; Byrd, Allyson L; Smelkinson, Margery; Bouladoux, Nicolas; Bliska, James B; Brenchley, Jason M; Brodsky, Igor E; Belkaid, Yasmine

2017-12-19

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory. Published by Elsevier Inc.

p300/CBP Histone Acetyltransferase Activity Is Required for Newly Acquired and Reactivated Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

Maddox, Stephanie A.; Watts, Casey S.; Schafe, Glenn E.

2013-01-01

Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation.…

Antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: Results from 2 long-term follow-up studies

PubMed Central

Wysocki, Jacek; Brzostek, Jerzy; Konior, Ryszard; Panzer, Falko G.; François, Nancy A.; Ravula, Sudheer M.; Kolhe, Devayani A.; Song, Yue; Dieussaert, Ilse; Schuerman, Lode; Borys, Dorota

2017-01-01

ABSTRACT To investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (NCT00624819 – Study A) and 5 years (NCT00891176 – Study B) post-booster vaccination. In Study A, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with PHiD-CV, or primed with the 7-valent pneumococcal conjugate vaccine (7vCRM) and boosted with either PHiD-CV or 7vCRM. In Study B, PHiD-CV was co-administered with meningococcal vaccines, and pneumococcal antibody persistence was measured 2, 3 and 5 years post-booster. An age-matched control group, unvaccinated against Streptococcus pneumoniae, was enrolled in Study A, allowing assessment of immunologic memory by administration of one dose of PHiD-CV to both primed (4 years post-booster) and unprimed 6-year-old children. Four years post-booster (Study A), antibody concentrations and opsonophagocytic activity (OPA) titers remained higher compared to the pre-booster timepoint, with no major differences between the 3 primed groups. Antibody persistence was also observed in Study B, with minimal differences between groups. The additional PHiD-CV dose administered 4 years post-booster in Study A elicited more robust immune responses in primed children than in unprimed children. Long-term serotype-specific antibody persistence and robust immunologic memory responses observed in these 2 studies suggest induction of long-term protection against pneumococcal disease after PHiD-CV vaccination. PMID:27736293

Antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: Results from 2 long-term follow-up studies.

PubMed

Wysocki, Jacek; Brzostek, Jerzy; Konior, Ryszard; Panzer, Falko G; François, Nancy A; Ravula, Sudheer M; Kolhe, Devayani A; Song, Yue; Dieussaert, Ilse; Schuerman, Lode; Borys, Dorota

2017-03-04

To investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (NCT00624819 - Study A) and 5 years (NCT00891176 - Study B) post-booster vaccination. In Study A, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with PHiD-CV, or primed with the 7-valent pneumococcal conjugate vaccine (7vCRM) and boosted with either PHiD-CV or 7vCRM. In Study B, PHiD-CV was co-administered with meningococcal vaccines, and pneumococcal antibody persistence was measured 2, 3 and 5 years post-booster. An age-matched control group, unvaccinated against Streptococcus pneumoniae, was enrolled in Study A, allowing assessment of immunologic memory by administration of one dose of PHiD-CV to both primed (4 years post-booster) and unprimed 6-year-old children. Four years post-booster (Study A), antibody concentrations and opsonophagocytic activity (OPA) titers remained higher compared to the pre-booster timepoint, with no major differences between the 3 primed groups. Antibody persistence was also observed in Study B, with minimal differences between groups. The additional PHiD-CV dose administered 4 years post-booster in Study A elicited more robust immune responses in primed children than in unprimed children. Long-term serotype-specific antibody persistence and robust immunologic memory responses observed in these 2 studies suggest induction of long-term protection against pneumococcal disease after PHiD-CV vaccination.

Original antigenic sin: A comprehensive review.

PubMed

Vatti, Anup; Monsalve, Diana M; Pacheco, Yovana; Chang, Christopher; Anaya, Juan-Manuel; Gershwin, M Eric

2017-09-01

The concept of "original antigenic sin" was first proposed by Thomas Francis, Jr. in 1960. This phenomenon has the potential to rewrite what we understand about how the immune system responds to infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been demonstrated to occur in several infectious diseases in both animals and humans, including human influenza infection and dengue fever. The basis of "original antigenic sin" requires immunological memory, and our immune system ability to autocorrect. In the context of viral infections, it is expected that if we are exposed to a native strain of a pathogen, we should be able to mount a secondary immune response on subsequent exposure to the same pathogen. "Original antigenic sin" will not contradict this well-established immunological process, as long as the subsequent infectious antigen is identical to the original one. But "original antigenic sin" implies that when the epitope varies slightly, then the immune system relies on memory of the earlier infection, rather than mount another primary or secondary response to the new epitope which would allow faster and stronger responses. The result is that the immunological response may be inadequate against the new strain, because the immune system does not adapt and instead relies on its memory to mount a response. In the case of vaccines, if we only immunize to a single strain or epitope, and if that strain/epitope changes over time, then the immune system is unable to mount an accurate secondary response. In addition, depending of the first viral exposure the secondary immune response can result in an antibody-dependent enhancement of the disease or at the opposite, it could induce anergy. Both of them triggering loss of pathogen control and inducing aberrant clinical consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Humoral and cell-mediated immune responses after a booster dose of HBV vaccine in HIV-infected children, adolescents and young adults.

PubMed

Giacomet, Vania; Masetti, Michela; Nannini, Pilar; Forlanini, Federica; Clerici, Mario; Zuccotti, Gian Vincenzo; Trabattoni, Daria

2018-01-01

HBV vaccine induces protective antibodies only in 23-56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth. 53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response. All patients received a booster dose of HBV vaccine (HBVAXPRO 10 μg i.m.). HBV-specific Ab titer, viral load and CD4+ T cells were measured at baseline (T0), T1, T6 and T12 months. In a subgroup of 16 patients HBV-specific cell mediated immune responses were evaluated at baseline, at T1 and T6. The booster dose induced seroconversion in 51% of patients at T1, 57% at T6, and49% at T12; seroconversion rate was significantly correlated with CD4+T cells at T0 and to the CD4 nadir. The booster dose induced HBV-specific cell mediated immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV-specific TNFα-, IFNγ-, granzyme secreting CD8+ T cells and IL2-secreting CD4+ T cells were significantly increased in Rs compared to T0. In Non Responders (NRs), HBV-specific IL2-secreting CD4+ T cells, Central and Effector Memory CD8+ T cells were the only parameters modified at T6. Seroconversion induced by a booster dose of vaccine correlates with the development of T cell immunological memory in HIV-infected patients who did not respond to the standard immunization. Alternate immunization schedules need to be considered in NRs.

Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

PubMed

Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

2009-03-01

To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1 infected, Treatment-Naïve Subjects

PubMed Central

Skowron, Gail; Spritzler, John G.; Weidler, Jodi; Robbins, Gregory K.; Johnson, Victoria A.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Lie, Yolanda; Bates, Michael; Pollard, Richard B.

2012-01-01

Objectives To evaluate the association between baseline (BL) replication capacity (RC) [RCBL] and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1 infected subjects initiating antiretroviral therapy. Methods RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naïve subjects from ACTG384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Results Higher RCBL was associated with lower baseline CD4 (CD4BL) (r=−0.23, p<0.0001), higher baseline HIV-1 (RNABL) (r=0.25, p<0.0001), higher CD4BL activation percent (r=0.23, p<0.0001) and lower CD4BL memory count (r=−0.21, p=0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL naive percent (p=0.004, p=0.015, respectively). The interaction between CD4BL and RCBL was significant (p=0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL, and a negative association at lower absCD4BL. Conclusions At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different baseline CD4 counts. PMID:19194319

Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru

ClinicalTrials.gov

2015-12-10

HIV Infections; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

The Role of Costimulatory Molecules in the Development of Memory and Effector T Helper 2 Cells During an in vivo Immune Response to the Murine Gastrointestinal Parasite Heligmosomoides polygyrus

DTIC Science & Technology

2002-09-24

immunotherapies which manipulate the development of immunological memory. 96 BIBLIOGRAPHY 1. Intestinal Parasites [Internet]. World Health...Seed, and M. B. Kightlinger. 1995. The epidemiology of Ascaris lumbricoides, Trichuris trichiura, and hookworm in children in the Ranomafana...Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour

Identification and immunological characterization of the ligand domain of Plasmodium vivax reticulocyte binding protein 1a.

PubMed

Ntumngia, Francis B; Thomson-Luque, Richard; Galusic, Sandra; Frato, Gabriel; Frischmann, Sarah; Peabody, David S; Chackerian, Bryce; Ferreira, Marcelo U; King, Christopher L; Adams, John H

2018-05-07

Erythrocyte invasion by malaria parasites is essential for blood-stage development. Consequently, parasite proteins critically involved in erythrocyte invasion such as the Plasmodium vivax reticulocyte-binding proteins (RBPs) that mediate preferential invasion of reticulocytes are considered potential vaccine targets. Thus, targeting the RBPs could prevent blood-stage infection and disease. The RBPs are large and little is known about their functional domains and whether individuals naturally exposed to P. vivax acquire binding-inhibitory antibodies to these critical binding regions. This study aims at functionally and immunologically characterize Plasmodium vivax RBP1a. Recombinant proteins of overlapping fragments of RBP1a were used to determine binding specificity to erythrocytes and immunogenicity in laboratory animals. Naturally-acquired antibody response to these proteins was evaluated using serum samples from individuals in endemic regions. The N-terminal extracellular region, RBP1157-650 (RBP1:F8) was determined to bind both reticulocytes and normocytes, with a preference for immature reticulocytes. Antibodies elicited against rRBP1:F8 blocked RBP1:F8-erythrocyte binding. Naturally-acquired anti-RBP1 binding-inhibitory antibodies were detected in serum of P. vivax exposed-individuals from Papua New Guinea and Brazil. Recombinant RBP1:F8 binds human erythrocytes, elicits artificially-induced functional blocking antibodies and is a target of naturally acquired binding-inhibitory antibodies.

Immunology for physicists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perelson, A.S.; Weisbuch, G.

1997-10-01

The immune system is a complex system of cells and molecules that can provide us with a basic defense against pathogenic organisms. Like the nervous system, the immune system performs pattern recognition tasks, learns, and retains a memory of the antigens that it has fought. The immune system contains more than 10{sup 7} different clones of cells that communicate via cell-cell contact and the secretion of molecules. Performing complex tasks such as learning and memory involves cooperation among large numbers of components of the immune system and hence there is interest in using methods and concepts from statistical physics. Furthermore,more » the immune response develops in time and the description of its time evolution is an interesting problem in dynamical systems. In this paper, the authors provide a brief introduction to the biology of the immune system and discuss a number of immunological problems in which the use of physical concepts and mathematical methods has increased our understanding. {copyright} {ital 1997} {ital The American Physical Society}« less

ENHANCEMENT OF ANTIBODY SYNTHESIS BY 6-MERCAPTOPURINE

PubMed Central

Chanmougan, Devendrathan; Schwartz, Robert S.

1966-01-01

The administration of 6-MP to rabbits led to either suppression or enhancement of antibody production, depending on when the drug was given in relation to the antigenic challenge. Maximum enhancement of antibody synthesis was found when a small dose of BGG was administered 5 days after the last dose of a 1 wk course of 6-MP. There were no indications that the macrophage system or immunological memory was affected in animals with augmented antibody synthesis. It was proposed that enhancement of antibody production by 6-MP was due to nucleic acids released from cells killed or injured by the drug. It was suggested that lymphocytes incorporating these nucleic acids were transformed into specialized cells capable of direct and immediate stimulation by antigen and lacking immunological memory (hemocytoblasts). A relatively small dose of antigen was apparently capable of stimulating all the hemocytoblasts representing a given clone) with the result that large amounts of antibody rapidly appeared in the serum. PMID:4162484

Infections by Pasteuria do not protect its natural host Daphnia magna from subsequent infections.

PubMed

Duneau, David; Ebert, Dieter; Du Pasquier, Louis

2016-04-01

The existence of immunological memory in invertebrates remains a contentious topic. Exposure of Daphnia magna crustaceans to a noninfectious dose of the bacterium Pasteuria ramosa has been reported to reduce the chance of future infection upon exposure to higher doses. Using clonal hosts and parasites, we tested whether initial exposure of the host to the parasite (priming), followed by clearing of the parasite with antibiotic, protects the host from a second exposure (challenge). Our experiments included three treatments: priming and challenge with the same or with a different parasite clone, or no priming. Two independent experiments showed that both the likelihood of infection and the degree of parasite proliferation did not differ between treatments, supporting the conclusion that there is no immunological memory in this system. We discuss the possibility that previous discordant reports could result from immune or stress responses that did not fade following initial priming. Copyright © 2015 Elsevier Ltd. All rights reserved.

The fate of memory: Reconsolidation and the case of Prediction Error.

PubMed

Fernández, Rodrigo S; Boccia, Mariano M; Pedreira, María E

2016-09-01

The ability to make predictions based on stored information is a general coding strategy. A Prediction-Error (PE) is a mismatch between expected and current events. It was proposed as the process by which memories are acquired. But, our memories like ourselves are subject to change. Thus, an acquired memory can become active and update its content or strength by a labilization-reconsolidation process. Within the reconsolidation framework, PE drives the updating of consolidated memories. Moreover, memory features, such as strength and age, are crucial boundary conditions that limit the initiation of the reconsolidation process. In order to disentangle these boundary conditions, we review the role of surprise, classical models of conditioning, and their neural correlates. Several forms of PE were found to be capable of inducing memory labilization-reconsolidation. Notably, many of the PE findings mirror those of memory-reconsolidation, suggesting a strong link between these signals and memory process. Altogether, the aim of the present work is to integrate a psychological and neuroscientific analysis of PE into a general framework for memory-reconsolidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ray Owen and the history of naturally acquired chimerism

PubMed Central

Martin, Aryn

2015-01-01

abstract This article interweaves a history of Ray Owen's early work with a broader account of the conceptual landscape of immunology in the mid 1950's. In particular, Owen's openness to the very possibility of chimeric phenomena is recognized. PMID:27093621

Immunology and immunity against infection: General rules

NASA Astrophysics Data System (ADS)

Zinkernagel, Rolf M.

2005-12-01

Simplified and generalizable rules of immune responses against infections or vaccines have been summarized into 20 statements previously (Scand. J. Immunol. 60 (2004) 9-13) and are restated in a slightly different form here. The key terms of immunology (e.g. specificity, tolerance and memory) are explained in terms of their co-evolutionary importance in the equilibrium between infectious agents and diseases with higher vertebrate hosts. Specificity is best defined by protective antibodies or protective activated T cells; e.g. serotype specific neutralizing antibodies against polio viruses represent the discriminatory power of an immune response very well indeed. Tolerance is reviewed in terms of reactivity rather than self-nonself discrimination. Immune respones are deleted against antigens expressed at sufficient levels within the lymphoheamopoetic system, but may well exist at both, the T and the B cell level against antigens strictly outside of secondary lymphatic organs. In this respect the immune system behaves identically against virus infections and against self antigens. Persistent virus infections delete responsive T cells, once eliminated immune T cell responses wane, if a virus keeps outside of secondary lymphatic tissues no immune response is induced. Immunological memory is usually defined as earlier and greater responses but this does not correlate with protective immunity stringently. It is summarized here that pre-existing titers of protective neutralizing antibodies or pre-existence of activated T cells are the correlates of protection acute cytopathic lethal infections and toxins or against intracellular parasites. It is concluded that many discrepancies and uncertainties in immunological research derive from model situations and experimental results that are correctly measured but cannot be related to co-evolutionary contexts, i.e. survival.

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels

PubMed Central

Gossel, Graeme; Hogan, Thea; Cownden, Daniel

2017-01-01

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment. DOI: http://dx.doi.org/10.7554/eLife.23013.001 PMID:28282024

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels.

PubMed

Gossel, Graeme; Hogan, Thea; Cownden, Daniel; Seddon, Benedict; Yates, Andrew J

2017-03-10

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy.

PubMed

Abzug, Mark J; Warshaw, Meredith; Rosenblatt, Howard M; Levin, Myron J; Nachman, Sharon A; Pelton, Stephen I; Borkowsky, William; Fenton, Terence

2009-09-15

Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)-infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated. HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received 3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later. At entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a 4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4-5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a 4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load. HIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV.

Selective resistance of CD44hi T cells to p53-dependent cell death results in persistence of immunologic memory after total body irradiation.

PubMed

Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

2011-10-15

Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation markedly changes the balance of residual T cell subsets to favor CD4(+)CD44(hi) NKT cells because of the differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results showed that CD4(+) T cells were markedly more resistant than CD8(+) T cells, and CD44(hi) T cells, including NKT cells and memory T cells, were markedly more resistant than CD44(lo) (naive) T cells. The memory T cells immunized to alloantigens persisted even after myeloablative (1000 cGy) TBI and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1000 cGy was prevented in p53(-/-) mice, there was progressive T cell death in p53(-/-) mice at higher doses. Although p53-dependent T cell death changed the balance of subsets, p53-independent T cell death did not. In conclusion, resistance of CD44(hi) T cells to p53-dependent cell death results in the persistence of immunological memory after TBI and can explain the immune-mediated rejection of marrow transplants in sensitized recipients.

Potent CD4+ T cell-associated antitumor memory responses induced by trifunctional bispecific antibodies in combination with immune checkpoint inhibition

PubMed Central

Deppisch, Nina; Ruf, Peter; Eißler, Nina; Lindhofer, Horst; Mocikat, Ralph

2017-01-01

Combinatorial approaches of immunotherapy hold great promise for the treatment of malignant disease. Here, we examined the potential of combining an immune checkpoint inhibitor and trifunctional bispecific antibodies (trAbs) in a preclinical melanoma mouse model using surrogate antibodies of Ipilimumab and Catumaxomab, both of which have already been approved for clinical use. The specific binding arms of trAbs redirect T cells to tumor cells and trigger direct cytotoxicity, while the Fc region activates accessory cells eventually giving rise to a long-lasting immunologic memory. We show here that T cells redirected to tumor cells by trAbs strongly upregulate CTLA-4 expression in vitro and in vivo. This suggested that blocking of CTLA-4 in combination with trAb treatment enhances T-cell activation in a tumor-selective manner. However, when mice were challenged with melanoma cells and subsequently treated with antibodies, there was only a moderate beneficial effect of the combinatorial approach in vivo with regard to direct tumor destruction in comparison to trAb therapy alone. By contrast, a significantly improved vaccination effect was obtained by CTLA-4 blocking during trAb-dependent immunization. This resulted in enhanced rejection of melanoma cells given after pre-immunization. The improved immunologic memory induced by the combinatorial approach correlated with an increased humoral antitumor response as measured in the sera and an expansion of CD4+ memory T cells found in the spleens. PMID:27966460

Potent CD4+ T cell-associated antitumor memory responses induced by trifunctional bispecific antibodies in combination with immune checkpoint inhibition.

PubMed

Deppisch, Nina; Ruf, Peter; Eißler, Nina; Lindhofer, Horst; Mocikat, Ralph

2017-01-17

Combinatorial approaches of immunotherapy hold great promise for the treatment of malignant disease. Here, we examined the potential of combining an immune checkpoint inhibitor and trifunctional bispecific antibodies (trAbs) in a preclinical melanoma mouse model using surrogate antibodies of Ipilimumab and Catumaxomab, both of which have already been approved for clinical use. The specific binding arms of trAbs redirect T cells to tumor cells and trigger direct cytotoxicity, while the Fc region activates accessory cells eventually giving rise to a long-lasting immunologic memory. We show here that T cells redirected to tumor cells by trAbs strongly upregulate CTLA-4 expression in vitro and in vivo. This suggested that blocking of CTLA-4 in combination with trAb treatment enhances T-cell activation in a tumor-selective manner. However, when mice were challenged with melanoma cells and subsequently treated with antibodies, there was only a moderate beneficial effect of the combinatorial approach in vivo with regard to direct tumor destruction in comparison to trAb therapy alone. By contrast, a significantly improved vaccination effect was obtained by CTLA-4 blocking during trAb-dependent immunization. This resulted in enhanced rejection of melanoma cells given after pre-immunization. The improved immunologic memory induced by the combinatorial approach correlated with an increased humoral antitumor response as measured in the sera and an expansion of CD4+ memory T cells found in the spleens.

Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

PubMed

Staines, Donald R

2004-01-01

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.

Reactivation-Dependent Amnesia in Pavlovian Approach and Instrumental Transfer

ERIC Educational Resources Information Center

Lee, Jonathan L. C.; Everitt, Barry J.

2008-01-01

The theory of memory reconsolidation relates to the hypothesized restabilisation process that occurs following the reactivation of a memory through retrieval. Thus, the demonstration of reactivation-dependent amnesia for a previously acquired memory is a prerequisite for showing that such a memory undergoes reconsolidation. Here, we show that the…

[Memory engram of brain circuit].

PubMed

Kojima, Hiroto; Sakaguchi, Tetsuya; Ikegaya, Yuji

2015-05-01

How are memories stored in the brain and retrieved on demand? This is a frequently asked question. Indeed, we acquire new memories daily and remember old ones. However, how we can memorize one-time experiences is yet to be investigated. Here, we review possible mechanisms by which memories are maintained in neural networks.

Design and DSP implementation of star image acquisition and star point fast acquiring and tracking

NASA Astrophysics Data System (ADS)

Zhou, Guohui; Wang, Xiaodong; Hao, Zhihang

2006-02-01

Star sensor is a special high accuracy photoelectric sensor. Attitude acquisition time is an important function index of star sensor. In this paper, the design target is to acquire 10 samples per second dynamic performance. On the basis of analyzing CCD signals timing and star image processing, a new design and a special parallel architecture for improving star image processing are presented in this paper. In the design, the operation moving the data in expanded windows including the star to the on-chip memory of DSP is arranged in the invalid period of CCD frame signal. During the CCD saving the star image to memory, DSP processes the data in the on-chip memory. This parallelism greatly improves the efficiency of processing. The scheme proposed here results in enormous savings of memory normally required. In the scheme, DSP HOLD mode and CPLD technology are used to make a shared memory between CCD and DSP. The efficiency of processing is discussed in numerical tests. Only in 3.5ms is acquired the five lightest stars in the star acquisition stage. In 43us, the data in five expanded windows including stars are moved into the internal memory of DSP, and in 1.6ms, five star coordinates are achieved in the star tracking stage.

ILC2 memory: Recollection of previous activation.

PubMed

Martinez-Gonzalez, Itziar; Ghaedi, Maryam; Steer, Catherine A; Mathä, Laura; Vivier, Eric; Takei, Fumio

2018-05-01

Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed "trained immunity" and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life. These "training" of neonatal ILC2s may have an impact on the generation of memory ILC2s in the adulthood. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emotional Modulation of Learning and Memory: Pharmacological Implications.

PubMed

LaLumiere, Ryan T; McGaugh, James L; McIntyre, Christa K

2017-07-01

Memory consolidation involves the process by which newly acquired information becomes stored in a long-lasting fashion. Evidence acquired over the past several decades, especially from studies using post-training drug administration, indicates that emotional arousal during the consolidation period influences and enhances the strength of the memory and that multiple different chemical signaling systems participate in this process. The mechanisms underlying the emotional influences on memory involve the release of stress hormones and activation of the basolateral amygdala, which work together to modulate memory consolidation. Moreover, work suggests that this amygdala-based memory modulation occurs with numerous types of learning and involves interactions with many different brain regions to alter consolidation. Additionally, studies suggest that emotional arousal and amygdala activity in particular influence synaptic plasticity and associated proteins in downstream brain regions. This review considers the historical understanding for memory modulation and cellular consolidation processes and examines several research areas currently using this foundational knowledge to develop therapeutic treatments. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Distinct Cytokine and Chemokine Profiles in Autism Spectrum Disorders

PubMed Central

Han, Yvonne M. Y.; Cheung, Winnie K. Y.; Wong, Chun Kwok; Sze, Sophia L.; Cheng, Timmy W. S.; Yeung, Michael K.; Chan, Agnes S.

2017-01-01

Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). However, this research has been conducted almost exclusively in Western contexts, and only a handful of studies on immune measures have been conducted in Asian populations, such as Chinese populations. The present study examined whether immunological abnormalities are associated with cognitive deficits and problem behaviors in Chinese children with ASD and whether these children show different immunological profiles. Thirteen typically developing (TD) children and 22 children with ASD, aged 6–17 years, participated voluntarily in the study. Executive functions and short-term memory were measured using neuropsychological tests, and behavioral measures were assessed using parent ratings. The children were also assessed on immunological measures, specifically, the levels of cytokines and chemokines in the blood serum. Children with ASD showed greater deficits in cognitive functions, as well as altered levels of immunological measures, including CCL2, CCL5, and CXCL9 levels, compared to TD children, and the cognitive functions and associated behavioral deficits of children with ASD were significantly associated with different immunological measures. The children were further sub-classified into ASD with only autistic features (ASD-only) or ASD comorbid with attention deficit hyperactivity disorder (ASD + ADHD). The comorbidity results showed that there were no differences between the two groups of ASD children in any of the cognitive or behavioral measures. However, the results pertaining to immunological measures showed that the children with ASD-only and ASD + ADHD exhibited distinct cytokine and chemokine profiles and that abnormal immunologic function was associated with cognitive functions and inattention/hyperactivity symptoms. These results support the notion that altered immune functions may play a role in the selective cognitive and behavioral symptoms of ASD. PMID:28167942

Total Recall: Can We Reshape T Cell Memory by Lymphoablation?

PubMed

Nicosia, M; Valujskikh, A

2017-07-01

Despite recent advances in immunosuppression, donor-reactive memory T cells remain a serious threat to successful organ transplantation. To alleviate damaging effects of preexisting immunologic memory, lymphoablative induction therapies are used as part of standard care in sensitized recipients. However, accumulating evidence suggests that memory T cells have advantages over their naive counterparts in surviving depletion and expanding under lymphopenic conditions. This may at least partially explain the inability of existing lymphoablative strategies to improve long-term allograft outcome in sensitized recipients, despite the well-documented decrease in the frequency of early acute rejection episodes. This minireview summarizes the insights gained from both experimental and clinical transplantation as to the effects of existing lymphoablative strategies on memory T cells and discusses the latest research developments aimed at improving the efficacy and safety of lymphoablation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Immunologic considerations for generating memory CD8 T cells through vaccination.

PubMed

Butler, Noah S; Nolz, Jeffrey C; Harty, John T

2011-07-01

Following infection or vaccination, naïve CD8 T cells that receive the appropriate integration of antigenic, co-stimulatory and inflammatory signals undergo a programmed series of biological changes that ultimately results in the generation of memory cells. Memory CD8 T cells, in contrast to naïve cells, more effectively limit or prevent pathogen re-infection because of both qualitative and quantitative changes that occur following their induction. Unlike vaccination strategies aimed at generating antibody production, the ability to generate protective memory CD8 T cells has proven more complicated and problematic. However, recent experimental results have revealed important principles regarding the molecular and genetic basis for memory CD8 T cell formation, as well as identified ways to manipulate their development through vaccination, resulting in potential new avenues to enhance protective immunity. © 2011 Blackwell Publishing Ltd.

Trained immunity: a program of innate immune memory in health and disease

PubMed Central

Netea, Mihai G.; Joosten, Leo A.B.; Latz, Eicke; Mills, Kingston H.G.; Natoli, Gioacchino; Stunnenberg, Hendrik G.; O’Neill, Luke A.J.; Xavier, Ramnik J.

2016-01-01

The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed trained immunity or innate immune memory. Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. PMID:27102489

The Memory of What We Do Not Recall: Dissociations and Theoretical Debates in the Study of Implicit Memory

ERIC Educational Resources Information Center

Ramos, Tania; Marques, João; Garcia-Marques, Leonel

2017-01-01

Implicit memory reflects itself on situations in which previously acquired information is expressed, without awareness or intention. The study of implicit memory has had a profound impact on how researchers have investigated the human memory. In this paper, we review the main studies which have revealed dissociations between direct and indirect…

Optometric Education's Challenge: AIDS in the Curriculum.

ERIC Educational Resources Information Center

Wilson, Roger J.

1988-01-01

A national survey of schools of optometry suggests that acquired immune deficiency syndrome (AIDS) needs to be more thoroughly addressed in some curricula. Suggestions are made for curriculum development in the areas of public health, basic coursework, immunology, clinical medicine, psychology, ocular manifestations, and contact lenses. (MSE)

Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

ERIC Educational Resources Information Center

Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

2006-01-01

The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

Making Contact: The NAMES Project in Comparison to the Vietnam Memorial.

ERIC Educational Resources Information Center

Jensen, Marvin D.

Several principles of gestalt therapy are applied in an analysis of the similarities between the Vietnam Veterans Memorial and The NAMES Project Quilt. The NAMES Project Quilt memorializes people who have died of Acquired Immune Deficiency Syndrome (AIDS). The creators of the two memorials engaged in the initial searches for "whole"…

Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis.

PubMed

Tonaco, Marcela M; Moreira, Jôsimar D; Nunes, Fernanda F C; Loures, Cristina M G; Souza, Larissa R; Martins, Janaina M; Silva, Henrique R; Porto, Arthur Henrique R; Toledo, Vicente Paulo C P; Miranda, Silvana S; Guimarães, Tânia Mara P D

2017-12-01

The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-ɣ+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-ɣ+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better understanding of the immunologic changes in M. tuberculosis infection and the development of new strategies for diagnosis and prevention of tuberculosis. Copyright © 2017. Published by Elsevier B.V.

Integration of immunological aspects in the European Human Embryonic Stem Cell Registry.

PubMed

Borstlap, Joeri; Kurtz, Andreas

2008-05-01

The immunological properties of stem cells are of increasing importance in regenerative medicine. Immunomodulatory mechanisms seem to play an important role not only with respect to the understanding of underlying mechanisms of autologous versus allogenic therapeutic approaches, but also for endogeneous tissue regeneration. The newly established European human embryonic stem cell registry (hESCreg) offers an international database for the registration, documentation and characterisation of human embryonic stem cells (hESC) and their use. By doing so, hESCreg aims to develop a model procedure for further standardisation efforts in the field of stem cell research and regenerative medicine, and eventually the registry may lead to a repository of therapy-related information. Currently the stem cell characterisation data acquired by the registry are divided into several categories such as cell derivation, culture conditions, genetic constitution, stem cell marker expression and degree of modification. This article describes immunological aspects of stem cell characterisation and explores the layout and relevance of a possible additional section to the hESCreg repository to include immunological characteristics of human embryonic stem cells.

Evolution of costly explicit memory and cumulative culture.

PubMed

Nakamaru, Mayuko

2016-06-21

Humans can acquire new information and modify it (cumulative culture) based on their learning and memory abilities, especially explicit memory, through the processes of encoding, consolidation, storage, and retrieval. Explicit memory is categorized into semantic and episodic memories. Animals have semantic memory, while episodic memory is unique to humans and essential for innovation and the evolution of culture. As both episodic and semantic memory are needed for innovation, the evolution of explicit memory influences the evolution of culture. However, previous theoretical studies have shown that environmental fluctuations influence the evolution of imitation (social learning) and innovation (individual learning) and assume that memory is not an evolutionary trait. If individuals can store and retrieve acquired information properly, they can modify it and innovate new information. Therefore, being able to store and retrieve information is essential from the perspective of cultural evolution. However, if both storage and retrieval were too costly, forgetting and relearning would have an advantage over storing and retrieving acquired information. In this study, using mathematical analysis and individual-based simulations, we investigate whether cumulative culture can promote the coevolution of costly memory and social and individual learning, assuming that cumulative culture improves the fitness of each individual. The conclusions are: (1) without cumulative culture, a social learning cost is essential for the evolution of storage-retrieval. Costly storage-retrieval can evolve with individual learning but costly social learning does not evolve. When low-cost social learning evolves, the repetition of forgetting and learning is favored more than the evolution of costly storage-retrieval, even though a cultural trait improves the fitness. (2) When cumulative culture exists and improves fitness, storage-retrieval can evolve with social and/or individual learning, which is not influenced by the degree of the social learning cost. Whether individuals socially learn a low level of culture from observing a high or the low level of culture influences the evolution of memory and learning, especially individual learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness.

PubMed

Muszynski, Jennifer A; Spinella, Philip C; Cholette, Jill M; Acker, Jason P; Hall, Mark W; Juffermans, Nicole P; Kelly, Daniel P; Blumberg, Neil; Nicol, Kathleen; Liedel, Jennifer; Doctor, Allan; Remy, Kenneth E; Tucci, Marisa; Lacroix, Jacques; Norris, Philip J

2017-01-01

Transfusion-related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research directions. © 2016 AABB.

Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.

PubMed

Kishimoto, Kenji; Kobayashi, Ryoji; Sano, Hirozumi; Suzuki, Daisuke; Maruoka, Hayato; Yasuda, Kazue; Chida, Natsuko; Yamada, Masafumi; Kobayashi, Kunihiko

2014-07-01

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Virus diseases of the salmonidae in the western United States. III. Immunopathological aspects

USGS Publications Warehouse

Klontz, George W.; Yasutake, William T.; Parisot, T.J.

1965-01-01

The immune response among fish, from a phylogenetic standpoint, presents a progressive pattern of increasing development. The cyclostomes have been shown to have only feeble immunologic responsiveness. One of their number, the hagfish, appeared to be totally lacking in the ability to actively acquire antibodies.Among the elasmobranchs, the sharks have received the most study immunologically. This group demonstrated a variable response to antigenic stimulationOf the teleosts, the salmonids and the cyprinids have been the more frequent recipients of experimentally introduced antigens. These fishes, as well as other species of teleosts, are quite active and quite consistent in their response to various antigens.

[Acquired amegacaryocytic thrombocytopenic purpura hiding acute myeloid leukemia].

PubMed

Eddou, Hicham; Zinebi, Ali; Khalloufi, Abdelaziz; Sina, Mohammed; Mahtat, Mehdi; Doghmi, Kamal; Mikdame, Mohammed; Moudden, Mohammed Karim; Baaj, Mohammed El

2017-01-01

Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition characterized by severe thrombocytopenia linked to the reduction or disappearance of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary to many pathological conditions including hematologic disorders. We report the case of a 24-year-old patient admitted for haemorrhagic syndrome caused by immunological thrombocytopenic purpura. The diagnosis was acquired amegakaryocytosis after the failure of corticotherapy and the performance of myelography. The patient was treated with ciclosporin with rapid progression to acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to acute leukemia is reported but it is generally not so rapid and above all it is preceded by myelodysplastic syndrome or medullary aplasia. This study highlights the importance of a close follow-up of these pathologies with a benign-like appearance.

An Application of the Patient-Oriented Problem-Solving (POPS) System.

ERIC Educational Resources Information Center

Chiodo, Gary T.; And Others

1991-01-01

The Patient-Oriented Problem-Solving System, a cooperative learning model, was implemented in a second year immunology course at the Oregon Health Sciences University School of Dentistry, to correlate basic and clinical sciences information about Acquired Immune Deficiency Syndrome. Student enthusiasm and learning were substantial. (MSE)

Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis.

PubMed

Abdelsamed, Hossam A; Moustaki, Ardiana; Fan, Yiping; Dogra, Pranay; Ghoneim, Hazem E; Zebley, Caitlin C; Triplett, Brandon M; Sekaly, Rafick-Pierre; Youngblood, Ben

2017-06-05

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T EM ), and longer-lived central memory (T CM ) and stem cell memory (T SCM ) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T CM and T SCM memory cells resulted in phenotypic conversion into T EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T EM -associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. © 2017 Abdelsamed et al.

Innate immune memory in plants.

PubMed

Reimer-Michalski, Eva-Maria; Conrath, Uwe

2016-08-01

The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Innate immune memory in the brain shapes neurological disease hallmarks.

PubMed

Wendeln, Ann-Christin; Degenhardt, Karoline; Kaurani, Lalit; Gertig, Michael; Ulas, Thomas; Jain, Gaurav; Wagner, Jessica; Häsler, Lisa M; Wild, Katleen; Skodras, Angelos; Blank, Thomas; Staszewski, Ori; Datta, Moumita; Centeno, Tonatiuh Pena; Capece, Vincenzo; Islam, Md Rezaul; Kerimoglu, Cemil; Staufenbiel, Matthias; Schultze, Joachim L; Beyer, Marc; Prinz, Marco; Jucker, Mathias; Fischer, André; Neher, Jonas J

2018-04-01

Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.

Protein Synthesis Underlies Post-Retrieval Memory Consolidation to a Restricted Degree Only when Updated Information Is Obtained

ERIC Educational Resources Information Center

Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutierrez, Ranier; Bermudez-Rattoni, Federico

2005-01-01

Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here…

Short-term stress experienced at time of immunization induces a long-lasting increase in immunologic memory.

PubMed

Dhabhar, Firdaus S; Viswanathan, Kavitha

2005-09-01

It would be extremely beneficial if one could harness natural, endogenous, health-promoting defense mechanisms to fight disease and restore health. The psychophysiological stress response is the most underappreciated of nature's survival mechanisms. We show that acute stress experienced before primary immunization induces a long-lasting increase in immunity. Compared with controls, mice restrained for 2.5 h before primary immunization with keyhole limpet hemocyanin (KLH) show a significantly enhanced immune response when reexposed to KLH 9 mo later. This immunoenhancement is mediated by an increase in numbers of memory and effector helper T cells in sentinel lymph nodes at the time of primary immunization. Further analyses show that the early stress-induced increase in T cell memory may stimulate the robust increase in infiltrating lymphocyte and macrophage numbers observed months later at a novel site of antigen reexposure. Enhanced leukocyte infiltration may be driven by increased levels of the type 1 cytokines, IL-2 and IFN-gamma, and TNF-alpha, observed at the site of antigen reexposure in animals that had been stressed at the time of primary immunization. In contrast, no differences were observed in type 2 cytokines, IL-4 or IL-5. Given the importance of inducing long-lasting increases in immunologic memory during vaccination, we suggest that the neuroendocrine stress response is nature's adjuvant that could be psychologically and/or pharmacologically manipulated to safely increase vaccine efficacy. These studies introduce the novel concept that a psychophysiological stress response is nature's fundamental survival mechanism that could be therapeutically harnessed to augment immune function during vaccination, wound healing, or infection.

Immunogenicity and Immunologic Memory after Hepatitis B Virus Booster Vaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

PubMed Central

Abzug, Mark J.; Warshaw, Meredith; Rosenblatt, Howard M.; Levin, Myron J.; Nachman, Sharon A.; Pelton, Stephen I.; Borkowsky, William; Fenton, Terence

2010-01-01

Background Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)–infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated. Methods HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received ≥3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later. Results At entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a ≥4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4–5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a ≥4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load. Conclusions HIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV. PMID:19663708

Selective Resistance of CD44hi T Cells to p53 Dependent Cell Death Results in Persistence of Immunologic Memory after Total Body Irradiation1,2,3

PubMed Central

Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

2011-01-01

Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation (TLI) markedly changes the balance of residual T cell subsets to favor CD4+CD44hi natural killer T (NKT) cells due to differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results show that CD4+ T cells were markedly more resistant than CD8+ T cells, and CD44hi T cells including NKT cells and memory T cells were markedly more resistant than CD44lo (naïve) T cells. The memory T cells immunized to alloantigens persisted even after myeloabloative (1,000cGy) TBI, and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1,000cGy was prevented in p53−/− mice, there was progressive T cell death in p53−/− mice at higher doses. Whereas, p53 dependent T cell death changed the balance of subsets, the p53 independent T cell death did not. In conclusion, resistance of CD44hi T cells to p53 dependent cell death results in the persistence of immunological memory after TBI, and can explain the immune mediated rejection of marrow transplants in sensitized recipients. PMID:21930972

Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

PubMed

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

Ratio of Circulating IFNγ + “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

PubMed Central

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ +Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ +Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

Immunologic Difference between Hypersensitivity to Mosquito Bite and Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus Infection

PubMed Central

Hsieh, Meng-Ying; Lin, Syh-Jae; Jaing, Tang-Her; Chen, Shih-Hsiang; Hung, Iou-Jih; Yang, Chao-Ping; Chen, Chin-Jung; Huang, Yhu-Chering; Li, Shin-Pai; Huang, Jing-Long

2013-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, virus-triggered immune disease. Hypersensitivity to mosquito bite (HMB), a presentation of Chronic Active Epstein-Barr Virus infection (CAEBV), may progress to HLH. This study aimed to investigate the immunologic difference between the HMB episodes and the HLH episodes associated with EBV infection. Immunologic changes of immunoglobulins, lymphocyte subsets, cytotoxicity, intracellular perforin and granzyme expressions, EBV virus load and known candidate genes for hereditary HLH were evaluated and compared. In 12 HLH episodes (12 patients) and 14 HMB episodes (4 patients), there were both decreased percentages of CD4+ and CD8+ and increased memory CD4+ and activated (CD2+HLADR+) lymphocytes. In contrast to HMB episodes that had higher IgE levels and EBV virus load predominantly in NK cells, those HLH episodes with virus load predominantly in CD3+ lymphocyte had decreased perforin expression and cytotoxicity that were recovered in the convalescence period. However, there was neither significant difference of total virus load in these episodes nor candidate genetic mutations responsible for hereditary HLH. In conclusion, decreased perforin expression in the HLH episodes with predominant-CD3+ EBV virus load is distinct from those HMB episodes with predominant-NK EBV virus load. Whether the presence of non-elevated memory CD4+ cells or activated lymphocytes (CD2+HLADR+) increases the mortality rate in the HLH episodes remains to be further warranted through larger-scale studies. PMID:24204658

Implicit memory in music and language.

PubMed

Ettlinger, Marc; Margulis, Elizabeth H; Wong, Patrick C M

2011-01-01

Research on music and language in recent decades has focused on their overlapping neurophysiological, perceptual, and cognitive underpinnings, ranging from the mechanism for encoding basic auditory cues to the mechanism for detecting violations in phrase structure. These overlaps have most often been identified in musicians with musical knowledge that was acquired explicitly, through formal training. In this paper, we review independent bodies of work in music and language that suggest an important role for implicitly acquired knowledge, implicit memory, and their associated neural structures in the acquisition of linguistic or musical grammar. These findings motivate potential new work that examines music and language comparatively in the context of the implicit memory system.

Computer-based cognitive retraining for adults with chronic acquired brain injury: a pilot study.

