Antibody Memory Research Articles

Hydroxyurea for sickle-cell anaemia in Africa: mind the gap.

Hydroxyurea for sickle-cell anaemia in Africa: mind the gap.

B淋巴细胞活化分子事件及相关病理机制

B cells are important immune cells for humoral immune responses. B cell activation is a critical step for antibody production in response to pathogen invasion. In this review, we focused on the recent achievements in B cell studies using high-resolution high-speed live cell imaging techniques. These studies substantially improve our understanding of the molecular events governing the initiation of B cell activation. We summarized the recent studies about tonic B cell receptor (BCR) signaling which is thought to be responsible for B cell survival. We proposed several models to explain the origin of tonic BCR signaling. Meanwhile, we described the BCR signaling pathway driven by antigen stimulation, and discussed the possible mechanisms initiating B cell activation. Especially, we described how the high-resolution high-speed live cell imaging techniques help scientists to capture the dynamic events during B cell activation. Moreover, we discussed the molecular nature of the memory B cell with special focus placed on the roles of the evolutionarily conserved IgG cytoplasmic tail in memory antibody responses. Abnormal regulation of BCR activation may lead to diseases. In this regard, we discussed the recent findings in the last part of this review and also summarized the relationship of the mutation in the BCR inhibitory co-receptor FcγRIIB and autoimmune diseases. Furthermore, we discussed the relationship between the mutation in BCR signaling molecules and B cell tumor. This work improves our understanding about B cell diseases and may benefit the clinical therapy.

Application of Immune Algorithm Optimizing PID Parameters in Simulink

The PID control model of alternating current governor system was established in Simulink and using immune algorithm to optimize PID controller parameters. It takes PID controller parameters as antibody and the optimal solution as antigens,dynamically adjust PID control parameters in the control process through the immune algorithm of memory cells and antibody concentration regulation mechanism of genetic algorithm.. The antibody coding method, diversity evaluation of the solution, immune operation and Optimization method of steps were detailed. The simulation results show that the immune algorithm was fewer iteration times and high efficiency. The optimized control system reduced the overshoot, improved the response speed and improved the system performance which is a kind of effective optimization method to PID controller parameters.

Memory B-cell and antibody responses induced by Plasmodium falciparum sporozoite immunization.

BackgroundImmunization of healthy volunteers during receipt of chemoprophylaxis with Plasmodium falciparum sporozoites (CPS-immunization) induces sterile protection from malaria. Antibody responses have long been known to contribute to naturally acquired immunity against malaria, but their association with sterile protection after whole sporozoite immunization is not well established. We therefore studied the induction and kinetics of malaria parasite antigen-specific antibodies and memory B-cells (MBCs) during CPS-immunization and their correlation with protection from challenge infection.MethodsWe assessed humoral reactivity to 9 antigens representing different stages of the life cycle of P. falciparum by performing standardized MBC enzyme-linked immunospot and enzyme-linked immunosorbent assays on peripheral blood mononuclear cells and plasma samples from 38 Dutch volunteers enrolled in 2 randomized controlled clinical trials.ResultsMBCs and antibodies recognizing pre-erythrocytic and cross-stage antigens were gradually acquired during CPS-immunization. The magnitude of these humoral responses did not correlate with protection but directly reflected parasite exposure in CPS-immunization and challenge.ConclusionsHumoral responses to the malarial antigens circumsporozoite protein, liver-stage antigen-1, apical membrane antigen-1, and merozoite surface protein-1 do not to predict protection from challenge infection but can be used as sensitive marker of recent parasite exposure.Clinical Trials RegistrationNCT01236612 and NCT01218893.

No receptor stands alone: IgG B-cell receptor intrinsic and extrinsic mechanisms contribute to antibody memory.

Acquired immunological memory is a striking phenomenon. A lethal epidemic sweeps through a naïve population, many die but those who survive are never “attacked twice ― never at least fatally”, as the historian Thucydides observed in 430 BCE. Antibody memory is critical for protection against many human infectious diseases and is the basis for nearly all current human vaccines. Antibody memory is encoded, in part, in isotype-switched immunoglobulin (Ig)G-expressing memory B cells that are generated in the primary response to antigen and give rise to rapid, high-affinity and high-titered antibody responses upon challenge with the same antigen. How IgG-B-cell receptors (BCRs) and antigen-induced IgG-BCR signaling contribute to memory antibody responses are not fully understood. In this review, we summarize exciting new advances that are revealing the cellular and molecular mechanisms at play in antibody memory and discuss how studies using different experimental approaches will help elucidate the complex phenomenon of B-cell memory.