PubMed

Li, Kitsum; Robertson, Julie; Ramos, Joshua; Gella, Stephanie

2013-10-01

This study evaluated the effectiveness of a computer-based cognitive retraining (CBCR) program on improving memory and attention deficits in individuals with a chronic acquired brain injury (ABI). Twelve adults with a chronic ABI demonstrating deficits in memory and attention were recruited from a convenience sample from the community. Using a quasi-experimental one-group pretest-posttest design, a significant improvement was found in both memory and attention scores postintervention using the cognitive screening tool. This study supported the effectiveness of CBCR programs in improving cognitive deficits in memory and attention in individuals with chronic ABI. Further research is recommended to validate these findings with a larger ABI population and to investigate transfer to improvement in occupational performance that supports daily living skills.

A New Local Bipolar Autoassociative Memory Based on External Inputs of Discrete Recurrent Neural Networks With Time Delay.

PubMed

Zhou, Caigen; Zeng, Xiaoqin; Luo, Chaomin; Zhang, Huaguang

In this paper, local bipolar auto-associative memories are presented based on discrete recurrent neural networks with a class of gain type activation function. The weight parameters of neural networks are acquired by a set of inequalities without the learning procedure. The global exponential stability criteria are established to ensure the accuracy of the restored patterns by considering time delays and external inputs. The proposed methodology is capable of effectively overcoming spurious memory patterns and achieving memory capacity. The effectiveness, robustness, and fault-tolerant capability are validated by simulated experiments.In this paper, local bipolar auto-associative memories are presented based on discrete recurrent neural networks with a class of gain type activation function. The weight parameters of neural networks are acquired by a set of inequalities without the learning procedure. The global exponential stability criteria are established to ensure the accuracy of the restored patterns by considering time delays and external inputs. The proposed methodology is capable of effectively overcoming spurious memory patterns and achieving memory capacity. The effectiveness, robustness, and fault-tolerant capability are validated by simulated experiments.

Sleep-mediated memory consolidation depends on the level of integration at encoding.

PubMed

Himmer, Lea; Müller, Elias; Gais, Steffen; Schönauer, Monika

2017-01-01

There is robust evidence that sleep facilitates declarative memory consolidation. Integration of newly acquired memories into existing neocortical knowledge networks has been proposed to underlie this effect. Here, we test whether sleep affects memory retention for word-picture associations differently when it was learned explicitly or using a fast mapping strategy. Fast mapping is an incidental form of learning that references new information to existing knowledge and possibly allows neocortical integration already during encoding. If the integration of information into neocortical networks is a main function of sleep-dependent memory consolidation, material learned via fast mapping should therefore benefit less from sleep. Supporting this idea, we find that sleep has a protective effect on explicitly learned associations. In contrast, memory for associations learned by fast mapping does not benefit from sleep and remains stable regardless of whether sleep or wakefulness follows learning. Our results thus indicate that the need for sleep-mediated consolidation depends on the strategy used for learning and might thus be related to the level of integration of newly acquired memory achieved during encoding. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeted Memory Reactivation during Sleep Adaptively Promotes the Strengthening or Weakening of Overlapping Memories.

PubMed

Oyarzún, Javiera P; Morís, Joaquín; Luque, David; de Diego-Balaguer, Ruth; Fuentemilla, Lluís

2017-08-09

System memory consolidation is conceptualized as an active process whereby newly encoded memory representations are strengthened through selective memory reactivation during sleep. However, our learning experience is highly overlapping in content (i.e., shares common elements), and memories of these events are organized in an intricate network of overlapping associated events. It remains to be explored whether and how selective memory reactivation during sleep has an impact on these overlapping memories acquired during awake time. Here, we test in a group of adult women and men the prediction that selective memory reactivation during sleep entails the reactivation of associated events and that this may lead the brain to adaptively regulate whether these associated memories are strengthened or pruned from memory networks on the basis of their relative associative strength with the shared element. Our findings demonstrate the existence of efficient regulatory neural mechanisms governing how complex memory networks are shaped during sleep as a function of their associative memory strength. SIGNIFICANCE STATEMENT Numerous studies have demonstrated that system memory consolidation is an active, selective, and sleep-dependent process in which only subsets of new memories become stabilized through their reactivation. However, the learning experience is highly overlapping in content and thus events are encoded in an intricate network of related memories. It remains to be explored whether and how memory reactivation has an impact on overlapping memories acquired during awake time. Here, we show that sleep memory reactivation promotes strengthening and weakening of overlapping memories based on their associative memory strength. These results suggest the existence of an efficient regulatory neural mechanism that avoids the formation of cluttered memory representation of multiple events and promotes stabilization of complex memory networks. Copyright © 2017 the authors 0270-6474/17/377748-11$15.00/0.

Cyclic Nucleotide-Gated Channels, Calmodulin, Adenylyl Cyclase, and Calcium/Calmodulin-Dependent Protein Kinase II Are Required for Late, but Not Early, Long-Term Memory Formation in the Honeybee

ERIC Educational Resources Information Center

Matsumoto, Yukihisa; Sandoz, Jean-Christophe; Devaud, Jean-Marc; Lormant, Flore; Mizunami, Makoto; Giurfa, Martin

2014-01-01

Memory is a dynamic process that allows encoding, storage, and retrieval of information acquired through individual experience. In the honeybee "Apis mellifera," olfactory conditioning of the proboscis extension response (PER) has shown that besides short-term memory (STM) and mid-term memory (MTM), two phases of long-term memory (LTM)…

Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

PubMed

Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathy D; Draber, Peter; Stepanek, Ondrej

2018-05-11

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8 + T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Cytomegalovirus Retinitis and the Acquired Immune Deficiency Syndrome: Bench to Bedside: LXVII Edward Jackson Memorial Lecture

PubMed Central

Jabs, Douglas A.

2010-01-01

Purpose To update information on cytomegalovirus (CMV) retinitis in patients with the acquired immune deficiency syndrome (AIDS) and to integrate information on its pathogenesis and clinical outcomes. Design Literature review. Methods Selected articles from the medical literature, particularly large epidemiologic studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus Retinitis and Viral Resistance Study, were reviewed. Clinical information is discussed in light of knowledge on CMV, its pathogenesis, and its interactions with human immunodeficiency virus (HIV). Results Cytomegalovirus uses several mechanisms to evade the immune system and establish latent infection in immunologically normal hosts. With immune deficiency, such as late-stage AIDS, CMV reactivates, is disseminated to the eye, and establishes a productive infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV accelerates HIV disease, and CMV retinitis is associated with increased mortality. Randomized clinical trials have demonstrated the efficacy of treatments for CMV retinitis. Systemically-administered treatment for CMV retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART), effectively suppresses HIV replication, resulting in immune recovery, which, if sufficient, controls retinitis without anti-CMV therapy. Resistant CMV, detected in the blood, correlates with resistant virus in the eye and is associated with worse clinical outcomes, including mortality. Host factors, including host genetics and access to care, play a role in the development of CMV retinitis. Conclusions Clinical outcomes of CMV retinitis in patients with AIDS are dependent on characteristics of the virus and host and on HIV–CMV interactions. PMID:21168815

Aggregated Recombinant Human Interferon Beta Induces Antibodies but No Memory in Immune-Tolerant Transgenic Mice

PubMed Central

Sauerborn, Melody; Gilli, Francesca; Brinks, Vera; Schellekens, Huub; Jiskoot, Wim

2010-01-01

ABSTRACT Purpose To study the influence of protein aggregation on the immunogenicity of recombinant human interferon beta (rhIFNβ) in wild-type mice and transgenic, immune-tolerant mice, and to evaluate the induction of immunological memory. Methods RhIFNβ-1b and three rhIFNβ-1a preparations with different aggregate levels were injected intraperitoneally in mice 15× during 3 weeks, and the mice were rechallenged with rhIFNβ-1a. The formation of binding (BABs) and neutralizing antibodies (NABs) was monitored. Results Bulk rhIFNβ-1a contained large, mainly non-covalent aggregates and stressed rhIFNβ-1a mainly covalent, homogeneous (ca. 100 nm) aggregates. Reformulated rhIFNβ-1a was essentially aggregate-free. All products induced BABs and NABs in wild-type mice. Immunogenicity in the transgenic mice was product dependent. RhIFNβ-1b showed the highest and reformulated rhIFNβ-1a the lowest immunogenicity. In contrast with wild-type mice, transgenic mice did not show NABs, nor did they respond to the rechallenge. Conclusions The immunogenicity of the products in transgenic mice, unlike in wild-type mice, varied. In the transgenic mice, neither NABs nor immunological memory developed. The immunogenicity of rhIFNβ in a model reflecting the human immune system depends on the presence and the characteristics of aggregates. PMID:20499141

Monomeric and polymeric forms of ependymin: a brain extracellular glycoprotein implicated in memory consolidation processes.

PubMed

Shashoua, V E

1988-07-01

Ependymin, a brain extracellular glycoprotein that appears to be implicated in neural circuit modifications associated with the process of memory consolidation, can rapidly polymerize into fibrous aggregates when the Ca2+ concentration in solution is reduced by the addition of EGTA or by dialysis. Such aggregates, once formed, could not be redissolved in boiling 1% SDS in 6 M urea, acetic acid, saturated aqueous potassium thiocyanate, and trifluoroacetic acid. They were, however, soluble in formic acid. Investigations of the immunological properties of ependymin indicated that various monomers, oligomers and polymers of the molecule with differing carbohydrate contents can be obtained. The polymerization properties of the ependymins may play an important role in their functions in memory consolidation mechanisms.

In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory.

PubMed Central

Powers, D C; Fries, L F; Murphy, B R; Thumar, B; Clements, M L

1991-01-01

In a double-blind, randomized trial, 102 healthy elderly subjects were inoculated with one of four preparations: (i) intranasal bivalent live attenuated influenza vaccine containing cold-adapted A/Kawasaki/86 (H1N1) and cold-adapted A/Bethesda/85 (H3N2) viruses; (ii) parenteral trivalent inactivated subvirion vaccine containing A/Taiwan/86 (H1N1), A/Leningrad/86 (H3N2), and B/Ann Arbor/86 antigens; (iii) both vaccines; or (iv) placebo. To determine whether local or systemic immunization augmented mucosal immunologic memory, all volunteers were challenged intranasally 12 weeks later with the inactivated virus vaccine. We used a hemagglutination inhibition assay to measure antibodies in sera and a kinetic enzyme-linked immunosorbent assay to measure immunoglobulin G (IgG) and IgA antibodies in sera and nasal washes, respectively. In comparison with the live virus vaccine, the inactivated virus vaccine elicited higher and more frequent rises of serum antibodies, while nasal wash antibody responses were similar. The vaccine combination induced serum and local antibodies slightly more often than the inactivated vaccine alone did. Coadministration of live influenza A virus vaccine did not alter the serum antibody response to the influenza B virus component of the inactivated vaccine. The anamnestic nasal antibody response elicited by intranasal inactivated virus challenge did not differ in the live, inactivated, or combined vaccine groups from that observed in the placebo group not previously immunized. These results suggest that in elderly persons cold-adapted influenza A virus vaccines offer little advantage over inactivated virus vaccines in terms of inducing serum or secretory antibody or local immunological memory. Studies are needed to determine whether both vaccines in combination are more efficacious than inactivated vaccine alone in people in this age group. PMID:2037667

Exploration of use of SenseCam to support autobiographical memory retrieval within a cognitive-behavioural therapeutic intervention following acquired brain injury.

PubMed

Brindley, Rob; Bateman, Andrew; Gracey, Fergus

2011-10-01

Delivering effective psychotherapy to address the significant emotional consequences of acquired brain injury (ABI) is challenged by the presence of acquired cognitive impairments, especially retrieval of detailed autobiographical memories of emotional trigger events. Initial studies using a wearable camera (SenseCam) suggest long-term improvements in autobiographical retrieval of recorded events. In this study a single-case experimental design was implemented to explore the use of SenseCam as a memory aid for a man with a specific anxiety disorder and memory and executive difficulties following ABI. We predicted that SenseCam supported rehearsal of memories of events that trigger high levels of anxiety would yield improved retrieval of both factual detail and internal state information (thoughts and feelings) compared with a conventional psychotherapy aid (automatic thought record sheets, ATRs) and no strategy. The findings indicated SenseCam supported retrieval of anxiety trigger events was superior to ATRs or no strategy in terms of both detail and internal state information, with 94% of the information being recalled in the SenseCam condition, compared to 39% for the "no strategy" and 22% for the ATR conditions. It is concluded that SenseCam may be of use as a compensatory aid in psychotherapies relying on retrieval of emotionally salient trigger events.

[Report on the 34th meeting of the German Clinical Immunology Workgroup, Frankfurt, 03.-04.11.2006].

PubMed

Aries, P M; Witte, T; Lamprecht, P

2007-02-01

The annual meeting of the Clinical Immunology Workgroup focused on autoimmune vasculitides. The role of innate immunity, T- and B-cells, and innovative therapies for autoimmune vasculitides was discussed. Further topics of the meeting were the role of endothelial microparticles, ghrelin and leptin, regulatory and effector-memory T-cells in ANCA-associated vasculitides, as well as the lethal midline granuloma, intracytoplasmic cytokine-profile in Behcet's disease, autoantibodies in rheumatoid arthritis, polyarteritis nodosa with cranial manifestation, ILT6 as genetic marker in multiple sclerosis and Sjögren's syndrome, alpha-fodrin autoantibodies in multiple sclerosis, interferon-g autoantibodies in a patient with atypical mycobacteriosis, and autoreactive T-cells in murine lupus.

Reversible Hippocampal Lesions Disrupt Water Maze Performance during Both Recent and Remote Memory Tests

ERIC Educational Resources Information Center

Broadbent, Nicola J.; Squire, Larry R.; Clark, Robert E.

2006-01-01

Conventional lesion methods have shown that damage to the rodent hippocampus can impair previously acquired spatial memory in tasks such as the water maze. In contrast, work with reversible lesion methods using a different spatial task has found remote memory to be spared. To determine whether the finding of spared remote spatial memory depends on…

A shared neural ensemble links distinct contextual memories encoded close in time

NASA Astrophysics Data System (ADS)

Cai, Denise J.; Aharoni, Daniel; Shuman, Tristan; Shobe, Justin; Biane, Jeremy; Song, Weilin; Wei, Brandon; Veshkini, Michael; La-Vu, Mimi; Lou, Jerry; Flores, Sergio E.; Kim, Isaac; Sano, Yoshitake; Zhou, Miou; Baumgaertel, Karsten; Lavi, Ayal; Kamata, Masakazu; Tuszynski, Mark; Mayford, Mark; Golshani, Peyman; Silva, Alcino J.

2016-06-01

Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information.

Anatomical causes of female infertility and their management.

PubMed

Abrao, Mauricio S; Muzii, Ludovico; Marana, Riccardo

2013-12-01

The main female anatomical causes of infertility include post-infectious tubal damage, endometriosis, and congenital/acquired uterine anomalies. Congenital (septate uterus) and acquired (myomas and synechiae) diseases of the uterus may lead to infertility, pregnancy loss, and other obstetric complications. Pelvic inflammatory disease represents the most common cause of tubal damage. Surgery still remains an important option for tubal factor infertility, with results in terms of reproductive outcome that compare favorably with those of in vitro fertilization. Endometriosis is a common gynecologic condition affecting women of reproductive age, which can cause pain and infertility. The cause of infertility associated with endometriosis remains elusive, suggesting a multifactorial mechanism involving immunologic, genetic, and environmental factors. Despite the high prevalence of endometriosis, the exact mechanisms of its pathogenesis are unknown. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. In the majority of cases, surgical treatment of endometriosis has promoted significant increases in fertilization rates. There are obvious associations between endometriosis and the immune system, and future strategies to treat endometriosis might be based on immunologic concepts. © 2013.

About sleep's role in memory.

PubMed

Rasch, Björn; Born, Jan

2013-04-01

Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.

Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

PubMed

Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

2017-05-01

Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4 + T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4 + T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4 + T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4 + T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular regulation of effector and memory T cell differentiation

PubMed Central

Chang, John T; Wherry, E John; Goldrath, Ananda W

2015-01-01

Immunological memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Here we highlight advances in the understanding of the diverse T lymphocyte subsets that provide acute and long-term protection from infection. These include new insights into the transcription factors, and the upstream ‘pioneering’ factors that regulate their accessibility to key sites of gene regulation, as well as metabolic regulators that contribute to the differentiation of effector and memory subsets; ontogeny and defining characteristics of tissue-resident memory lymphocytes; and origins of the remarkable heterogeneity exhibited by activated T cells. Collectively, these findings underscore progress in delineating the underlying pathways that control diversification in T cell responses but also reveal gaps in the knowledge, as well as the challenges that arise in the application of this knowledge to rationally elicit desired T cell responses through vaccination and immunotherapy. PMID:25396352

Mucosal adjuvants and long-term memory development with special focus on CTA1-DD and other ADP-ribosylating toxins.

PubMed

Lycke, N; Bemark, M

2010-11-01

The ultimate goal for vaccination is to stimulate protective immunological memory. Protection against infectious diseases not only relies on the magnitude of the humoral immune response, but more importantly on the quality and longevity of it. Adjuvants are critical components of most non-living vaccines. Although little attention has been given to qualitative aspects of the choice of vaccine adjuvant, emerging data demonstrate that this function may be central to vaccine efficacy. In this review we describe efforts to understand more about how adjuvants influence qualitative aspects of memory development. We describe recent advances in understanding how vaccines induce long-lived plasma and memory B cells, and focus our presentation on the germinal center reaction. As mucosal vaccination requires powerful adjuvants, we have devoted much attention to the adenosine diphosphate (ADP)-ribosylating cholera toxin and the CTA1-DD adjuvants as examples of how mucosal adjuvants can influence induction of long-term memory.

Remote semantic memory is impoverished in hippocampal amnesia

PubMed Central

Klooster, Nathaniel B.; Duff, Melissa C.

2015-01-01

The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. PMID:26474741

[Comparison of the Wechsler Memory Scale-III and the Spain-Complutense Verbal Learning Test in acquired brain injury: construct validity and ecological validity].

PubMed

Luna-Lario, P; Pena, J; Ojeda, N

2017-04-16

To perform an in-depth examination of the construct validity and the ecological validity of the Wechsler Memory Scale-III (WMS-III) and the Spain-Complutense Verbal Learning Test (TAVEC). The sample consists of 106 adults with acquired brain injury who were treated in the Area of Neuropsychology and Neuropsychiatry of the Complejo Hospitalario de Navarra and displayed memory deficit as the main sequela, measured by means of specific memory tests. The construct validity is determined by examining the tasks required in each test over the basic theoretical models, comparing the performance according to the parameters offered by the tests, contrasting the severity indices of each test and analysing their convergence. The external validity is explored through the correlation between the tests and by using regression models. According to the results obtained, both the WMS-III and the TAVEC have construct validity. The TAVEC is more sensitive and captures not only the deficits in mnemonic consolidation, but also in the executive functions involved in memory. The working memory index of the WMS-III is useful for predicting the return to work at two years after the acquired brain injury, but none of the instruments anticipates the disability and dependence at least six months after the injury. We reflect upon the construct validity of the tests and their insufficient capacity to predict functionality when the sequelae become chronic.

Remote semantic memory is impoverished in hippocampal amnesia.

PubMed

Klooster, Nathaniel B; Duff, Melissa C

2015-12-01

The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Role of Working Memory and Divided Attention in Metaphor Interpretation

ERIC Educational Resources Information Center

Iskandar, Sam; Baird, Anne D.

2014-01-01

Although several types of figurative language exist, neuropsychological tests of non-literal language have focused on proverbs. Metaphors in the form X is (a) Y (e.g., "The body's immunological response is a battle against disease.") place a lower demand on language skills and are more easily manipulated for novelty than proverbs.…

Antibody-based vaccine strategies against intracellular pathogens.

PubMed

Casadevall, Arturo

2018-04-25

Historically, antibody-mediated immunity was considered effective against toxins, extracellular pathogens and viruses, while control of intracellular pathogens was the domain of cellular immunity. However, numerous observations in recent decades have conclusively shown that antibody can protect against intracellular pathogens. This paradigmatic shift has tremendous implications for immunology and vaccine design. For immunology the observation that antibody can protect against intracellular pathogens has led to the discovery of new mechanisms of antibody action. For vaccine design the knowledge that humoral immunity can be effective in protection means that the knowledge acquired in more than a century of antibody studies can be applied to make new vaccines against this class of pathogens. Copyright © 2018 Elsevier Ltd. All rights reserved.

Implicit Memory in Music and Language

PubMed Central

Ettlinger, Marc; Margulis, Elizabeth H.; Wong, Patrick C. M.

2011-01-01

Research on music and language in recent decades has focused on their overlapping neurophysiological, perceptual, and cognitive underpinnings, ranging from the mechanism for encoding basic auditory cues to the mechanism for detecting violations in phrase structure. These overlaps have most often been identified in musicians with musical knowledge that was acquired explicitly, through formal training. In this paper, we review independent bodies of work in music and language that suggest an important role for implicitly acquired knowledge, implicit memory, and their associated neural structures in the acquisition of linguistic or musical grammar. These findings motivate potential new work that examines music and language comparatively in the context of the implicit memory system. PMID:21927608

Working memory for braille is shaped by experience.

PubMed

Cohen, Henri; Scherzer, Peter; Viau, Robert; Voss, Patrice; Lepore, Franco

2011-03-01

Tactile working memory was found to be more developed in completely blind (congenital and acquired) than in semi-sighted subjects, indicating that experience plays a crucial role in shaping working memory. A model of working memory, adapted from the classical model proposed by Baddeley and Hitch1 and Baddeley2 is presented where the connection strengths of a highly cross-modal network are altered through experience.

CD4 memory T cells develop and acquire functional competence by sequential cognate interactions and stepwise gene regulation

PubMed Central

Kaji, Tomohiro; Hijikata, Atsushi; Ishige, Akiko; Kitami, Toshimori; Watanabe, Takashi; Ohara, Osamu; Yanaka, Noriyuki; Okada, Mariko; Shimoda, Michiko; Taniguchi, Masaru

2016-01-01

Memory CD4+ T cells promote protective humoral immunity; however, how memory T cells acquire this activity remains unclear. This study demonstrates that CD4+ T cells develop into antigen-specific memory T cells that can promote the terminal differentiation of memory B cells far more effectively than their naive T-cell counterparts. Memory T cell development requires the transcription factor B-cell lymphoma 6 (Bcl6), which is known to direct T-follicular helper (Tfh) cell differentiation. However, unlike Tfh cells, memory T cell development did not require germinal center B cells. Curiously, memory T cells that develop in the absence of cognate B cells cannot promote memory B-cell recall responses and this defect was accompanied by down-regulation of genes associated with homeostasis and activation and up-regulation of genes inhibitory for T-cell responses. Although memory T cells display phenotypic and genetic signatures distinct from Tfh cells, both had in common the expression of a group of genes associated with metabolic pathways. This gene expression profile was not shared to any great extent with naive T cells and was not influenced by the absence of cognate B cells during memory T cell development. These results suggest that memory T cell development is programmed by stepwise expression of gatekeeper genes through serial interactions with different types of antigen-presenting cells, first licensing the memory lineage pathway and subsequently facilitating the functional development of memory T cells. Finally, we identified Gdpd3 as a candidate genetic marker for memory T cells. PMID:26714588

[Inflammatory bowel diseases: an immunological approach].

PubMed

Sepúlveda, Sofía E; Beltrán, Caroll J; Peralta, Alexis; Rivas, Paola; Rojas, Néstor; Figueroa, Carolina; Quera, Rodrigo; Hermoso, Marcela A

2008-03-01

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.

Contextual analysis of immunological response through whole-organ fluorescent imaging.

PubMed

Woodruff, Matthew C; Herndon, Caroline N; Heesters, B A; Carroll, Michael C

2013-09-01

As fluorescent microscopy has developed, significant insights have been gained into the establishment of immune response within secondary lymphoid organs, particularly in draining lymph nodes. While established techniques such as confocal imaging and intravital multi-photon microscopy have proven invaluable, they provide limited insight into the architectural and structural context in which these responses occur. To interrogate the role of the lymph node environment in immune response effectively, a new set of imaging tools taking into account broader architectural context must be implemented into emerging immunological questions. Using two different methods of whole-organ imaging, optical clearing and three-dimensional reconstruction of serially sectioned lymph nodes, fluorescent representations of whole lymph nodes can be acquired at cellular resolution. Using freely available post-processing tools, images of unlimited size and depth can be assembled into cohesive, contextual snapshots of immunological response. Through the implementation of robust iterative analysis techniques, these highly complex three-dimensional images can be objectified into sortable object data sets. These data can then be used to interrogate complex questions at the cellular level within the broader context of lymph node biology. By combining existing imaging technology with complex methods of sample preparation and capture, we have developed efficient systems for contextualizing immunological phenomena within lymphatic architecture. In combination with robust approaches to image analysis, these advances provide a path to integrating scientific understanding of basic lymphatic biology into the complex nature of immunological response.

Explicit Pre-Training Instruction Does Not Improve Implicit Perceptual-Motor Sequence Learning

ERIC Educational Resources Information Center

Sanchez, Daniel J.; Reber, Paul J.

2013-01-01

Memory systems theory argues for separate neural systems supporting implicit and explicit memory in the human brain. Neuropsychological studies support this dissociation, but empirical studies of cognitively healthy participants generally observe that both kinds of memory are acquired to at least some extent, even in implicit learning tasks. A key…

Trade-Offs between Gaze and Working Memory Use

ERIC Educational Resources Information Center

Droll, Jason A.; Hayhoe, Mary M.

2007-01-01

Eye movements during natural tasks suggest that observers do not use working memory to capacity but instead use eye movements to acquire relevant information immediately before needed. Results here however, show that this strategy is sensitive to memory load and to observers' expectations about what information will be relevant. Depending upon the…

Autobiographical Thinking Interferes with Episodic Memory Consolidation

PubMed Central

Craig, Michael; Della Sala, Sergio; Dewar, Michaela

2014-01-01

New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an ‘internal’ memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues. PMID:24736665

Autobiographical thinking interferes with episodic memory consolidation.

PubMed

Craig, Michael; Della Sala, Sergio; Dewar, Michaela

2014-01-01

New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an 'internal' memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues.

Training of attention and memory deficits in children with acquired brain injury.

PubMed

Sjö, N Madsen; Spellerberg, S; Weidner, S; Kihlgren, M

2010-02-01

This pilot study concerns cognitive rehabilitation of children with acquired brain injury (ABI). The aim is threefold; to determine (1) whether the Amsterdam Memory and Attention Training for Children (AMAT-C) programme for children with ABI can be integrated in the child's school, (2) whether supervision in the school-setting maintains the child's motivation throughout the training programme and (3) whether positive changes in memory, attention and executive functions are found with this implementation of the training method. Seven children with memory and/or attention deficits after ABI were trained with AMAT-C. Measures used were programme evaluation questions, neuropsychological tests and a questionnaire concerning executive functions. Overall, children, parents and trainers were satisfied with the programme and the children were motivated throughout the programme. The children showed significant improvements in neuropsychological subtests, primarily in tests of learning and memory. No overall change in executive functions was noted. Provision of AMAT-C training and supervision at the child's school appears to ensure (1) satisfaction with the programme, (2) sustaining of motivation and (3) improvements in learning and memory.

Virtual reality-based prospective memory training program for people with acquired brain injury.

PubMed

Yip, Ben C B; Man, David W K

2013-01-01

Acquired brain injuries (ABI) may display cognitive impairments and lead to long-term disabilities including prospective memory (PM) failure. Prospective memory serves to remember to execute an intended action in the future. PM problems would be a challenge to an ABI patient's successful community reintegration. While retrospective memory (RM) has been extensively studied, treatment programs for prospective memory are rarely reported. The development of a treatment program for PM, which is considered timely, can be cost-effective and appropriate to the patient's environment. A 12-session virtual reality (VR)-based cognitive rehabilitation program was developed using everyday PM activities as training content. 37 subjects were recruited to participate in a pretest-posttest control experimental study to evaluate its treatment effectiveness. Results suggest that significantly better changes were seen in both VR-based and real-life PM outcome measures, related cognitive attributes such as frontal lobe functions and semantic fluency. VR-based training may be well accepted by ABI patients as encouraging improvement has been shown. Large-scale studies of a virtual reality-based prospective memory (VRPM) training program are indicated.

Endocannabinoid signaling and memory dynamics: A synaptic perspective.

PubMed

Drumond, Ana; Madeira, Natália; Fonseca, Rosalina

2017-02-01

Memory acquisition is a key brain feature in which our human nature relies on. Memories evolve over time. Initially after learning, memories are labile and sensitive to disruption by the interference of concurrent events. Later on, after consolidation, memories are resistant to disruption. However, reactivation of previously consolidated memories renders them again in an unstable state and therefore susceptible to perturbation. Additionally, and depending on the characteristics of the stimuli, a parallel process may be initiated which ultimately leads to the extinction of the previously acquired response. This dynamic aspect of memory maintenance opens the possibility for an updating of previously acquired memories but it also creates several conceptual challenges. What is the time window for memory updating? What determines whether reconsolidation or extinction is triggered? In this review, we tried to re-examine the relationship between consolidation, reconsolidation and extinction, aiming for a unifying view of memory dynamics. Since cellular models of memory share common principles, we present the evidence that similar rules apply to the maintenance of synaptic plasticity. Recently, a new function of the endocannabinoid (eCB) signaling system has been described for associative forms of synaptic plasticity in amygdala synapses. The eCB system has emerged as a key modulator of memory dynamics by adjusting the outcome to stimuli intensity. We propose a key function of eCB in discriminative forms of learning by restricting associative plasticity in amygdala synapses. Since many neuropsychiatric disorders are associated with a dysregulation in memory dynamics, understanding the rules underlying memory maintenance paves the path to better clinical interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Is grandma like a lichen planus? The problem of image perception and knowledge retention in pathology

NASA Astrophysics Data System (ADS)

Mello-Thoms, Claudia; Legowski, Elizabeth; Tseytlin, Eugene

2013-03-01

Medicine is the science of acquiring a lot of obscure knowledge and the art of knowing when to apply it, even if only once in a physician's lifetime. Although medical experts seem to have it all figured out, being significantly better and faster than trainees, many studies have suggested that it is not only the amount of knowledge - which comes with experience - that differentiates the experts, but it is also how the knowledge is structured in memory. To acquire new knowledge, trainees will first encode both `surface' (i.e., irrelevant) and `structural' (relevant) features, and repeated presentations of the material will allow for dismissal of the unimportant elements from memory. However, just because knowledge has been encoded it does not mean that it is safely guarded in the physician's memory; as with any information, if it is not tended to, it will slowly decay, and eventually it may be completely forgotten. In this study we investigated knowledge retention in a specific sub-domain of Pathology which is rarely, if ever, used by trainees. We wanted to determine the relationship between the way long-term memory is accessed (i.e., through recognition or free recall) and trainee performance. We also sought to determine whether access to long-term memory through either mechanism led to better transfer of newly acquired knowledge to never before seen cases.

Models and the mosaic of scientific knowledge. The case of immunology.

PubMed

Baetu, Tudor M

2014-03-01

A survey of models in immunology is conducted and distinct kinds of models are characterized based on whether models are material or conceptual, the distinctiveness of their epistemic purpose, and the criteria for evaluating the goodness of a model relative to its intended purpose. I argue that the diversity of models in interdisciplinary fields such as immunology reflects the fact that information about the phenomena of interest is gathered from different sources using multiple methods of investigation. To each model is attached a description specifying how information about a phenomenon of interest has been acquired, highlighting points of commonality and difference between the methodological and epistemic histories of the information encapsulated in different models. These points of commonality and difference allow investigators to integrate findings from different models into more comprehensive explanatory accounts, as well as to troubleshoot anomalies and faulty accounts by going back to the original building blocks. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory

PubMed Central

Kaji, Tomohiro; Ishige, Akiko; Hikida, Masaki; Taka, Junko; Hijikata, Atsushi; Kubo, Masato; Nagashima, Takeshi; Takahashi, Yoshimasa; Kurosaki, Tomohiro; Okada, Mariko; Ohara, Osamu

2012-01-01

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen. PMID:23027924

CHARACTERISTICS OF IMMUNOLOGICAL MEMORY IN MICE

PubMed Central

Black, S. J.; Inchley, C. J.

1974-01-01

The kinetics of the generation of primed IgM and IgG antibody-forming cell precursors, and of helper T-cell populations, were analyzed in mice whose primary responses to high and low doses of SRBC were arrested at intervals by the immunosuppressive agents cyclophosphamide monohydrate and specific antibody. The extent to which immunological memory was established in these animals before blockade of the primary response was assessed by the hemolytic plaque assay following challenge 12 wk after priming. The presence of IgG B-memory cells and T-memory cells in suppressed mice was further investigated by the transfer into these animals of syngeneic SRBC-stimulated thymocytes or anti-θ-treated spleen cells. It was found that the progenitors of secondary IgM-synthesizing cells were primed almost immediately after injection of antigen, and that early blockade of the primary response resulted in a raised IgM response after challenge. On the other hand, priming for a secondary IgG response took at least 4 days, and was dose-dependent, although helper T populations for a secondary IgG response appeared 3 days after antigen injection. It appeared that both IgM and IgG memory cells may be considered as Y cells in terms of the X-Y-Z scheme of lymphocyte activation, but that the two populations are generated at different times after exposure to antigen. The size of either Y-cell population at any given time is dependent upon the amount of antigen available to provoke differentiation to antibody-forming Z cells, and the IgM Y-cell population in particular is likely to be depleted during the course of a normal 1° response. When IgM Y cells were maintained for long periods as a result of immunosuppression, their secondary antibody response was independent of the primed T cells necessary for a secondary IgG response. PMID:4602981

Working memory for braille is shaped by experience

PubMed Central

Scherzer, Peter; Viau, Robert; Voss, Patrice; Lepore, Franco

2011-01-01

Tactile working memory was found to be more developed in completely blind (congenital and acquired) than in semi-sighted subjects, indicating that experience plays a crucial role in shaping working memory. A model of working memory, adapted from the classical model proposed by Baddeley and Hitch1 and Baddeley2 is presented where the connection strengths of a highly cross-modal network are altered through experience. PMID:21655448

Qualitative differences in memory for vista and environmental spaces are caused by opaque borders, not movement or successive presentation.

PubMed

Meilinger, Tobias; Strickrodt, Marianne; Bülthoff, Heinrich H

2016-10-01

Two classes of space define our everyday experience within our surrounding environment: vista spaces, such as rooms or streets which can be perceived from one vantage point, and environmental spaces, for example, buildings and towns which are grasped from multiple views acquired during locomotion. However, theories of spatial representations often treat both spaces as equal. The present experiments show that this assumption cannot be upheld. Participants learned exactly the same layout of objects either within a single room or spread across multiple corridors. By utilizing a pointing and a placement task we tested the acquired configurational memory. In Experiment 1 retrieving memory of the object layout acquired in environmental space was affected by the distance of the traveled path and the order in which the objects were learned. In contrast, memory retrieval of objects learned in vista space was not bound to distance and relied on different ordering schemes (e.g., along the layout structure). Furthermore, spatial memory of both spaces differed with respect to the employed reference frame orientation. Environmental space memory was organized along the learning experience rather than layout intrinsic structure. In Experiment 2 participants memorized the object layout presented within the vista space room of Experiment 1 while the learning procedure emulated environmental space learning (movement, successive object presentation). Neither factor rendered similar results as found in environmental space learning. This shows that memory differences between vista and environmental space originated mainly from the spatial compartmentalization which was unique to environmental space learning. Our results suggest that transferring conclusions from findings obtained in vista space to environmental spaces and vice versa should be made with caution. Copyright © 2016 Elsevier B.V. All rights reserved.

AIDS Education Curriculum Guide. Grades 7-10. Bulletin 1827, 1988.

ERIC Educational Resources Information Center

Louisiana State Dept. of Education, Baton Rouge.

This curriculum guide on acquired immune deficiency syndrome (AIDS) was developed for students at the junior high school level. There are five major sections: (1) introduction, an overview of AIDS; (2) an overview of the history of AIDS; (3) basic immunology; (4) the effects of AIDS on the host; and (5) prevention of AIDS. The appendices include…

Oct1 and OCA-B are selectively required for CD4 memory T cell function.

PubMed

Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N; Snook, Jeremy; Kuchroo, Vijay K; Yosef, Nir; Chan, Raymond C; Regev, Aviv; Williams, Matthew A; Tantin, Dean

2015-11-16

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4(+) T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4(+) T cell memory. © 2015 Shakya et al.

Oct1 and OCA-B are selectively required for CD4 memory T cell function

PubMed Central

Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N.; Snook, Jeremy; Kuchroo, Vijay K.; Yosef, Nir; Chan, Raymond C.; Regev, Aviv

2015-01-01

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4+ memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4+ T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4+ T cell memory. PMID:26481684

Protein A sepharose immunoadsorption: immunological and haemostatic effects in two cases of acquired haemophilia.

PubMed

Guillet, B; Kriaa, F; Huysse, M G; Proulle, V; George, C; Tchernia, G; D'Oiron, R; Laurian, Y; Charpentier, B; Lambert, T; Dreyfus, M

2001-09-01

Acquired haemophilia is a life-threatening disorder caused by circulating auto-antibodies that inhibit factor VIII coagulant activity (FBIII:C). Immunoadsorption on protein A sepharose (IA-PA) was performed in two bleeding patients with acquired haemophilia: we observed a dramatic and quick decrease in the anti-FVIII:C inhibitor titre leading to a normal, albeit transient, haemostatic status. In one case, IA-PA was the only procedure which succeeded in stopping massive haemorrhage. In the second case, IA-PA reinforced the haemostatic effect of recombinant activated factor VII by increasing the endogenous plasma factor VIII level. The efficacy of IA-PA was sustained with immunosuppressive treatment introduced, respectively, 10 and 15 d before the IA-PA procedures. Our experience with IA-PA suggests that this extracorporeal anti-FVIII:C removal procedure is a valuable therapeutic tool for acquired haemophilia and can alleviate life-threatening haemorrhages.

[Noopept improves the spatial memory and stimulates prefibrillar beta-amyloid(25-35) antibody production in mice].

PubMed

Bobkova, N V; Gruden', M A; Samokhin, A N; Medvinskaia, N I; Morozova-Roch, L; Uudasheva, T A; Ostrovskaia, R U; Seredinin, S B

2005-01-01

The effects of the novel proline-containing nootropic and neuroprotective dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were studied on NMRI mice upon olfactory bulbectomy, which had been previously shown to imitate the main morphological and biochemical signs of Alzheimer's disease (AD). The spatial memory was assessed using the Morris (water maze) test; the immunological status was characterized by ELISA with antibodies to prefibrillar beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which are the molecular factors involved in the pathogenesis of AD. The control (sham-operated) animals during the Morris test preferred a sector where the safety platform was placed during the learning session. Bulbectomized animals treated with saline failed to recognize this sector, while bulbectomized animals treated with noopept (0.01 mg/kg for 21 days) restored this predominance, thus demonstrating the improvement of the spatial memory. These animals also demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the effect, which was more pronounced in the sham-operated than in bulbectomized mice. The latter demonstrated a profound decrease of immunological reactivity in a large number of tests. Noopept, stimulating the production of antibodies to beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta-amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept are indicative of good prospects for the clinical usage of this drug in the therapy of patients with neurodegenerative diseases.

Selective pre-priming of HA-specific CD4 T cells restores immunological reactivity to HA on heterosubtypic influenza infection.

PubMed

Alam, Shabnam; Chan, Cory; Qiu, Xing; Shannon, Ian; White, Chantelle L; Sant, Andrea J; Nayak, Jennifer L

2017-01-01

A hallmark of the immune response to influenza is repeated encounters with proteins containing both genetically conserved and variable components. Therefore, the B and T cell repertoire is continually being remodeled, with competition between memory and naïve lymphocytes. Our previous work using a mouse model of secondary heterosubtypic influenza infection has shown that this competition results in a focusing of CD4 T cell response specificity towards internal virion proteins with a selective decrease in CD4 T cell reactivity to the novel HA epitopes. Strikingly, this shift in CD4 T cell specificity was associated with a diminished anti-HA antibody response. Here, we sought to determine whether the loss in HA-specific reactivity that occurs as a consequence of immunological memory could be reversed by selectively priming HA-specific CD4 T cells prior to secondary infection. Using a peptide-based priming strategy, we found that selective expansion of the anti-HA CD4 T cell memory repertoire enhanced HA-specific antibody production upon heterosubtypic infection. These results suggest that the potentially deleterious consequences of repeated exposure to conserved influenza internal virion proteins could be reversed by vaccination strategies that selectively arm the HA-specific CD4 T cell compartment. This could be a potentially useful pre-pandemic vaccination strategy to promote accelerated neutralizing antibody production on challenge with a pandemic influenza strain that contains few conserved HA epitopes.

Absence of LTB4/BLT1 axis facilitates generation of mouse GM-CSF-induced long-lasting antitumor immunologic memory by enhancing innate and adaptive immune systems.

PubMed

Yokota, Yosuke; Inoue, Hiroyuki; Matsumura, Yumiko; Nabeta, Haruka; Narusawa, Megumi; Watanabe, Ayumi; Sakamoto, Chika; Hijikata, Yasuki; Iga-Murahashi, Mutsunori; Takayama, Koichi; Sasaki, Fumiyuki; Nakanishi, Yoichi; Yokomizo, Takehiko; Tani, Kenzaburo

2012-10-25

BLT1 is a high-affinity receptor for leukotriene B4 (LTB4) that is a potent lipid chemoattractant for myeloid leukocytes. The role of LTB4/BLT1 axis in tumor immunology, including cytokine-based tumor vaccine, however, remains unknown. We here demonstrated that BLT1-deficient mice rejected subcutaneous tumor challenge of GM-CSF gene-transduced WEHI3B (WGM) leukemia cells (KO/WGM) and elicited robust antitumor responses against second tumor challenge with WEHI3B cells. During GM-CSF-induced tumor regression, the defective LTB4/BLT1 signaling significantly reduced tumor-infiltrating myeloid-derived suppressor cells, increased the maturation status of dendritic cells in tumor tissues, enhanced their CD4(+) T-cell stimulation capacity and migration rate of dendritic cells that had phagocytosed tumor-associated antigens into tumor-draining lymph nodes, suggesting a positive impact on GM-CSF-sensitized innate immunity. Furthermore, KO/WGM mice displayed activated adaptive immunity by attenuating regulatory CD4(+) T subsets and increasing numbers of Th17 and memory CD44(hi)CD4(+) T subsets, both of which elicited superior antitumor effects as evidenced by adoptive cell transfer. In vivo depletion assays also revealed that CD4(+) T cells were the main effectors of the persistent antitumor immunity. Our data collectively underscore a negative role of LTB4/BLT1 signaling in effective generation and maintenance of GM-CSF-induced antitumor memory CD4(+) T cells.

Areas of Left Perisylvian Cortex Mediate Auditory-Verbal Short-Term Memory

ERIC Educational Resources Information Center

Koenigs, Michael; Acheson, Daniel J.; Barbey, Aron K.; Solomon, Jeffrey; Postle, Bradley R.; Grafman, Jordan

2011-01-01

A contentious issue in memory research is whether verbal short-term memory (STM) depends on a neural system specifically dedicated to the temporary maintenance of information, or instead relies on the same brain areas subserving the comprehension and production of language. In this study, we examined a large sample of adults with acquired brain…

Reactivation-Dependent Amnesia for Appetitive Memories Is Determined by the Contingency of Stimulus Presentation

ERIC Educational Resources Information Center

Lee, Jonathan L. C.; Everitt, Barry J.

2008-01-01

Previously acquired aversive and appetitive memories are not stable and permanent. The reactivation of such memories by re-exposure to training stimuli renders them vulnerable to disruption by amnestic agents such as the noncompetitive N-methyl-"D"-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-"SH"-dibenzo{a,d}cyclohepten-5,10imine…

A statistical mechanics approach to autopoietic immune networks

NASA Astrophysics Data System (ADS)

Barra, Adriano; Agliari, Elena

2010-07-01

In this work we aim to bridge theoretical immunology and disordered statistical mechanics. We introduce a model for the behavior of B-cells which naturally merges the clonal selection theory and the autopoietic network theory as a whole. From the analysis of its features we recover several basic phenomena such as low-dose tolerance, dynamical memory of antigens and self/non-self discrimination.

Music evoked autobiographical memory after severe acquired brain injury: preliminary findings from a case series.

PubMed

Baird, A; Samson, S

2014-01-01

Music evoked autobiographical memories (MEAMs) have been characterised in the healthy population, but not, to date, in patients with acquired brain injury (ABI). Our aim was to investigate music compared with verbal evoked autobiographical memories. Five patients with severe ABI and matched controls completed the experimental music (MEAM) task (a written questionnaire) while listening to 50 "Number 1 Songs of the Year" (from 1960 to 2010). Patients also completed the Autobiographical Memory Interview (AMI) and a standard neuropsychological assessment. With the exception of Case 5, who reported no MEAMs and no autobiographical incidents on the AMI and who also had impaired pitch perception, the range of frequency and type of MEAMs in patients was broadly in keeping with their matched controls. The relative preservation of MEAMs in four cases was particularly noteworthy given their impaired verbal and/or visual anterograde memory, and in three cases, autobiographical memory impairment. The majority of MEAMs in both cases and matched controls were of a person/people or a period of life. In three patients music was more efficient at evoking autobiographical memories than the AMI verbal prompts. This is the first study of MEAMs after ABI. The findings suggest that music is an effective stimulus for eliciting autobiographical memories, and may be beneficial in the rehabilitation of autobiographical amnesia, but only in patients without a fundamental deficit in autobiographical recall memory and intact pitch perception.

Immunogenicity of a Booster Dose of Quadrivalent Meningococcal Conjugate Vaccine in Previously Immunized HIV-Infected Children and Youth.

PubMed

Warshaw, Meredith G; Siberry, George K; Williams, Paige; Decker, Michael D; Jean-Philippe, Patrick; Lujan-Zilbermann, Jorge

2017-09-01

The US Advisory Committee on Immunization Practices recommends a booster dose of quadrivalent meningococcal conjugate vaccine (MCV4) after initial immunization for patients at high risk for meningococcal infection. The International Maternal Pediatric Adolescents AIDS Clinical Trials (IMPAACT) P1065 trial evaluated the use of MCV4 in human immunodeficiency virus (HIV)-infected children and youth. The final step of this trial was an open-label study of an MCV4 booster dose 3.5 years after primary MCV4 immunization. Antibody titers were evaluated at the time of the booster vaccine and 1, 4, and 24 weeks after the booster. Immunogenicity was measured by rabbit serum bactericidal antibody (rSBA) against each meningococcal serogroup. Immunologic memory was defined as either seroprotection (rSBA titer ≥1:128) or a ≥4-fold increase 1 week after the booster dose. Primary response was defined as either a ≥4-fold response or seropositivity 4 weeks after the booster in the absence of immunologic memory. Adverse events were assessed for 4 weeks after the booster dose. Of 174 participants with serology results at entry and 1 and 4 weeks later, the percentage with protective antibody levels at entry varied according to serogroup, ranging from a low of 26% for serogroup C to a high of 68% for serogroup A. A memory response to at least 1 serogroup occurred in 98% of the participants: 93% each for serogroups A and Y, 88% for serogroup C, and 94% for serogroup W-135; 83% had a memory response to all 4 serogroups. Overall, rates of any memory or primary response were ≥90% for all serogroups. No serious adverse events were encountered. A booster dose of MCV4 elicited a memory response in 88% to 94% of previously immunized HIV-infected participants depending on serogroup, including those who lacked a protective titer level for that serogroup before booster vaccination. © The Author 2017. Published by the Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

PubMed

Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

2015-01-01

Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.

Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma.

PubMed

Cooke, Rachel E; Gherardin, Nicholas A; Harrison, Simon J; Quach, Hang; Godfrey, Dale I; Prince, Miles; Koldej, Rachel; Ritchie, David S

2016-09-06

The Vk*MYC transgenic and transplant mouse models of multiple myeloma (MM) are well established as a research tool for anti-myeloma drug discovery. However, little is known of the immune response in these models. Understanding the immunological relevance of these models is of increasing importance as immunotherapeutic drugs are developed against MM. We set out to examine how cellular immunity is affected in Vk*MYC mouse models and compare that to the immunology of patients with newly diagnosed and relapsed/refractory MM. We found that there were significant immunological responses in mice developing either spontaneous (transgenic) or transplanted MM as a consequence of the degree of tumor burden. Particularly striking were the profound B cell lymphopenia and the expansion of CD8(+) effector memory T cells within the lymphocyte population that progressively developed with advancing disease burden, mirroring changes seen in human MM. High disease burden was also associated with increased inflammatory cytokine production by T lymphocytes, which is more fitting with relapsed/refractory MM in humans. These findings have important implications for the application of this mouse model in the development of MM immunotherapies. Trial registration LitVacc ANZCTR trial ID ACTRN12613000344796; RevLite ANZCTR trial ID NCT00482261.

Immunology of Gut Mucosal Vaccines

PubMed Central

Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

2011-01-01

Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

Pneumococcal conjugate vaccine use in adults - Addressing an unmet medical need for non-bacteremic pneumococcal pneumonia.

PubMed

Sings, Heather L

2017-09-25

Streptococcus pneumoniae is a frequent cause of community acquired pneumonia (CAP), with the largest burden of disease attributed to non-bacteremic pneumonia. Due to the high persistent burden of disease, pneumococcal pneumonia, particularly non-bacteremic pneumococcal pneumonia, continues to be a major public health concern. There are currently two pneumococcal vaccines approved for use in adults in the United States (US) and other countries worldwide: a 23-valent pneumococcal simple polysaccharide vaccine (PPV23), and a 13-valent pneumococcal conjugate vaccine (PCV13). The capsular polysaccharides included in PPV23 induce antibodies primarily by a T-cell independent mechanism, thus the immune response is short lived and lacks the ability to elicit an anamnestic response. PCV13, on the other hand, has the bacterial polysaccharides covalently conjugated to an immunogenic carrier protein resulting in the formation of memory B lymphocytes, thus proving long-acting immunologic memory and an anamnestic response. Despite 30years of use, the question of PPV23 vaccine efficacy, particularly with respect to efficacy for non-bacteremic pneumonia, has been extensively debated and investigated; whereas PCV13 efficacy against vaccine-type pneumococcal CAP, both bacteremic and non-bacteremic, was confirmed in a large randomized controlled trial in older adults. PCV13 was approved under the US Food and Drug Administration's accelerated pathway, which allows for earlier approval of products that provide meaningful benefit over existing treatments - in this case, protection of adults from non-bacteremic pneumococcal pneumonia. Its use is now increasingly recommended globally. This article summarizes the history and use of PPV23 and PCV13 in adults and how vaccination of adults with PCV13 addresses an unmet medical need. Copyright © 2017 Elsevier Ltd. All rights reserved.

About Sleep's Role in Memory

PubMed Central

2013-01-01

Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of “sleep and memory” research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems. PMID:23589831

[Evaluation of memory in acquired brain injury: a comparison between the Wechsler Memory Scale and the Rivermead Behaviour Memory Test].

PubMed

Guinea-Hidalgo, A; Luna-Lario, P; Tirapu-Ustárroz, J

Learning processes and memory are frequently compromised in acquired brain injury (ABI), while at the same time such involvement is often heterogeneous and a source of deficits in other cognitive capacities and significant functional limitations. A good neuropsychological evaluation of memory is designed to study not only the type, intensity and nature of the problems, but also the way they manifest in daily life. This study examines the correlation between a traditional memory test, the Wechsler Memory Scale-III (WMS-III), and a memory test that is considered to be functional, the Rivermead Behavioural Memory Test (RBMT), in a sample of 60 patients with ABI. All the correlations that were observed were moderate. Greater correlations were found among the verbal memory subtests than among the visual memory tests. An important number of subjects with below-normal scalar scores on the WMS-III correctly performed (either fully or partially) the corresponding test in the RBMT. The joint use of the WMS-III and RBMT in evaluation can provide a more comprehensive analysis of the memory deficits and their rehabilitation. The lower scores obtained in the WMS-III compared to those of the RBMT indicate greater sensitivity of the former. Nevertheless, further testing needs to be carried out in the future to compare the performance in the tests after the patients and those around them have subjectively assessed their functional limitations. This would make it possible to determine which of the two tests offers the best balance between sensitivity and specificity, as well as a higher predictive value.

A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector1

PubMed Central

Bolinger, Beatrice; Sims, Stuart; O’Hara, Geraldine; de Lara, Catherine; Tchilian, Elma; Firner, Sonja; Engeler, Daniel; Ludewig, Burkhard; Klenerman, Paul

2013-01-01

CD8+ T cell memory inflation, first described in murine cytomegalovirus (MCMV) infection, is characterized by the accumulation of high-frequency, functional antigen-specific CD8+ T cell pools with an effector-memory phenotype and enrichment in peripheral organs. Although persistence of antigen is considered essential, the rules underpinning memory inflation are still unclear. The MCMV model is, however, complicated by the virus’s low-level persistence, and stochastic reactivation. We developed a new model of memory inflation based upon a βgal-recombinant adenovirus vector (Ad-LacZ). After i.v. administration in C57BL/6 mice we observe marked memory inflation in the βgal96 epitope, while a second epitope, βgal497, undergoes classical memory formation. The inflationary T cell responses show kinetics, distribution, phenotype and functions similar to those seen in MCMV and are reproduced using alternative routes of administration. Memory inflation in this model is dependent on MHC Class II. As in MCMV, only the inflating epitope showed immunoproteasome-independence. These data define a new model for memory inflation, which is fully replication-independent, internally controlled and reproduces the key immunologic features of the CD8+ T cell response. This model provides insight into the mechanisms responsible for memory inflation, and since it is based on a vaccine vector, also is relevant to novel T cell-inducing vaccines in humans. PMID:23509359

The CD8+ memory T-cell state of readiness is actively maintained and reversible

PubMed Central

Allam, Atef; Conze, Dietrich B.; Giardino Torchia, Maria Letizia; Munitic, Ivana; Yagita, Hideo; Sowell, Ryan T.; Marzo, Amanda L.

2009-01-01

The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cycle state and responded to stimulation like naive T cells, as assessed by proliferation, dependence upon costimulation, and interferon-γ production, without losing cell surface markers associated with memory. The memory state was maintained by signaling via members of the tumor necrosis factor receptor superfamily, CD27 and 4-1BB. Foxo1, a transcription factor involved in T-cell quiescence, was reduced in memory cells, and stimulation of naive CD8 cells via CD27 caused Foxo1 to be phosphorylated and emigrate from the nucleus in a phosphatidylinositol-3 kinase–dependent manner. Consistent with these results, maintenance of G1 in vivo was compromised in antigen-specific memory T cells in vesicular stomatitis virus-infected CD27-deficient mice. Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance. PMID:19617575

When Delays Improve Memory: Stabilizing Memory in Children May Require Time.

PubMed

Darby, Kevin P; Sloutsky, Vladimir M

2015-12-01

Memory is critical for learning, cognition, and cognitive development. Recent work has suggested that preschool-age children are vulnerable to catastrophic levels of memory interference, in which new learning dramatically attenuates memory for previously acquired knowledge. In the work reported here, we investigated the effects of consolidation on children's memory by introducing a 48-hr delay between learning and testing. In Experiment 1, the delay improved children's memory and eliminated interference. Results of Experiment 2 suggest that the benefit of this delay is limited to situations in which children are given enough information to form complex memory structures. These findings have important implications for understanding consolidation processes and memory development. © The Author(s) 2015.

Lymphadenopathy, productive cough, eosinophilia, and a new-onset acquired immunodeficiency syndrome.

PubMed

Dzhindzhikhashvili, Megi; Absy-Jaghab, Minou; Frieri, Marianne

2011-01-01

We present a complicated case of a human immunodeficiency virus (HIV)-infected male patient with a complexity of confounding and overlapping symptoms that can masquerade as another diagnosis. This is the case of a patient with multiple secondary sexually transmitted infectious diseases, lymphadenopathy, B-cell lymphoma, a productive cough, a clinical picture suggestive of pulmonary tuberculosis, eosinophilia, and a new-onset acquired immunodeficiency syndrome. Our presentation highlights those deteriorations seen in our patient as well as various underlying immunologic changes in the content of HIV infection. This case may not be unique, but less severe cases occur and can be underdiagnosed, indicating the need of timely screening, close evaluation, and monitoring of HIV-infected patients as well as those with high risk of acquiring HIV.

Behavioral correlates of changes in hippocampal gray matter structure during acquisition of foreign vocabulary.

PubMed

Bellander, Martin; Berggren, Rasmus; Mårtensson, Johan; Brehmer, Yvonne; Wenger, Elisabeth; Li, Tie-Qiang; Bodammer, Nils C; Shing, Yee-Lee; Werkle-Bergner, Markus; Lövdén, Martin

2016-05-01

Experience can affect human gray matter volume. The behavioral correlates of individual differences in such brain changes are not well understood. In a group of Swedish individuals studying Italian as a foreign language, we investigated associations among time spent studying, acquired vocabulary, baseline performance on memory tasks, and gray matter changes. As a way of studying episodic memory training, the language learning focused on acquiring foreign vocabulary and lasted for 10weeks. T1-weighted structural magnetic resonance imaging and cognitive testing were performed before and after the studies. Learning behavior was monitored via participants' use of a smartphone application dedicated to the study of vocabulary. A whole-brain analysis showed larger changes in gray matter structure of the right hippocampus in the experimental group (N=33) compared to an active control group (N=23). A first path analyses revealed that time spent studying rather than acquired knowledge significantly predicted change in gray matter structure. However, this association was not significant when adding performance on baseline memory measures into the model, instead only the participants' performance on a short-term memory task with highly similar distractors predicted the change. This measure may tap similar individual difference factors as those involved in gray matter plasticity of the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive Load Theory: A Broader View on the Role of Memory in Learning and Education

ERIC Educational Resources Information Center

Paas, Fred; Ayres, Paul

2014-01-01

According to cognitive load theory (CLT), the limitations of working memory (WM) in the learning of new tasks together with its ability to cooperate with an unlimited long-term memory (LTM) for familiar tasks enable human beings to deal effectively with complex problems and acquire highly complex knowledge and skills. With regard to WM, CLT has…

Updating Existing Emotional Memories Involves the Frontopolar/Orbito-frontal Cortex in Ways that Acquiring New Emotional Memories Does Not

ERIC Educational Resources Information Center

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2011-01-01

In life, we must often learn new associations to people, places, or things we already know. The current fMRI study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral…

Honeybees consolidate navigation memory during sleep.

PubMed

Beyaert, Lisa; Greggers, Uwe; Menzel, Randolf

2012-11-15

Sleep is known to support memory consolidation in animals, including humans. Here we ask whether consolidation of novel navigation memory in honeybees depends on sleep. Foragers were exposed to a forced navigation task in which they learned to home more efficiently from an unexpected release site by acquiring navigational memory during the successful homing flight. This task was quantified using harmonic radar tracking and applied to bees that were equipped with a radio frequency identification device (RFID). The RFID was used to record their outbound and inbound flights and continuously monitor their behavior inside the colony, including their rest during the day and sleep at night. Bees marked with the RFID behaved normally inside and outside the hive. Bees slept longer during the night following forced navigation tasks, but foraging flights of different lengths did not lead to different rest times during the day or total sleep time during the night. Sleep deprivation before the forced navigation task did not alter learning and memory acquired during the task. However, sleep deprivation during the night after forced navigation learning reduced the probability of returning successfully to the hive from the same release site. It is concluded that consolidation of novel navigation memory is facilitated by night sleep in bees.

The hippocampus and memory for orderly stimulus relations

PubMed Central

Dusek, Jeffery A.; Eichenbaum, Howard

1997-01-01

Human declarative memory involves a systematic organization of information that supports generalizations and inferences from acquired knowledge. This kind of memory depends on the hippocampal region in humans, but the extent to which animals also have declarative memory, and whether inferential expression of memory depends on the hippocampus in animals, remains a major challenge in cognitive neuroscience. To examine these issues, we used a test of transitive inference pioneered by Piaget to assess capacities for systematic organization of knowledge and logical inference in children. In our adaptation of the test, rats were trained on a set of four overlapping odor discrimination problems that could be encoded either separately or as a single representation of orderly relations among the odor stimuli. Normal rats learned the problems and demonstrated the relational memory organization through appropriate transitive inferences about items not presented together during training. By contrast, after disconnection of the hippocampus from either its cortical or subcortical pathway, rats succeeded in acquiring the separate discrimination problems but did not demonstrate transitive inference, indicating that they had failed to develop or could not inferentially express the orderly organization of the stimulus elements. These findings strongly support the view that the hippocampus mediates a general declarative memory capacity in animals, as it does in humans. PMID:9192700

Acquired Immunological Tolerance to a Fraction of Bovine Gamma Globulin

PubMed Central

Dresser, D. W.

1961-01-01

A state of acquired immunological tolerance to bovine gamma globulin (BGG) has been observed in CBA mice injected with 10 mg. BGG within 12 hours of birth. Tolerance was demonstrated by a lack of immune elimination of 131I labelled BGG (BGG-131I) after prior challenge with Freund's adjuvant containing BGG. The degree of tolerance was found to diminish when the time between the tolerance injection and the challenge injection with adjuvant was increased. Mice were found to be tolerant 4 months after injection of 10 mg. BGG at birth but other similarly treated mice were found to be partially immune when challenged 6 months after the tolerance injection. This diminution of tolerance could be prevented by injections of antigen into adult mice whilst they were still tolerant. Precipitin and haemagglutination tests showed that antibody to BGG was present in mice shown to be tolerant to BGG by the antigen-elimination technique. The Ouchterlony double-diffusion technique showed that the mice were tolerant to one fraction of BGG but immune to at least one other fraction. The tolerated fraction of BGG was identified by means of starch-gel electrophoresis. ImagesFIG. 2 PMID:13724353

How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future.

PubMed

Sissons, J G Patrick; Wills, Mark R

2015-06-01

Several decades of research on human cytomegalovirus (HCMV) and the principal mammalian cytomegaloviruses which to varying degrees act as models of HCMV infection, particularly murine, guinea pig and rhesus CMV, have led to the recognition of the CMVs as interesting models of persistent infection with a large and complex DNA virus, which have been highly informative of the immunology and molecular pathogenesis of the virus-host relationship in the normal host. However, it is appropriate to ask how this relative wealth of knowledge has influenced the understanding and management of clinical disease due to HCMV. This article considers the immunology of cytomegalovirus in the normal human host, and the interrelated issue of the sites of HCMV latency and mechanisms of reactivation in the myeloid cell lineage, and in related in vitro model systems. The way in which this site of latency conditions the immune response, and emerging information on the special features of the adaptive immune response to HCMV during latency are also considered. Examples of HCMV disease associated with acquired immunosuppression, principally in the context of transplantation, but also as a consequence of HIV/AIDS and immune reconstitution inflammatory syndrome, are then discussed, with a particular emphasis on how understanding the immunology of persistent infection may contribute to managing CMV disease now and in future.

Immunologic and Infectious Diseases in Pediatric Cardiac Critical Care: Proceedings of the 10th International Pediatric Cardiac Intensive Care Society Conference.

PubMed

Axelrod, David M; Alten, Jeffrey A; Berger, John T; Hall, Mark W; Thiagarajan, Ravi; Bronicki, Ronald A

2015-10-01

Since the inception of the Pediatric Cardiac Intensive Care Society (PCICS) in 2003, remarkable advances in the care of children with critical cardiac disease have been developed. Specialized surgical approaches, anesthesiology practices, and intensive care management have all contributed to improved outcomes. However, significant morbidity often results from immunologic or infectious disease in the perioperative period or during a medical intensive care unit admission. The immunologic or infectious illness may lead to fever, which requires the attention and resources of the cardiac intensivist. Frequently, cardiopulmonary bypass leads to an inflammatory state that may present hemodynamic challenges or complicate postoperative care. However, inflammation unchecked by a compensatory anti-inflammatory response may also contribute to the development of capillary leak and lead to a complicated intensive care unit course. Any patient admitted to the intensive care unit is at risk for a hospital acquired infection, and no patients are at greater risk than the child treated with mechanical circulatory support. In summary, the prevention, diagnosis, and management of immunologic and infectious diseases in the pediatric cardiac intensive care unit is of paramount importance for the clinician. This review from the tenth PCICS International Conference will summarize the current knowledge in this important aspect of our field. © The Author(s) 2015.

Cerebellar contribution to spatial event processing: involvement in procedural and working memory components.

PubMed

Mandolesi, L; Leggio, M G; Graziano, A; Neri, P; Petrosini, L

2001-12-01

Spatial function is one of the cognitive functions altered in the presence of cerebellar lesions. We investigated the cerebellar contribution to the acquisition of spatial procedural and working memory components by means of a radial maze. To establish whether a cerebellar lesion would cause a deficit in solving the radial maze, a first experiment was carried out by using a full-baited maze procedure in different experimental groups, with or without cerebellar lesion and with or without pretraining. Non-pretrained hemicerebellectomized (HCbed) animals exhibited impaired performances in all (motor, spatial and procedural) task aspects. Pre-trained HCbed animals performed similarly to control animals in the task aspects linked to the processing of spatial and procedural factors. To distinguish procedural from working memory components, a forced-choice paradigm of the radial maze was used in the second experiment. Non-pretrained HCbed rats continued to make a lot of errors and show severe perseverative tendencies, already observed in the first experiment, supporting a specific cerebellar role in acquiring new behaviours and in modifying them in relation to the context. Interestingly, hindered from putting the acquired explorative patterns into action and compelled to use only working memory abilities, the pretrained HCbed group exhibited a dramatic worsening of performance. In conclusion, the present findings demonstrate that cerebellar damage induces a specific behaviour in radial maze tasks, characterized by an inflexible use of the procedures (if indeed any procedure was acquired before the lesion) and by a severe impairment in working memory processes.

Explicit pre-training instruction does not improve implicit perceptual-motor sequence learning

PubMed Central

Sanchez, Daniel J.; Reber, Paul J.

2012-01-01

Memory systems theory argues for separate neural systems supporting implicit and explicit memory in the human brain. Neuropsychological studies support this dissociation, but empirical studies of cognitively healthy participants generally observe that both kinds of memory are acquired to at least some extent, even in implicit learning tasks. A key question is whether this observation reflects parallel intact memory systems or an integrated representation of memory in healthy participants. Learning of complex tasks in which both explicit instruction and practice is used depends on both kinds of memory, and how these systems interact will be an important component of the learning process. Theories that posit an integrated, or single, memory system for both types of memory predict that explicit instruction should contribute directly to strengthening task knowledge. In contrast, if the two types of memory are independent and acquired in parallel, explicit knowledge should have no direct impact and may serve in a “scaffolding” role in complex learning. Using an implicit perceptual-motor sequence learning task, the effect of explicit pre-training instruction on skill learning and performance was assessed. Explicit pre-training instruction led to robust explicit knowledge, but sequence learning did not benefit from the contribution of pre-training sequence memorization. The lack of an instruction benefit suggests that during skill learning, implicit and explicit memory operate independently. While healthy participants will generally accrue parallel implicit and explicit knowledge in complex tasks, these types of information appear to be separately represented in the human brain consistent with multiple memory systems theory. PMID:23280147

Acquired amnesia in childhood: a single case study.

PubMed

Vicari, Stefano; Menghini, Deny; Di Paola, Margherita; Serra, Laura; Donfrancesco, Alberto; Fidani, Paola; Milano, Giuseppe Maria; Carlesimo, Giovanni Augusto

2007-03-02

We report the case of C.L., an 8-year-old child who, following the surgical removal of an ependymoma from the left cerebral ventricle at the age of 4 years, developed significant difficulties in retaining day-to-day events and information. A thorough neuropsychological analysis documented in C.L. a severe anterograde amnesic syndrome, characterised by normal short-term memory, but poor performance on episodic long-term memory tests. In particular, C.L. demonstrated virtually no ability to recollect new verbal information several minutes after the presentation. As for semantic memory, C.L. demonstrated general semantic competencies, which, depending on the test, ranged from the level of a 6-year-old girl to a level corresponding to her actual chronological age. Finding a patient who, despite being severely impaired in the ability to recollect new episodic memories, still demonstrates at least partially preserved abilities to acquire new semantic knowledge suggests that neural circuits implicated in the memorisation of autobiographical events and factual information do not overlap completely. This case is examined in the light of growing literature concerned with the dissociation between episodic and semantic memory in childhood amnesia.

Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux.

PubMed

Ahmed, Raya; Roger, Laureline; Costa Del Amo, Pedro; Miners, Kelly L; Jones, Rhiannon E; Boelen, Lies; Fali, Tinhinane; Elemans, Marjet; Zhang, Yan; Appay, Victor; Baird, Duncan M; Asquith, Becca; Price, David A; Macallan, Derek C; Ladell, Kristin

2016-12-13

Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (T SCM ) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the T SCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of T SCM cells in vivo using stable isotope labeling with heavy water. The data indicate that T SCM cells in both young and elderly subjects are maintained by ongoing proliferation. In line with this finding, T SCM cells displayed limited telomere length erosion coupled with high expression levels of active telomerase and Ki67. Collectively, these observations show that T SCM cells exist in a state of perpetual flux throughout the human lifespan. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Structural synaptic plasticity in the hippocampus induced by spatial experience and its implications in information processing.

PubMed

Carasatorre, M; Ramírez-Amaya, V; Díaz Cintra, S

2016-10-01

Long-lasting memory formation requires that groups of neurons processing new information develop the ability to reproduce the patterns of neural activity acquired by experience. Changes in synaptic efficiency let neurons organise to form ensembles that repeat certain activity patterns again and again. Among other changes in synaptic plasticity, structural modifications tend to be long-lasting which suggests that they underlie long-term memory. There is a large body of evidence supporting that experience promotes changes in the synaptic structure, particularly in the hippocampus. Structural changes to the hippocampus may be functionally implicated in stabilising acquired memories and encoding new information. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Protein synthesis underlies post-retrieval memory consolidation to a restricted degree only when updated information is obtained

PubMed Central

Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutiérrez, Ranier; Bermudez-Rattoni, Federico

2005-01-01

Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here we show that intracortical blockade of protein synthesis in the gustatory cortex after retrieval of taste-recognition memory disrupts previously consolidated memory to a restricted degree only if the experience is updated. Our results suggest that retrieved memory can be modified as part of a mechanism for incorporating updated information into previously consolidated memory. PMID:16166395

Cellular Immune Response in Young Children Accounts for Recurrent Acute Otitis Media

PubMed Central

Sharma, Sharad K.; Pichichero, Michael E.

2013-01-01

Acute otitis media (AOM) is a common disease in young children. Streptococcus pneumoniae(Spn) and Haemophilus influenzae (NTHi) are the two most common pathogens that cause AOM. Over the past 5 years our group has been studying the immunologic profile of children that experience repeated AOM infections despite tympanocentesis drainage of middle ear fluid and individualized antibiotic treatment; we call these children stringently-defined otitis-prone (sOP). Although protection against AOM is primarily mediated by ototpathogen-specific antibody, our recent studies suggest that suboptimal memory B-& T- cell responses and an immaturity in antigen presenting cells may play a significant role in the propensity to recurrent AOM infections. This review focuses on the studies performed to define immunologic dysfunction in sOP children. PMID:24022464

Maintenance of CCL5 mRNA stores by post-effector and memory CD8 T cells is dependent on transcription and is coupled to increased mRNA stability.

PubMed

Marçais, Antoine; Tomkowiak, Martine; Walzer, Thierry; Coupet, Charles-Antoine; Ravel-Chapuis, Aymeric; Marvel, Jacqueline

2006-10-01

Immunological memory is associated with the display of improved effector functions by cells of the adaptive immune system. The storage of untranslated mRNA coding for the CCL5 chemokine by CD8 memory cells is a new process supporting the immediate display of an effector function. Here, we show that, after induction during the primary response, high CCL5 mRNA levels are specifically preserved in CD8 T cells. We have investigated the mechanisms involved in the long-term maintenance of CCL5 mRNA levels by memory CD8 T cells. We demonstrate that the CCL5 mRNA half-life is increased in memory CD8 T cells and that these cells constitutively transcribe ccl5 gene. By inhibiting ccl5 transcription using IL-4, we demonstrate the essential role of transcription in the maintenance of CCL5 mRNA stores. Finally, we show that these stores are spontaneously reconstituted when the inhibitory signal is removed, indicating that the transcription of ccl5 is a default feature of memory CD8 T cells imprinted in their genetic program.

Mapping the navigational knowledge of individually foraging ants, Myrmecia croslandi

PubMed Central

Narendra, Ajay; Gourmaud, Sarah; Zeil, Jochen

2013-01-01

Ants are efficient navigators, guided by path integration and visual landmarks. Path integration is the primary strategy in landmark-poor habitats, but landmarks are readily used when available. The landmark panorama provides reliable information about heading direction, routes and specific location. Visual memories for guidance are often acquired along routes or near to significant places. Over what area can such locally acquired memories provide information for reaching a place? This question is unusually approachable in the solitary foraging Australian jack jumper ant, since individual foragers typically travel to one or two nest-specific foraging trees. We find that within 10 m from the nest, ants both with and without home vector information available from path integration return directly to the nest from all compass directions, after briefly scanning the panorama. By reconstructing panoramic views within the successful homing range, we show that in the open woodland habitat of these ants, snapshot memories acquired close to the nest provide sufficient navigational information to determine nest-directed heading direction over a surprisingly large area, including areas that animals may have not visited previously. PMID:23804615

Recent versus Remote: Flashbulb Memory for 9/11 and Self-Selected Events from the Reminiscence Bump

ERIC Educational Resources Information Center

Denver, Jenny Y.; Lane, Sean M.; Cherry, Katie E.

2010-01-01

In two related studies, we examined flashbulb memories acquired from different points in the lifespan in younger and older adults. When asked to remember flashbulb memories from their lives, older adults were most likely to recall events from the reminiscence bump (Study 1A). In Study 1B, younger and older adults recalled 9/11 and a personal…

Maintenance of memory-type pathogenic Th2 cells in the pathophysiology of chronic airway inflammation.

PubMed

Hirahara, Kiyoshi; Shinoda, Kenta; Endo, Yusuke; Ichikawa, Tomomi; Nakayama, Toshinori

2018-01-01

Immunological memory is critical for long-standing protection against microorganisms; however, certain antigen-specific memory CD4 + T helper (Th) cells drive immune-related pathology, including chronic allergic inflammation such as asthma. The IL-5-producing memory-type Tpath2 subset is important for the pathogenesis of chronic allergic inflammation. This memory-type pathogenic Th2 cell population (Tpath2) can be detected in various allergic inflammatory lesions. However, how these pathogenic populations are maintained at the local inflammatory site has remained unclear. We performed a series of experiments using mice model for chronic airway inflammation. We also investigated the human samples from patients with eosinophilic chronic rhinosinusitis. We recently reported that inducible bronchus-associated lymphoid tissue (iBALT) was shaped during chronic inflammation in the lung. We also found that memory-type Tpath2 cells are maintained within iBALT. The maintenance of the Tpath2 cells within iBALT is supported by specific cell subpopulations within the lung. Furthermore, ectopic lymphoid structures consisting of memory CD4 + T cells were found in nasal polyps of eosinophilic chronic rhinosinusitis patients, indicating that the persistence of inflammation is controlled by these structures. Thus, the cell components that organize iBALT formation may be therapeutic targets for chronic allergic airway inflammation.

Multi-layered epigenetic mechanisms contribute to transcriptional memory in T lymphocytes.

PubMed

Dunn, Jennifer; McCuaig, Robert; Tu, Wen Juan; Hardy, Kristine; Rao, Sudha

2015-05-06

Immunological memory is the ability of the immune system to respond more rapidly and effectively to previously encountered pathogens, a key feature of adaptive immunity. The capacity of memory T cells to "remember" previous cellular responses to specific antigens ultimately resides in their unique patterns of gene expression. Following re-exposure to an antigen, previously activated genes are transcribed more rapidly and robustly in memory T cells compared to their naïve counterparts. The ability for cells to remember past transcriptional responses is termed "adaptive transcriptional memory". Recent global epigenome studies suggest that epigenetic mechanisms are central to establishing and maintaining transcriptional memory, with elegant studies in model organisms providing tantalizing insights into the epigenetic programs that contribute to adaptive immunity. These epigenetic mechanisms are diverse, and include not only classical acetylation and methylation events, but also exciting and less well-known mechanisms involving histone structure, upstream signalling pathways, and nuclear localisation of genomic regions. Current global health challenges in areas such as tuberculosis and influenza demand not only more effective and safer vaccines, but also vaccines for a wider range of health priorities, including HIV, cancer, and emerging pathogens such as Ebola. Understanding the multi-layered epigenetic mechanisms that underpin the rapid recall responses of memory T cells following reactivation is a critical component of this development pathway.

Gender Differences in Mental Simulation during Sentence and Word Processing

ERIC Educational Resources Information Center

Wassenburg, Stephanie I.; de Koning, Björn B.; de Vries, Meinou H.; Boonstra, A. Marije; van der Schoot, Menno

2017-01-01

Text comprehension requires readers to mentally simulate the described situation by reactivating previously acquired sensory and motor information from (episodic) memory. Drawing upon research demonstrating gender differences, favouring girls, in tasks involving episodic memory retrieval, the present study explores whether gender differences exist…

Working Memory Compensates for Hearing Related Phonological Processing Deficit

ERIC Educational Resources Information Center

Classon, Elisabet; Rudner, Mary; Ronnberg, Jerker

2013-01-01

Acquired hearing impairment is associated with gradually declining phonological representations. According to the Ease of Language Understanding (ELU) model, poorly defined representations lead to mismatch in phonologically challenging tasks. To resolve the mismatch, reliance on working memory capacity (WMC) increases. This study investigated…

Color Memory: A Yang-Mills Analog of Gravitational Wave Memory.

PubMed

Pate, Monica; Raclariu, Ana-Maria; Strominger, Andrew

2017-12-29

A transient color flux across null infinity in classical Yang-Mills theory is considered. It is shown that a pair of test "quarks" initially in a color singlet generically acquire net color as a result of the flux. A nonlinear formula is derived for the relative color rotation of the quarks. For a weak color flux, the formula linearizes to the Fourier transform of the soft gluon theorem. This color memory effect is the Yang-Mills analog of the gravitational memory effect.

Color Memory: A Yang-Mills Analog of Gravitational Wave Memory

NASA Astrophysics Data System (ADS)

Pate, Monica; Raclariu, Ana-Maria; Strominger, Andrew

2017-12-01

A transient color flux across null infinity in classical Yang-Mills theory is considered. It is shown that a pair of test "quarks" initially in a color singlet generically acquire net color as a result of the flux. A nonlinear formula is derived for the relative color rotation of the quarks. For a weak color flux, the formula linearizes to the Fourier transform of the soft gluon theorem. This color memory effect is the Yang-Mills analog of the gravitational memory effect.

A case of amnesia at an early age.

PubMed

Brizzolara, Daniela; Casalini, Claudia; Montanaro, Domenico; Posteraro, Federico

2003-01-01

A dissociation between short- and long-term memory (LTM) and between the episodic and the semantic component of LTM is reported in a young girl who became amnesic at the age of 6 after an episode of acute encephalopathy resulting in bilateral frontal, insular, thalamic, ponto-mesencephalic, hippocampal and temporal lesions, as documented by MRI. The girl became amnesic a few months after starting school. A follow-up investigation showed that she was able to learn to read, write and acquire number facts and procedures and to improve her semantic knowledge. Our results show that the features of adult amnesia can also be found in children and that new semantic knowledge can be acquired in spite of an anterograde memory deficit. This dissociation does not agree with theories viewing long-term declarative memory as a unitary process mediated by the hippocampal system, but supports recent hypotheses that the acquisition of semantic knowledge is independent from episodic memory processes, and takes place through spared cortical regions subjacent to the hippocampi (Vargha-Khadem et al., 1997).

Impairment of pneumococcal antigen specific isotype-switched Igg memory B-cell immunity in HIV infected Malawian adults.

PubMed

Iwajomo, Oluwadamilola H; Finn, Adam; Ogunniyi, Abiodun D; Williams, Neil A; Heyderman, Robert S

2013-01-01

Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+) CD27(+) IgM(+) IgD(+)) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.

Immunologic effects of hydroxyurea in sickle cell anemia.

PubMed

Lederman, Howard M; Connolly, Margaret A; Kalpatthi, Ram; Ware, Russell E; Wang, Winfred C; Luchtman-Jones, Lori; Waclawiw, Myron; Goldsmith, Jonathan C; Swift, Andrea; Casella, James F

2014-10-01

Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses. T-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG). Compared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use. Hydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced. Copyright © 2014 by the American Academy of Pediatrics.

Immunologic Effects of Hydroxyurea in Sickle Cell Anemia

PubMed Central

Lederman, Howard M.; Connolly, Margaret A.; Kalpatthi, Ram; Ware, Russell E.; Wang, Winfred C.; Luchtman-Jones, Lori; Waclawiw, Myron; Goldsmith, Jonathan C.; Swift, Andrea

2014-01-01

BACKGROUND AND OBJECTIVE: Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea’s effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1–S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses. METHODS: T-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG). RESULTS: Compared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use. CONCLUSIONS: Hydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced. PMID:25180279

Cognitive Rehabilitation for Children with Acquired Brain Injury

ERIC Educational Resources Information Center

Slomine, Beth; Locascio, Gianna

2009-01-01

Cognitive deficits are frequent consequences of acquired brain injury (ABI) and often require intervention. We review the theoretical and empirical literature on cognitive rehabilitation in a variety of treatment domains including attention, memory, unilateral neglect, speech and language, executive functioning, and family involvement/education.…

The use of the chick embryo chorioallantoic membrane as experimental model to study virus growth and to test the clonal selection hypothesis. The contribution of Sir Mac Farlane Burnet.

PubMed

Ribatti, Domenico

2018-06-07

Sir Mac Farlane Burnet was the most honored of all Australian scientists. In 1960, Burnet shared the Nobel Prize for Medicine with Peter Medawar of Britain for the discovery of acquired immunological tolerance. He developed techniques for growing influenza viruses in the chorioallantoic membrane of the chick embryo. This became a standard laboratory practice. He continued to work with chick embryos long after the use of cell cultures had become general. His virology research resulted in significant discoveries concerning the nature and replication of viruses and their interaction with the immune system. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Role of adult neurogenesis in hippocampal-cortical memory consolidation

PubMed Central

2014-01-01

Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

Empowering Malaria Vaccination by Drug Administration

DTIC Science & Technology

2010-01-01

uric acid . J lmmuno/2009, 183:5208-5220. 13. Mestas J, Hughes CCW: Of mice and not men: differences between mouse and human Immunology. J lmmunol 2004...a strategy to meet this objective. Natural acquisition and evasion of malaria immunity Malaria parasites gene rate strong immune responses, and a...epidemiological observation that naturally acquired immunity fails to prevent re-infection even in areas with high infection rates . CDS+ responses

MEMORY MODULATION

PubMed Central

Roozendaal, Benno; McGaugh, James L.

2011-01-01

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis

PubMed Central

Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Easley, Kirk; Chahroudi, Ann; Mackel, Joseph; Keele, Brandon F.; Long, Samuel; Lifson, Jeffrey; Paiardini, Mirko

2016-01-01

ABSTRACT Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4+ central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4+ transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4+ TCM cells, (ii) increased levels of CD4+ T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8+ T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4+ TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV-infected sooty mangabeys, a natural host for the infection, with a potent antiretroviral therapy (ART) regimen for periods ranging from 2 to 12 months and monitored in detail how suppression of virus replication affected the main virological and immunological features of this nonpathogenic infection. The observed findings provide novel information on both the pathogenesis of residual immunological disease under ART during pathogenic infection and the mechanisms involved in virus persistence during primate lentiviral infections. PMID:27279614

Stress-Induced Cortisol Hampers Memory Generalization

ERIC Educational Resources Information Center

Dandolo, Lisa C.; Schwabe, Lars

2016-01-01

Integrative encoding and generalization across past experiences depends largely on the hippocampus, an area known to be particularly sensitive to stress. Yet, whether stress influences the ability to generalize memories is unknown. We exposed volunteers to a stressor or a control manipulation before they completed an acquired equivalence task…

The magic shrinking machine revisited: The presence of props at recall facilitates memory in 3-year-olds.

PubMed

Dahl, Jonna J; Kingo, Osman S; Krøjgaard, Peter

2015-12-01

In a seminal study Simcock and Hayne (2002) showed that 3-year-olds were unable to use newly acquired words to describe a "magic" event experienced 6 or 12 months earlier. In the reference study the children's verbal recall was tested without props being present. Inspired by recent evidence, the original design was replicated, testing 33-and 39-month-olds (n = 180), but with props present at recall while controlling for potential online reasoning. The results revealed that the children did use newly acquired words to describe their preverbal memory. Thus, the present study shows that nonverbal memories can be verbalized if the recall setting provides a high level of contextual support, a finding relevant to researchers investigating the offset of childhood amnesia. (c) 2015 APA, all rights reserved).

Orexin A Differentially Influences the Extinction Retention of Recent and Remote Fear Memory.

PubMed

Shi, Le; Chen, Wenhao; Deng, Jiahui; Chen, Sijing; Han, Ying; Khan, Muhammad Z; Liu, Jiajia; Que, Jianyu; Bao, Yanping; Lu, Lin; Shi, Jie

2018-01-01

Recently the role of the orexin system in the learning and memory, especially orexin A, which could enhance fear memory through regulating the activity of amygdala, has drawn considerable attention. However, the relationship between orexin A and extinction memory remains unclear. To investigate the effect of orexin A on extinction memory in humans, we recruited 43 male subjects and divided them into a recent group and remote group. After acquiring Pavlovian fear conditioning, individuals in recent group experienced fear extinction 24 h after acquisition, and remote group underwent extinction 2 weeks later. Meanwhile, plasma orexin A levels before extinction were measured by enzyme-linked immunosorbent assay. Both groups received memory test 24 h after fear extinction. The results showed that both recent and remote groups successfully acquired fear conditioning and had spontaneous recovery at test. In particular, the correlational analysis indicated that orexin A levels before extinction were negatively associated with fear responses during test only in recent group, but not in remote group. Moreover, individuals with high orexin A levels still kept low fear responses after extinction in recent group by subgroup analyses. The results suggest that orexin A could influence the retention of recent fear memory extinction, without affecting remote fear extinction. These findings remind us the orexin system can be a potential treatment target for fear-related disorders, and the mechanisms of recent and remote fear extinction may be different.

Evaluation of an attention and memory intervention post-childhood acquired brain injury: Preliminary efficacy, immediate and 6 months post-intervention.

PubMed

Catroppa, Cathy; Stone, Kate; Hearps, Stephen J C; Soo, Cheryl; Anderson, Vicki; Rosema, Stefanie

2015-01-01

Impairments in attention and memory are common sequelae following paediatric acquired brain injury (ABI). While it has been established that such impairments are long-term and, therefore, affect quality-of-life, there is a scarcity of evidence-based interventions to treat these difficulties. The current study aimed to pilot the efficacy of the Amsterdam Memory and Attention Training for Children (Amat-c: English version) using both neuropsychological and ecologically sensitive measures. It was expected that children with attention and memory difficulties post-ABI would show improved performance post-intervention on cognitive and ecological measures, with maintenance at 6 months post-intervention. Ten children with an ABI, between the ages of 8-13 years at the time of recruitment were identified through audits of presentations to a metropolitan paediatric hospital. Each child underwent screening, the 18 week intervention programme, pre-intervention, immediate and 6 month post-intervention assessments. Findings supported the hypothesis that children would show post-intervention (immediate and 6 month) improvement in areas of attention and memory, with generalization to everyday life. Preliminary results provide support for the efficacy of the Amat-c post-childhood ABI. A larger study is needed to confirm these findings, as a reduction in attention and memory difficulties will enhance everyday functioning.

Postreactivation glucocorticoids impair recall of established fear memory.

PubMed

Cai, Wen-Hui; Blundell, Jacqueline; Han, Jie; Greene, Robert W; Powell, Craig M

2006-09-13

Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.

Effects of Prior Knowledge on Memory: Implications for Education

ERIC Educational Resources Information Center

Shing, Yee Lee; Brod, Garvin

2016-01-01

The encoding, consolidation, and retrieval of events and facts form the basis for acquiring new skills and knowledge. Prior knowledge can enhance those memory processes considerably and thus foster knowledge acquisition. But prior knowledge can also hinder knowledge acquisition, in particular when the to-be-learned information is inconsistent with…

State-Space Analysis of Working Memory in Schizophrenia: An FBIRN Study

ERIC Educational Resources Information Center

Janoos, Firdaus; Brown, Gregory; Morocz, Istvan A.; Wells, William M., III

2013-01-01

The neural correlates of "working memory" (WM) in schizophrenia (SZ) have been extensively studied using the multisite fMRI data acquired by the Functional Biomedical Informatics Research Network (fBIRN) consortium. Although univariate and multivariate analysis methods have been variously employed to localize brain responses under differing task…

Similarities of Recently Acquired and Reactivated Memories in Interference

ERIC Educational Resources Information Center

Gordon, William C.

1977-01-01

Together, these studies replicate and extend Gordon and Spear's (1973a) findings that proactive interference decreases as the interval between prior and subsequent learning increases and that reactivation of a prior memory just before subsequent learning significantly increases the proactive interference due to the prior learning. (Author/RK)

Single or Dual Representations for Reading and Spelling?

ERIC Educational Resources Information Center

Holmes, Virginia M.; Babauta, Mariko L.

2005-01-01

Neuropsychological models postulate that the memory representation acquired for use in reading words is separate from the one acquired for use in spelling, while developmental models assume that the same representation is developed for access in both reading and spelling. The dual-representation model contends that there is often more precise…

Subliminally and Supraliminally Acquired Long-Term Memories Jointly Bias Delayed Decisions.

PubMed

Ruch, Simon; Herbert, Elizabeth; Henke, Katharina

2017-01-01

Common wisdom and scientific evidence suggest that good decisions require conscious deliberation. But growing evidence demonstrates that not only conscious but also unconscious thoughts influence decision-making. Here, we hypothesize that both consciously and unconsciously acquired memories guide decisions. Our experiment measured the influence of subliminally and supraliminally presented information on delayed (30-40 min) decision-making. Participants were presented with subliminal pairs of faces and written occupations for unconscious encoding. Following a delay of 20 min, participants consciously (re-)encoded the same faces now presented supraliminally along with either the same written occupations, occupations congruous to the subliminally presented occupations (same wage-category), or incongruous occupations (opposite wage-category). To measure decision-making, participants viewed the same faces again (with occupations absent) and decided on the putative income of each person: low, low-average, high-average, or high. Participants were encouraged to decide spontaneously and intuitively. Hence, the decision task was an implicit or indirect test of relational memory. If conscious thought alone guided decisions (= H 0 ), supraliminal information should determine decision outcomes independently of the encoded subliminal information. This was, however, not the case. Instead, both unconsciously and consciously encoded memories influenced decisions: identical unconscious and conscious memories exerted the strongest bias on income decisions, while both incongruous and congruous (i.e., non-identical) subliminally and supraliminally formed memories canceled each other out leaving no bias on decisions. Importantly, the increased decision bias following the formation of identical unconscious and conscious memories and the reduced decision bias following to the formation of non-identical memories were determined relative to a control condition, where conscious memory formation alone could influence decisions. In view of the much weaker representational strength of subliminally vs. supraliminally formed memories, their long-lasting impact on decision-making is noteworthy.

Boosting Long-Term Memory via Wakeful Rest: Intentional Rehearsal Is Not Necessary, Consolidation Is Sufficient

PubMed Central

Dewar, Michaela; Alber, Jessica; Cowan, Nelson; Della Sala, Sergio

2014-01-01

People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition. PMID:25333957

Subliminally and Supraliminally Acquired Long-Term Memories Jointly Bias Delayed Decisions

PubMed Central

Ruch, Simon; Herbert, Elizabeth; Henke, Katharina

2017-01-01

Common wisdom and scientific evidence suggest that good decisions require conscious deliberation. But growing evidence demonstrates that not only conscious but also unconscious thoughts influence decision-making. Here, we hypothesize that both consciously and unconsciously acquired memories guide decisions. Our experiment measured the influence of subliminally and supraliminally presented information on delayed (30–40 min) decision-making. Participants were presented with subliminal pairs of faces and written occupations for unconscious encoding. Following a delay of 20 min, participants consciously (re-)encoded the same faces now presented supraliminally along with either the same written occupations, occupations congruous to the subliminally presented occupations (same wage-category), or incongruous occupations (opposite wage-category). To measure decision-making, participants viewed the same faces again (with occupations absent) and decided on the putative income of each person: low, low-average, high-average, or high. Participants were encouraged to decide spontaneously and intuitively. Hence, the decision task was an implicit or indirect test of relational memory. If conscious thought alone guided decisions (= H0), supraliminal information should determine decision outcomes independently of the encoded subliminal information. This was, however, not the case. Instead, both unconsciously and consciously encoded memories influenced decisions: identical unconscious and conscious memories exerted the strongest bias on income decisions, while both incongruous and congruous (i.e., non-identical) subliminally and supraliminally formed memories canceled each other out leaving no bias on decisions. Importantly, the increased decision bias following the formation of identical unconscious and conscious memories and the reduced decision bias following to the formation of non-identical memories were determined relative to a control condition, where conscious memory formation alone could influence decisions. In view of the much weaker representational strength of subliminally vs. supraliminally formed memories, their long-lasting impact on decision-making is noteworthy. PMID:28955268

Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient.

PubMed

Dewar, Michaela; Alber, Jessica; Cowan, Nelson; Della Sala, Sergio

2014-01-01

People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.

Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia

PubMed Central

Brocca-Cofano, Egidio; McKinnon, Katherine; Demberg, Thorsten; Venzon, David; Hidajat, Rachmat; Xiao, Peng; Daltabuit-Test, Mara; Patterson, L. Jean; Robert-Guroff, Marjorie

2011-01-01

An effective HIV vaccine requires strong systemic and mucosal, cellular and humoral immunity. Numerous non-human primate studies have investigated memory T cells, but not memory B cells. Humoral immunologic memory is mediated by long-lived antibody-secreting plasma cells and differentiation of memory B cells into short-lived plasma blasts following re-exposure to immunizing antigen. Here we studied memory B cells in vaccinated rhesus macaques. PBMC were stimulated polyclonally using CD40 Ligand, IL-21 and CpG to induce B cell proliferation and differentiation into antibody secreting cells (ASC). Flow cytometry was used for phenotyping and evaluating proliferation by CFSE dilution. B cell responses were quantified by ELISPOT. Methodology was established using PBMC of vaccinated elite-controller macaques that exhibited strong, multi-functional antibody activities. Subsequently, memory B cells elicited by two replicating Ad-recombinant prime/envelope boost regimens were retrospectively evaluated pre- and post- SIV and SHIV challenges. The vaccine regimens induced SIV and HIV Env-specific IgG and IgA memory B cells. Prior to challenge, IgA memory B cells were more numerous than IgG memory B cells, reflecting the mucosal priming immunizations. Pre- and post-challenge memory B cells were correlated with functional antibody responses including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI) and transcytosis inhibition. Post-challenge, Env-specific IgG and IgA memory B cells were correlated with reduced chronic viremia. We conclude that functional antibody responses elicited by our prime/boost regimen were effectively incorporated into the memory B cell pool where they contributed to control of viremia following re-exposure to the immunizing antigen. PMID:21382487

[Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age].

PubMed

Albrecht, Piotr; Antczak, Adam; Hryniewicz, Waleria; Skoczyńska, Anna; Radzikowski, Andrzej; Kedziora-Kornatowska, Kornelia; Bernatowska, Ewa; Stompór, Tomasz; Grodzicki, Tomasz; Gyrczuk, Ewa; Imiela, Jacek; Jedrzejczak, Wiesław; Windak, Adam

2014-02-01

Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD risk groups in the age > 19 years. At these work research findings were described above PPV23 and PCV13 at adults and world recommendations of applying both vaccines in risk groups from 19 years up to the advanced years. Also Polish recommendations of optimum applying of these vaccines were presented. They are recommending applying PCV13 at first in them, while PPV23, if to her readings exist should be given to > or = 8 of weeks from PCV13. In persons > or = 19 years which earlier received 1 or should receive more PPV23 doses first PCV13 dose should be given after the year or later than the last PPV23 dose, and then again PPV23 > or = 8 of weeks from PCV13 and the second PPV23 dose not earlier than 5 years from last PPV23. If the PPV23 application seems to be justified, it is irrespective of the more previous state vaccination against pneumococci, PCV13 should be given to as first.

Memory for light as a quantum process.

PubMed

Lobino, M; Kupchak, C; Figueroa, E; Lvovsky, A I

2009-05-22

We report complete characterization of an optical memory based on electromagnetically induced transparency. We recover the superoperator associated with the memory, under two different working conditions, by means of a quantum process tomography technique that involves storage of coherent states and their characterization upon retrieval. In this way, we can predict the quantum state retrieved from the memory for any input, for example, the squeezed vacuum or the Fock state. We employ the acquired superoperator to verify the nonclassicality benchmark for the storage of a Gaussian distributed set of coherent states.

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2015-10-01

accomplish this, we apply comparative assessments of fMRI mappings of language, memory , and motor function, and performance on clinical neurocognitive...community at a target rate of 13 volunteers per quarter period; acquire fMRI data for language, memory , and visual-motor functions (months 3-12). c...consensus fMRI activation maps for language, memory , and visual-motor tasks (months 8-12). f) Subtask 1f. Prepare publication to disseminate our

What a Nostril Knows: Olfactory Nerve-Evoked AMPA Responses Increase while NMDA Responses Decrease at 24-h Post-Training for Lateralized Odor Preference Memory in Neonate Rat

ERIC Educational Resources Information Center

Yuan, Qi; Harley, Carolyn W.

2012-01-01

Increased AMPA signaling is proposed to mediate long-term memory. Rat neonates acquire odor preferences in a single olfactory bulb if one nostril is occluded at training. Memory testing here confirmed that only trained bulbs support increased odor preference at 24 h. Olfactory nerve field potentials were tested at 24 h in slices from trained and…

Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference.

PubMed

Ellenbogen, Jeffrey M; Hulbert, Justin C; Stickgold, Robert; Dinges, David F; Thompson-Schill, Sharon L

2006-07-11

Mounting behavioral evidence in humans supports the claim that sleep leads to improvements in recently acquired, nondeclarative memories. Examples include motor-sequence learning; visual-discrimination learning; and perceptual learning of a synthetic language. In contrast, there are limited human data supporting a benefit of sleep for declarative (hippocampus-mediated) memory in humans (for review, see). This is particularly surprising given that animal models (e.g.,) and neuroimaging studies (e.g.,) predict that sleep facilitates hippocampus-based memory consolidation. We hypothesized that we could unmask the benefits of sleep by challenging the declarative memory system with competing information (interference). This is the first study to demonstrate that sleep protects declarative memories from subsequent associative interference, and it has important implications for understanding the neurobiology of memory consolidation.

Toxoplasmosis as an unusual cause of massive lymph node enlargement.

PubMed

Jacobs, P

1981-11-14

An immunologically competent adult with acquired toxoplasmosis presented with inguinal lymphadenopathy and associated lymphatic and venous obstruction. A diagnosis of toxoplasmosis was made by demonstration the presence of the trophozoite, and response to therapy, while satisfactory, was slow. Recrudescence of lymphadenopathy was associated with a change from reactive lymphadenitis to angioimmunoblastic lymphadenopathy. There was a dramatic improvement following local therapy and systemic corticosteroids and chlorambucil. The patient remains well.

Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

PubMed

Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

2008-08-01

Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.

Current Features of Secondary (Acquired) Types of Immune Deficiency.

PubMed

Kovalchuk, Leonid V.; Pinegin, Boris V.

1999-12-01

Secondary (acquired) types of immune deficiencies (SID) take a leading place in practice of modern clinical immunology. The causes for SID development are extremely variable. Special attention is concerned with accumulating facts about target action of microorganisms, and first of all viruses, on certain processes in immune system. Damageable action of HIV-1 on cell elements expressing CD4 molecules is known in most precise manner. It is noteworthy that the search of real molecular defects, induced by microorganisms in immune system is required. It is not to be ruled out that the increased level of apoptosis of immune system cells is one of the causes of SID. The basis of it is disbalance between positive and negative activation processes of immunocompetent cells. Multiple factors may serve as apoptogens, including drugs (glucocorticoids etc.), xenobiotics, physical factors (radiation) and many others. In practice of clinical laboratories a certain spectrum of immunological investigations is recommended that allows to diagnose the degree of immunopathology. At present, in clinical practice these methods are focused around flow cytometry (immunophenotyping), immunodiffusion and immunoenzyme tests (determination of immunoglobulins, cytokines, other soluble components of immune system), tests of estimation of immunocompetent cell activation, proliferation and differentiation. As a prospective, some methods, based on identification of molecular defects in cells and soluble factors of immune system, may be taken into consideration.

Depletion of CD8 Memory T Cells for Induction of Tolerance of a Previously Transplanted Kidney Allograft

PubMed Central

Koyama, I.; Nadazdin, O.; Boskovic, S.; Ochiai, T.; Smith, R. N.; Sykes, M.; Sogawa, H.; Murakami, T.; Strom, T. B.; Colvin, R. B.; Sachs, D. H.; Benichou, G.; Cosimi, A. B.; Kawai, T.

2013-01-01

Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti- CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naïve T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide ‘proof of principle’ that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled. PMID:17286617

IMMUNOLOGY OF TAENIA SOLIUM TAENIASIS AND HUMAN CYSTICERCOSIS

PubMed Central

Garcia, Hector H.; Rodriguez, Silvia; Friedland, Jon S.

2018-01-01

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by fecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data is limited by the relative lack of animal models. This manuscript manuscript revises the available information on the immunology of human taeniasis and cysticercosis. PMID:24962350

Immunology of Taenia solium taeniasis and human cysticercosis.

PubMed

Garcia, H H; Rodriguez, S; Friedland, J S

2014-08-01

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by faecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data are limited by the relative lack of animal models. This manuscript revises the available information on the immunology of human taeniasis and cysticercosis. © 2014 John Wiley & Sons Ltd.

Multiple memory systems as substrates for multiple decision systems

PubMed Central

Doll, Bradley B.; Shohamy, Daphna; Daw, Nathaniel D.

2014-01-01

It has recently become widely appreciated that value-based decision making is supported by multiple computational strategies. In particular, animal and human behavior in learning tasks appears to include habitual responses described by prominent model-free reinforcement learning (RL) theories, but also more deliberative or goal-directed actions that can be characterized by a different class of theories, model-based RL. The latter theories evaluate actions by using a representation of the contingencies of the task (as with a learned map of a spatial maze), called an “internal model.” Given the evidence of behavioral and neural dissociations between these approaches, they are often characterized as dissociable learning systems, though they likely interact and share common mechanisms. In many respects, this division parallels a longstanding dissociation in cognitive neuroscience between multiple memory systems, describing, at the broadest level, separate systems for declarative and procedural learning. Procedural learning has notable parallels with model-free RL: both involve learning of habits and both are known to depend on parts of the striatum. Declarative memory, by contrast, supports memory for single events or episodes and depends on the hippocampus. The hippocampus is thought to support declarative memory by encoding temporal and spatial relations among stimuli and thus is often referred to as a relational memory system. Such relational encoding is likely to play an important role in learning an internal model, the representation that is central to model-based RL. Thus, insofar as the memory systems represent more general-purpose cognitive mechanisms that might subserve performance on many sorts of tasks including decision making, these parallels raise the question whether the multiple decision systems are served by multiple memory systems, such that one dissociation is grounded in the other. Here we investigated the relationship between model-based RL and relational memory by comparing individual differences across behavioral tasks designed to measure either capacity. Human subjects performed two tasks, a learning and generalization task (acquired equivalence) which involves relational encoding and depends on the hippocampus; and a sequential RL task that could be solved by either a model-based or model-free strategy. We assessed the correlation between subjects’ use of flexible, relational memory, as measured by generalization in the acquired equivalence task, and their differential reliance on either RL strategy in the decision task. We observed a significant positive relationship between generalization and model-based, but not model-free, choice strategies. These results are consistent with the hypothesis that model-based RL, like acquired equivalence, relies on a more general-purpose relational memory system. PMID:24846190

Characteristics of memory B cells elicited by a highly efficacious HPV vaccine in subjects with no pre-existing immunity.

PubMed

Scherer, Erin M; Smith, Robin A; Simonich, Cassandra A; Niyonzima, Nixon; Carter, Joseph J; Galloway, Denise A

2014-10-01

Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses.

In Search for Boundary Conditions of Reconsolidation: A Failure of Fear Memory Interference

PubMed Central

Schroyens, Natalie; Beckers, Tom; Kindt, Merel

2017-01-01

The presentation of a fear memory cue can result in mere memory retrieval, destabilization of the reactivated memory trace, or the formation of an extinction memory. The interaction between the degree of novelty during reactivation and previous learning conditions is thought to determine the outcome of a reactivation session. This study aimed to evaluate whether contextual novelty can prevent cue-induced destabilization and disruption of a fear memory acquired by non-asymptotic learning. To this end, fear memory was reactivated in a novel context or in the original context of learning, and fear memory reactivation was followed by the administration of propranolol, an amnestic drug. Remarkably, fear memory was not impaired by post-reactivation propranolol administration or extinction training under the usual conditions used in our lab, irrespective of the reactivation context. These unexpected findings are discussed in the light of our current experimental parameters and alleged boundary conditions on memory destabilization. PMID:28469565

Contextual Fear Memories Formed in the Absence of the Dorsal Hippocampus Decay Across Time

PubMed Central

Zelikowsky, Moriel; Bissiere, Stephanie; Fanselow, Michael S.

2012-01-01

Mammals suffering damage to the hippocampus display a dramatic loss of explicit, recently formed memories (retrograde amnesia). In contrast, deficits in the ability to form new memories following hippocampal damage (anterograde amnesia) can be overcome with sufficient training. By combining contextual fear conditioning with lesions of the dorsal hippocampus in rats, we discovered that while animals can form long-term contextual fear memories in the absence of the hippocampus, these memories decay with time, lacking the permanence that is a hallmark characteristic of normal fear memories. These findings indicate that while it is initially possible to acquire explicit memories when the hippocampus is compromised, these memories cannot transfer from a recent to remote state. This suggests that memories formed outside the hippocampus may nevertheless require the hippocampus to undergo systems consolidation, which has important clinical implications for the treatment of memory disorders. PMID:22399761

Does reactivation trigger episodic memory change? A meta-analysis.

PubMed

Scully, Iiona D; Napper, Lucy E; Hupbach, Almut

2017-07-01

According to the reconsolidation hypothesis, long-term memories return to a plastic state upon their reactivation, leaving them vulnerable to interference effects and requiring re-storage processes or else these memories might be permanently lost. The present study used a meta-analytic approach to critically evaluate the evidence for reactivation-induced changes in human episodic memory. Results indicated that reactivation makes episodic memories susceptible to physiological and behavioral interference. When applied shortly after reactivation, interference manipulations altered the amount of information that could be retrieved from the original learning event. This effect was more pronounced for remote memories and memories of narrative structure. Additionally, new learning following reactivation reliably increased the number of intrusions from new information into the original memory. These findings support a dynamic view of long-term memory by showing that memories can be changed long after they were acquired. Copyright © 2016 Elsevier Inc. All rights reserved.

Validity of the MicroDYN Approach: Complex Problem Solving Predicts School Grades beyond Working Memory Capacity

ERIC Educational Resources Information Center

Schweizer, Fabian; Wustenberg, Sascha; Greiff, Samuel

2013-01-01

This study examines the validity of the complex problem solving (CPS) test MicroDYN by investigating a) the relation between its dimensions--rule identification (exploration strategy), rule knowledge (acquired knowledge), rule application (control performance)--and working memory capacity (WMC), and b) whether CPS predicts school grades in…

Event-Related Potential Correlates of Declarative and Non-Declarative Sequence Knowledge

ERIC Educational Resources Information Center

Ferdinand, Nicola K.; Runger, Dennis; Frensch, Peter A.; Mecklinger, Axel

2010-01-01

The goal of the present study was to demonstrate that declarative and non-declarative knowledge acquired in an incidental sequence learning task contributes differentially to memory retrieval and leads to dissociable ERP signatures in a recognition memory task. For this purpose, participants performed a sequence learning task and were classified…

Reverberation, Storage, and Postsynaptic Propagation of Memories during Sleep

ERIC Educational Resources Information Center

Ribeiro, Sidarta; Nicolelis, Miguel A. L.

2004-01-01

In mammals and birds, long episodes of nondreaming sleep ("slow-wave" sleep, SW) are followed by short episodes of dreaming sleep ("rapid-eye-movement" sleep, REM). Both SW and REM sleep have been shown to be important for the consolidation of newly acquired memories, but the underlying mechanisms remain elusive. Here we review…

Hebb, pandemonium and catastrophic hypermnesia: the hippocampus as a suppressor of inappropriate associations.

PubMed

McNaughton, Neil; Wickens, Jeff

2003-01-01

The hippocampus has been proposed as a key component of a "behavioural inhibition system". We explore the implications of this idea for the nature of associative memory--i.e. learning that is distinct from the moulding of response sequences by error correction and reinforcement. It leads to the view that all associative memory depends on purely Hebbian mechanisms. Memories involve acquisition of new goals not the strengthening of new stimulus-response links. Critically, memories will consist of affectively positive and affectively negative associations as well "purely cognitive" information. The hippocampus is seen as a supervisor that is normally "just checking" information about current available goals. When one available goal is pre-eminent there is no hippocampal output and the goal controls the response system. When two or more goals are similarly and highly primed there is conflict. This is detected by the hippocampus which sends output that increases the valence of affectively negative perceptions and so resolves the conflict by suppressing more aversive goals. Such conflict resolution occurs with innate as well as acquired goals and is fundamentally non-memorial. But, in memory paradigms, it can often act to suppress interference on the current trial and, through Hebbian association of the increase in negative affect, decrease the probability of interference on later trials and during consolidation. Both memory-driven and innate behaviour is made hippocampal-dependent by innate and acquired conflicting tendencies and not the class of stimulus presented.

Orexin A Differentially Influences the Extinction Retention of Recent and Remote Fear Memory

PubMed Central

Shi, Le; Chen, Wenhao; Deng, Jiahui; Chen, Sijing; Han, Ying; Khan, Muhammad Z.; Liu, Jiajia; Que, Jianyu; Bao, Yanping; Lu, Lin; Shi, Jie

2018-01-01

Recently the role of the orexin system in the learning and memory, especially orexin A, which could enhance fear memory through regulating the activity of amygdala, has drawn considerable attention. However, the relationship between orexin A and extinction memory remains unclear. To investigate the effect of orexin A on extinction memory in humans, we recruited 43 male subjects and divided them into a recent group and remote group. After acquiring Pavlovian fear conditioning, individuals in recent group experienced fear extinction 24 h after acquisition, and remote group underwent extinction 2 weeks later. Meanwhile, plasma orexin A levels before extinction were measured by enzyme-linked immunosorbent assay. Both groups received memory test 24 h after fear extinction. The results showed that both recent and remote groups successfully acquired fear conditioning and had spontaneous recovery at test. In particular, the correlational analysis indicated that orexin A levels before extinction were negatively associated with fear responses during test only in recent group, but not in remote group. Moreover, individuals with high orexin A levels still kept low fear responses after extinction in recent group by subgroup analyses. The results suggest that orexin A could influence the retention of recent fear memory extinction, without affecting remote fear extinction. These findings remind us the orexin system can be a potential treatment target for fear-related disorders, and the mechanisms of recent and remote fear extinction may be different. PMID:29773974

Increased peripheral blood CD4+ T cell responses to deamidated but not to native gliadin in children with coeliac disease.

PubMed

Lammi, A; Arikoski, P; Vaarala, O; Kinnunen, T; Ilonen, J

2012-05-01

T cell recognition of gliadin from dietary gluten is essential for the pathogenesis of coeliac disease (CD). The aim of the present study was to analyse whether gliadin-specific T cells are detectable in the circulation of children with newly diagnosed coeliac disease by using a sensitive carboxfluorescein diacetate succinimidyl ester (CFSE) dilution method. Peripheral blood CD4(+) T cell responses were analysed in 20 children at diagnosis of CD and compared to those in 64 healthy control children carrying the CD-associated human leucocyte antigen (HLA)-DQ2 or -DQ8 alleles. Deamidated gliadin (gTG)-specific T cells were detectable in the peripheral blood of more than half the children with CD (11 of 20, 55%) compared to 15 of 64 (23.4%) of the control children (P = 0.008). Proliferative responses to gTG were also significantly stronger in children with CD than in controls (P = 0.01). In contrast, T cells specific to native gliadin were detectable at comparable frequencies in children with CD (two of 19, 10.5%) and controls (13 of 64, 20.3%). gTG-specific T cells had a memory phenotype more often than those specific to native gliadin in children with CD (P = 0.02), whereas controls had similar percentages of memory cells in both stimulations. Finally, gTG-specific CD4(+) T cells had a higher expression of the gut-homing molecule β7 integrin than those specific to the control antigen tetanus toxoid. Collectively, our current results demonstrate that the frequency of circulating memory CD4(+) T cells specific to gTG but not native gliadin is increased in children with newly diagnosed CD. © 2012 The Authors;Clinical and Experimental Immunology © 2012 British Society for Immunology.

Evaluation of a Computer-Based Revision Prompting Intervention for Undergraduate Writers with Acquired Brain Injury

ERIC Educational Resources Information Center

Ledbetter, Alexander K.

2017-01-01

People with acquired brain injury (ABI) present with impairments in working memory and executive functions, and these cognitive deficits contribute to difficulty self-regulating the production of expository writing. Cognitive processes involved in carrying out complex writing tasks include planning, generating text, and reviewing or revising text…

Head west or left, east or right: interactions between memory systems in neurocognitive aging

PubMed Central

Pereira, Inês Tomás; Gallagher, Michela; Rapp, Peter R.

2018-01-01

Cognitive aging is accompanied by decline in multiple domains of memory. Here, we developed a T-maze task that required rats to learn competing hippocampal, and striatal navigation strategies in succession, across days. A final session increased demands on cognitive flexibility and required within-day switching between strategies, emphasizing capacities that engage the prefrontal cortex. Background characterization in young and aged rats used a water maze protocol optimized for individual differences in hippocampal integrity. Consistent with earlier work, young adults acquired place strategies in the T-maze faster than response, whereas the opposite was observed in aged rats with impaired spatial memory. The novel result was that aged animals with preserved spatial memory displayed a qualitatively distinct pattern, acquiring place and response strategies equally rapidly, without disruption when switching between them. Subsequent in situ hybridization for the plasticity-related immediate-early gene Arc revealed that while increasing demands on cognitive flexibility and within-day strategy switching potently engaged the prefrontal cortex in young adult and aged-impaired rats, Arc expression was insensitive in aged rats with normal spatial memory and superior switching abilities. Together, the results indicate that cognitive aging is an emergent property of the interactions between memory systems, and that successful cognitive outcomes reflect a distinct neuroadaptive process rather than a slower rate of aging. PMID:26281759

Effect of episodic and working memory impairments on semantic and cognitive procedural learning at alcohol treatment entry.

PubMed

Pitel, Anne Lise; Witkowski, Thomas; Vabret, François; Guillery-Girard, Bérengère; Desgranges, Béatrice; Eustache, Francis; Beaunieux, Hélène

2007-02-01

Chronic alcoholism is known to impair the functioning of episodic and working memory, which may consequently reduce the ability to learn complex novel information. Nevertheless, semantic and cognitive procedural learning have not been properly explored at alcohol treatment entry, despite its potential clinical relevance. The goal of the present study was therefore to determine whether alcoholic patients, immediately after the weaning phase, are cognitively able to acquire complex new knowledge, given their episodic and working memory deficits. Twenty alcoholic inpatients with episodic memory and working memory deficits at alcohol treatment entry and a control group of 20 healthy subjects underwent a protocol of semantic acquisition and cognitive procedural learning. The semantic learning task consisted of the acquisition of 10 novel concepts, while subjects were administered the Tower of Toronto task to measure cognitive procedural learning. Analyses showed that although alcoholic subjects were able to acquire the category and features of the semantic concepts, albeit slowly, they presented impaired label learning. In the control group, executive functions and episodic memory predicted semantic learning in the first and second halves of the protocol, respectively. In addition to the cognitive processes involved in the learning strategies invoked by controls, alcoholic subjects seem to attempt to compensate for their impaired cognitive functions, invoking capacities of short-term passive storage. Regarding cognitive procedural learning, although the patients eventually achieved the same results as the controls, they failed to automate the procedure. Contrary to the control group, the alcoholic groups' learning performance was predicted by controlled cognitive functions throughout the protocol. At alcohol treatment entry, alcoholic patients with neuropsychological deficits have difficulty acquiring novel semantic and cognitive procedural knowledge. Compared with controls, they seem to use more costly learning strategies, which are nonetheless less efficient. These learning disabilities need to be considered when treatment requiring the acquisition of complex novel information is envisaged.

Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection.

PubMed

Smelser, Lisa K; Walker, Callum; Burns, Erin M; Curry, Michael; Black, Nathanael; Metzler, Jennifer A; McDowell, Susan A; Bruns, Heather A

Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function.

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia.

PubMed

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Wasihun, Araya Gebreyesus; Dejene, Tsehaye Asmelash

2018-01-01

Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. The current result shows that immunological and virological failure is a problem in a setting where highly active antiretroviral therapy has been largely scale up. The problem is more in patients with poor adherence. This will in turn affect the global targets of 90% viral suppression by 2020. This may indicate the need for more investment and commitment to improving patient adherence in the study area.

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia

PubMed Central

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Dejene, Tsehaye Asmelash

2018-01-01

Background Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. Methods A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. Result A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. Conclusions The current result shows that immunological and virological failure is a problem in a setting where highly active antiretroviral therapy has been largely scale up. The problem is more in patients with poor adherence. This will in turn affect the global targets of 90% viral suppression by 2020. This may indicate the need for more investment and commitment to improving patient adherence in the study area. PMID:29715323

Overview of current immunotherapeutic strategies for glioma

PubMed Central

Calinescu, Anda-Alexandra; Kamran, Neha; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro Ricardo; Castro, Maria Graciela

2015-01-01

In the last decade, numerous studies of immunotherapy for malignant glioma (glioblastoma multiforme) have brought new knowledge and new hope for improving the prognosis of this incurable disease. Some clinical trials have reached Phase III, following positive outcomes in Phase I and II, with respect to safety and immunological end points. Results are encouraging especially when considering the promise of sustained efficacy by inducing antitumor immunological memory. Progress in understanding the mechanisms of tumor-induced immune suppression led to the development of drugs targeting immunosuppressive checkpoints, which are used in active clinical trials for glioblastoma multiforme. Insights related to the heterogeneity of the disease bring new challenges for the management of glioma and underscore a likely cause of therapeutic failure. An emerging therapeutic strategy is represented by a combinatorial, personalized approach, including the standard of care: surgery, radiation, chemotherapy with added active immunotherapy and multiagent targeting of immunosuppressive checkpoints. PMID:26598957

A roadmap towards personalized immunology.

PubMed

Delhalle, Sylvie; Bode, Sebastian F N; Balling, Rudi; Ollert, Markus; He, Feng Q

2018-01-01

Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions. There is still a long way ahead on translating our capability to identify potentially targetable personalized biomarkers into effective personalized therapy in immune-centralized diseases. Here, we discuss the recent advances and successful applications in "Omics" data utilization and network analysis on patients' samples of clinical trials and studies, as well as the major challenges and strategies towards personalized stratification and treatment for infectious or non-communicable inflammatory diseases such as autoimmune diseases or allergies. We provide a roadmap and highlight experimental, clinical, computational analysis, data management, ethical and regulatory issues to accelerate the implementation of personalized immunology.

Chronic bystander infections and immunity to unrelated antigens

PubMed Central

Stelekati, Erietta; Wherry, E. John

2012-01-01

Chronic infections with persistent pathogens such as helminths, mycobacteria, Plasmodium and hepatitis viruses affect more than a third of the human population and are associated with increased susceptibility to other pathogens as well as reduced vaccine efficacy. Although these observations suggest an impact of chronic infections in modulating immunity to unrelated antigens, little is known regarding the underlying mechanisms. Here, we summarize evidence of the most prevalent infections affecting immunity to unrelated pathogens and vaccines, and discuss potential mechanisms of how different bystander chronic infections might impact immune responses. We suggest that bystander chronic infections affect different stages of host responses and may impact transmission of other pathogens, recognition and innate immune responses, priming and differentiation of adaptive effector responses, as well as the development and maintenance of immunological memory. Further understanding of the immunological effects of co-infection should provide opportunities to enhance vaccine efficacy and control infectious diseases. PMID:23084915

Importing perceived features into false memories.

PubMed

Lyle, Keith B; Johnson, Marcia K

2006-02-01

False memories sometimes contain specific details, such as location or colour, about events that never occurred. Based on the source-monitoring framework, we investigated one process by which false memories acquire details: the reactivation and misattribution of feature information from memories of similar perceived events. In Experiments 1A and 1B, when imagined objects were falsely remembered as seen, participants often reported that the objects had appeared in locations where visually or conceptually similar objects, respectively, had actually appeared. Experiment 2 indicated that colour and shape features of seen objects were misattributed to false memories of imagined objects. Experiment 3 showed that perceived details were misattributed to false memories of objects that had not been explicitly imagined. False memories that imported perceived features, compared to those that presumably did not, were subjectively more like memories for perceived events. Thus, perception may be even more pernicious than imagination in contributing to false memories.

Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells

PubMed Central

Luckey, Chance John; Bhattacharya, Deepta; Goldrath, Ananda W.; Weissman, Irving L.; Benoist, Christophe; Mathis, Diane

2006-01-01

The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8+ T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8+ T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8+ T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. PMID:16492737

[Sleep-wake cycle and memory consolidation].

PubMed

Baratti, Carlos M; Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B

2007-01-01

Although several hypothesis and theories have been advanced as explanations for the functions of sleep, a unified theory of sleep function remains elusive. Sleep has been implicated in the plastic cerebral changes that underlie learning and memory, in particular those related to memory consolidation of recently acquired new information. Despite steady accumulations of positive findings over the last ten years, the precise role of sleep in memory and brain plasticity is unproven at all. This situation might be solved by more integrated approaches that combine behavioral and neurophysiological measurements in well described in vivo models of neuronal activity and brain plasticity.

A comparison of automatic and intentional instructions when using the method of vanishing cues in acquired brain injury.

PubMed

Riley, Gerard A; Venn, Paul

2015-01-01

Thirty-four participants with acquired brain injury learned word lists under two forms of vanishing cues - one in which the learning trial instructions encouraged intentional retrieval (i.e., explicit memory) and one in which they encouraged automatic retrieval (which encompasses implicit memory). The automatic instructions represented a novel approach in which the cooperation of participants was actively sought to avoid intentional retrieval. Intentional instructions resulted in fewer errors during the learning trials and better performance on immediate and delayed retrieval tests. The advantage of intentional over automatic instructions was generally less for those who had more severe memory and/or executive impairments. Most participants performed better under intentional instructions on both the immediate and the delayed tests. Although those who were more severely impaired in both memory and executive function also did better with intentional instructions on the immediate retrieval test, they were significantly more likely to show an advantage for automatic instructions on the delayed test. It is suggested that this pattern of results may reflect impairments in the consolidation of intentional memories in this group. When using vanishing cues, automatic instructions may be better for those with severe consolidation impairments, but otherwise intentional instructions may be better.

A Naturally-Occurring Histone Acetyltransferase Inhibitor Derived from Garcinia indica Impairs Newly Acquired and Reactivated Fear Memories

PubMed Central

Maddox, Stephanie A.; Watts, Casey S.; Doyère, Valérie; Schafe, Glenn E.

2013-01-01

The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA) impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories. PMID:23349897

Neonicotinoids Interfere with Specific Components of Navigation in Honeybees

PubMed Central

Fischer, Johannes; Müller, Teresa; Spatz, Anne-Kathrin; Greggers, Uwe; Grünewald, Bernd; Menzel, Randolf

2014-01-01

Three neonicotinoids, imidacloprid, clothianidin and thiacloprid, agonists of the nicotinic acetylcholine receptor in the central brain of insects, were applied at non-lethal doses in order to test their effects on honeybee navigation. A catch-and-release experimental design was applied in which feeder trained bees were caught when arriving at the feeder, treated with one of the neonicotinoids, and released 1.5 hours later at a remote site. The flight paths of individual bees were tracked with harmonic radar. The initial flight phase controlled by the recently acquired navigation memory (vector memory) was less compromised than the second phase that leads the animal back to the hive (homing flight). The rate of successful return was significantly lower in treated bees, the probability of a correct turn at a salient landscape structure was reduced, and less directed flights during homing flights were performed. Since the homing phase in catch-and-release experiments documents the ability of a foraging honeybee to activate a remote memory acquired during its exploratory orientation flights, we conclude that non-lethal doses of the three neonicotinoids tested either block the retrieval of exploratory navigation memory or alter this form of navigation memory. These findings are discussed in the context of the application of neonicotinoids in plant protection. PMID:24646521

Noradrenergic Action in Prefrontal Cortex in the Late Stage of Memory Consolidation

ERIC Educational Resources Information Center

Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

2004-01-01

These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory…

Short-Term Memories in "Drosophila" Are Governed by General and Specific Genetic Systems

ERIC Educational Resources Information Center

Zars, Troy

2010-01-01

In a dynamic environment, there is an adaptive value in the ability of animals to acquire and express memories. That both simple and complex animals can learn is therefore not surprising. How animals have solved this problem genetically and anatomically probably lies somewhere in a range between a single molecular/anatomical mechanism that applies…

Neuroanatomy of episodic and semantic memory in humans: a brief review of neuroimaging studies.

PubMed

García-Lázaro, Haydée G; Ramirez-Carmona, Rocio; Lara-Romero, Ruben; Roldan-Valadez, Ernesto

2012-01-01

One of the most basic functions in every individual and species is memory. Memory is the process by which information is saved as knowledge and retained for further use as needed. Learning is a neurobiological phenomenon by which we acquire certain information from the outside world and is a precursor to memory. Memory consists of the capacity to encode, store, consolidate, and retrieve information. Recently, memory has been defined as a network of connections whose function is primarily to facilitate the long-lasting persistence of learned environmental cues. In this review, we present a brief description of the current classifications of memory networks with a focus on episodic memory and its anatomical substrate. We also present a brief review of the anatomical basis of memory systems and the most commonly used neuroimaging methods to assess memory, illustrated with magnetic resonance imaging images depicting the hippocampus, temporal lobe, and hippocampal formation, which are the main brain structures participating in memory networks.

Using Emotions and Personal Memory Associations to Acquire Vocabulary

ERIC Educational Resources Information Center

Randolph, Patrick T.

2018-01-01

Of all the possible tools available to help out English language Learners (ELLs) acquire vocabulary, the use of emotions is one of the most powerful because "we are learning that emotions are the result of multiple brain and body systems that are distributed over the whole person". If we go one step further and connect emotions to…

75 FR 60749 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

...) (BHC Act) and Regulation Y (12 CFR Part 225) to engage de novo, or to acquire or control voting... than October 18, 2010. A. Federal Reserve Bank of Kansas City (Dennis Denney, Assistant Vice President) 1 Memorial Drive, Kansas City, Missouri 64198-0001: 1. Raton Capital Corporation, Raton, New Mexico...

Immunological Tolerance to Muscle Autoantigens Involves Peripheral Deletion of Autoreactive CD8+ T Cells

PubMed Central

Franck, Emilie; Bonneau, Carole; Jean, Laetitia; Henry, Jean-Paul; Lacoume, Yann; Salvetti, Anna; Boyer, Olivier; Adriouch, Sahil

2012-01-01

Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4+ T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8+ T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8+ tolerance in SM-Ova mice. We show herein that Ova-specific CD8+ T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8+ T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells. PMID:22570714

Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes.

PubMed

Tsuji, Hiroko; Miyoshi, Shunichiro; Ikegami, Yukinori; Hida, Naoko; Asada, Hironori; Togashi, Ikuko; Suzuki, Junshi; Satake, Masaki; Nakamizo, Hikaru; Tanaka, Mamoru; Mori, Taisuke; Segawa, Kaoru; Nishiyama, Nobuhiro; Inoue, Junko; Makino, Hatsune; Miyado, Kenji; Ogawa, Satoshi; Yoshimura, Yasunori; Umezawa, Akihiro

2010-05-28

Amniotic membrane is known to have the ability to transdifferentiate into multiple organs and is expected to stimulate a reduced immunologic reaction. Determine whether human amniotic membrane-derived mesenchymal cells (hAMCs) can be an ideal allograftable stem cell source for cardiac regenerative medicine. We established hAMCs. After cardiomyogenic induction in vitro, hAMCs beat spontaneously, and the calculated cardiomyogenic transdifferentiation efficiency was 33%. Transplantation of hAMCs 2 weeks after myocardial infarction improved impaired left ventricular fractional shortening measured by echocardiogram (34+/-2% [n=8] to 39+/-2% [n=11]; P<0.05) and decreased myocardial fibrosis area (18+/-1% [n=9] to 13+/-1% [n=10]; P<0.05), significantly. Furthermore hAMCs transplanted into the infarcted myocardium of Wistar rats were transdifferentiated into cardiomyocytes in situ and survived for more than 4 weeks after the transplantation without using any immunosuppressant. Immunologic tolerance was caused by the hAMC-derived HLA-G expression, lack of MHC expression of hAMCs, and activation of FOXP3-positive regulatory T cells. Administration of IL-10 or progesterone, which is known to play an important role in feto-maternal tolerance during pregnancy, markedly increased HLA-G expression in hAMCs in vitro and, surprisingly, also increased cardiomyogenic transdifferentiation efficiency in vitro and in vivo. Because hAMCs have a high ability to transdifferentiate into cardiomyocytes and to acquire immunologic tolerance in vivo, they can be a promising cellular source for allograftable stem cells for cardiac regenerative medicine.

Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

PubMed

Simpson, Elizabeth

2015-04-19

'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency.

PubMed

Chan, Jean L; Moschos, Stergios J; Bullen, John; Heist, Kathleen; Li, Xian; Kim, Young-Bum; Kahn, Barbara B; Mantzoros, Christos S

2005-03-01

Studies of congenital complete leptin deficiency in animals and humans support a role for leptin in regulating immune function. Whether acquired relative leptin deficiency affects immunological parameters in healthy humans remains unknown. We thus used experimental models of relative leptin deficiency and recombinant methionyl human leptin (r-metHuLeptin) administration in humans to investigate whether r-metHuLeptin would activate signaling pathways in peripheral blood mononuclear cells (PBMCs) and whether acquired relative leptin deficiency and/or increasing circulating leptin levels into the physiologic range would change PBMC subpopulations and cytokines important in the T-helper cell and systemic immune responses. We found that r-metHuLeptin administration to healthy humans activates signal transducer and activator of transcription-3 signaling in PBMCs in vivo. Neither short-term leptin deficiency, induced by 3-d complete fasting, nor physiologic r-metHuLeptin replacement for the same period of time had a major effect on PBMC subpopulations or serum cytokines in healthy men. In contrast, normalizing serum leptin levels over 8 wk in lean women with relative leptin deficiency for 5.1 +/- 1.4 yr (mean +/- se) due to chronic energy deficit increased soluble TNFalpha receptor levels, indicating activation of the TNFalpha system. These findings suggest that relative leptin deficiency due to more long-term energy deprivation is associated with defects in immunological parameters that may be corrected with exogenous r-metHuLeptin administration. Further studies are warranted to assess the implications of acquired relative hypoleptinemia and/or r-metHuLeptin administration on the immunosuppression associated with energy- and leptin-deficient states in humans.

Episodic memory, semantic memory, and amnesia.

PubMed

Squire, L R; Zola, S M

1998-01-01

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.

Myasthenia gravis: recent advances in immunopathology and therapy.

PubMed

Lee, John-Ih; Jander, Sebastian

2017-03-01

Myasthenia gravis is the most frequent acquired disorder of neuromuscular transmission. In the majority of cases, pathogenic antibodies against components of the postsynaptic muscle endplate membrane can be detected. In recent years there have been significant advances in the pathophysiological understanding and therapy of the disease. Areas covered: PubMed searches were conducted for the term 'myasthenia gravis' cross-referenced with the terms 'immunology', 'subgroups', 'antibody', 'ocular', 'thymoma', 'treatment' and 'thymectomy'. Additionally, we summarized the current state of immunopathology and therapy. Expert commentary: Immunological research defined new target antigens at the postsynaptic neuromuscular junction which along with clinical features allow a refined definition of disease subgroups. Overall the prognosis of myasthenia gravis with best possible symptomatic, immunosuppressive and supportive treatment is good but new immunomodulatory treatment options are developed for patients who do not respond well to the first line therapy. For most patients individually adapted long-term drug therapy is needed.

Dendritic cell control of tolerogenic responses

PubMed Central

Manicassamy, Santhakumar; Pulendran, Bali

2011-01-01

Summary One of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body’s own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. A fundamental role for the innate immune system, particularly dendritic cells (DCs), in orchestrating immunological tolerance has been appreciated, but emerging studies have highlighted the nature of the innate receptors and the signaling pathways that program DCs to a tolerogenic state. Furthermore, several studies have emphasized the major role played by cellular interactions, and the microenvironment in programming tolerogenic DCs. Here we review these studies and suggest that the innate control of tolerogenic responses can be viewed as different hierarchies of organization, in which DCs, their innate receptors and signaling networks, and their interactions with other cells and local microenvironments represent different levels of the hierarchy. PMID:21488899

Differential cross-reactivity of monoclonal antibody OPD4 (anti-CD45RO) in macaques.

PubMed

Wang, Xiaolei; Pahar, Bapi; Rasmussen, Terri; Alvarez, Xavier; Dufour, Jason; Rasmussen, Kelsi; Lackner, Andrew A; Veazey, Ronald S

2008-01-01

Immunologic research in nonhuman primates is occasionally limited by the availability of reagents that cross-react in nonhuman primates. One major limitation has been the lack of a monoclonal antibody to CD45RO. Although the monoclonal antibody UCHL-1 is used to detect CD45RO isoforms in humans, it does not react with nonhuman primates, mandating the use of alternative strategies to define "memory" T cell responses in nonhuman primates. The current study examined the reactivity and specificity of another antibody against CD45RO, clone OPD4, in macaques. Here we demonstrate that OPD4 specifically labels memory CD4+ T cells in approximately 44% of rhesus macaques (Macaca mulatta) of Indian but not Chinese origin. In contrast, tissues from pigtail macaques (Macaca nemestrina) react with this clone, indicating that OPD4 may be useful for examining memory CD4+ T cells in certain macaques, but its utility may be limited in other species or even among individual macaques.

Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

PubMed Central

Richmond, Peter; Borrow, Ray; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Cartwright, Keith; Miller, Elizabeth

2001-01-01

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy. PMID:11254596

Adenoviral vaccine induction of CD8+ T cell memory inflation: Impact of co-infection and infection order.

PubMed

Lee, Lian N; Bolinger, Beatrice; Banki, Zoltan; de Lara, Catherine; Highton, Andrew J; Colston, Julia M; Hutchings, Claire; Klenerman, Paul

2017-12-01

The efficacies of many new T cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory CD8 T cells. However, it is now increasingly recognized that prior infection history impacts on the host immune response. Additionally, the order in which these infections are acquired could have a major effect. Exploiting the ability to generate large sustained effector memory (i.e. inflationary) T cell populations from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, the impact of new infections on pre-existing memory and the capacity of the host's memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model. Simultaneous and sequential infections, first with MCMV followed by Ad-lacZ, generated inflationary populations towards both viruses with similar kinetics and magnitude to mono-infected groups. However, in Ad-lacZ immune mice, subsequent acute MCMV infection led to a rapid decline of the pre-existing Ad-LacZ-specific inflating population, associated with bystander activation of Fas-dependent apoptotic pathways. However, responses were maintained long-term and boosting with Ad-lacZ led to rapid re-expansion of the inflating population. These data indicate firstly that multiple specificities of inflating memory cells can be acquired at different times and stably co-exist. Some acute infections may also deplete pre-existing memory populations, thus revealing the importance of the order of infection acquisition. Importantly, immunization with an AdHu5 vector did not alter the size of the pre-existing memory. These phenomena are relevant to the development of adenoviral vectors as novel vaccination strategies for diverse infections and cancers. (241 words).

Adenoviral vaccine induction of CD8+ T cell memory inflation: Impact of co-infection and infection order

PubMed Central

Bolinger, Beatrice; de Lara, Catherine; Hutchings, Claire

2017-01-01

The efficacies of many new T cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory CD8 T cells. However, it is now increasingly recognized that prior infection history impacts on the host immune response. Additionally, the order in which these infections are acquired could have a major effect. Exploiting the ability to generate large sustained effector memory (i.e. inflationary) T cell populations from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, the impact of new infections on pre-existing memory and the capacity of the host’s memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model. Simultaneous and sequential infections, first with MCMV followed by Ad-lacZ, generated inflationary populations towards both viruses with similar kinetics and magnitude to mono-infected groups. However, in Ad-lacZ immune mice, subsequent acute MCMV infection led to a rapid decline of the pre-existing Ad-LacZ-specific inflating population, associated with bystander activation of Fas-dependent apoptotic pathways. However, responses were maintained long-term and boosting with Ad-lacZ led to rapid re-expansion of the inflating population. These data indicate firstly that multiple specificities of inflating memory cells can be acquired at different times and stably co-exist. Some acute infections may also deplete pre-existing memory populations, thus revealing the importance of the order of infection acquisition. Importantly, immunization with an AdHu5 vector did not alter the size of the pre-existing memory. These phenomena are relevant to the development of adenoviral vectors as novel vaccination strategies for diverse infections and cancers. (241 words) PMID:29281733

Monkey׳s short-term auditory memory nearly abolished by combined removal of the rostral superior temporal gyrus and rhinal cortices.

PubMed

Fritz, Jonathan B; Malloy, Megan; Mishkin, Mortimer; Saunders, Richard C

2016-06-01

While monkeys easily acquire the rules for performing visual and tactile delayed matching-to-sample, a method for testing recognition memory, they have extraordinary difficulty acquiring a similar rule in audition. Another striking difference between the modalities is that whereas bilateral ablation of the rhinal cortex (RhC) leads to profound impairment in visual and tactile recognition, the same lesion has no detectable effect on auditory recognition memory (Fritz et al., 2005). In our previous study, a mild impairment in auditory memory was obtained following bilateral ablation of the entire medial temporal lobe (MTL), including the RhC, and an equally mild effect was observed after bilateral ablation of the auditory cortical areas in the rostral superior temporal gyrus (rSTG). In order to test the hypothesis that each of these mild impairments was due to partial disconnection of acoustic input to a common target (e.g., the ventromedial prefrontal cortex), in the current study we examined the effects of a more complete auditory disconnection of this common target by combining the removals of both the rSTG and the MTL. We found that the combined lesion led to forgetting thresholds (performance at 75% accuracy) that fell precipitously from the normal retention duration of ~30 to 40s to a duration of ~1 to 2s, thus nearly abolishing auditory recognition memory, and leaving behind only a residual echoic memory. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

Professionals' views on the use of smartphone technology to support children and adolescents with memory impairment due to acquired brain injury.

PubMed

Plackett, Ruth; Thomas, Sophie; Thomas, Shirley

2017-04-01

Purpose To identify from a health-care professionals' perspective whether smartphones are used by children and adolescents with acquired brain injury as memory aids; what factors predict smartphone use and what barriers prevent the use of smartphones as memory aids by children and adolescents. Method A cross-sectional online survey was undertaken with 88 health-care professionals working with children and adolescents with brain injury. Results Children and adolescents with brain injury were reported to use smartphones as memory aids by 75% of professionals. However, only 42% of professionals helped their clients to use smartphones. The only factor that significantly predicted reported smartphone use was the professionals' positive attitudes toward assistive technology. Several barriers to using smartphones as memory aids were identified, including the poor accessibility of devices and cost of devices. Conclusion Many children and adolescents with brain injury are already using smartphones as memory aids but this is often not facilitated by professionals. Improving the attitudes of professionals toward using smartphones as assistive technology could help to increase smartphone use in rehabilitation. Implications for Rehabilitation Smartphones could be incorporated into rehabilitation programs for young people with brain injury as socially acceptable compensatory aids. Further training and support for professionals on smartphones as compensatory aids could increase professionals' confidence and attitudes in facilitating the use of smartphones as memory aids. Accessibility could be enhanced by the development of a smartphone application specifically designed to be used by young people with brain injury.

Interference Conditions of the Reconsolidation Process in Humans: The Role of Valence and Different Memory Systems

PubMed Central

Fernández, Rodrigo S.; Bavassi, Luz; Kaczer, Laura; Forcato, Cecilia; Pedreira, María E.

2016-01-01

Following the presentation of a reminder, consolidated memories become reactivated followed by a process of re-stabilization, which is referred to as reconsolidation. The most common behavioral tool used to reveal this process is interference produced by new learning shortly after memory reactivation. Memory interference is defined as a decrease in memory retrieval, the effect is generated when new information impairs an acquired memory. In general, the target memory and the interference task used are the same. Here we investigated how different memory systems and/or their valence could produce memory reconsolidation interference. We showed that a reactivated neutral declarative memory could be interfered by new learning of a different neutral declarative memory. Then, we revealed that an aversive implicit memory could be interfered by the presentation of a reminder followed by a threatening social event. Finally, we showed that the reconsolidation of a neutral declarative memory is unaffected by the acquisition of an aversive implicit memory and conversely, this memory remains intact when the neutral declarative memory is used as interference. These results suggest that the interference of memory reconsolidation is effective when two task rely on the same memory system or both evoke negative valence. PMID:28066212

Interference Conditions of the Reconsolidation Process in Humans: The Role of Valence and Different Memory Systems.

PubMed

Fernández, Rodrigo S; Bavassi, Luz; Kaczer, Laura; Forcato, Cecilia; Pedreira, María E

2016-01-01

Following the presentation of a reminder, consolidated memories become reactivated followed by a process of re-stabilization, which is referred to as reconsolidation. The most common behavioral tool used to reveal this process is interference produced by new learning shortly after memory reactivation. Memory interference is defined as a decrease in memory retrieval, the effect is generated when new information impairs an acquired memory. In general, the target memory and the interference task used are the same. Here we investigated how different memory systems and/or their valence could produce memory reconsolidation interference. We showed that a reactivated neutral declarative memory could be interfered by new learning of a different neutral declarative memory. Then, we revealed that an aversive implicit memory could be interfered by the presentation of a reminder followed by a threatening social event. Finally, we showed that the reconsolidation of a neutral declarative memory is unaffected by the acquisition of an aversive implicit memory and conversely, this memory remains intact when the neutral declarative memory is used as interference. These results suggest that the interference of memory reconsolidation is effective when two task rely on the same memory system or both evoke negative valence.

Lack of Original Antigenic Sin in Recall CD8+ T Cell Responses

PubMed Central

Zehn, Dietmar; Turner, Michael J.; Lefrançois, Leo; Bevan, Michael J.

2010-01-01

In the real world, mice and men are not immunologically naive, having been exposed to numerous antigenic challenges. Prior infections sometimes negatively impact the response to a subsequent infection. This can occur in serial infections with pathogens sharing cross-reactive Ags. At the T cell level it has been proposed that preformed memory T cells, which cross-react with low avidity to epitopes presented in subsequent infections, dampen the response of high-avidity T cells. We investigated this with a series of related MHC class-I restricted Ags expressed by bacterial and viral pathogens. In all cases, we find that high-avidity CD8+ T cell precursors, either naive or memory, massively expand in secondary cross-reactive infections to dominate the response over low-avidity memory T cells. This holds true even when >10% of the CD8+ T cell compartment consists of memory T cells that cross-react weakly with the rechallenge ligand. Occasionally, memory cells generated by low-avidity stimulation in a primary infection recognize a cross-reactive epitope with high avidity and contribute positively to the response to a second infection. Taken together, our data show that the phenomenon of original antigenic sin does not occur in all heterologous infections. PMID:20439913

Direct Detection of T- and B-Memory Lymphocytes by ImmunoSpot® Assays Reveals HCMV Exposure that Serum Antibodies Fail to Identify.

PubMed

Terlutter, Fredrik; Caspell, Richard; Nowacki, Tobias M; Lehmann, Alexander; Li, Ruliang; Zhang, Ting; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

2018-05-19

It is essential to identify donors who have not been infected with human cytomegalovirus (HCMV) in order to avoid transmission of HCMV to recipients of blood transfusions or organ transplants. In the present study, we tested the reliability of seronegativity as an indicator for the lack of HCMV exposure in healthy human blood donors. Eighty-two HCMV seronegative individuals were identified, and their peripheral blood mononuclear cells (PBMC) were tested in ImmunoSpot® assays for the presence of HCMV-specific T- and B-memory lymphocytes. Eighty-two percent (67 of 82) of these HCMV seronegative individuals featured at least one memory cell that was lineage specific for HCMV, with the majority of these subjects possessing CD4+ and CD8+ T cells, as well as B cells, providing three independent lines of evidence for having developed immunity to HCMV. Only 15 of these 82 donors (18%) showed neither T- nor B-cell memory to HCMV, consistent with immunological naïveté to the virus. The data suggest that measurements of serum antibodies frequently fail to reveal HCMV exposure in humans, which may be better identified by direct detection of HCMV-specific memory lymphocytes.

Memory as behavior: The importance of acquisition and remembering strategies

PubMed Central

Delaney, Peter F.; Austin, John

1998-01-01

The study of memory has traditionally been the province of cognitive psychology, which has postulated different memory systems that store memory traces to explain remembering. Behavioral psychologists have been unsuccessful at empirically identifying the behavior that occurs during remembering because so much of it occurs rapidly and covertly. In addition, behavior analysts have generally been disinterested in studying transient phenomena such as memory. As a result, the cognitive interpretation has been the only one that has made and tested useful predictions. Recent experimental evidence acquired while having participants “think aloud” suggests that a behavioral approach to memory may provide a superior account of memory performance and allow applied scientists to observe and modify memory-related behavior with well-known applied behavior-analytic techniques. We review evidence supporting and extending the interpretation of memory provided by Palmer (1991), who described memory in terms of precurrent behavior that occurs at the time of acquisition in preparation for problem solving that occurs at the time of remembering. ImagesFig. 1 PMID:22477129

Methods for Assessment of Memory Reactivation.

PubMed

Liu, Shizhao; Grosmark, Andres D; Chen, Zhe

2018-04-13

It has been suggested that reactivation of previously acquired experiences or stored information in declarative memories in the hippocampus and neocortex contributes to memory consolidation and learning. Understanding memory consolidation depends crucially on the development of robust statistical methods for assessing memory reactivation. To date, several statistical methods have seen established for assessing memory reactivation based on bursts of ensemble neural spike activity during offline states. Using population-decoding methods, we propose a new statistical metric, the weighted distance correlation, to assess hippocampal memory reactivation (i.e., spatial memory replay) during quiet wakefulness and slow-wave sleep. The new metric can be combined with an unsupervised population decoding analysis, which is invariant to latent state labeling and allows us to detect statistical dependency beyond linearity in memory traces. We validate the new metric using two rat hippocampal recordings in spatial navigation tasks. Our proposed analysis framework may have a broader impact on assessing memory reactivations in other brain regions under different behavioral tasks.

Impaired social recognition memory in Recombination Activating Gene 1-deficient mice

PubMed Central

McGowan, Patrick O.; Hope, Thomas A.; Meck, Warren H.; Kelsoe, Garnett; Williams, Christina L.

2012-01-01

The Recombination Activating Genes (RAGs) encode two enzymes that play key roles in the adaptive immune system. RAG1 and RAG2 mediate VDJ recombination, a process necessary for the maturation of B- and T-cells. Interestingly, RAG1 is also expressed in the brain, particularly in areas of high neural density such as the hippocampus, although its function is unknown. We tested evidence that RAG1 plays a role in brain function using a social recognition memory task, an assessment of the acquisition and retention of conspecific identity. In a first experiment, we found that RAG1-deficient mice show impaired social recognition memory compared to mice wildtype for the RAG1 allele. In a second experiment, by breeding to homogenize background genotype we found that RAG1-deficient mice show impaired social recognition memory relative to heterozygous or RAG2-deficient littermates. Because RAG1 and RAG2 null mice are both immunodeficient, the results suggest that the memory impairment is not an indirect effect of immunological dysfunction. RAG1-deficient mice show normal habituation to non-socially derived odors and habituation to an open-field, indicating that the observed effect is not likely a result of a general deficit in habituation to novelty. These data trace the origin of the impairment in social recognition memory in RAG1-deficient mice to the RAG1 gene locus and implicate RAG1 in memory formation. PMID:21354115

B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients.

PubMed

Marasco, Emiliano; Farroni, Chiara; Cascioli, Simona; Marcellini, Valentina; Scarsella, Marco; Giorda, Ezio; Piano Mortari, Eva; Leonardi, Lucia; Scarselli, Alessia; Valentini, Diletta; Cancrini, Caterina; Duse, Marzia; Grimsholm, Ola; Carsetti, Rita

2017-01-01

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system. © 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monkey’s short-term auditory memory nearly abolished by combined removal of the rostral superior temporal gyrus and rhinal cortices

PubMed Central

Fritz, Jonathan B.; Malloy, Megan; Mishkin, Mortimer; Saunders, Richard C.

2016-01-01

While monkeys easily acquire the rules for performing visual and tactile delayed matching-to-sample, a method for testing recognition memory, they have extraordinary difficulty acquiring a similar rule in audition. Another striking difference between the modalities is that whereas bilateral ablation of the rhinal cortex (RhC) leads to profound impairment in visual and tactile recognition, the same lesion has no detectable effect on auditory recognition memory (Fritz et al., 2005). In our previous study, a mild impairment in auditory memory was obtained following bilateral ablation of the entire medial temporal lobe (MTL), including the RhC, and an equally mild effect was observed after bilateral ablation of the auditory cortical areas in the rostral superior temporal gyrus (rSTG). In order to test the hypothesis that each of these mild impairments was due to partial disconnection of acoustic input to a common target (e.g., the ventromedial prefrontal cortex), in the current study we examined the effects of a more complete auditory disconnection of this common target by combining the removals of both the rSTG and the MTL. We found that the combined lesion led to forgetting thresholds (performance at 75% accuracy) that fell precipitously from the normal retention duration of ~30–40 seconds to a duration of ~1–2 seconds, thus nearly abolishing auditory recognition memory, and leaving behind only a residual echoic memory. PMID:26707975

Pioneer Mothers' Memorial Forest revisited

Treesearch

R.C. Schlesinger; D.T. Funk; P.L. Roth; C.C. Myers

1991-01-01

The area now known as Pioneer Mothers' Memorial Forest was acquired by Joseph Cox in 1816 from the public domain. In 1944, a portion of that property, including the area referred to as Cox Woods, was established as a National Forest Research Natural Area. This beech-maple forest, located in the Knobs area of southern Indiana, is considered to be one of the few...

Primacy Versus Recency in a Quantitative Model: Activity Is the Critical Distinction

PubMed Central

Greene, Anthony J.; Prepscius, Colin; Levy, William B.

2000-01-01

Behavioral and neurobiological evidence shows that primacy and recency are subserved by memory systems for intermediate- and short-term memory, respectively. A widely accepted explanation of recency is that in short-term memory, new learning overwrites old learning. Primacy is not as well understood, but many hypotheses contend that initial items are better encoded into long-term memory because they have had more opportunity to be rehearsed. A simple, biologically motivated neural network model supports an alternative hypothesis of the distinct processing requirements for primacy and recency given single-trial learning without rehearsal. Simulations of the model exhibit either primacy or recency, but not both simultaneously. The incompatibility of primacy and recency clarifies possible reasons for two neurologically distinct systems. Inhibition, and its control of activity, determines those list items that are acquired and retained. Activity levels that are too low do not provide sufficient connections for learning to occur, while higher activity diminishes capacity. High recurrent inhibition, and progressively diminishing activity, allows acquisition and retention of early items, while later items are never acquired. Conversely, low recurrent inhibition, and the resulting high activity, allows continuous acquisition such that acquisition of later items eventually interferes with the retention of early items. PMID:10706602

Recall of briefly presented chess positions and its relation to chess skill.

PubMed

Gong, Yanfei; Ericsson, K Anders; Moxley, Jerad H

2015-01-01

Individual differences in memory performance in a domain of expertise have traditionally been accounted for by previously acquired chunks of knowledge and patterns. These accounts have been examined experimentally mainly in chess. The role of chunks (clusters of chess pieces recalled in rapid succession during recall of chess positions) and their relations to chess skill are, however, under debate. By introducing an independent chunk-identification technique, namely repeated-recall technique, this study identified individual chunks for particular chess players. The study not only tested chess players with increasing chess expertise, but also tested non-chess players who should not have previously acquired any chess related chunks in memory. For recall of game positions significant differences between players and non-players were found in virtually all the characteristics of chunks recalled. Size of the largest chunks also correlates with chess skill within the group of rated chess players. Further research will help us understand how these memory encodings can explain large differences in chess skill.

"I know your name, but not your number"--Patients with verbal short-term memory deficits are impaired in learning sequences of digits.

PubMed

Bormann, Tobias; Seyboth, Margret; Umarova, Roza; Weiller, Cornelius

2015-06-01

Studies on verbal learning in patients with impaired verbal short-term memory (vSTM) have revealed dissociations among types of verbal information. Patients with impaired vSTM are able to learn lists of known words but fail to acquire new word forms. This suggests that vSTM is involved in new word learning. The present study assessed both new word learning and the learning of digit sequences in two patients with impaired vSTM. In two experiments, participants were required to learn people's names, ages and professions, or their four digit 'phone numbers'. The STM patients were impaired on learning unknown family names and phone numbers, but managed to acquire other verbal information. In contrast, a patient with a severe verbal episodic memory impairment was impaired across information types. These results indicate verbal STM involvement in the learning of digit sequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recall of Briefly Presented Chess Positions and Its Relation to Chess Skill

PubMed Central

Moxley, Jerad H.

2015-01-01

Individual differences in memory performance in a domain of expertise have traditionally been accounted for by previously acquired chunks of knowledge and patterns. These accounts have been examined experimentally mainly in chess. The role of chunks (clusters of chess pieces recalled in rapid succession during recall of chess positions) and their relations to chess skill are, however, under debate. By introducing an independent chunk-identification technique, namely repeated-recall technique, this study identified individual chunks for particular chess players. The study not only tested chess players with increasing chess expertise, but also tested non-chess players who should not have previously acquired any chess related chunks in memory. For recall of game positions significant differences between players and non-players were found in virtually all the characteristics of chunks recalled. Size of the largest chunks also correlates with chess skill within the group of rated chess players. Further research will help us understand how these memory encodings can explain large differences in chess skill. PMID:25774693

Reprint of: Semantic impairment disrupts perception, memory, and naming of secondary but not primary colours.

PubMed

Rogers, Timothy T; Graham, Kim S; Patterson, Karalyn

2015-09-01

To investigate how basic aspects of perception are shaped by acquired knowledge about the world, we assessed colour perception and cognition in patients with semantic dementia (SD), a disorder that progressively erodes conceptual knowledge. We observed a previously undocumented pattern of impairment to colour perception and cognition characterized by: (i) a normal ability to discriminate between only subtly different colours but an impaired ability to group different colours into categories, (ii) normal perception and memory for the colours red, green, and blue but impaired perception and memory for colours lying between these regions of a fully-saturated and luminant spectrum, and (iii) normal naming of polar colours in the opponent-process colour system (red, green, blue, yellow, white, and black) but impaired naming of other basic colours (brown, gray, pink, and orange). The results suggest that fundamental aspects of perception can be shaped by acquired knowledge about the world, but only within limits. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Semantic impairment disrupts perception, memory, and naming of secondary but not primary colours.

PubMed Central

Rogers, Timothy T.; Graham, Kim S.; Patterson, Karalyn

2015-01-01

To investigate how basic aspects of perception are shaped by acquired knowledge about the world, we assessed colour perception and cognition in patients with semantic dementia (SD), a disorder that progressively erodes conceptual knowledge. We observed a previously undocumented pattern of impairment to colour perception and cognition characterized by: (i) a normal ability to discriminate between only subtly different colours but an impaired ability to group different colours into categories, (ii) normal perception and memory for the colours red, green, and blue but impaired perception and memory for colours lying between these regions of a fully-saturated and luminant spectrum, and (iii) normal naming of polar colours in the opponent-process colour system (red, green, blue, yellow, white, and black) but impaired naming of other basic colours (brown, gray, pink, and orange). The results suggest that fundamental aspects of perception can be shaped by acquired knowledge about the world, but only within limits. PMID:25637227

Semantic impairment disrupts perception, memory, and naming of secondary but not primary colours.

PubMed

Rogers, Timothy T; Graham, Kim S; Patterson, Karalyn

2015-04-01

To investigate how basic aspects of perception are shaped by acquired knowledge about the world, we assessed colour perception and cognition in patients with semantic dementia (SD), a disorder that progressively erodes conceptual knowledge. We observed a previously undocumented pattern of impairment to colour perception and cognition characterized by: (i) a normal ability to discriminate between only subtly different colours but an impaired ability to group different colours into categories, (ii) normal perception and memory for the colours red, green, and blue but impaired perception and memory for colours lying between these regions of a fully-saturated and luminant spectrum, and (iii) normal naming of polar colours in the opponent-process colour system (red, green, blue, yellow, white, and black) but impaired naming of other basic colours (brown, gray, pink, and orange). The results suggest that fundamental aspects of perception can be shaped by acquired knowledge about the world, but only within limits. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Blood Fluke Exploitation of Innate-Adaptive Immune Interactions to Facilitate Parasite Development

DTIC Science & Technology

2007-01-01

epidemiology 25:1292-1300. 7. Alonso , D., J. Munoz, J. Gascon, M. E. Valls, and M. Corachan. 2006. Failure of standard treatment with praziquantel in two...of naive and memory CD8 T cells in vivo. Nature immunology 1:426-432. 105. Pearce, E. J., A. Cheever, S. Leonard, M. Covalesky, R. Fernandez - Botran...Transactions of the Royal Society of Tropical Medicine and Hygiene 48:3–4. 149 148. Garcia , S., J. DiSanto, and B. Stockinger. 1999. Following the

Semantic memory in developmental amnesia.

PubMed

Elward, Rachael L; Vargha-Khadem, Faraneh

2018-04-30

Patients with developmental amnesia resulting from bilateral hippocampal atrophy associated with neonatal hypoxia-ischaemia typically show relatively preserved semantic memory and factual knowledge about the natural world despite severe impairments in episodic memory. Understanding the neural and mnemonic processes that enable this context-free semantic knowledge to be acquired throughout development without the support of the contextualised episodic memory system is a serious challenge. This review describes the clinical presentation of patients with developmental amnesia, contrasts its features with those reported for adult-onset hippocampal amnesia, and analyses the effects of variables that influence the learning of new semantic information. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Seventeen-Year Journey Working With a Master.

PubMed

Zhu, Jinfang

2018-01-01

It had been a great honor for me to work with the late Dr. William E. Paul for 17 years in the Laboratory of Immunology (LI) from 1998 until his passing in 2015. He was such a master in the immunology field. Under his outstanding guidance, my research has been focusing on transcriptional regulation of T helper (Th) cell differentiation, especially, on the role of a master transcription factor GATA3 during Th2 cell differentiation. Just as enormous scientific contributions of Dr. Paul (we all call him Bill) to the immunology community are far beyond his serving as the Chief of the LI, GATA3 also plays important roles in different lymphocytes at various developmental stages besides its critical functions in Th2 cells. In this special review dedicated to the memory of Bill, I will summarize the research that I have carried out in Bill's lab working on GATA3 in the context of related studies by other groups in the field of T cell differentiation and innate lymphoid cell (ILC) development. These include the essential role of GATA3 in regulating Th2/ILC2 differentiation/development and their functions, the critical role of GATA3 during the development of T cells and innate lymphoid cells, and dynamic and quantitative expression of GATA3 in controlling lymphocyte homeostasis and functions.

Epigenetic memory: the Lamarckian brain

PubMed Central

Fischer, Andre

2014-01-01

Recent data support the view that epigenetic processes play a role in memory consolidation and help to transmit acquired memories even across generations in a Lamarckian manner. Drugs that target the epigenetic machinery were found to enhance memory function in rodents and ameliorate disease phenotypes in models for brain diseases such as Alzheimer's disease, Chorea Huntington, Depression or Schizophrenia. In this review, I will give an overview on the current knowledge of epigenetic processes in memory function and brain disease with a focus on Morbus Alzheimer as the most common neurodegenerative disease. I will address the question whether an epigenetic therapy could indeed be a suitable therapeutic avenue to treat brain diseases and discuss the necessary steps that should help to take neuroepigenetic research to the next level. PMID:24719207

Longevity of T-cell memory following acute viral infection.

PubMed

Walker, Joshua M; Slifka, Mark K

2010-01-01

Investigation of T-cell-mediated immunity following acute viral infection represents an area of research with broad implications for both fundamental immunology research as well as vaccine development. Here, we review techniques that are used to assess T-cell memory including limiting dilution analysis, enzyme-linked immunospot (ELISPOT) assays, intracellular cytokine staining (ICCS) and peptide-MHC Class I tetramer staining. The durability of T-cell memory is explored in the context of several acute viral infections including vaccinia virus (VV), measles virus (MV) and yellow fever virus (YFV). Following acute infection, different virus-specific T-cell subpopulations exhibit distinct cytokine profiles and these profiles change over the course of infection. Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and perforin are also observed in virus-specific T cells following infection. As a result of this work, we have gained a broader understanding of the kinetics and magnitude of antiviral T-cell immunity as well as new insight into the patterns of immunodominance and differential regulation of cytokines and cytotoxicity-associated molecules. This information may eventually lead to the generation of more effective vaccines that elicit T-cell memory with the optimal combination of functional characteristics required for providing protective immunity against infectious disease.

Evaluation of soluble CD30 as an immunologic marker in heart transplant recipients.

PubMed

Spiridon, C; Hunt, J; Mack, M; Rosenthal, J; Anderson, A; Eichhorn, E; Magee, M; Dewey, T; Currier, M; Nikaein, A

2006-12-01

CD30 is an immunologic molecule that belongs to the TNF-R superfamily. CD30 serves as a T-cell signal transducing molecule that is expressed by a subset of activated T lymphocytes, CD45RO+ memory T cells. Augmentation of soluble CD30 during kidney transplant rejection has been reported. Our study sought to determine whether the level of sCD30 prior to heart transplant could categorize patients into high versus low immunologic risk for a poor outcome. A significant correlation was observed between high levels of soluble CD30 and a reduced incidence of infection. None of the 35 patients with high pretransplant levels of sCD30 level (>90 U/mL) developed infections posttransplantation. However, 9 of 65 patients who had low levels of sCD30 (<90 U/mL) developed infections posttransplantation (P < .02). No remarkable differences were noted among the other clinical parameters. The results also showed that the high-definition flow-bead (HDB) assay detected both weak and strong class I and class II HLA antibodies, some of which (weak class II HLA Abs) were undetectable by the anti-human globulin cytotoxicity method. In addition, more antibody specificities were detected by HDB. In conclusion, we have observed that high levels of sCD30 prior to heart transplant may be associated with greater immunologic ability and therefore produce a protective effect on the development of infection post heart transplant. We have also shown that the HDB assay is superior to the visual cytotoxicity method to detect HLA antibodies, especially those to class II HLA antigens.

Effects of semantic relatedness on recall of stimuli preceding emotional oddballs.

PubMed

Smith, Ryan M; Beversdorf, David Q

2008-07-01

Semantic and episodic memory networks function as highly interconnected systems, both relying on the hippocampal/medial temporal lobe complex (HC/MTL). Episodic memory encoding triggers the retrieval of semantic information, serving to incorporate contextual relationships between the newly acquired memory and existing semantic representations. While emotional material augments episodic memory encoding at the time of stimulus presentation, interactions between emotion and semantic memory that contribute to subsequent episodic recall are not well understood. Using a modified oddball task, we examined the modulatory effects of negative emotion on semantic interactions with episodic memory by measuring the free-recall of serially presented neutral or negative words varying in semantic relatedness. We found increased free-recall for words related to and preceding emotionally negative oddballs, suggesting that negative emotion can indirectly facilitate episodic free-recall by enhancing semantic contributions during encoding. Our findings demonstrate the ability of emotion and semantic memory to interact to mutually enhance free-recall.

Volume of the human septal forebrain region is a predictor of source memory accuracy.

PubMed

Butler, Tracy; Blackmon, Karen; Zaborszky, Laszlo; Wang, Xiuyuan; DuBois, Jonathan; Carlson, Chad; Barr, William B; French, Jacqueline; Devinsky, Orrin; Kuzniecky, Ruben; Halgren, Eric; Thesen, Thomas

2012-01-01

Septal nuclei, components of basal forebrain, are strongly and reciprocally connected with hippocampus, and have been shown in animals to play a critical role in memory. In humans, the septal forebrain has received little attention. To examine the role of human septal forebrain in memory, we acquired high-resolution magnetic resonance imaging scans from 25 healthy subjects and calculated septal forebrain volume using recently developed probabilistic cytoarchitectonic maps. We indexed memory with the California Verbal Learning Test-II. Linear regression showed that bilateral septal forebrain volume was a significant positive predictor of recognition memory accuracy. More specifically, larger septal forebrain volume was associated with the ability to recall item source/context accuracy. Results indicate specific involvement of septal forebrain in human source memory, and recall the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases.

Multiple myeloma associated with acquired cutis laxa.

PubMed

Cho, S Y; Maguire, R F

1980-08-01

Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

No Evidence for Memory Decontextualization across One Night of Sleep

PubMed Central

Jurewicz, Katarzyna; Cordi, Maren Jasmin; Staudigl, Tobias; Rasch, Björn

2016-01-01

Sleep after learning strengthens memory consolidation. According to the active system consolidation hypothesis, sleep supports the integration of newly acquired memories into cortical knowledge networks, presumably accompanied by a process of decontextualization of the memory trace (i.e., a gradual loss of memory for the learning context). However, the availability of contextual information generally facilitates memory recall and studies on the interaction of sleep and context on memory retrieval have revealed inconsistent results. Here, we do not find any evidence for a role of sleep in the decontextualization of newly learned declarative memories. In two separate studies, 104 healthy young adults incidentally learned words associated with a context. After a 12 h retention interval filled with either sleep or wakefulness, recall (Experiment 1) or recognition (Experiment 2) was tested with the same or different context. Overall, memory retrieval was significantly improved when the learning context was reinstated, as compared to a different context. However, this context effect of memory was not modulated by sleep vs. wakefulness. These findings argue against a decontextualization of memories, at least across a single night of sleep. PMID:26858622

Immediate-Early Gene Transcriptional Activation in Hippocampus Ca1 and Ca3 Does Not Accurately Reflect Rapid, Pattern Completion-Based Retrieval of Context Memory

ERIC Educational Resources Information Center

Pevzner, Aleksandr; Guzowski, John F.

2015-01-01

No studies to date have examined whether immediate-early gene (IEG) activation is driven by context memory recall. To address this question, we utilized the context preexposure facilitation effect (CPFE) paradigm. In CPFE, animals acquire contextual fear conditioning through hippocampus-dependent rapid retrieval of a previously formed contextual…

Task Specificity and the Influence of Memory on Visual Search: Comment on Vo and Wolfe (2012)

ERIC Educational Resources Information Center

Hollingworth, Andrew

2012-01-01

Recent results from Vo and Wolfe (2012b) suggest that the application of memory to visual search may be task specific: Previous experience searching for an object facilitated later search for that object, but object information acquired during a different task did not appear to transfer to search. The latter inference depended on evidence that a…

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

PubMed Central

Orsini, Caitlin A.; Maren, Stephen

2012-01-01

Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

Achieving enlightenment: what do we know about the implicit learning system and its interaction with explicit knowledge?

PubMed

Vidoni, Eric D; Boyd, Lara A

2007-09-01

Two major memory and learning systems operate in the brain: one for facts and ideas (ie, the declarative or explicit system), one for habits and behaviors (ie, the procedural or implicit system). Broadly speaking these two memory systems can operate either in concert or entirely independently of one another during the performance and learning of skilled motor behaviors. This Special Issue article has two parts. In the first, we present a review of implicit motor skill learning that is largely centered on the interactions between declarative and procedural learning and memory. Because distinct neuroanatomical substrates support unique aspects of learning and memory and thus focal injury can cause impairments that are dependent on lesion location, we also broadly consider which brain regions mediate implicit and explicit learning and memory. In the second part of this article, the interactive nature of these two memory systems is illustrated by the presentation of new data that reveal that both learning implicitly and acquiring explicit knowledge through physical practice lead to motor sequence learning. In our new data, we discovered that for healthy individuals use of the implicit versus explicit memory system differently affected variability of performance during acquisition practice; variability was higher early in practice for the implicit group and later in practice for the acquired explicit group. Despite the difference in performance variability, by retention both groups demonstrated comparable change in tracking accuracy and thus, motor sequence learning. Clinicians should be aware of the potential effects of implicit and explicit interactions when designing rehabilitation interventions, particularly when delivering explicit instructions before task practice, working with individuals with focal brain damage, and/or adjusting therapeutic parameters based on acquisition performance variability.

Elevation of Hippocampal Neurogenesis Induces a Temporally Graded Pattern of Forgetting of Contextual Fear Memories.

PubMed

Gao, Aijing; Xia, Frances; Guskjolen, Axel J; Ramsaran, Adam I; Santoro, Adam; Josselyn, Sheena A; Frankland, Paul W

2018-03-28

Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis. By virally expressing the inhibitory designer receptor exclusively activated by designer drugs, hM4Di, we first confirmed that chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent (day-old) but not remote (month-old) contextual fear memories in male mice. We then contrasted the effects of increasing hippocampal neurogenesis at recent versus remote time points after contextual fear conditioning in male and female mice. Increasing hippocampal neurogenesis immediately following training reduced conditioned freezing when mice were replaced in the context 1 month later. In contrast, when hippocampal neurogenesis was increased time points remote to training, conditioned freezing levels were unaltered when mice were subsequently tested. These temporally graded forgetting effects were observed using both environmental and genetic interventions to increase hippocampal neurogenesis. Our experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting and suggest that, as contextual fear memories mature, they become less sensitive to changes in hippocampal neurogenesis levels because they no longer depend on the hippocampus for their expression. SIGNIFICANCE STATEMENT New neurons are generated in the hippocampus throughout life. As they integrate into the hippocampus, they remodel neural circuitry, potentially making information stored in those circuits harder to access. Consistent with this, increasing hippocampal neurogenesis after learning induces forgetting of the learnt information. The current study in mice asks whether these forgetting effects depend on the age of the memory. We found that post-training increases in hippocampal neurogenesis only impacted recently acquired, and not remotely acquired, hippocampal memories. These experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting, and suggest remote memories are less sensitive to changes in hippocampal neurogenesis levels because they no longer depend critically on the hippocampus for their expression. Copyright © 2018 the authors 0270-6474/18/383190-09$15.00/0.

Deciding to buy expensive technology. The case of biliary lithotripsy.

PubMed

Weingart, S N

1995-01-01

Acquiring expensive, new medical technology requires an evaluation of the efficacy and effectiveness, safety, profitability, feasibility, and risk of a project in the context of the hospital's social responsibility and institutional strategy. A case study of the decision to bring biliary lithotripsy to Strong Memorial Hospital illustrates how these criteria offer managers a coherent approach to difficult and consequential decisions about acquiring medical technology.

Immunological alteration & toxic molecular inductions leading to cognitive impairment & neurotoxicity in transgenic mouse model of Alzheimer's disease.

PubMed

Ahuja, Manuj; Buabeid, Manal; Abdel-Rahman, Engy; Majrashi, Mohammed; Parameshwaran, Kodeeswaran; Amin, Rajesh; Ramesh, Sindhu; Thiruchelvan, Kariharan; Pondugula, Satyanarayana; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

2017-05-15

Inflammation is considered to be one of the crucial pathological factors associated with the development of Alzheimer's disease, although supportive experimental evidence remains undiscovered. Therefore, the current study was carried out to better understand and establish the pathophysiological involvement of chronic inflammation in a double transgenic mouse model of Alzheimer's disease. We analyzed amyloid-beta deposition, oxidative stress, biochemical, neurochemical and immunological markers in a 10month old (APΔE9) mouse model. Memory functions were assessed by behavioral testing followed by measurement of synaptic plasticity via extracellular field recordings. Substantial increases in amyloid-beta levels, beta-secretase activity, and oxidative stress, along with significant neurochemical alterations in glutamate and GABA levels were detected in the brain of APΔE9 mice. Interestingly, marked elevations of pro-inflammatory cytokines in whole brain lysate of APΔE9 mice were observed. Flow cytometric analysis revealed a higher frequency of CD4+ IL-17a and IFN-γ secreting T-cells in APΔE9 brain, indicating a robust T-cell infiltration and activation. Behavioral deficits in learning and memory tasks, along with impairment in long-term potentiation and associated biochemical changes in the expression of glutamatergic receptor subunits were evident. Thus, this study establishes the role by which oxidative stress, alterations in glutamate and GABA levels and inflammation increases hippocampal and cortical neurotoxicity resulting in the cognitive deficits associated with Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

A Feedback Control Model of Comprehensive Therapy for Treating Immunogenic Tumours

NASA Astrophysics Data System (ADS)

Tang, Biao; Xiao, Yanni; Tang, Sanyi; Cheke, Robert A.

Surgery is the traditional method for treating cancers, but it often fails to cure patients for complex reasons so new therapeutic approaches that include both surgery and immunotherapy have recently been proposed. These have been shown to be effective, clinically, in inhibiting cancer cells while allowing retention of immunologic memory. This comprehensive strategy is guided by whether a population of tumour cells has or has not exceeded a threshold density. Conditions for successful control of tumours in an immune tumour system were modeled and the related dynamics were addressed. A mathematical model with state-dependent impulsive interventions is formulated to describe combinations of surgery with immunotherapy. By analyzing the properties of the Poincaré map, we examine the global dynamics of the immune tumour system with state-dependent feedback control, including the existence and stability of the semi-trivial order-1 periodic solution and the positive order-k periodic solution. The main results showed that surgery alone can only control the tumour size below a certain level while there is no immunologic memory. If comprehensive therapy involving combining surgery with immunotherapy is considered, then not only can the cancers be controlled below a certain level, but the immune system can also retain its activity. The existence of positive order-k periodic solutions implies that periodical therapy is needed to control the cancers. However, choosing the treatment frequency and the strength of the therapy remains challenging, and hence a strategy of individual-based therapy is suggested.

Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

PubMed Central

Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

2016-01-01

Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model.

PubMed

Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

2016-09-01

Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction.

Prior parity positively regulates learning and memory in young and middle-aged rats.

PubMed

Zimberknopf, Erica; Xavier, Gilberto F; Kinsley, Craig H; Felicio, Luciano F

2011-08-01

Reproductive experience in female rats modifies acquired behaviors, induces long-lasting functional neuroadaptations and can also modify spatial learning and memory. The present study supports and expands this knowledge base by employing the Morris water maze, which measures spatial memory. Age-matched young adult (YNG) nulliparous (NULL; nonmated) and primiparous (PRIM; one pregnancy and lactation) female rats were tested 15 d after the litter's weaning. In addition, corresponding middle-aged (AGD) PRIM (mated in young adulthood so that pregnancy, parturition, and lactation occurred at the same age as in YNG PRIM) and NULL female rats were tested at 18 mo of age. Behavioral evaluation included: 1) acquisition of reference memory (platform location was fixed for 14 to 19 d of testing); 2) retrieval of this information associated with extinction of the acquired response (probe test involving removal of the platform 24 h after the last training session); and 3) performance in a working memory version of the task (platform presented in a novel location every day for 13 d, and maintained in a fixed location within each day). YNG PRIM outperformed NULL rats and showed different behavioral strategies. These results may be related to changes in locomotor, mnemonic, and cognitive processes. In addition, YNG PRIM exhibited less anxiety-like behavior. Compared with YNG rats, AGD rats showed less behavioral flexibility but stronger memory consolidation. These data, which were obtained by using a well-documented spatial task, demonstrate long lasting modifications of behavioral strategies in both YNG and AGD rats associated with a single reproductive experience.

Th cells promote CTL survival and memory via acquired pMHC-I and endogenous IL-2 and CD40L signaling and by modulating apoptosis-controlling pathways.

PubMed

Umeshappa, Channakeshava Sokke; Xie, Yufeng; Xu, Shulin; Nanjundappa, Roopa Hebbandi; Freywald, Andrew; Deng, Yulin; Ma, Hong; Xiang, Jim

2013-01-01

Involvement of CD4(+) helper T (Th) cells is crucial for CD8(+) cytotoxic T lymphocyte (CTL)-mediated immunity. However, CD4(+) Th's signals that govern CTL survival and functional memory are still not completely understood. In this study, we assessed the role of CD4(+) Th cells with acquired antigen-presenting machineries in determining CTL fates. We utilized an adoptive co-transfer into CD4(+) T cell-sufficient or -deficient mice of OTI CTLs and OTII Th cells or Th cells with various gene deficiencies pre-stimulated in vitro by ovalbumin (OVA)-pulsed dendritic cell (DCova). CTL survival was kinetically assessed in these mice using FITC-anti-CD8 and PE-H-2K(b)/OVA257-264 tetramer staining by flow cytometry. We show that by acting via endogenous CD40L and IL-2, and acquired peptide-MHC-I (pMHC-I) complex signaling, CD4(+) Th cells enhance survival of transferred effector CTLs and their differentiation into the functional memory CTLs capable of protecting against highly-metastasizing tumor challenge. Moreover, RT-PCR, flow cytometry and Western blot analysis demonstrate that increased survival of CD4(+) Th cell-helped CTLs is matched with enhanced Akt1/NF-κB activation, down-regulation of TRAIL, and altered expression profiles with up-regulation of prosurvival (Bcl-2) and down-regulation of proapoptotic (Bcl-10, Casp-3, Casp-4, Casp-7) molecules. Taken together, our results reveal a previously unexplored mechanistic role for CD4(+) Th cells in programming CTL survival and memory recall responses. This knowledge could also aid in the development of efficient adoptive CTL cancer therapy.

Th Cells Promote CTL Survival and Memory via Acquired pMHC-I and Endogenous IL-2 and CD40L Signaling and by Modulating Apoptosis-Controlling Pathways

PubMed Central

Umeshappa, Channakeshava Sokke; Xie, Yufeng; Xu, Shulin; Nanjundappa, Roopa Hebbandi; Freywald, Andrew; Deng, Yulin; Ma, Hong; Xiang, Jim

2013-01-01

Involvement of CD4+ helper T (Th) cells is crucial for CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity. However, CD4+ Th’s signals that govern CTL survival and functional memory are still not completely understood. In this study, we assessed the role of CD4+ Th cells with acquired antigen-presenting machineries in determining CTL fates. We utilized an adoptive co-transfer into CD4+ T cell-sufficient or -deficient mice of OTI CTLs and OTII Th cells or Th cells with various gene deficiencies pre-stimulated in vitro by ovalbumin (OVA)-pulsed dendritic cell (DCova). CTL survival was kinetically assessed in these mice using FITC-anti-CD8 and PE-H-2Kb/OVA257-264 tetramer staining by flow cytometry. We show that by acting via endogenous CD40L and IL-2, and acquired peptide-MHC-I (pMHC-I) complex signaling, CD4+ Th cells enhance survival of transferred effector CTLs and their differentiation into the functional memory CTLs capable of protecting against highly-metastasizing tumor challenge. Moreover, RT-PCR, flow cytometry and Western blot analysis demonstrate that increased survival of CD4+ Th cell-helped CTLs is matched with enhanced Akt1/NF-κB activation, down-regulation of TRAIL, and altered expression profiles with up-regulation of prosurvival (Bcl-2) and down-regulation of proapoptotic (Bcl-10, Casp-3, Casp-4, Casp-7) molecules. Taken together, our results reveal a previously unexplored mechanistic role for CD4+ Th cells in programming CTL survival and memory recall responses. This knowledge could also aid in the development of efficient adoptive CTL cancer therapy. PMID:23785406

The impact of time and repeated exposure on famous person knowledge in amnestic mild cognitive impairment and Alzheimer's disease.

PubMed

Benoit, Sophie; Rouleau, Isabelle; Langlois, Roxane; Dostie, Valérie; Kergoat, Marie-Jeanne; Joubert, Sven

2017-10-01

Famous people knowledge has been shown to be impaired early in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, the question of whether recently acquired knowledge is more impaired than remotely acquired knowledge remains a matter of debate. The aim of this study was to investigate the patterns of semantic memory impairment in aMCI and AD by investigating 2 factors that may influence the retrieval of such knowledge, namely remoteness and frequency of repetition of information over time. Three groups (19 controls, 20 aMCI, and 20 AD patients) were compared on a test assessing general and specific biographical knowledge about famous people, where the period of acquired fame (remote vs. recent) and the type of fame (enduring vs. transient) were controlled for. Global performance of aMCI and AD patients was significantly poorer than that of controls. However, different patterns of recall were observed as a function of time and type of fame. A temporal gradient was found in both patient groups for enduring names but not for transient ones, whereby knowledge about remote enduring famous persons was better recalled. Patients were more impaired at questions assessing specific biographical knowledge (unique to an individual) than more general knowledge. Tests of famous people knowledge offer a unique opportunity to investigate semantic deficits in aMCI and AD, because they make it possible to estimate the time at which memories were acquired, as well as the type of fame. Results are discussed in light of memory consolidation models. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

T-Cell Tropism of Simian Varicella Virus during Primary Infection

PubMed Central

Ouwendijk, Werner J. D.; Mahalingam, Ravi; de Swart, Rik L.; Haagmans, Bart L.; van Amerongen, Geert; Getu, Sarah; Gilden, Don; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.

2013-01-01

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. PMID:23675304

Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses

PubMed Central

Hurt, Aeron C.; Oshansky, Christine M.; Oh, Ding Yuan; Reading, Patrick C.; Chua, Brendon Y.; Sun, Yilun; Tang, Li; Handel, Andreas; Jackson, David C.; Turner, Stephen J.; Thomas, Paul G.; Kedzierska, Katherine

2015-01-01

CD8+ T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8+ T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8+ T cell responses and the establishment of immunological CD8+ T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8+ T cell responses. Importantly, functional memory CD8+ T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4+ T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8+ T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves. PMID:26086392

Verbal short-term memory and vocabulary learning in polyglots.

PubMed

Papagno, C; Vallar, G

1995-02-01

Polyglot and non-polyglot Italian subjects were given tests assessing verbal (phonological) and visuo-spatial short-term and long-term memory, general intelligence, and vocabulary knowledge in their native language. Polyglots had a superior level of performance in verbal short-term memory tasks (auditory digit span and nonword repetition) and in a paired-associate learning test, which assessed the subjects' ability to acquire new (Russian) words. By contrast, the two groups had comparable performance levels in tasks assessing general intelligence, visuo-spatial short-term memory and learning, and paired-associate learning of Italian words. These findings, which are in line with neuropsychological and developmental evidence, as well as with data from normal subjects, suggest a close relationship between the capacity of phonological memory and the acquisition of foreign languages.

A short history of research on immunity to infectious diseases in fish.

PubMed

Van Muiswinkel, Willem B; Nakao, Miki

2014-04-01

This review describes the history of research on immunity to infectious diseases of fish in the period between 1965 and today. Special attention is paid to those studies, which are dealing with the interaction between immune system and invading pathogens in bony fish. Moreover, additional biographic information will be provided of people involved. In the 1960s and 1970s the focus of most studies was on humoral (Ig, B-cell) responses. Thorough studies on specific cellular (T-cell) responses and innate immunity (lectins, lysozyme, interferon, phagocytic cells) became available later. In the period between 1980 and today an overwhelming amount of data on regulation (e.g. cell cooperation, cytokines) and cell surface receptors (e.g. T-cell receptor; MHC) was published. It became also clear, that innate responses were often interacting with the acquired immune responses. Fish turned out to be vertebrates like all others with a sophisticated immune system showing specificity and memory. These basic data on the immune system could be applied in vaccination or in selection of disease resistant fish. Successful vaccines against bacterial diseases became available in the 1970s and 1980s. Effective anti-viral vaccines appeared from the 1980s onwards. There is no doubt, that Fish Immunology has become a flourishing science by the end of the 20th century and has contributed to our understanding of fish diseases as well as the success of aquaculture. Copyright © 2013 Elsevier Ltd. All rights reserved.

Space Flight Immunodeficiency

NASA Technical Reports Server (NTRS)

Shearer, William T.

1999-01-01

The National Aeronautics and Space Administration (NASA) has had sufficient concern for the well-being of astronauts traveling in space to create the National Space Biomedical Research Institute (NSBRI), which is investigating several areas of biomedical research including those of immunology. As part of the Immunology, Infection, and Hematology Team, the co-investigators of the Space Flight Immunodeficiency Project began their research projects on April 1, 1998 and are now just into the second year of work. Two areas of research have been targeted: 1) specific immune (especially antibody) responses and 2) non-specific inflammation and adhesion. More precise knowledge of these two areas of research will help elucidate the potential harmful effects of space travel on the immune system, possibly sufficient to create a secondary state of immunodeficiency in astronauts. The results of these experiments are likely to lead to the delineation of functional alterations in antigen presentation, specific immune memory, cytokine regulation of immune responses, cell to cell interactions, and cell to endothelium interactions.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

NASA Astrophysics Data System (ADS)

Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

2016-10-01

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

Lessons learned at the intersection of immunology and neuroscience

PubMed Central

Steinman, Lawrence

2012-01-01

Neurobiologists and immunologists study concepts often signified with identical terminology. Scientists in both fields study a structure known as the synapse, and each group analyzes a subject called memory. Is this a quirk of human language, or are there real similarities between these two physiological systems? Not only are the linguistic concepts expressed in the words “synapse” and “memory” shared between the fields, but the actual molecules of physiologic importance in one system play parallel roles in the other: complement, the major histocompatibility molecules, and even “neuro”-transmitters all have major impacts on health and on disease in both the brain and the immune system. Not only are the same molecules found in diverse roles in each system, but we have learned that there is real “hard-wired” crosstalk between nerves and lymphoid organs. This issue of the JCI highlights some of the lessons learned from experts who are working at this scintillating intersection between immunology and neuroscience. PMID:22466655

Distinct Effects of Saracatinib on Memory CD8+ T-cell Differentiation

PubMed Central

Takai, Shinji; Sabzevari, Helen; Farsaci, Benedetto; Schlom, Jeffrey; Greiner, John W.

2012-01-01

Immunologic memory involving CD8+ T-cells is a hallmark of an adaptive antigen-specific immune response and comprises a critical component of protective immunity. Designing approaches that enhance long-term T-cell memory would, for the most part, fortify vaccines and enhance host protection against infectious diseases and, perhaps, cancer immunotherapy. A better understanding of the cellular programs involved in the antigen-specific T-cell response has led to new approaches that target the magnitude and quality of the memory T-cell response. Here we show that T-cells from T-cell receptor transgenic mice for the nucleoprotein of influenza virus NP68 exhibit the distinct phases priming, expansion, contraction, memory - of an antigen-specific T-cell response when exposed in vitro to the cognate peptide. Saracatinib, a specific inhibitor of Src family kinases, administered at low doses during the expansion or contraction phases, increased CD62Lhigh/CD44high central memory CD8+ T-cells and IFN-γ production, while suppressing immunity when added during the priming phase. These effects by saracatinib were not accompanied by the expected decline of Src family kinases, but were accompanied by Akt-mTOR suppression and/or mediated via another pathway. Increased central memory cells by saracatinib were recapitulated in mice using a poxvirus-based influenza vaccine, thus underscoring the importance of dose and timing of the inhibitor in the context of memory T-cell differentiation. Finally, vaccine plus saracatinib treatment showed better protection against tumor challenge. The immune-potentiating effects on CD8+ T-cells by a low dose of saracatinib might afford better protection from pathogen or cancer when combined with vaccine. PMID:22450814

Placebo-mediated, Naloxone-sensitive suggestibility of short-term memory performance.

PubMed

Stern, Jair; Candia, Victor; Porchet, Roseline I; Krummenacher, Peter; Folkers, Gerd; Schedlowski, Manfred; Ettlin, Dominik A; Schönbächler, Georg

2011-03-01

Physiological studies of placebo-mediated suggestion have been recently performed beyond their traditional clinical context of pain and analgesia. Various neurotransmitter systems and immunological modulators have been used in successful placebo suggestions, including Dopamine, Cholecystokinin and, most extensively, opioids. We adhered to an established conceptual framework of placebo research and used the μ-opioid-antagonist Naloxone to test the applicability of this framework within a cognitive domain (e.g. memory) in healthy volunteers. Healthy men (n=62, age 29, SD=9) were required to perform a task-battery, including standardized and custom-designed memory tasks, to test short-term recall and delayed recognition. Tasks were performed twice, before and after intravenous injection of either NaCl (0.9%) or Naloxone (both 0.15 mg/kg), in a double-blind setting. While one group was given neutral information (S-), the other was told that it might receive a drug with suspected memory-boosting properties (S+). Objective and subjective indexes of memory performance and salivary cortisol (as a stress marker) were recorded during both runs and differences between groups were assessed. Short-term memory recall, but not delayed recognition, was objectively increased after placebo-mediated suggestion in the NaCl-group. Naloxone specifically blocked the suggestion effect without interfering with memory performance. These results were not affected when changes in salivary cortisol levels were considered. No reaction time changes, recorded to uncover unspecific attentional impairment, were seen. Placebo-mediated suggestion produced a training-independent, objective and Naloxone-sensitive increase in memory performance. These results indicate an opioid-mediated placebo effect within a circumscribed cognitive domain in healthy volunteers. Copyright © 2011 Elsevier Inc. All rights reserved.

Effectiveness of a Computer-Based Training Program of Attention and Memory in Patients with Acquired Brain Damage

PubMed Central

Fernandez, Elizabeth; Bergado Rosado, Jorge A.; Rodriguez Perez, Daymi; Salazar Santana, Sonia; Torres Aguilar, Maydane; Bringas, Maria Luisa

2017-01-01

Many training programs have been designed using modern software to restore the impaired cognitive functions in patients with acquired brain damage (ABD). The objective of this study was to evaluate the effectiveness of a computer-based training program of attention and memory in patients with ABD, using a two-armed parallel group design, where the experimental group (n = 50) received cognitive stimulation using RehaCom software, and the control group (n = 30) received the standard cognitive stimulation (non-computerized) for eight weeks. In order to assess the possible cognitive changes after the treatment, a post-pre experimental design was employed using the following neuropsychological tests: Wechsler Memory Scale (WMS) and Trail Making test A and B. The effectiveness of the training procedure was statistically significant (p < 0.05) when it established the comparison between the performance in these scales, before and after the training period, in each patient and between the two groups. The training group had statistically significant (p < 0.001) changes in focused attention (Trail A), two subtests (digit span and logical memory), and the overall score of WMS. Finally, we discuss the advantages of computerized training rehabilitation and further directions of this line of work. PMID:29301194

Pain-relief learning in flies, rats, and man: basic research and applied perspectives

PubMed Central

Gerber, Bertram; Yarali, Ayse; Diegelmann, Sören; Wotjak, Carsten T.; Pauli, Paul; Fendt, Markus

2014-01-01

Memories relating to a painful, negative event are adaptive and can be stored for a lifetime to support preemptive avoidance, escape, or attack behavior. However, under unfavorable circumstances such memories can become overwhelmingly powerful. They may trigger excessively negative psychological states and uncontrollable avoidance of locations, objects, or social interactions. It is therefore obvious that any process to counteract such effects will be of value. In this context, we stress from a basic-research perspective that painful, negative events are “Janus-faced” in the sense that there are actually two aspects about them that are worth remembering: What made them happen and what made them cease. We review published findings from fruit flies, rats, and man showing that both aspects, respectively related to the onset and the offset of the negative event, induce distinct and oppositely valenced memories: Stimuli experienced before an electric shock acquire negative valence as they signal upcoming punishment, whereas stimuli experienced after an electric shock acquire positive valence because of their association with the relieving cessation of pain. We discuss how memories for such punishment- and relief-learning are organized, how this organization fits into the threat-imminence model of defensive behavior, and what perspectives these considerations offer for applied psychology in the context of trauma, panic, and nonsuicidal self-injury. PMID:24643725

Acquisition and retrieval of conditioned taste aversion is impaired by brain damage caused by two hours of pilocarpine-induced status epilepticus.

PubMed

Sroubek, J; Hort, J; Komárek, V; Langmeier, M; Brozek, G

2001-01-01

The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.

Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells.

PubMed

Nishida, Atsushi; Nagahama, Kiyotaka; Imaeda, Hirotsugu; Ogawa, Atsuhiro; Lau, Cindy W; Kobayashi, Taku; Hisamatsu, Tadakazu; Preffer, Frederic I; Mizoguchi, Emiko; Ikeuchi, Hiroki; Hibi, Toshifumi; Fukuda, Minoru; Andoh, Akira; Blumberg, Richard S; Mizoguchi, Atsushi

2012-12-17

Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1-expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell-mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease.

Verification of immune response optimality through cybernetic modeling.

PubMed

Batt, B C; Kompala, D S

1990-02-09

An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included.

Top-down cortical input during NREM sleep consolidates perceptual memory.

PubMed

Miyamoto, D; Hirai, D; Fung, C C A; Inutsuka, A; Odagawa, M; Suzuki, T; Boehringer, R; Adaikkan, C; Matsubara, C; Matsuki, N; Fukai, T; McHugh, T J; Yamanaka, A; Murayama, M

2016-06-10

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation. Copyright © 2016, American Association for the Advancement of Science.

Hippocampal awake replay in fear memory retrieval

PubMed Central

Wu, Chun-Ting; Haggerty, Daniel; Kemere, Caleb; Ji, Daoyun

2017-01-01

Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. Here, after rats acquired a fear memory by receiving mild foot-shocks at a shock zone of a track, we analyzed place cells when the animals were placed back to the track and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal’s current positions to the shock zone, but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place cell pattern underlying the inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval. PMID:28218916

Brain substrates of implicit and explicit memory: the importance of concurrently acquired neural signals of both memory types.

PubMed

Voss, Joel L; Paller, Ken A

2008-11-01

A comprehensive understanding of human memory requires cognitive and neural descriptions of memory processes along with a conception of how memory processing drives behavioral responses and subjective experiences. One serious challenge to this endeavor is that an individual memory process is typically operative within a mix of other contemporaneous memory processes. This challenge is particularly disquieting in the context of implicit memory, which, unlike explicit memory, transpires without the subject necessarily being aware of memory retrieval. Neural correlates of implicit memory and neural correlates of explicit memory are often investigated in different experiments using very different memory tests and procedures. This strategy poses difficulties for elucidating the interactions between the two types of memory process that may result in explicit remembering, and for determining the extent to which certain neural processing events uniquely contribute to only one type of memory. We review recent studies that have succeeded in separately assessing neural correlates of both implicit memory and explicit memory within the same paradigm using event-related brain potentials (ERPs) and functional magnetic resonance imaging (fMRI), with an emphasis on studies from our laboratory. The strategies we describe provide a methodological framework for achieving valid assessments of memory processing, and the findings support an emerging conceptualization of the distinct neurocognitive events responsible for implicit and explicit memory.

Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

PubMed

Hardcastle, Sharni Lee; Brenu, Ekua Weba; Johnston, Samantha; Nguyen, Thao; Huth, Teilah; Wong, Naomi; Ramos, Sandra; Staines, Donald; Marshall-Gradisnik, Sonya

2015-06-02

Abnormal immune function is often an underlying component of illness pathophysiology and symptom presentation. Functional and phenotypic immune-related alterations may play a role in the obscure pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The objective of this study was to investigate the functional ability of innate and adaptive immune cells in moderate and severe CFS/ME patients. The 1994 Fukuda criteria for CFS/ME were used to define CFS/ME patients. CFS/ME participants were grouped based on illness severity with 15 moderately affected (moderate) and 12 severely affected (severe) CFS/ME patients who were age and sex matched with 18 healthy controls. Flow cytometric protocols were used for immunological analysis of dendritic cells, monocytes and neutrophil function as well as measures of lytic proteins and T, natural killer (NK) and B cell receptors. CFS/ME patients exhibited alterations in NK receptors and adhesion markers and receptors on CD4(+)T and CD8(+)T cells. Moderate CFS/ME patients had increased CD8(+) CD45RA effector memory T cells, SLAM expression on NK cells, KIR2DL5(+) on CD4(+)T cells and BTLA4(+) on CD4(+)T central memory cells. Moderate CFS/ME patients also had reduced CD8(+)T central memory LFA-1, total CD8(+)T KLRG1, naïve CD4(+)T KLRG1 and CD56(dim)CD16(-) NK cell CD2(+) and CD18(+)CD2(+). Severe CFS/ME patients had increased CD18(+)CD11c(-) in the CD56(dim)CD16(-) NK cell phenotype and reduced NKp46 in CD56(bright)CD16(dim) NK cells. This research accentuated the presence of immunological abnormalities in CFS/ME and highlighted the importance of assessing functional parameters of both innate and adaptive immune systems in the illness.

Representation in development: from a model system to some general processes.

PubMed

Montuori, Luke M; Honey, Robert C

2015-03-01

The view that filial imprinting might serve as a useful model system for studying the neurobiological basis of memory was inspired, at least in part, by a simple idea: acquired filial preferences reflect the formation of a memory or representation of the imprinting object itself, as opposed to the change in the efficacy of stimulus-response pathways, for example. We provide a synthesis of the evidence that supports this idea; and show that the processes of memory formation observed in filial imprinting find surprisingly close counterparts in other species, including our own. Copyright © 2014 Elsevier Ltd. All rights reserved.

Eight microprocessor-based instrument data systems in the Galileo Orbiter spacecraft

NASA Technical Reports Server (NTRS)

Barry, R. C.

1980-01-01

Instrument data systems consist of a microprocessor, 3K bytes of Read Only Memory and 3K bytes of Random Access Memory. It interfaces with the spacecraft data bus through an isolated user interface with a direct memory access bus adaptor, and/or parallel data from instrument devices such as registers, buffers, analog to digital converters, multiplexers, and solid state sensors. These data systems support the spacecraft hardware and software communication protocol, decode and process instrument commands, generate continuous instrument operating modes, control the instrument mechanisms, acquire, process, format, and output instrument science data.

Learning and memory in disease vector insects

PubMed Central

Vinauger, Clément; Lahondère, Chloé; Cohuet, Anna; Lazzari, Claudio R.; Riffell, Jeffrey A.

2016-01-01

Learning and memory plays an important role in host preference and parasite transmission by disease vector insects. Historically there has been a dearth of standardized protocols that permit testing their learning abilities, thus limiting discussion on the potential epidemiological consequences of learning and memory to a largely speculative extent. However, with increasing evidence that individual experience and associative learning can affect processes such as oviposition site selection and host preference, it is timely to review the recently acquired knowledge, identify research gaps and discuss the implication of learning in disease vector insects in perspective with control strategies. PMID:27450224

Acquisition of generic memory in amnesia.

PubMed

Verfaellie, M; Cermak, L S

1994-06-01

Amnesic patients' ability to acquire generic, semantic information was assessed relative to their own level of episodic memory. Patients studied a list of words in which some items were presented twice and others once. Upon each presentation, the words were tagged episodically by presenting them in a unique color. Recall of the colors in which words were presented suggested that individual presentations of repeated items were less likely to be recalled than presentations of nonrepeated items; however, actual recall of repeated items exceeded that of nonrepeated items. This outcome demonstrated that amnesics can recall some items generically without recalling either of their individual presentations. However, amnesics' recall of twice-presented items remained far below that of the control group, even when their recall of once-presented items was matched by testing the control group after a delay. This finding suggests that amnesic patients can acquire new generic knowledge but do so much less efficiently than do normal individuals. Furthermore, this deficit occurs independently of the amnesics' episodic memory impairments, reflecting instead a disruption in semantic learning per se.

Influence of diagnosis threat and illness cognitions on the cognitive performance of people with acquired brain injury.

PubMed

Fresson, Megan; Dardenne, Benoit; Meulemans, Thierry

2018-02-27

Illness cognitions - cognitive representations of illness - have been found to influence health outcomes in chronic diseases: more adaptive illness cognitions generally lead to better outcomes. Concomitantly, diagnosis threat (DT) is a phenomenon whereby participants with acquired brain injury (ABI) underperform on neuropsychological tasks due to stereotype activation. This randomised study examined the impact of illness cognitions and DT on cognitive performance. People with ABI completed the Illness Cognitions Questionnaire and were then exposed to either a DT condition or a reduced DT condition (in which stereotype cues were reduced). They then completed memory and attentional tasks. Control participants performed only the tasks under one of the two conditions. Under the reduced DT condition, higher adaptive illness cognitions were associated with better memory and attentional performance. However, the DT condition diminished memory (but not attentional) performance in participants with a high level of adaptive illness cognitions, often leading to performance at the pathological level. This study confirms the detrimental impact of DT in people with ABI and highlights the necessity for clinicians to consider psychosocial influences when assessing and treating this population.

The large intestine as a major reservoir for simian immunodeficiency virus in macaques with long-term, nonprogressing infection.

PubMed

Ling, Binhua; Mohan, Mahesh; Lackner, Andrew A; Green, Linda C; Marx, Preston A; Doyle, Lara A; Veazey, Ronald S

2010-12-15

Although patients with human immunodeficiency virus type 1 infection who are receiving antiretroviral therapy and those with long-term, nonprogressive infection (LTNPs) usually have undetectable viremia, virus persists in tissue reservoirs throughout infection. However, the distribution and magnitude of viral persistence and replication in tissues has not been adequately examined. Here, we used the simian immunodeficiency virus (SIV) macaque model to quantify and compare viral RNA and DNA in the small (jejunum) and large (colon) intestine of LTNPs. In LTNPs with chronic infection, the colon had consistently higher viral levels than did the jejunum. The colon also had higher percentages of viral target cells (memory CD4(+) CCR5(+) T cells) and proliferating memory CD4(+) T cells than did the jejunum, whereas markers of cell activation were comparable in both compartments. These data indicate that the large intestine is a major viral reservoir in LTNPs, which may be the result of persistent, latently infected cells and higher turnover of naive and central memory CD4(+) T cells in this major immunologic compartment.

Disruption of human fear reconsolidation using imaginal and in vivo extinction.

PubMed

Agren, Thomas; Björkstrand, Johannes; Fredrikson, Mats

2017-02-15

Memories are not set forever, but can be altered following reactivation, which renders memories malleable, before they are again stabilized through reconsolidation. Fear memories can be attenuated by using extinction during the malleable period. The present study adopts a novel form of extinction, using verbal instructions, in order to examine whether fear memory reconsolidation can be affected by an imaginal exposure. The extinction using verbal instructions, called imaginal extinction, consists of a recorded voice encouraging participants to imagine the scene in which fear was acquired, and to envision the stimuli before their inner eye. The voice signals stimuli appearance, and identical to standard (in vivo) extinction, participants discover that the conditioned stimulus no longer is followed by unconditioned stimulus (UCS). In this way, imaginal extinction translates clinically used imaginal exposure into the standard experimental fear conditioning paradigm. Fear was acquired by pairing pictorial stimuli with an electric shock UCS. Then, both standard and imaginal extinction were given following fear memory reactivation, either after 10min, within the reconsolidation interval, or after 6h, outside of the reconsolidation interval. In vivo and imaginal extinction produced comparable reductions in conditioned responses during extinction and importantly, both disrupted reconsolidation of conditioned fear and abolished stimulus discrimination between reinforced and non-reinforced cues. Thus, disrupted reconsolidation of fear conditioning can be achieved without in vivo stimulus presentation, through purely cognitive means, suggesting possible therapeutic applications. Copyright © 2016 Elsevier B.V. All rights reserved.

The fish parasite Ichthyophthirius multifiliis - Host immunology, vaccines and novel treatments.

PubMed

Jørgensen, Louise von Gersdorff

2017-08-01

Ichthyophthirius multifiliis, the causative agent of white spot disease (ichthyophthiriasis) is a major burden for fish farmers and aquarists globally. The parasite infects the skin and the gills of freshwater fish, which may acquire a protective adaptive immune response against this disease, making vaccine strategies feasible. However, there is no prophylactic treatment available and repetitive treatments with auxiliary substances are needed to control the infection. Historically, a variety of drugs and chemicals have been used to combat the disease but due to changing regulations and recognition of carcinogenic and environmentally damaging effects the most efficient compounds are prohibited. A continuous search for novel substances, which are highly effective against the parasites and harmless for the fish is ongoing. These compounds should be environmentally friendly and cost-effective. This review presents recent progress within host immunology, vaccinology and a description of novel substances, which have been tested as treatments against ichthyophthiriasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of virologic and immunologic factors in mother-to-child transmission of HIV-1.

PubMed

Colognesi, C; Halapi, E; Jansson, M; Hodara, V; Steuer, G; Tresoldi, E; Leitner, T; Scarlatti, G

1997-09-01

More than 90% of human immunodeficiency virus type 1 (HIV-1) infection in children is acquired by mother-to-child transmission. However, infection of the child occurs in between 14 and 35% of cases. To understand the mechanisms involved in HIV-1 transmission, we have investigated the antigenic, molecular, and phenotypic characteristics of the virus harbored in infected mothers and their children. A clear correlation was observed between the transmission of the virus and the isolation of viral variants with a rapidly replicating and syncytium-inducing phenotype from the mother. Furthermore, non-transmitting mothers were able to neutralize several primary isolates more frequently than transmitting mothers. The comparison of the viral phenotype and genotype of mother-child pairs showed that the transmitted virus did not have common features, suggesting that transmission is usually not a selective process. This study suggests that transmission is governed by an interaction of both viral and immunological factors. The results obtained indicate that different strategies can be applied for the prevention of transmission.

The immunological synapse as a pharmacological target.

PubMed

Francesca, Finetti; Baldari, Cosima T

2018-06-10

The development of T cell mediated immunity relies on the assembly of a highly specialized interface between T cell and antigen presenting cell (APC), known as the immunological synapse (IS). IS assembly is triggered when the T cell receptor (TCR) binds to specific peptide antigen presented in association to the major histocompatibility complex (MHC) by the APC, and is followed by the spatiotemporal dynamic redistribution of TCR, integrins, co-stimulatory receptors and signaling molecules, allowing for the fine-tuning and integration of the signals that lead to T cell activation. The knowledge acquired to date about the mechanisms of IS assembly underscores this structure as a robust pharmacological target. The activity of molecules involved in IS assembly and function can be targeted by specific compounds to modulate the immune response in a number of disorders, including cancers and autoimmune diseases, or in transplanted patients. Here, we will review the state-of-the art of the current therapies which exploit the IS to modulate the immune response. Copyright © 2018. Published by Elsevier Ltd.

Making the case that episodic recollection is attributable to operations occurring at retrieval rather than to content stored in a dedicated subsystem of long-term memory.

PubMed

Klein, Stanley B

2013-01-01

Episodic memory often is conceptualized as a uniquely human system of long-term memory that makes available knowledge accompanied by the temporal and spatial context in which that knowledge was acquired. Retrieval from episodic memory entails a form of first-person subjectivity called autonoetic consciousness that provides a sense that a recollection was something that took place in the experiencer's personal past. In this paper I expand on this definition of episodic memory. Specifically, I suggest that (1) the core features assumed unique to episodic memory are shared by semantic memory, (2) episodic memory cannot be fully understood unless one appreciates that episodic recollection requires the coordinated function of a number of distinct, yet interacting, "enabling" systems. Although these systems-ownership, self, subjective temporality, and agency-are not traditionally viewed as memorial in nature, each is necessary for episodic recollection and jointly they may be sufficient, and (3) the type of subjective awareness provided by episodic recollection (autonoetic) is relational rather than intrinsic-i.e., it can be lost in certain patient populations, thus rendering episodic memory content indistinguishable from the content of semantic long-term memory.

[Nondeclarative memory--neuropsychological findings and neuroanatomic principles].

PubMed

Daum, I; Ackermann, H

1997-03-01

The contents of long-term memory will influence behaviour, even if the acquired knowledge or the original learning episode are not remembered. These phenomena have been termed "non-declarative" or "implicit" memory, and they are contrasted with "declarative" or "explicit" memory which is characterised by conscious search and retrieval procedures. Non-declarative memory encompasses non-associative learning, simple conditioning, priming effects as well as motor, perceptual and cognitive skill acquisition. The dissociation of both forms of memory is documented by studies in health subjects which indicated that experimental manipulations or drugs may differentially affect declarative and non-declarative memory processes. Damage to the medial temporal or the medial thalamic regions is known to result in declarative memory deficits whereas non-declarative memory is largely unaffected by such lesions. Animal research and clinical findings indicate that several components of non-declarative memory such as motor and cognitive skill acquisition or certain types of classical conditioning are dependent upon the integrity of the basal ganglia or the cerebellum. These issues are therefore of increasing importance for the understanding of extrapyramidal and cerebellar diseases. This paper presents recent neuropsychological findings and neuroanatomical data relating to the issue of non-declarative memory.

Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

PubMed Central

Kurtulus, Sema; Tripathi, Pulak; Hildeman, David A.

2013-01-01

Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of effector T cells. PMID:23346085

Positive modulation of a neutral declarative memory by a threatening social event.

PubMed

Fernández, Rodrigo S; Bavassi, Luz; Campos, Jorge; Allegri, Ricardo F; Molina, Victor A; Forcato, Cecilia; Pedreira, María E

2015-12-01

Memories can be altered by negative or arousing experiences due to the activation of the stress-responsive sympatho-adrenal-medullary axis (SYM). Here, we used a neutral declarative memory that was acquired during multi-trial training to determine the effect of a threatening event on memory without emotional valence. To this end, participants received a new threatening social protocol before learning pairs of meaningless syllables and were tested either 15 min, 2 days or 8 days after acquisition. We first demonstrated that this threatening social situation activates not only the SYM axis (Experiment 1) and the hypothalamus-pituitary-adrenal axis (HPA; Experiment 2), but also, it improves the acquisition or early consolidation of the syllable pairs (Experiment 3). This improvement is not a transient effect; it can be observed after the memory is consolidated. Furthermore, this modulation increases the persistence of memory (Experiment 4). Thus, it is possible to affect memories with specific events that contain unrelated content and a different valence. Copyright © 2015 Elsevier Inc. All rights reserved.

A nap to recap or how reward regulates hippocampal-prefrontal memory networks during daytime sleep in humans

PubMed Central

Igloi, Kinga; Gaggioni, Giulia; Sterpenich, Virginie; Schwartz, Sophie

2015-01-01

Sleep plays a crucial role in the consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information that will be consolidated during sleep remains largely unknown. Here we show that post-learning sleep favors the selectivity of long-term consolidation: when tested three months after initial encoding, the most important (i.e., rewarded, strongly encoded) memories are better retained, and also remembered with higher subjective confidence. Our brain imaging data reveals that the functional interplay between dopaminergic reward regions, the prefrontal cortex and the hippocampus contributes to the integration of rewarded associative memories. We further show that sleep spindles strengthen memory representations based on reward values, suggesting a privileged replay of information yielding positive outcomes. These findings demonstrate that post-learning sleep determines the neural fate of motivationally-relevant memories and promotes a value-based stratification of long-term memory stores. DOI: http://dx.doi.org/10.7554/eLife.07903.001 PMID:26473618

Factors affecting graded and ungraded memory loss following hippocampal lesions.

PubMed

Winocur, Gordon; Moscovitch, Morris; Sekeres, Melanie J

2013-11-01

This review evaluates three current theories--Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Shift and rotation invariant photorefractive crystal-based associative memory

NASA Astrophysics Data System (ADS)

Uang, Chii-Maw; Lin, Wei-Feng; Lu, Ming-Huei; Lu, Guowen; Lu, Mingzhe

1995-08-01

A shift and rotation invariant photorefractive (PR) crystal based associative memory is addressed. The proposed associative memory has three layers: the feature extraction, inner- product, and output mapping layers. The feature extraction is performed by expanding an input object into a set of circular harmonic expansions (CHE) in the Fourier domain to acquire both the shift and rotation invariant properties. The inner product operation is performed by taking the advantage of Bragg diffraction of the bulky PR-crystal. The output mapping is achieved by using the massive storage capacity of the PR-crystal. In the training process, memories are stored in another PR-crystal by using the wavelength multiplexing technique. During the recall process, the output from the winner-take-all processor decides which wavelength should be used to read out the memory from the PR-crystal.

Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells

PubMed Central

Hayashi, Nobuki; Liu, Dacai; Min, Booki; Ben-Sasson, Shlomo Z.; Paul, William E.

2002-01-01

TH1 memory T cells derived from T cell receptor transgenic mice, in which the T cell antigen receptor is specific for a cytochrome C peptide in association with I-Ek, were transferred into normal B10.A mice and allowed to adopt a resting phenotype. When challenged, 30–60 days after transfer, with i.v. cytochrome C, the transgenic cells rapidly became activated, expressed mRNA for IFNγ, and began to divide. However, after 48 h, the frequency of the cells fell progressively, reaching levels only slightly above the limit of detection by day 8 and thereafter remain depressed for up to 90 days. The remaining cells were anergic as shown by limitation in proliferation and IFNγ production in response to in vitro antigen stimulation. Even if challenged with antigen emulsified in complete Freund's adjuvant, the overall pattern was similar, except that in the draining lymph nodes, the surviving antigen-specific cells were not anergic, although spleen cells were still strikingly anergic. Thus, antigenic challenge of mice possessing resting memory TH1 CD4 T cells leads to the unanticipated loss of most of the specific cells and an apparent depletion rather than enhancement of immunologic memory. PMID:11959916

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

PubMed

Foley, P T; Kavnoudias, H; Cameron, P U; Czarnecki, C; Paul, E; Lyon, S M

2015-10-01

To compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels. Patients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population. Of the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 did not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation-a difference that could not be attributed to differences in age, grade of injury or residual splenic volume. IgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function.

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foley, P. T., E-mail: pfoley@doctors.org.uk; Kavnoudias, H., E-mail: h.kavnoudias@alfred.org.au; Cameron, P. U., E-mail: paul.cameron@unimelb.edu.au

PurposeTo compare the impact of proximal or distal splenic artery embolisation versus that of splenectomy on splenic immune function as measured by IgM memory B cell levels.Materials and MethodsPatients with splenic trauma who were treated by splenic artery embolisation (SAE) were enrolled. After 6 months splenic volume was assessed by CT, and IgM memory B cells in peripheral blood were measured and compared to a local normal reference population and to a post-splenectomy population.ResultsOf the 71 patients who underwent embolisation, 38 underwent proximal embolisation, 11 underwent distal embolisation, 22 patients were excluded, 1 had both proximal and distal embolisation, 5 didmore » not survive and 16 did not return for evaluation. There was a significant difference between splenectomy and proximal or distal embolisation and a trend towards greater preservation of IgM memory B cell number in those with distal embolisation—a difference that could not be attributed to differences in age, grade of injury or residual splenic volume.ConclusionIgM memory B cell levels are significantly higher in those treated with SAE compared to splenectomy. Our data provide evidence that splenic embolisation should reduce immunological complications of spleen trauma and suggest that distal embolisation may maintain better function.« less

Curtailed T-cell activation curbs effector differentiation and generates CD8+ T cells with a naturally-occurring memory stem cell phenotype.

PubMed

Zanon, Veronica; Pilipow, Karolina; Scamardella, Eloise; De Paoli, Federica; De Simone, Gabriele; Price, David A; Martinez Usatorre, Amaia; Romero, Pedro; Mavilio, Domenico; Roberto, Alessandra; Lugli, Enrico

2017-09-01

Human T memory stem (T SCM ) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long-lived T-cell memory and are thus considered an attractive population to be used in adoptive transfer-based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T-cell receptor stimulation curbs human effector CD8 + T-cell differentiation and allows the generation of CD45RO - CD45RA + CCR7 + CD27 + CD95 + -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human T SCM . These cells proliferate extensively in vitro and in vivo, express low amounts of effector-associated genes and transcription factors and undergo considerable self-renewal in response to IL-15 while retaining effector differentiation potential. Such a phenotype is associated with a lower number of mitochondria compared to highly-activated effector T cells committed to terminal differentiation. These results shed light on the molecular signals that are required to generate long-lived memory T cells with potential application in adoptive cell transfer immunotherapy. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim.

Memory consolidation from seconds to weeks: a three-stage neural network model with autonomous reinstatement dynamics

PubMed Central

Fiebig, Florian; Lansner, Anders

2014-01-01

Declarative long-term memories are not created in an instant. Gradual stabilization and temporally shifting dependence of acquired declarative memories in different brain regions—called systems consolidation—can be tracked in time by lesion experiments. The observation of temporally graded retrograde amnesia (RA) following hippocampal lesions points to a gradual transfer of memory from hippocampus to neocortical long-term memory. Spontaneous reactivations of hippocampal memories, as observed in place cell reactivations during slow-wave-sleep, are supposed to drive neocortical reinstatements and facilitate this process. We propose a functional neural network implementation of these ideas and furthermore suggest an extended three-state framework that includes the prefrontal cortex (PFC). It bridges the temporal chasm between working memory percepts on the scale of seconds and consolidated long-term memory on the scale of weeks or months. We show that our three-stage model can autonomously produce the necessary stochastic reactivation dynamics for successful episodic memory consolidation. The resulting learning system is shown to exhibit classical memory effects seen in experimental studies, such as retrograde and anterograde amnesia (AA) after simulated hippocampal lesioning; furthermore the model reproduces peculiar biological findings on memory modulation, such as retrograde facilitation of memory after suppressed acquisition of new long-term memories—similar to the effects of benzodiazepines on memory. PMID:25071536

Memory skills mediating superior memory in a world-class memorist.

PubMed

Ericsson, K Anders; Cheng, Xiaojun; Pan, Yafeng; Ku, Yixuan; Ge, Yi; Hu, Yi

2017-10-01

Laboratory studies have investigated how individuals with normal memory spans attained digit spans over 80 digits after hundreds of hours of practice. Experimental analyses of their memory skills suggested that their attained memory spans were constrained by the encoding time, for the time needed will increase if the length of digit sequences to be memorised becomes longer. These constraints seemed to be violated by a world-class memorist, Feng Wang (FW), who won the World Memory Championship by recalling 300 digits presented at 1 digit/s. In several studies we examined FW's memory skills underlying his exceptional performance. First FW reproduced his superior memory span of 200 digits under laboratory condition, and we obtained his retrospective reports describing his encoding/retrieval processes (Experiment 1). Further experiments used self-paced memorisation to identify temporal characteristics of encoding of digits in 4-digit clusters (Experiment 2), and explored memory encoding at presentation speeds much faster than 1 digit/s (Experiment 3). FW's superiority over previous digit span experts is explained by his acquisition of well-known mnemonic techniques and his training that focused on rapid memorisation. His memory performance supports the feasibility of acquiring memory skills for improved working memory based on storage in long-term memory.

Gustatory processing and taste memory in Drosophila

PubMed Central

Masek, Pavel; Keene, Alex C.

2018-01-01

Taste allows animals to discriminate the value and potential toxicity of food prior to ingestion. Many tastants elicit an innate attractive or avoidance response that is modifiable with nutritional state and prior experience. A powerful genetic tool kit, well-characterized gustatory system, and standardized behavioral assays make the fruit fly, Drosophila melanogaster, an excellent system for investigating taste processing and memory. Recent studies have used this system to identify the neural basis for acquired taste preference. These studies have revealed a role for dopamine-mediated plasticity of the mushroom bodies that modulate the threshold of response to appetitive tastants. The identification of neural circuitry regulating taste memory provides a system to study the genetic and physiological processes that govern plasticity within a defined memory circuit. PMID:27328844

Thematic Effects of Person Judgments on Impression Organization.

ERIC Educational Resources Information Center

Lingle, John H.; And Others

1979-01-01

Three experiments investigated how people remember previously acquired information about others when it must be transmitted or judged for accuracy, and how memory is drawn upon when a judgment is made. (CM)

Selective preservation of memory for people in the context of semantic memory disorder: patterns of association and dissociation.

PubMed

Lyons, Frances; Kay, Janice; Hanley, J Richard; Haslam, Catherine

2006-01-01

A number of single cases in the literature demonstrate that person-specific semantic knowledge can be selectively impaired after acquired brain damage compared with that of object categories. However, there has been little unequivocal evidence for the reverse dissociation, selective preservation of person-specific semantic knowledge. Recently, three case studies have been published which provide support for the claim that such knowledge can be selectively preserved [Kay, J., & Hanley, J. R. (2002). Preservation of memory for people in semantic memory disorder: Further category-specific semantic dissociation. Cognitive Neuropsychology, 19, 113-134; Lyons, F., Hanley, J. R., & Kay, J. (2002). Anomia for common names and geographical names with preserved retrieval of names of people: A semantic memory disorder. Cortex, 38, 23-35; Thompson, S. A, Graham, K. S., Williams, G., Patterson, K., Kapur, N., & Hodges, J. R. (2004). Dissociating person-specific from general semantic knowledge: Roles of the left and right temporal lobes. Neuropsychologia, 42, 359-370]. In this paper, we supply further evidence from a series of 18 patients with acquired language disorder. Of this set, a number were observed to be impaired on tests of semantic association and word-picture matching using names of object categories (e.g. objects, animals and foods), but preserved on similar tests using names of famous people. Careful methodology was applied to match object and person-specific categories for item difficulty. The study also examined whether preservation of person-specific semantic knowledge was associated with preservation of knowledge of 'biological categories' such as fruit and vegetables and animals, or with preservation of 'token' knowledge of singular categories such as countries. The findings are discussed in the context of a variety of accounts that examine whether semantic memory has a categorical structure.

Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

PubMed

Roman-Urrestarazu, Andres; Lindholm, Päivi; Moilanen, Irma; Kiviniemi, Vesa; Miettunen, Jouko; Jääskeläinen, Erika; Mäki, Pirjo; Hurtig, Tuula; Ebeling, Hanna; Barnett, Jennifer H; Nikkinen, Juha; Suckling, John; Jones, Peter B; Veijola, Juha; Murray, Graham K

2016-05-01

When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

Does touch inhibit visual imagery? A case study on acquired blindness.

PubMed

von Trott Zu Solz, Jana; Paolini, Marco; Silveira, Sarita

2017-06-01

In a single-case study of acquired blindness, differential brain activation patterns for visual imagery of familiar objects with and without tactile exploration as well as of tactilely explored unfamiliar objects were observed. Results provide new insight into retrieval of visual images from episodic memory and point toward a potential tactile inhibition of visual imagery. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Fish T cells: recent advances through genomics

USGS Publications Warehouse

Laing, Kerry J.; Hansen, John D.

2011-01-01

This brief review is intended to provide a concise overview of the current literature concerning T cells, advances in identifying distinct T cell functional subsets, and in distinguishing effector cells from memory cells. We compare and contrast a wealth of recent progress made in T cell immunology of teleost, elasmobranch, and agnathan fish, to knowledge derived from mammalian T cell studies. From genome studies, fish clearly have most components associated with T cell function and we can speculate on the presence of putative T cell subsets, and the ability to detect their differentiation to form memory cells. Some recombinant proteins for T cell associated cytokines and antibodies for T cell surface receptors have been generated that will facilitate studying the functional roles of teleost T cells during immune responses. Although there is still a long way to go, major advances have occurred in recent years for investigating T cell responses, thus phenotypic and functional characterization is on the near horizon.

Liver-resident NK cells and their potential functions.

PubMed

Peng, Hui; Sun, Rui

2017-09-18

Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells. Here, we present a brief historical perspective on the discovery of liver-resident NK cells and discuss their relationship to cNK cells and other emerging NK cell subsets and their potential functions.Cellular &Molecular Immunology advance online publication, 18 September 2017; doi:10.1038/cmi.2017.72.

[General aspects of homeopathy].

PubMed

Avello L, Marcia; Avendaño O, Cristian; Mennickent C, Sigrid

2009-01-01

Homeopathic medicine is a type of therapy that appeared in Europe at the end of the eighteenth century. At the present time, it is widely accepted in developed countries as a form of alternative medicine. In Chile, health regulation includes homeopathy as pharmaceutical products and homeopathy is also considered a form of complementary medicine, that is well accepted by the public. The scientific rationale of homeopathy is based on an empiric type of thought that goes from the general to the particular. The symptoms that are valued are those that are particular to each sick individual. It uses diluted solutions of plants, minerals, animals and even venoms. There are basically two hypotheses to explain its mechanisms of action: The "immunological memory" and the "memory of water" or the transmission of electromagnetic information of the water. There still is needed to perform new studies to scientifically assess homeopathy and its usefulness, as an accepted alternative therapy.

Rehabilitation of everyday memory deficits in paediatric brain injury: self-instruction and diary training.

PubMed

Ho, Joanna; Epps, Adrienne; Parry, Louise; Poole, Miriam; Lah, Suncica

2011-04-01

Memory problems that interfere with everyday living are frequently reported in children who have sustained acquired brain injury (ABI), but their nature and rehabilitation is under-researched. This study aimed to (1) determine neuropsychological correlates of everyday memory deficits in children with ABI, and (2) investigate the effectiveness of a newly developed programme for their rehabilitation. We assessed everyday memory, verbal memory, attention and behaviour in 15 children with ABI. The children attended the everyday memory rehabilitation programme: six weekly sessions that involved diary training, self-instruction training and case examples. At the onset we found that everyday memory problems were related to impaired attention and behavioural difficulties. On completion of the programme there was a significant increase in children's abilities to perform daily routines that demanded recall of information and events. In addition, children used diaries more frequently. Moreover, significant secondary gains were found in attention and mood (anxiety and depression). In conclusion, the results provided preliminary evidence that our six week programme could be effective in reducing everyday memory difficulties and improving psychological well-being in children with ABI.

Working Memory Delay Activity Predicts Individual Differences in Cognitive Abilities

PubMed Central

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K.

2015-01-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contra-lateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory. PMID:25436671

Working memory delay activity predicts individual differences in cognitive abilities.

PubMed

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K

2015-05-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contralateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory.

Protein and Antigen Diversity in the Vesicular Fluid of Taenia Solium Cysticerci Dissected from Naturally Infected Pigs

PubMed Central

Esquivel-Velázquez, Marcela; Larralde, Carlos; Morales, Julio; Ostoa-Saloma, Pedro

2011-01-01

Cysticercosis caused by Taenia solium is a health threat for humans and pigs living in developing countries, for which there is neither a flawless immunodiagnostic test nor a totally effective vaccine. Suspecting of individual diversity of hosts and parasites as possible sources of the variations of the parasite loads among cysticercotic animals and of the limited success of such immunological applications as well as, we explored and measured both in nine cases of naturally acquired porcine cysticercosis. For this purpose, 2-Dimensional IgG immunoblots were performed by reacting the sera of each cysticercotic pig with the antigens contained in the vesicular fluid (VF) of their own cysticerci. We found an unexpectedly large diversity among the proteins and antigens contained in each of the nine VFs. Also diverse were the serum IgG antibody responses of the nine pigs, as none of their 2D- immunoblot images exhibited the same number of spots and resembled each other in only 6.3% to 65.3% of their features. So large an individual immunological diversity of the cysticercal antigens and of the infected pigs´ IgG antibody response should be taken into account in the design of immunological tools for diagnosis and prevention of cysticercosis and should also be considered as a possibly significant source of diversity in Taenia solium´s infectiveness and pathogenicity. PMID:22110381

Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis.

PubMed

Jaleco, Sara; Swainson, Louise; Dardalhon, Valérie; Burjanadze, Maryam; Kinet, Sandrina; Taylor, Naomi

2003-07-01

Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.

Topological Schemas of Memory Spaces.

PubMed

Babichev, Andrey; Dabaghian, Yuri A

2018-01-01

Hippocampal cognitive map-a neuronal representation of the spatial environment-is widely discussed in the computational neuroscience literature for decades. However, more recent studies point out that hippocampus plays a major role in producing yet another cognitive framework-the memory space-that incorporates not only spatial, but also non-spatial memories. Unlike the cognitive maps, the memory spaces, broadly understood as "networks of interconnections among the representations of events," have not yet been studied from a theoretical perspective. Here we propose a mathematical approach that allows modeling memory spaces constructively, as epiphenomena of neuronal spiking activity and thus to interlink several important notions of cognitive neurophysiology. First, we suggest that memory spaces have a topological nature-a hypothesis that allows treating both spatial and non-spatial aspects of hippocampal function on equal footing. We then model the hippocampal memory spaces in different environments and demonstrate that the resulting constructions naturally incorporate the corresponding cognitive maps and provide a wider context for interpreting spatial information. Lastly, we propose a formal description of the memory consolidation process that connects memory spaces to the Morris' cognitive schemas-heuristic representations of the acquired memories, used to explain the dynamics of learning and memory consolidation in a given environment. The proposed approach allows evaluating these constructs as the most compact representations of the memory space's structure.

Topological Schemas of Memory Spaces

PubMed Central

Babichev, Andrey; Dabaghian, Yuri A.

2018-01-01

Hippocampal cognitive map—a neuronal representation of the spatial environment—is widely discussed in the computational neuroscience literature for decades. However, more recent studies point out that hippocampus plays a major role in producing yet another cognitive framework—the memory space—that incorporates not only spatial, but also non-spatial memories. Unlike the cognitive maps, the memory spaces, broadly understood as “networks of interconnections among the representations of events,” have not yet been studied from a theoretical perspective. Here we propose a mathematical approach that allows modeling memory spaces constructively, as epiphenomena of neuronal spiking activity and thus to interlink several important notions of cognitive neurophysiology. First, we suggest that memory spaces have a topological nature—a hypothesis that allows treating both spatial and non-spatial aspects of hippocampal function on equal footing. We then model the hippocampal memory spaces in different environments and demonstrate that the resulting constructions naturally incorporate the corresponding cognitive maps and provide a wider context for interpreting spatial information. Lastly, we propose a formal description of the memory consolidation process that connects memory spaces to the Morris' cognitive schemas-heuristic representations of the acquired memories, used to explain the dynamics of learning and memory consolidation in a given environment. The proposed approach allows evaluating these constructs as the most compact representations of the memory space's structure. PMID:29740306

The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation.

PubMed

Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

2017-01-01

Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5-4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

PubMed Central

Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

2017-01-01

Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep. PMID:29213231

Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

PubMed Central

2016-01-01

The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems operate independently and in parallel when rats learn one type of task at a time, but interact cooperatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex. PMID:27307234

Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience.

PubMed

Ferbinteanu, Janina

2016-06-15

The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue-response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel "other" task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue-response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems operate independently and in parallel when rats learn one type of task at a time, but interact cooperatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex. Copyright © 2016 the authors 0270-6474/16/366459-12$15.00/0.

Abacavir-Reactive Memory T Cells Are Present in Drug Naïve Individuals

PubMed Central

Lucas, Andrew; Lucas, Michaela; Strhyn, Anette; Keane, Niamh M.; McKinnon, Elizabeth; Pavlos, Rebecca; Moran, Ellen M.; Meyer-Pannwitt, Viola; Gaudieri, Silvana; D’Orsogna, Lloyd; Kalams, Spyros; Ostrov, David A.; Buus, Søren; Peters, Bjoern; Mallal, Simon; Phillips, Elizabeth

2015-01-01

Background Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. Methods To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Results Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. Conclusions We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection. PMID:25674793

Abacavir-reactive memory T cells are present in drug naïve individuals.

PubMed

Lucas, Andrew; Lucas, Michaela; Strhyn, Anette; Keane, Niamh M; McKinnon, Elizabeth; Pavlos, Rebecca; Moran, Ellen M; Meyer-Pannwitt, Viola; Gaudieri, Silvana; D'Orsogna, Lloyd; Kalams, Spyros; Ostrov, David A; Buus, Søren; Peters, Bjoern; Mallal, Simon; Phillips, Elizabeth

2015-01-01

Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.

Memory CD8+ T cells are sufficient to alleviate impaired host resistance to influenza A virus infection caused by neonatal oxygen supplementation.

PubMed

Giannandrea, Matthew; Yee, Min; O'Reilly, Michael A; Lawrence, B Paige

2012-09-01

Supplemental oxygen administered to preterm infants is an important clinical intervention, but it is associated with life-long changes in lung development and increased sensitivity to respiratory viral infections. The precise immunological changes caused by neonatal oxygen treatment remain poorly understood. We previously reported that adult mice exposed to supplemental oxygen as neonates display persistent pulmonary inflammation and enhanced mortality after a sublethal influenza A virus infection. These changes suggest that neonatal hyperoxia impairs the cytotoxic CD8(+) T cell response required to clear the virus. In this study, we show that although host resistance to several different strains of influenza A virus is reduced by neonatal hyperoxia, this treatment does not impair viral clearance, nor does it alter the magnitude of the virus-specific CD8(+) T cell response to primary infection. Moreover, memory T cells are sufficient to ameliorate the increased morbidity and mortality and alleviate the excessive lung damage observed in mice exposed to high oxygen levels as neonates, and we attribute this sufficiency principally to virus-specific memory CD8(+) T cells. Thus, we show that neonatal hyperoxia reduces host resistance to influenza virus infection without diminishing the function of cytotoxic T lymphocytes or the generation of virus-specific memory T cells and that CD8(+) memory T cells are sufficient to provide protection from negative consequences of this important life-saving intervention. Our findings suggest that vaccines that generate robust T cell memory may be efficacious at reducing the increased sensitivity to respiratory viral infections in people born prematurely.

Immunological characteristics of subjects with asymptomatic skin sensitization to birch and grass pollen.

PubMed

Assing, K; Nielsen, C H; Poulsen, L K

2006-03-01

Asymptomatic skin sensitization (AS) has been shown to be a risk factor for respiratory allergic disease. We investigated allergen and recall antigen-driven T cell proliferation, cytokine production and T cell expression of the chemokine receptor CCR4, in cultures derived from symptomatic atopics (SA), subjects with AS and healthy controls (HC). Numbers of allergen-specific precursor T cells in all three groups were also estimated. Peripheral blood mononuclear cells from the three groups were isolated and stimulated with allergen and tetanus toxoid. Proliferation, cytokine production and CCR4 expression were measured by flow cytometry. A significantly increased proportion of CD4(+) memory T cells proliferated in response to allergen in SA as compared with subjects with AS (P<0.001) and HC (P<0.001). Only in SA was expansion of CD4(+)CCR4(+) T cells, after allergen stimulation observed. SA had higher frequencies of allergen-specific T cells than subjects with AS and HC (P=0.02, for both). With regard to allergen-induced production of T-helper type 1 (Th1) and Th2 cytokines, subjects with AS and HC resembled each other, while differing significantly from SA. We conclude, that subjects with AS, although clearly IgE sensitized, have significant diminished numbers of allergen-specific T cells as well as decreased allergen-induced CD4(+) memory T cell proliferation as compared with SA. To a large extent, our findings are capable of explaining the immunological characteristics associated with AS. Our findings may serve as better prognostic markers for subsequent allergic progression, than previously described clinical and paraclinical characteristics.

Data Acquisition for Modular Biometric Monitoring System

NASA Technical Reports Server (NTRS)

Grodsinsky, Carlos M. (Inventor); Chmiel, Alan J. (Inventor); Humphreys, Bradley T. (Inventor)

2014-01-01

A modular system for acquiring biometric data includes a plurality of data acquisition modules configured to sample biometric data from at least one respective input channel at a data acquisition rate. A representation of the sampled biometric data is stored in memory of each of the plurality of data acquisition modules. A central control system is in communication with each of the plurality of data acquisition modules through a bus. The central control system is configured to collect data asynchronously, via the bus, from the memory of the plurality of data acquisition modules according to a relative fullness of the memory of the plurality of data acquisition modules.

Association between memory B-cells and clinical and immunological features of primary Sjögren's syndrome and Sicca patients.

PubMed

Barcelos, Filipe; Martins, Catarina; Papoila, Ana; Geraldes, Carlos; Cardigos, Joana; Nunes, Glória; Lopes, Teresa; Alves, Nuno; Vaz-Patto, José; Branco, Jaime; Borrego, Luís-Miguel

2018-06-01

B-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.

Transfer of Old ‘Reactivated’ Memory Retrieval Cues in Rats

PubMed Central

Briggs, James F.; Riccio, David C.

2008-01-01

The present studies examined whether the retrieval of an old ‘reactivated’ memory could be brought under the control of new contextual cues. In Experiment 1 rats trained in one context were exposed to different contextual cues either immediately, 60 min, or 120 min after a cued reactivation of the training memory. When tested in the shifted context, subjects exposed shortly after reactivation treated the shifted context as the original context. This transfer diminished with longer post-reactivation delays. Experiment 2 replicated the basic finding and demonstrated that the transfer of the old retrieval cues was specific to the contextual cues present during exposure. These findings are consistent with previous research (i.e., Briggs, Fitz, & Riccio, in press) showing the transfer of retrieval cues for a new memory, and demonstrating a similarity (in this case) between newly acquired and old reactivated memories. PMID:19190707

B-cell development and pneumococcal immunity in vertically acquired HIV infection.

PubMed

Eisen, Sarah; Hayden, Clare; Young, Carmel J; Gilson, Richard; Jungmann, Eva; Jacobsen, Marianne C; Poulsom, Hannah; Goldblatt, David; Klein, Nigel J; Baxendale, Helen E

2016-07-31

Many children with HIV infection now survive into adulthood. This study explored the impact of vertically acquired HIV in the era of antiretroviral therapy on the development of humoral immunity. Natural and vaccine-related immunity to pneumococcus and B-cell phenotype was characterized and compared in three groups of young adults: those with vertically-acquired infection, those with horizontally acquired infection and healthy controls. Serotype-specific pneumococcal (Pnc) immunoglobulin M and G concentrations before and up to 1 year post-Pnc polysaccharide (Pneumovax) immunization were determined, and opsonophagocytic activity was analysed. B-cell subpopulations and dynamic markers of B-cell signalling, turnover and susceptibility to apoptosis were evaluated by flow cytometry. HIV-infected patients showed impaired natural Pnc immunity and reduced humoral responses to immunization with Pneumovax; this was greatest in those viraemic at time of the study. Early-life viral control before the age of 10 years diminished these changes. Expanded populations of abnormally activated and immature B-cells were seen in both HIV-infected cohorts. Vertically infected patients were particularly vulnerable to reductions in marginal zone and switched memory populations. These aberrations were reduced in patients with early-life viral control. In children with HIV, damage to B-cell memory populations and impaired natural and vaccine immunity to pneumococcus is evident in early adult life. Sustained viral control from early childhood may help to limit this effect and optimize humoral immunity in adult life.

The role of working memory and divided attention in metaphor interpretation.

PubMed

Iskandar, Sam; Baird, Anne D

2014-10-01

Although several types of figurative language exist, neuropsychological tests of non-literal language have focused on proverbs. Metaphors in the form X is (a) Y (e.g., The body's immunological response is a battle against disease.) place a lower demand on language skills and are more easily manipulated for novelty than proverbs. Forty healthy participants completed the Metaphor Interpretation Test (developed by the authors). The task includes 20 items chosen from a list of metaphors that were rated on several scales (e.g. imagery, aptness) in a study by Katz et al. (Metaphor Symb Act 3(4):191-214, 1988). Participants were asked to rate the familiarity and provide an explanation of each metaphor. A scoring system was developed to categorize answers into: abstract complete (AC), abstract partial (AP), concrete (CT), and other/unrelated (OT) types. Participants also completed short-term memory and divided attention tests. Overall, participants produced 56 % AC, 25.38 % AP, 7.88 % CT, and 10.88 % OT responses. It was found that a measure of verbal short-term memory span was the best predictor of performance on this task (adjusted R(2) = .369). It appears that short-term memory span, not working memory or divided attention, contributes most to providing abstract responses in explaining metaphors. This is in line with the idea that when one accesses the semantic network associated with a novel metaphor, one must hold this information in mind long enough to search for and link similar cognitive networks.

Reduced Memory CD4+ T-Cell Generation in the Circulation of Young Children May Contribute to the Otitis-Prone Condition

PubMed Central

Sharma, Sharad K.; Casey, Janet R.

2011-01-01

Background. An explanation for the immunologic dysfunction that causes children to be prone to repeated episodes of acute otitis media (AOM) has long been sought. Poor antibody response has been associated with the otitis-prone condition; however, there is no precise mechanistic explanation for this condition. Methods. Non–otitis-prone and otitis-prone children with AOM or nasopharyngeal (NP) colonization caused by either Streptococcus pneumoniae or Haemophilus influenzae were compared for pathogen-specific CD4+ T-helper memory responses by stimulating peripheral blood mononuclear cells using 6 vaccine candidate S. pneumoniae and 3 H. influenzae protein antigens. Samples were analyzed by multi-parameter flow cytometry. Results. Significantly reduced percentages of functional CD45RALow memory CD4+ T cells producing specific cytokines (interferon γ, interleukin [IL]–2, IL-4 and IL-17a) were observed in otitis-prone children following AOM and NP colonization with either S. pneumoniae or H. influenzae. Immunoglobulin (Ig) G responses to the studied protein antigens were reduced, which suggests that antigen-specific B-cell function may be compromised as a result of poor T-cell help. Staphylococcal enterotoxin B stimulated similar cytokine patterns in memory CD4+T cells in both groups of children. Conclusions. Otitis-prone children have suboptimal circulating functional T-helper memory and reduced IgG responses to S. pneumoniae or H. influenzae after colonization and after AOM; this immune dysfunction causes susceptibility to recurrent AOM infections. PMID:21791667

Determinants to trigger memory reconsolidation: The role of retrieval and updating information.

PubMed

Rodriguez-Ortiz, Carlos J; Bermúdez-Rattoni, Federico

2017-07-01

Long-term memories can undergo destabilization/restabilization processes, collectively called reconsolidation. However, the parameters that trigger memory reconsolidation are poorly understood and are a matter of intense investigation. Particularly, memory retrieval is widely held as requisite to initiate reconsolidation. This assumption makes sense since only relevant cues will induce reconsolidation of a specific memory. However, recent studies show that pharmacological inhibition of retrieval does not avoid memory from undergoing reconsolidation, indicating that memory reconsolidation occurs through a process that can be dissociated from retrieval. We propose that retrieval is not a unitary process but has two dissociable components; one leading to the expression of memory and the other to reconsolidation, referred herein as executer and integrator respectively. The executer would lead to the behavioral expression of the memory. This component would be the one disrupted on the studies that show reconsolidation independence from retrieval. The integrator would deal with reconsolidation. This component of retrieval would lead to long-term memory destabilization when specific conditions are met. We think that an important number of reports are consistent with the hypothesis that reconsolidation is only initiated when updating information is acquired. We suggest that the integrator would initiate reconsolidation to integrate updating information into long-term memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Making the case that episodic recollection is attributable to operations occurring at retrieval rather than to content stored in a dedicated subsystem of long-term memory

PubMed Central

Klein, Stanley B.

2013-01-01

Episodic memory often is conceptualized as a uniquely human system of long-term memory that makes available knowledge accompanied by the temporal and spatial context in which that knowledge was acquired. Retrieval from episodic memory entails a form of first–person subjectivity called autonoetic consciousness that provides a sense that a recollection was something that took place in the experiencer's personal past. In this paper I expand on this definition of episodic memory. Specifically, I suggest that (1) the core features assumed unique to episodic memory are shared by semantic memory, (2) episodic memory cannot be fully understood unless one appreciates that episodic recollection requires the coordinated function of a number of distinct, yet interacting, “enabling” systems. Although these systems—ownership, self, subjective temporality, and agency—are not traditionally viewed as memorial in nature, each is necessary for episodic recollection and jointly they may be sufficient, and (3) the type of subjective awareness provided by episodic recollection (autonoetic) is relational rather than intrinsic—i.e., it can be lost in certain patient populations, thus rendering episodic memory content indistinguishable from the content of semantic long-term memory. PMID:23378832

Autobiographical memory decline in Alzheimer’s Disease

PubMed Central

EL HAJ, Mohamad; Antoine, Pascal; Nandrino, Jean-Louis; Kapogiannis, Dimitrios

2016-01-01

Autobiographical memory, or memory for personal experiences, allows individuals to define themselves and construct a meaningful life story. Decline of this ability, as observed in Alzheimer’s Disease (AD), results in an impaired sense of self and identity. We present a critical review of theories and findings regarding cognitive and neuroanatomical underpinnings of autobiographical memory and its decline in AD and highlight studies on its clinical rehabilitation. We propose that autobiographical recall in AD is mainly characterized by loss of associated episodic information, which leads to de-contextualisation of autobiographical memories and a shift from reliving past events to a general sense of familiarity. This decline refers to retrograde, but also anterograde amnesia that affects newly acquired memories besides remote ones. One consequence of autobiographical memory decline in AD is decreased access to memories that shape self-consciousness, self-knowledge, and self-images, leading to a diminished sense of self and identity. The link between autobiographical decline and compromised sense of self in AD can also manifest itself as low correspondence and coherence between past memories and current goals and beliefs. By linking cognitive, neuroanatomical, and clinical aspects of autobiographical decline in AD, our review provides a theoretical foundation, which may lead to better rehabilitation strategies. PMID:26876367

Making memories: the development of long-term visual knowledge in children with visual agnosia.

PubMed

Metitieri, Tiziana; Barba, Carmen; Pellacani, Simona; Viggiano, Maria Pia; Guerrini, Renzo

2013-01-01

There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2  years and 3.7  years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment.

Making Memories: The Development of Long-Term Visual Knowledge in Children with Visual Agnosia

PubMed Central

Barba, Carmen; Pellacani, Simona; Viggiano, Maria Pia; Guerrini, Renzo

2013-01-01

There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2 years and 3.7 years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment. PMID:24319599

CaM Kinases: From Memories to Addiction.

PubMed

Müller, Christian P; Quednow, Boris B; Lourdusamy, Anbarasu; Kornhuber, Johannes; Schumann, Gunter; Giese, K Peter

2016-02-01

Drug addiction is a major psychiatric disorder with a neurobiological basis that is still insufficiently understood. Initially, non-addicted, controlled drug consumption and drug instrumentalization are established. They comprise highly systematic behaviours acquired by learning and the establishment of drug memories. Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are important Ca(2+) sensors translating glutamatergic activation into synaptic plasticity during learning and memory formation. Here we review the role of CaMKs in the establishment of drug-related behaviours in animal models and in humans. Converging evidence now shows that CaMKs are a crucial mechanism of how addictive drugs induce synaptic plasticity and establish various types of drug memories. Thereby, CaMKs are not only molecular relays for glutamatergic activity but they also directly control dopaminergic and serotonergic activity in the mesolimbic reward system. They can now be considered as major molecular pathways translating normal memory formation into establishment of drug memories and possibly transition to drug addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Landmark memories are more robust when acquired at the nest site than en route: experiments in desert ants.

PubMed

Bisch-Knaden, Sonja; Wehner, Rüdiger

2003-03-01

Foraging desert ants, Cataglyphis fortis, encounter different sequences of visual landmarks while navigating by path integration. This paper explores the question whether the storage of landmark information depends on the context in which the landmarks are learned during an ant's foraging journey. Two experimental set-ups were designed in which the ants experienced an artificial landmark panorama that was placed either around the nest entrance (nest marks) or along the vector route leading straight towards the feeder (route marks). The two training paradigms resulted in pronounced differences in the storage characteristics of the acquired landmark information: memory traces of nest marks were much more robust against extinction and/or suppression than those of route marks. In functional terms, this result is in accord with the observation that desert ants encounter new route marks during every foraging run but always pass the same landmarks when approaching the nest entrance.

Acquisition and improvement of human motor skills: Learning through observation and practice

NASA Technical Reports Server (NTRS)

Iba, Wayne

1991-01-01

Skilled movement is an integral part of the human existence. A better understanding of motor skills and their development is a prerequisite to the construction of truly flexible intelligent agents. We present MAEANDER, a computational model of human motor behavior, that uniformly addresses both the acquisition of skills through observation and the improvement of skills through practice. MAEANDER consists of a sensory-effector interface, a memory of movements, and a set of performance and learning mechanisms that let it recognize and generate motor skills. The system initially acquires such skills by observing movements performed by another agent and constructing a concept hierarchy. Given a stored motor skill in memory, MAEANDER will cause an effector to behave appropriately. All learning involves changing the hierarchical memory of skill concepts to more closely correspond to either observed experience or to desired behaviors. We evaluated MAEANDER empirically with respect to how well it acquires and improves both artificial movement types and handwritten script letters from the alphabet. We also evaluate MAEANDER as a psychological model by comparing its behavior to robust phenomena in humans and by considering the richness of the predictions it makes.

RNA Expression Analysis of Passive Transfer Myasthenia Supports Extraocular Muscle as a Unique Immunological Environment

PubMed Central

Zhou, Yuefang; Kaminski, Henry J.; Gong, Bendi; Cheng, Georgiana; Feuerman, Jason M.; Kusner, Linda

2014-01-01

Purpose. Myasthenia gravis demonstrates a distinct predilection for involvement of the extraocular muscles (EOM), and we have hypothesized that this may be due to a unique immunological environment. To assess this hypothesis, we took an unbiased approach to analyze RNA expression profiles in EOM, diaphragm, and extensor digitorum longus (EDL) in rats with experimentally acquired myasthenia gravis (EAMG). Methods. Experimentally acquired myasthenia gravis was induced in rats by intraperitoneal injection of antibody directed against the acetylcholine receptor (AChR), whereas control rats received antibody known to bind the AChR but not induce disease. After 48 hours, animals were killed and muscles analyzed by RNA expression profiling. Profiling results were validated using qPCR and immunohistochemical analysis. Results. Sixty-two genes common among all muscle groups were increased in expression. These fell into four major categories: 12.8% stress response, 10.5% immune response, 10.5% metabolism, and 9.0% transcription factors. EOM expressed 212 genes at higher levels, not shared by the other two muscles, and a preponderance of EOM gene changes fell into the immune response category. EOM had the most uniquely reduced genes (126) compared with diaphragm (26) and EDL (50). Only 18 downregulated genes were shared by the three muscles. Histological evaluation and disease load index (sum of fold changes for all genes) demonstrated that EOM had the greatest degree of pathology. Conclusions. Our studies demonstrated that consistent with human myasthenia gravis, EOM demonstrates a distinct RNA expression signature from EDL and diaphragm, which is based on differences in the degree of muscle injury and inflammatory response. PMID:24917137

Working Memory, Motivation, and Teacher-Initiated Learning

NASA Astrophysics Data System (ADS)

Brooks, David W.; Shell, Duane F.

2006-03-01

Working memory is where we "think" as we learn. A notion that emerges as a synthesis from several threads in the research literatures of cognition, motivation, and connectionism is that motivation in learning is the process whereby working memory resource allocation is instigated and sustained. This paper reviews much literature on motivation and working memory, and concludes that the apparent novelty of the proposal offered to describe motivation in terms of working memory results from the apparent lack of cross-channel exchange among these research traditions. The relation between working memory and motivation is explored in the context of the interactive compensatory model of learning (ICML) in which learning is considered to result from the interaction of ability, motivation, and prior learning. The ICML is recast in light of the revised definition of motivation offered here. This paper goes on to suggest ways in which a range of teaching and learning issues and activities may be reconceptualized in the context of a model emphasizing a learner's working memory that makes use of chunks of previously acquired knowledge.

Selective Enhancement of Systemic Th1 Immunity in Immunologically Immature Rats with an Orally Administered Bacterial Extract

PubMed Central

Bowman, L. M.; Holt, P. G.

2001-01-01

Infant rats primed during the first week of life with soluble antigen displayed adult-equivalent levels of T-helper 2 (Th2)-dependent immunological memory development as revealed by production of secondary immunoglobulin G1 (IgG1) antibody responses to subsequent challenge, but in contrast to adults failed to prime for Th1-dependent IgG2b responses. We demonstrate that this Th2 bias in immune function can be redressed by oral administration to neonates of a bacterial extract (Broncho-Vaxom OM-85) comprising lyophilized fractions of several common respiratory tract bacterial pathogens. Animals given OM-85 displayed a selective upregulation in primary and secondary IgG2b responses, accompanied by increased gamma interferon and decreased interleukin-4 production (both antigen specific and polyclonal), and increased capacity for development of Th1-dependent delayed hypersensitivity to the challenge antigen. We hypothesize that the bacterial extract functions via enhancement of the process of postnatal maturation of Th1 function, which is normally driven by stimuli from the gastrointestinal commensal microflora. PMID:11349036

Improving everyday memory performance after acquired brain injury: An RCT on recollection and working memory training.

PubMed

Richter, Kim Merle; Mödden, Claudia; Eling, Paul; Hildebrandt, Helmut

2018-04-26

To show the effectiveness of a combined recognition and working memory training on everyday memory performance in patients suffering from organic memory disorders. In this double-blind, randomized controlled Study 36 patients with organic memory impairments, mainly attributable to stroke, were assigned to either the experimental or the active control group. In the experimental group a working memory training was combined with a recollection training based on the repetition-lag procedure. Patients in the active control group received the memory therapy usually provided in the rehabilitation center. Both groups received nine hours of therapy. Prior (T0) and subsequent (T1) to the therapy, patients were evaluated on an everyday memory test (EMT) as well as on a neuropsychological test battery. Based on factor analysis of the neuropsychological test scores at T0 we calculated composite scores for working memory, verbal learning and word fluency. After treatment, the intervention group showed a significantly greater improvement for WM performance compared with the active control group. More importantly, performance on the EMT also improved significantly in patients receiving the recollection and working memory training compared with patients with standard memory training. Our results show that combining working memory and recollection training significantly improves performance on everyday memory tasks, demonstrating far transfer effects. The present study argues in favor of a process-based approach for treating memory impairments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Autobiographical memory decline in Alzheimer’s disease, a theoretical and clinical overview

PubMed Central

El Haj, Mohamad; Antoine, Pascal; Nandrino, Jean Louis; Kapogiannis, Dimitrios

2017-01-01

Autobiographical memory, or memory for personal experiences, allows individuals to define themselves and construct a meaningful life story. Decline of this ability, as observed in Alzheimer’s disease (AD), results in an impaired sense of self and identity. In our model (AMAD: Autobiographical Memory in Alzheimer’s Disease), we present a critical review of theories and findings regarding cognitive and neuroanatomical underpinnings of autobiographical memory and its decline in AD and highlight studies on its clinical rehabilitation. We propose that autobiographical recall in AD is mainly characterized by loss of associated episodic information, which leads to de-contextualization of autobiographical memories and a shift from reliving past events to a general sense of familiarity. This decline refers to retrograde, but also anterograde amnesia that affects newly acquired memories besides remote ones. One consequence of autobiographical memory decline in AD is decreased access to memories that shape self-consciousness, self-knowledge, and self-images, leading to a diminished sense of self and identity. The link between autobiographical decline and compromised sense of self in AD can also manifest itself as low correspondence and coherence between past memories and current goals and beliefs. By linking cognitive, neuroanatomical, and clinical aspects of autobiographical decline in AD, our review provides a theoretical foundation, which may lead to better rehabilitation strategies. PMID:26169474

Memory formation orchestrates the wiring of adult-born hippocampal neurons into brain circuits.

PubMed

Petsophonsakul, Petnoi; Richetin, Kevin; Andraini, Trinovita; Roybon, Laurent; Rampon, Claire

2017-08-01

During memory formation, structural rearrangements of dendritic spines provide a mean to durably modulate synaptic connectivity within neuronal networks. New neurons generated throughout the adult life in the dentate gyrus of the hippocampus contribute to learning and memory. As these neurons become incorporated into the network, they generate huge numbers of new connections that modify hippocampal circuitry and functioning. However, it is yet unclear as to how the dynamic process of memory formation influences their synaptic integration into neuronal circuits. New memories are established according to a multistep process during which new information is first acquired and then consolidated to form a stable memory trace. Upon recall, memory is transiently destabilized and vulnerable to modification. Using contextual fear conditioning, we found that learning was associated with an acceleration of dendritic spines formation of adult-born neurons, and that spine connectivity becomes strengthened after memory consolidation. Moreover, we observed that afferent connectivity onto adult-born neurons is enhanced after memory retrieval, while extinction training induces a change of spine shapes. Together, these findings reveal that the neuronal activity supporting memory processes strongly influences the structural dendritic integration of adult-born neurons into pre-existing neuronal circuits. Such change of afferent connectivity is likely to impact the overall wiring of hippocampal network, and consequently, to regulate hippocampal function.

Neuronal Oscillations Indicate Sleep-dependent Changes in the Cortical Memory Trace.

PubMed

Köster, Moritz; Finger, Holger; Kater, Maren-Jo; Schenk, Christoph; Gruber, Thomas

2017-04-01

Sleep promotes the consolidation of newly acquired associative memories. Here we used neuronal oscillations in the human EEG to investigate sleep-dependent changes in the cortical memory trace. The retrieval activity for object-color associations was assessed immediately after encoding and after 3 hr of sleep or wakefulness. Sleep had beneficial effects on memory performance and led to reduced event-related theta and gamma power during the retrieval of associative memories. Furthermore, event-related alpha suppression was attenuated in the wake group for memorized and novel stimuli. There were no sleep-dependent changes in retrieval activity for missed items or items retrieved without color. Thus, the sleep-dependent reduction in theta and gamma oscillations was specific for the retrieval of associative memories. In line with theoretical accounts on sleep-dependent memory consolidation, decreased theta may indicate reduced mediotemporal activity because of a transfer of information into neocortical networks during sleep, whereas reduced parietal gamma may reflect effects of synaptic downscaling. Changes in alpha suppression in the wake group possibly index reduced attentional resources that may also contribute to a lower memory performance in this group. These findings indicate that the consolidation of associative memories during sleep is associated with profound changes in the cortical memory trace and relies on multiple neuronal processes working in concert.

CRISPR/cas Loci of Type II Propionibacterium acnes Confer Immunity against Acquisition of Mobile Elements Present in Type I P. acnes

PubMed Central

Brüggemann, Holger; Lomholt, Hans B.; Tettelin, Hervé; Kilian, Mogens

2012-01-01

Propionibacterium acnes is a skin commensal that occasionally acts as an opportunistic pathogen. The population structure of this species shows three main lineages (I–III). While type I strains are mainly associated with sebaceous follicles of human skin and inflammatory acne, types II and III strains are more often associated with deep tissue infections. We investigated the occurrence and distribution of the clustered regularly interspaced short palindromic repeats (CRISPR) in P. acnes, assessed their immunological memory, and addressed the question if such a system could account for type-specific properties of the species. A collection of 108 clinical isolates covering all known phylotypes of P. acnes was screened for the existence of CRISPR/cas loci. We found that CRISPR loci are restricted to type II P. acnes strains. Sequence analyses of the CRISPR spacers revealed that the system confers immunity to P. acnes-specific phages and to two mobile genetic elements. These elements are found almost exclusively in type I P. acnes strains. Genome sequencing of a type I P. acnes isolate revealed that one element, 54 kb in size, encodes a putative secretion/tight adherence (TAD) system. Thus, CRISPR/cas loci in P. acnes recorded the exposure of type II strains to mobile genetic elements of type I strains. The CRISPR/cas locus is deleted in type I strains, which conceivably accounts for their ability to horizontally acquire fitness or virulence traits and might indicate that type I strains constitute a younger subpopulation of P. acnes. PMID:22479553

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells.

PubMed

Dardalhon, V; Jaleco, S; Kinet, S; Herpers, B; Steinberg, M; Ferrand, C; Froger, D; Leveau, C; Tiberghien, P; Charneau, P; Noraz, N; Taylor, N

2001-07-31

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4(+) cells proliferated in response to IL-7, whereas naive UC CD4(+) lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G(1b) phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4(+) lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4(+) UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4(+) T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates.

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells

PubMed Central

Dardalhon, Valérie; Jaleco, Sara; Kinet, Sandrina; Herpers, Bjorn; Steinberg, Marcos; Ferrand, Christophe; Froger, Delphine; Leveau, Christelle; Tiberghien, Pierre; Charneau, Pierre; Noraz, Nelly; Taylor, Naomi

2001-01-01

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4+ cells proliferated in response to IL-7, whereas naive UC CD4+ lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G1b phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4+ lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4+ UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4+ T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates. PMID:11470908

Induction of innate immunity in control of mucosal transmission of HIV.

PubMed

Wang, Yufei; Lehner, Thomas

2011-09-01

To present evidence of the role of innate mucosal immunity and to harness this arm of immunity in protection against HIV infection. Dendritic cells, monocytes, natural killer (NK) cells and γδ T cells are critical in innate immunity, which is mediated by Toll-like receptor (TLR) and recently identified stress pathways. Complement factors, cytokines and chemokines have diverse functions usually affecting HIV infection indirectly. A novel group of innate intracellular HIV restriction factors has been identified - APOBEC3G, TRIM5α and tetherin - all of which are upregulated by type I interferons and some by vaccination and TLR agonists. Whereas innate immunity conventionally lacks memory, recent evidence suggests that some of the cells and intracellular factors may express immunological memory-like features. Innate mucosal immunity may provide early effective control of HIV transmission and replication. Some vaccines can enhance innate immune factors, such as APOBEC3G and control HIV during the eclipse period, allowing full weight of neutralizing and/or cytotoxic T cells to develop and prevent mucosal HIV infection. The next generation of vaccines should be designed to target both innate and adaptive immune memory responses.

Innate Immunity and the Pathogenicity of Inhaled Microbial Particles

PubMed Central

Wolff, C. Henrik J.

2011-01-01

Non-infectious inhaled microbial particles can cause illness by triggering an inappropriate immunological response. From the pathogenic point of view these illnesses can be seen to be related to on one hand autoimmune diseases and on the other infectious diseases. In this review three such illnesses are discussed in some detail. Hypersensitivity pneumonitis (HP) is the best known of these illnesses and it has also been widely studied in animal models and clinically. In contrast to HP Pulmonary mycotoxicosis (PM) is not considered to involve immunological memory, it is an acute self-limiting condition is caused by an immediate "toxic" effect. Damp building related illness (DBRI) is a controversial and from a diagnostic point poorly defined entity that is however causing, or attributed to cause, much more morbidity than the two other diseases. In the recent decade there has been a shift in the focus of immunology from the lymphocyte centered, adaptive immunity towards innate immunity. The archetypal cell in innate immunity is the macrophage although many other cell types participate. Innate immunity relies on a limited number of germline coded receptors for the recognition of pathogens and signs of cellular damage. The focus on innate immunity has opened new paths for the understanding of many chronic inflammatory diseases. The purpose of this review is to discuss the impact of some recent studies, that include aspects concerning innate immunity, on our understanding of the pathogenesis of inflammatory diseases associated with exposure to inhaled microbial matter. PMID:21448336

Immunosenescence in vertebrates and invertebrates.

PubMed

Müller, Ludmila; Fülöp, Tamas; Pawelec, Graham

2013-04-02

There is an established consensus that it is primarily the adaptive arm of immunity, and the T cell subset in particular, that is most susceptible to the deleterious changes with age known as "immunosenescence". Can we garner any clues as to why this might be by considering comparative immunology and the evolutionary emergence of adaptive and innate immunity? The immune system is assumed to have evolved to protect the organism against pathogens, but the way in which this is accomplished is different in the innate-vs-adaptive arms, and it is unclear why the latter is necessary. Are there special characteristics of adaptive immunity which might make the system more susceptible to age-associated dysfunction? Given recent accumulating findings that actually there are age-associated changes to innate immunity and that these are broadly similar in vertebrates and invertebrates, we suggest here that it is the special property of memory in the adaptive immune system which results in the accumulation of cells with a restricted receptor repertoire, dependent on the immunological history of the individual's exposures to pathogens over the lifetime, and which is commonly taken as a hallmark of "immunosenescence". However, we further hypothesize that this immunological remodelling per se does not necessarily convey a disadvantage to the individual (ie. is not necessarily "senescence" if it is not deleterious). Indeed, under certain circumstances, or potentially even as a rule, this adaptation to the individual host environment may confer an actual survival advantage.

Common Variable Immunodeficiency Caused by FANC Mutations.

PubMed

Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

2017-07-01

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

Unstable Memories Create a High-Level Representation that Enables Learning Transfer.

PubMed

Mosha, Neechi; Robertson, Edwin M

2016-01-11

A memory is unstable, making it susceptible to interference and disruption, after its acquisition [1-4]. The function or possible benefit of a memory being unstable at its acquisition is not well understood. Potentially, instability may be critical for the communication between recently acquired memories, which would allow learning in one task to be transferred to the other subsequent task [1, 5]. Learning may be transferred between any memories that are unstable, even between different types of memory. Here, we test the link between a memory being unstable and the transfer of learning to a different type of memory task. We measured how learning in one task transferred to and thus improved learning in a subsequent task. There was transfer from a motor skill to a word list task and, vice versa, from a word list to a motor skill task. What was transferred was a high-level relationship between elements, rather than knowledge of the individual elements themselves. Memory instability was correlated with subsequent transfer, suggesting that transfer was related to the instability of the memory. Using different methods, we stabilized the initial memory, preventing it from being susceptible to interference, and found that these methods consistently prevented transfer to the subsequent memory task. This suggests that the transfer of learning across diverse tasks is due to a high-level representation that can only be formed when a memory is unstable. Our work has identified an important function of memory instability. Copyright © 2016 Elsevier Ltd. All rights reserved.

The neural basis of implicit learning and memory: a review of neuropsychological and neuroimaging research.

PubMed

Reber, Paul J

2013-08-01

Memory systems research has typically described the different types of long-term memory in the brain as either declarative versus non-declarative or implicit versus explicit. These descriptions reflect the difference between declarative, conscious, and explicit memory that is dependent on the medial temporal lobe (MTL) memory system, and all other expressions of learning and memory. The other type of memory is generally defined by an absence: either the lack of dependence on the MTL memory system (nondeclarative) or the lack of conscious awareness of the information acquired (implicit). However, definition by absence is inherently underspecified and leaves open questions of how this type of memory operates, its neural basis, and how it differs from explicit, declarative memory. Drawing on a variety of studies of implicit learning that have attempted to identify the neural correlates of implicit learning using functional neuroimaging and neuropsychology, a theory of implicit memory is presented that describes it as a form of general plasticity within processing networks that adaptively improve function via experience. Under this model, implicit memory will not appear as a single, coherent, alternative memory system but will instead be manifested as a principle of improvement from experience based on widespread mechanisms of cortical plasticity. The implications of this characterization for understanding the role of implicit learning in complex cognitive processes and the effects of interactions between types of memory will be discussed for examples within and outside the psychology laboratory. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amphibians acquire resistance to live and dead fungus overcoming fungal immunosuppression.

PubMed

McMahon, Taegan A; Sears, Brittany F; Venesky, Matthew D; Bessler, Scott M; Brown, Jenise M; Deutsch, Kaitlin; Halstead, Neal T; Lentz, Garrett; Tenouri, Nadia; Young, Suzanne; Civitello, David J; Ortega, Nicole; Fites, J Scott; Reinert, Laura K; Rollins-Smith, Louise A; Raffel, Thomas R; Rohr, Jason R

2014-07-10

Emerging fungal pathogens pose a greater threat to biodiversity than any other parasitic group, causing declines of many taxa, including bats, corals, bees, snakes and amphibians. Currently, there is little evidence that wild animals can acquire resistance to these pathogens. Batrachochytrium dendrobatidis is a pathogenic fungus implicated in the recent global decline of amphibians. Here we demonstrate that three species of amphibians can acquire behavioural or immunological resistance to B. dendrobatidis. Frogs learned to avoid the fungus after just one B. dendrobatidis exposure and temperature-induced clearance. In subsequent experiments in which B. dendrobatidis avoidance was prevented, the number of previous exposures was a negative predictor of B. dendrobatidis burden on frogs and B. dendrobatidis-induced mortality, and was a positive predictor of lymphocyte abundance and proliferation. These results suggest that amphibians can acquire immunity to B. dendrobatidis that overcomes pathogen-induced immunosuppression and increases their survival. Importantly, exposure to dead fungus induced a similar magnitude of acquired resistance as exposure to live fungus. Exposure of frogs to B. dendrobatidis antigens might offer a practical way to protect pathogen-naive amphibians and facilitate the reintroduction of amphibians to locations in the wild where B. dendrobatidis persists. Moreover, given the conserved nature of vertebrate immune responses to fungi and the fact that many animals are capable of learning to avoid natural enemies, these results offer hope that other wild animal taxa threatened by invasive fungi might be rescued by management approaches based on herd immunity.

Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Lieshout, P.; Renier, W.; Eling, P.

1990-02-01

This case study concerns an 18-year-old bilingual girl who suffered a radiation lesion in the left (dominant) thalamic and temporal region when she was 4 years old. Language and memory assessment revealed deficits in auditory short-term memory, auditory word comprehension, nonword repetition, syntactic processing, word fluency, and confrontation naming tasks. Both languages (English and Dutch) were found to be affected in a similar manner, despite the fact that one language (English) was acquired before and the other (Dutch) after the period of lesion onset. Most of the deficits appear to be related to verbal (short-term) memory dysfunction. Several hypotheses ofmore » subcortical involvement in memory processes are discussed with reference to existing theories in this area.« less

Etiology and pathogenesis of inflammatory bowel disease.

PubMed

Schmidt, C; Stallmach, A

2005-06-01

Despite of scientific efforts during the last decades, etiology and pathogenesis of the two major inflammatory bowel diseases, namely Crohn's disease and ulcerative colitis, remain rather unclear. According to the results of multiple studies it is accepted that the development of either disease is the result of an exaggerated or insufficiently suppressed immune response to a hitherto undefined luminal antigen, probably derived from the microbial flora. This inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting in an increased influx of bacteria into the intestinal wall, even further accelerating the inflammatory process. However, these immunological disturbances that have been investigated extensively during the past years have to be considered on the genetic background of the individual patient and the environmental factors the patient is exposed to. In this review we will attempt to summarize the current knowledge about risk factors for inflammatory bowel diseases, genetic and environmental factors of IBD and focus on the immunological alterations of innate and acquired immune system underlying Crohn's disease and ulcerative colitis.

Memory Dysfunction

PubMed Central

Matthews, Brandy R.

2015-01-01

Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

The strength of aversive and appetitive associations and maladaptive behaviors.

PubMed

Itzhak, Yossef; Perez-Lanza, Daniel; Liddie, Shervin

2014-08-01

Certain maladaptive behaviors are thought to be acquired through classical Pavlovian conditioning. Exaggerated fear response, which can develop through Pavlovian conditioning, is associated with acquired anxiety disorders such as post-traumatic stress disorders (PTSDs). Inflated reward-seeking behavior, which develops through Pavlovian conditioning, underlies some types of addictive behavior (e.g., addiction to drugs, food, and gambling). These maladaptive behaviors are dependent on associative learning and the development of long-term memory (LTM). In animal models, an aversive reinforcer (fear conditioning) encodes an aversive contextual and cued LTM. On the other hand, an appetitive reinforcer results in conditioned place preference (CPP) that encodes an appetitive contextual LTM. The literature on weak and strong associative learning pertaining to the development of aversive and appetitive LTM is relatively scarce; thus, this review is particularly focused on the strength of associative learning. The strength of associative learning is dependent on the valence of the reinforcer and the salience of the conditioned stimulus that ultimately sways the strength of the memory trace. Our studies suggest that labile (weak) aversive and appetitive LTM may share similar signaling pathways, whereas stable (strong) aversive and appetitive LTM is mediated through different pathways. In addition, we provide some evidence suggesting that extinction of aversive fear memory and appetitive drug memory is likely to be mediated through different signaling molecules. We put forward the importance of studies aimed to investigate the molecular mechanisms underlying the development of weak and strong memories (aversive and appetitive), which would ultimately help in the development of targeted pharmacotherapies for the management of maladaptive behaviors that arise from classical Pavlovian conditioning. © 2014 International Union of Biochemistry and Molecular Biology.

Modeling Coevolution between Language and Memory Capacity during Language Origin

PubMed Central

Gong, Tao; Shuai, Lan

2015-01-01

Memory is essential to many cognitive tasks including language. Apart from empirical studies of memory effects on language acquisition and use, there lack sufficient evolutionary explorations on whether a high level of memory capacity is prerequisite for language and whether language origin could influence memory capacity. In line with evolutionary theories that natural selection refined language-related cognitive abilities, we advocated a coevolution scenario between language and memory capacity, which incorporated the genetic transmission of individual memory capacity, cultural transmission of idiolects, and natural and cultural selections on individual reproduction and language teaching. To illustrate the coevolution dynamics, we adopted a multi-agent computational model simulating the emergence of lexical items and simple syntax through iterated communications. Simulations showed that: along with the origin of a communal language, an initially-low memory capacity for acquired linguistic knowledge was boosted; and such coherent increase in linguistic understandability and memory capacities reflected a language-memory coevolution; and such coevolution stopped till memory capacities became sufficient for language communications. Statistical analyses revealed that the coevolution was realized mainly by natural selection based on individual communicative success in cultural transmissions. This work elaborated the biology-culture parallelism of language evolution, demonstrated the driving force of culturally-constituted factors for natural selection of individual cognitive abilities, and suggested that the degree difference in language-related cognitive abilities between humans and nonhuman animals could result from a coevolution with language. PMID:26544876

Old-new ERP effects and remote memories: the late parietal effect is absent as recollection fails whereas the early mid-frontal effect persists as familiarity is retained

PubMed Central

Tsivilis, Dimitris; Allan, Kevin; Roberts, Jenna; Williams, Nicola; Downes, John Joseph; El-Deredy, Wael

2015-01-01

Understanding the electrophysiological correlates of recognition memory processes has been a focus of research in recent years. This study investigated the effects of retention interval on recognition memory by comparing memory for objects encoded four weeks (remote) or 5 min (recent) before testing. In Experiment 1, event related potentials (ERPs) were acquired while participants performed a yes-no recognition memory task involving remote, recent and novel objects. Relative to correctly rejected new items, remote and recent hits showed an attenuated frontal negativity from 300–500 ms post-stimulus. This effect, also known as the FN400, has been previously associated with familiarity memory. Recent and remote recognition ERPs did not differ from each other at this time-window. By contrast, recent but not remote recognition showed increased parietal positivity from around 500 ms post-stimulus. This late parietal effect (LPE), which is considered a correlate of recollection-related processes, also discriminated between recent and remote memories. A second, behavioral experiment confirmed that remote memories unlike recent memories were based almost exclusively on familiarity. These findings support the idea that the FN400 and LPE are indices of familiarity and recollection memory, respectively and show that remote and recent memories are functionally and anatomically distinct. PMID:26528163

Modeling Coevolution between Language and Memory Capacity during Language Origin.

PubMed

Gong, Tao; Shuai, Lan

2015-01-01

Memory is essential to many cognitive tasks including language. Apart from empirical studies of memory effects on language acquisition and use, there lack sufficient evolutionary explorations on whether a high level of memory capacity is prerequisite for language and whether language origin could influence memory capacity. In line with evolutionary theories that natural selection refined language-related cognitive abilities, we advocated a coevolution scenario between language and memory capacity, which incorporated the genetic transmission of individual memory capacity, cultural transmission of idiolects, and natural and cultural selections on individual reproduction and language teaching. To illustrate the coevolution dynamics, we adopted a multi-agent computational model simulating the emergence of lexical items and simple syntax through iterated communications. Simulations showed that: along with the origin of a communal language, an initially-low memory capacity for acquired linguistic knowledge was boosted; and such coherent increase in linguistic understandability and memory capacities reflected a language-memory coevolution; and such coevolution stopped till memory capacities became sufficient for language communications. Statistical analyses revealed that the coevolution was realized mainly by natural selection based on individual communicative success in cultural transmissions. This work elaborated the biology-culture parallelism of language evolution, demonstrated the driving force of culturally-constituted factors for natural selection of individual cognitive abilities, and suggested that the degree difference in language-related cognitive abilities between humans and nonhuman animals could result from a coevolution with language.

The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study.

PubMed

Maguire, Eleanor A; Frith, Christopher D; Rudge, Peter; Cipolotti, Lisa

2005-08-01

Bilateral hippocampal pathology typically results in significant memory problems. Despite apparently similar structural damage, patients with such lesions can differ in the pattern of impairment and preservation of memory functions. Previously, an fMRI study of a developmental amnesic patient whose anoxic hippocampal damage was incurred perinatally revealed his residual hippocampal tissue to be active during memory retrieval. This hippocampal activity was apparent during the retrieval of personal and general facts relative to a control task. In this study, we used a similar fMRI paradigm to investigate whether residual hippocampal activation was present also in patient VC with adult-acquired anoxic hippocampal pathology. VC's performance and reaction times on the experimental personal and general fact tasks were comparable to age-matched control subjects. However, in contrast to the elderly control sample and the previous developmental amnesic patient, his residual hippocampal tissue did not show activation changes during the experimental tasks. This finding indicates that patient VC's successful retrieval of personal and general facts was achieved without a significant hippocampal contribution. It further suggests that the hippocampal activation observed in the elderly controls and previous developmental amnesic patient was not necessary for successful task performance. The reason for this difference in hippocampal responsivity between VC and the developmental amnesic patient remains to be determined. We speculate that it may relate to the age at which hippocampal damage occurred reflecting plasticity within the developing brain, or to cognitive differences between VC, the developmental amnesic patient, and the control subjects.

Systematic Review of Neuropsychological Rehabilitation for Prospective Memory Deficits as a Consequence of Acquired Brain Injury.

PubMed

Mahan, Steven; Rous, Rebecca; Adlam, Anna

2017-01-19

Prospective memory (PM) impairments are common following acquired brain injury (ABI). PM is the ability to keep a goal in mind for future action and interventions have the potential to increase independence. This review aimed to evaluate studies examining PM rehabilitation approaches in adults and children with ABI. Relevant literature was identified using PsycARTICLES (1894 to present), PsycINFO (1880 to present), the Cochrane Library (1972 to present), MEDLINE PubMed, reference lists from relevant journal articles, and searches of key journals. Literature searches were conducted using variants of the terms brain injury, stroke, encephalitis, meningitis, and tumor, combined with variants of the terms rehabilitation and prospective memory. Of the 435 papers identified, 11 were included in the review. Findings demonstrated a variety of interventions to alleviate PM deficits, including compensatory strategies (e.g., external memory aids) that provide either content-specific or content-free cueing, and remediation strategies (e.g., meta-cognitive training programs) aimed at improving the self-monitoring of personal goals. Risk of bias for individual studies was considered and the strengths and limitations of each of the included studies and the review itself were discussed. Interventions used with adults can be effective; PM abilities can be improved by using simple reminder systems and performance can be generalized to facilitate everyday PM functioning. There is, however, a lack of research of PM interventions conducted with children with ABI, and pediatric interventions need to consider on-going cognitive maturation. (JINS, 2017, 22, 1-12).

Elaborative encoding through self-generation enhances outcomes with errorless learning: Findings from the Skypekids memory study.

PubMed

Haslam, Catherine; Wagner, Joseph; Wegener, Signy; Malouf, Tania

2017-01-01

Errorless learning has demonstrated efficacy in the treatment of memory impairment in adults and older adults with acquired brain injury. In the same population, use of elaborative encoding through supported self-generation in errorless paradigms has been shown to further enhance memory performance. However, the evidence base relevant to application of both standard and self-generation forms of errorless learning in children is far weaker. We address this limitation in the present study to examine recall performance in children with brain injury (n = 16) who were taught novel age-appropriate science and social science facts through the medium of Skype. All participants were taught these facts under conditions of standard errorless learning, errorless learning with self-generation, and trial-and-error learning after which memory was tested at 5-minute, 30-minute, 1-hour and 24-hour delays. Analysis revealed no main effect of time, with participants retaining most information acquired over the 24-hour testing period, but a significant effect of condition. Notably, self-generation proved more effective than both standard errorless and trial-and-error learning. Further analysis of the data revealed that severity of attentional impairment was less detrimental to recall performance under errorless conditions. This study extends the literature to provide further evidence of the value of errorless learning methods in children with ABI and the first demonstration of the effectiveness of self-generation when delivered via the Internet.

Acquired immunity against malaria as a tool for the control of the disease: the strategy proposed by the Malaria Commission of the League of Nations in 1933.

PubMed

Corbellini, G

1998-06-01

The Third General Report of the Malaria Commission, printed in 1933, suggested for the control of malaria a strategy aimed to promote the acquisition of a "relative immunity" through a non radical treatment of the infected people living in highly endemic areas. The paper discusses the content of the Report and describes the scientific (empirical) premises on which it stood. Moreover, it illustrates the criticism that was directed against the immunological strategy and that eventually led to its abandonment.

Two retrievals from a single cue: A bottleneck persists across episodic and semantic memory.

PubMed

Orscheschek, Franziska; Strobach, Tilo; Schubert, Torsten; Rickard, Timothy

2018-05-01

There is evidence in the literature that two retrievals from long-term memory cannot occur in parallel. To date, however, that work has explored only the case of two retrievals from newly acquired episodic memory. These studies demonstrated a retrieval bottleneck even after dual-retrieval practice. That retrieval bottleneck may be a global property of long-term memory retrieval, or it may apply only to the case of two retrievals from episodic memory. In the current experiments, we explored whether that apparent dual-retrieval bottleneck applies to the case of one retrieval from episodic memory and one retrieval from highly overlearned semantic memory. Across three experiments, subjects learned to retrieve a left or right keypress response form a set of 14 unique word cues (e.g., black-right keypress). In addition, they learned a verbal response which involved retrieving the antonym of the presented cue (e.g., black-"white"). In the dual-retrieval condition, subjects had to retrieve both the keypress response and the antonym word. The results suggest that the retrieval bottleneck is superordinate to specific long-term memory systems and holds across different memory components. In addition, the results support the assumption of a cue-level response chunking account of learned retrieval parallelism.

Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy.

PubMed

Geva, Sharon; Cooper, Janine M; Gadian, David G; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2016-08-01

One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task), between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Scarcity of autoreactive human blood IgA+ memory B cells

PubMed Central

Prigent, Julie; Lorin, Valérie; Kök, Ayrin; Hieu, Thierry; Bourgeau, Salomé

2016-01-01

Class‐switched memory B cells are key components of the “reactive” humoral immunity, which ensures a fast and massive secretion of high‐affinity antigen‐specific antibodies upon antigenic challenge. In humans, IgA class‐switched (IgA+) memory B cells and IgA antibodies are abundant in the blood. Although circulating IgA+ memory B cells and their corresponding secreted immunoglobulins likely possess major protective and/or regulatory immune roles, little is known about their specificity and function. Here, we show that IgA+ and IgG+ memory B‐cell antibodies cloned from the same healthy humans share common immunoglobulin gene features. IgA and IgG memory antibodies have comparable lack of reactivity to vaccines, common mucosa‐tropic viruses and commensal bacteria. However, the IgA+ memory B‐cell compartment contains fewer polyreactive clones and importantly, only rare self‐reactive clones compared to IgG+ memory B cells. Self‐reactivity of IgAs is acquired following B‐cell affinity maturation but not antibody class switching. Together, our data suggest the existence of different regulatory mechanisms for removing autoreactive clones from the IgG+ and IgA+ memory B‐cell repertoires, and/or different maturation pathways potentially reflecting the distinct nature and localization of the cognate antigens recognized by individual B‐cell populations. PMID:27469325

Immunogenicity and Immunological Memory Induced by the 13-Valent Pneumococcal Conjugate Followed by the 23-Valent Polysaccharide Vaccine in HIV-Infected Adults.

PubMed

Farmaki, Paraskevi F; Chini, Maria C; Mangafas, Nikolaos M; Tzanoudaki, Marianna T; Piperi, Christina P; Lazanas, Marios Z; Spoulou, Vana S

2018-06-05

Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. NCT03041051.

Adoptive transfer of CD8+ T cells generated from induced pluripotent stem cells triggers regressions of large tumors along with immunological memory

PubMed Central

Saito, Hidehito; Okita, Keisuke; Chang, Alfred E.; Ito, Fumito

2016-01-01

Current approaches to adoptive T cell therapy are limited by the difficulty of obtaining sufficient numbers of T cells against targeted antigens with useful in vivo characteristics. Theoretically, this limitation could be overcome by using induced pluripotent stem cells (iPSCs) that could provide an unlimited source of autologous T cells. However, the therapeutic efficacy of iPSC-derived regenerated T cells remains to be demonstrated. Here we report the first successful reprogramming of T-cell receptor (TCR) transgenic CD8+ T cells into pluripotency. As part of the work, we established a syngeneic mouse model for evaluating in vitro and in vivo antitumor reactivity of regenerated T cells from iPSCs bearing a rearranged TCR of known antigen specificity. Stably TCR retained T cell-derived iPSCs differentiated into CD4+CD8+ T cells that expressed CD3 and the desired TCR in vitro. Stimulation of iPSC-derived CD4+CD8+ T cells with the cognate antigen in the presence of IL-7 and IL-15 followed by expansion with IL-2, IL-7 and IL-15 generated large numbers of less-differentiated CD8+ T cells with antigen-specific potent cytokine production and cytolytic capacity. Furthermore, adoptively transferred iPSC-derived CD8+ T cells escaped immune rejection, mediated effective regression of large tumors, improved survival, and established antigen-specific immunological memory. Our findings illustrate the translational potential of iPSCs to provide an unlimited number of phenotypically defined, functional, and expandable autologous antigen-specific T cells with the characteristics needed to enable in vivo effectiveness. PMID:27197199

The effect of trauma-focused therapy on the altered T cell distribution in individuals with PTSD: evidence from a randomized controlled trial.

PubMed

Morath, Julia; Gola, Hannah; Sommershof, Annette; Hamuni, Gilava; Kolassa, Stephan; Catani, Claudia; Adenauer, Hannah; Ruf-Leuschner, Martina; Schauer, Maggie; Elbert, Thomas; Groettrup, Marcus; Kolassa, Iris-Tatjana

2014-07-01

Posttraumatic stress disorder (PTSD) is associated with a reduced ratio of naïve cytotoxic T lymphocytes, an increased ratio of memory cytotoxic T lymphocytes, and a reduced proportion of FoxP3(+) regulatory T lymphocytes. This study investigated whether these immunological alterations are reversible through an evidence-based psychotherapeutic treatment. Therefore, 34 individuals with PTSD were randomly assigned to either a treatment condition of 12 sessions narrative exposure therapy (NET) or a waitlist control (WLC) group. PTSD symptoms were significantly reduced in the NET group, but not in the WLC group, four months post-therapy (effect size: Hedges' g = -1.61). One year after therapy, PTSD symptoms were improved even further in the NET group compared to baseline (Hedges' g = -1.96). This symptom improvement was mirrored in an increase in the originally reduced proportion of regulatory T cells (Tregs) in the NET group at the one-year follow-up, when comparing subgroups matched for baseline Treg numbers. However, no changes were found for the initially reduced proportion of CD45RA(+)CCR7(+) naïve T lymphocytes. In conclusion, NET was effective in reducing trauma-related PTSD symptoms and had a positive effect on the proportion of Tregs cells, thus demonstrating an effect of psychotherapy on an immunological level. Yet, the shift in the proportion of naïve and memory T lymphocytes in individuals with PTSD, discussed in the literature as a correlate of premature immunosenescence, was not reversible and thus might render these patients permanently more susceptible to infectious diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T-cell-dependent protective immunity in MHC class II-deficient mice.

PubMed

Bathke, Barbara; Pätzold, Juliane; Kassub, Ronny; Giessel, Raphael; Lämmermann, Kerstin; Hinterberger, Maria; Brinkmann, Kay; Chaplin, Paul; Suter, Mark; Hochrein, Hubertus; Lauterbach, Henning

2017-12-27

The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen-presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T-cell receptor complex a plethora of co-stimulatory signals not only ensures a proper T-cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The tumour necrosis factor receptor/ligand pair CD27/CD70 gained a lot of attention because of its key role in regulating T-cell activation, survival, differentiation and maintenance, especially in the course of viral infections and cancer. We sought to investigate the role of CD70 co-stimulation for immune responses induced by the vaccine vector modified vaccinia virus Ankara-Bavarian Nordic ® (MVA-BN ® ). Short-term blockade of CD70 diminished systemic CD8 T-cell effector and memory responses in mice. The dependence on CD70 became even more apparent in the lungs of MHC class II-deficient mice. Importantly, genetically encoded CD70 in MVA-BN ® not only increased CD8 T-cell responses in wild-type mice but also substituted for CD4 T-cell help. MHC class II-deficient mice that were immunized with recombinant MVA-CD70 were fully protected against a lethal virus infection, whereas MVA-BN ® -immunized mice failed to control the virus. These data are in line with CD70 playing an important role for vaccine-induced CD8 T-cell responses and prove the potency of integrating co-stimulatory molecules into the MVA-BN ® backbone. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer.

PubMed

Salazar-Onfray, Flavio; Pereda, Cristián; Reyes, Diego; López, Mercedes N

2013-01-01

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

Mycobacterium tuberculosis PstS1 amplifies IFN-γ and induces IL-17/IL-22 responses by unrelated memory CD4+ T cells via dendritic cell activation.

PubMed

Palma, Carla; Schiavoni, Giovanna; Abalsamo, Laura; Mattei, Fabrizio; Piccaro, Giovanni; Sanchez, Massimo; Fernandez, Carmen; Singh, Mahavir; Gabriele, Lucia

2013-09-01

The immunological mechanisms that modulate protection during Mycobacterium tuberculosis (Mtb) infection or vaccination are not fully understood. Secretion of IFN-γ and, to a lesser extent, of IL-17 by CD4(+) T cells plays a major role both in protection and immunopathology. Few Mtb Ags interacting with DCs affect priming, activation, and regulation of Ag-unrelated CD4(+) T-cell responses. Here we demonstrate that PstS1, a 38 kDa-lipoprotein of Mtb, promotes Ag-independent activation of memory T lymphocytes specific for Ag85B or Ag85A, two immunodominant protective Ags of Mtb. PstS1 expands CD4(+) and CD8(+) memory T cells, amplifies secretion of IFN-γ and IL-22 and induces IL-17 production by effector memory cells in an Ag-unrelated manner in vitro and in vivo. These effects were mediated through the stimulation of DCs, particularly of the CD8α(-) subtype, which respond to PstS1 by undergoing phenotypic maturation and by secreting IL-6, IL-1β and, to a lower extent, IL-23. IL-6 secretion by PstS1-stimulated DCs was required for IFN-γ, and to a lesser extent for IL-22 responses by Ag85B-specific memory T cells. These results may open new perspectives for immunotherapeutic strategies to control Th1/Th17 immune responses in Mtb infections and in vaccinations against tuberculosis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

B-cell subset alterations and correlated factors in HIV-1 infection.

PubMed

Pensieroso, Simone; Galli, Laura; Nozza, Silvia; Ruffin, Nicolas; Castagna, Antonella; Tambussi, Giuseppe; Hejdeman, Bo; Misciagna, Donatella; Riva, Agostino; Malnati, Mauro; Chiodi, Francesca; Scarlatti, Gabriella

2013-05-15

During HIV-1 infection, the development, phenotype, and functionality of B cells are impaired. Transitional B cells and aberrant B-cell populations arise in blood, whereas a declined percentage of resting memory B cells is detected. Our study aimed at pinpointing the demographic, immunological, and viral factors driving these pathological findings, and the role of antiretroviral therapy in reverting these alterations. B-cell phenotype and correlating factors were evaluated. Variations in B-cell subsets were evaluated by flow cytometry in HIV-1-infected individuals naive to therapy, elite controllers, and patients treated with antiretroviral drugs (virological control or failure). Multivariable analysis was performed to identify variables independently associated with the B-cell alterations. Significant differences were observed among patients' groups in relation to all B-cell subsets. Resting memory B cells were preserved in patients naive to therapy and elite controllers, but reduced in treated patients. Individuals naive to therapy and experiencing multidrug failure, as well as elite controllers, had significantly higher levels of activated memory B cells compared to healthy controls. In the multivariate analysis, plasma viral load and nadir CD4 T cells independently correlated with major B-cell alterations. Coinfection with hepatitis C but not hepatitis B virus also showed an impact on specific B-cell subsets. Successful protracted antiretroviral treatment led to normalization of all B-cell subsets with exception of resting memory B cells. Our results indicate that viremia and nadir CD4 T cells are important prognostic markers of B-cell perturbations and provide evidence that resting memory B-cell depletion during chronic infection is not reverted upon successful antiretroviral therapy.

A trial of patient-oriented problem-solving system for immunology teaching in China: a comparison with dialectic lectures

PubMed Central

2013-01-01

Background The most common teaching method used in China is lecturing, but recently, efforts have been widely undertaken to promote the transition from teacher-centered to student-centered education. The patient-oriented problem-solving (POPS) system is an innovative teaching-learning method that permits students to work in small groups to solve clinical problems, promotes self-learning, encourages clinical reasoning and develops long-lasting memory. To our best knowledge, however, POPS has never been applied in teaching immunology in China. The aim of this study was to develop POPS in teaching immunology and assess students’ and teachers’ perception to POPS. Methods 321 second-year medical students were divided into two groups: I and II. Group I, comprising 110 students, was taught by POPS, and 16 immunology teachers witnessed the whole teaching process. Group II including the remaining 211 students was taught through traditional lectures. The results of the pre- and post-test of both groups were compared. Group I students and teachers then completed a self-structured feedback questionnaire for analysis before a discussion meeting attended only by the teachers was held. Results Significant improvement in the mean difference between the pre- and post-test scores of those in Groups I and II was seen, demonstrating the effectiveness of POPS teaching. Most students responded that POPS facilitates self-learning, helps them to understand topics and creates interest, and 88.12% of students favored POPS over simple lectures. Moreover, while they responded that POPS facilitated student learning better than lectures, teachers pointed out that limited teaching resources would make it difficult for wide POPS application in China. Conclusions While POPS can break up the monotony of dialectic lectures and serve as a better teaching method, it may not be feasible for the current educational environment in China. The main reason for this is the relative shortage of teaching resources such as space, library facilities and well-trained teachers. PMID:23356717

A trial of patient-oriented problem-solving system for immunology teaching in China: a comparison with dialectic lectures.

PubMed

Zhang, Zhiren; Liu, Wei; Han, Junfeng; Guo, Sheng; Wu, Yuzhang

2013-01-28

The most common teaching method used in China is lecturing, but recently, efforts have been widely undertaken to promote the transition from teacher-centered to student-centered education. The patient-oriented problem-solving (POPS) system is an innovative teaching-learning method that permits students to work in small groups to solve clinical problems, promotes self-learning, encourages clinical reasoning and develops long-lasting memory. To our best knowledge, however, POPS has never been applied in teaching immunology in China. The aim of this study was to develop POPS in teaching immunology and assess students' and teachers' perception to POPS. 321 second-year medical students were divided into two groups: I and II. Group I, comprising 110 students, was taught by POPS, and 16 immunology teachers witnessed the whole teaching process. Group II including the remaining 211 students was taught through traditional lectures. The results of the pre- and post-test of both groups were compared. Group I students and teachers then completed a self-structured feedback questionnaire for analysis before a discussion meeting attended only by the teachers was held. Significant improvement in the mean difference between the pre- and post-test scores of those in Groups I and II was seen, demonstrating the effectiveness of POPS teaching. Most students responded that POPS facilitates self-learning, helps them to understand topics and creates interest, and 88.12% of students favored POPS over simple lectures. Moreover, while they responded that POPS facilitated student learning better than lectures, teachers pointed out that limited teaching resources would make it difficult for wide POPS application in China. While POPS can break up the monotony of dialectic lectures and serve as a better teaching method, it may not be feasible for the current educational environment in China. The main reason for this is the relative shortage of teaching resources such as space, library facilities and well-trained teachers.

Neuronal correlate of visual associative long-term memory in the primate temporal cortex

NASA Astrophysics Data System (ADS)

Miyashita, Yasushi

1988-10-01

In human long-term memory, ideas and concepts become associated in the learning process1. No neuronal correlate for this cognitive function has so far been described, except that memory traces are thought to be localized in the cerebral cortex; the temporal lobe has been assigned as the site for visual experience because electric stimulation of this area results in imagery recall,2 and lesions produce deficits in visual recognition of objects3-9. We previously reported that in the anterior ventral temporal cortex of monkeys, individual neurons have a sustained activity that is highly selective for a few of the 100 coloured fractal patterns used in a visual working-memory task10. Here I report the development of this selectivity through repeated trials involving the working memory. The few patterns for which a neuron was conjointly selective were frequently related to each other through stimulus-stimulus association imposed during training. The results indicate that the selectivity acquired by these cells represents a neuronal correlate of the associative long-term memory of pictures.