Teriflunomide Does Not Significantly Affect Primary and Memory Antibody Responses to a Viral Antigen in Mice (P1.215)

Teriflunomide Does Not Significantly Affect Primary and Memory Antibody Responses to a Viral Antigen in Mice (P1.215)

Integrated intrusion detection model based on artificial immune

The author puts forward an integrated intrusion detection (ID) model based on artificial immune (IIDAI), a vaccination strategy based on the significance degree of genes and a method to generate initial memory antibodies with rough set (RS). IIDAI integrates two kinds of intrusion detection mode: misuse detection and anonymous detection. Misuse detection and anonymous detection are applied to detect the known and the unknown attacks, respectively. On the basis of IIDAI model, an ID algorithm is presented. Simulation shows that the IIDAI has better performance than traditional ID methods in feasibility and effectiveness. It is very prone to achieve a higher convergence rate by using the vaccination strategy. Moreover, RS can remove the redundancy attributes and increase the detection speed. It can also increase detection rate by applying the integrated method.

Hepatitis C virus (HCV)-specific memory B-cell responses in transiently and chronically infected HIV positive individuals

BackgroundAntibody responses to hepatitis C virus (HCV) occur delayed and overly decline after viral clearance indicating that the B-cell response to HCV is abnormal. Virus-specific memory B-cells have recently been found in infected individuals, but the viral exposure requirements for the generation of these cells is unknown. ObjectivesThe primary goal of this study was to quantify and compare the HCV-specific memory B-cell response between chronic and resolved HCV-infected individuals. A secondary goal was to examine if HIV-specific memory B-cell responses are maintained during HCV co-infection. Study designHCV core protein- and HIV-specific memory B-cell responses were examined in HIV/HCV-infected individuals treated 4–30 weeks after HCV diagnosis. Memory B-cell frequencies were compared between chronically and transiently infected individuals. ResultsChronically infected individuals had vigorous HCV-specific memory B-cell responses and antibodies, whereas subjects with transient viremia showed low or undetectable virus-specific B-cell responses. In addition, chronically HIV/HCV-infected subjects had robust HIV-specific memory B-cell responses. ConclusionsWhereas chronic HCV infection induces virus-specific antibodies and memory B-cells, transient infection in individuals with sustained viral response to therapy does not stimulate a durable HCV-specific B-cell response indicating that the formation of long-lived virus-specific B-cells is suppressed in the early phase of infection. This may contribute to the inability to spontaneously clear HCV infection.

Delivery of Polysaccharides Using Polymer Particles: Implications on Size-Dependent Immunogenicity, Opsonophagocytosis, and Protective Immunity

Bacterial capsular polysaccharides are components of many modern vaccines, but they are weakly immunogenic. Herein, we describe the delivery of pneumococcal capsular polysaccharide serotype-1 (PCP-1) in polylactide polymeric particles to enhance its immunogenicity. Immunization with PCP-1-entrapped particles elicited long-term memory antibody responses from a single intramuscular injection. PCP-1-entrapped nanoparticles (NPs) elicited significantly higher anti-PCP-1 IgG responses than that observed with soluble and microparticles (MPs) formulations. Delivering PCP-1 and pneumococcal proteins in same particles did not improve the IgG response. The sera of animals immunized with PCP-1-entrapped particles promoted efficient opsonophagocytosis of pneumococci by macrophages. Single-dose immunization with PCP-1-entrapped particles conferred a long-term serotype-specific protection against lethal pneumococcal challenge. The higher immunogenicity of PCP-1 nanoparticles showed correlation with enhanced uptake by antigen-presenting cells. The results highlight the potential of polymeric nanoparticles as an efficient means of presenting polysaccharide antigens to the immune system.

Fault Diagnosis of Oil-Immersed Transformers Using Self-Organization Antibody Network and Immune Operator

There are some drawbacks when diagnosis techniques based on one intelligent method are applied to identify incipient faults in power transformers. In this paper, a hybrid immune algorithm is proposed to improve the reliability of fault diagnosis. The proposed algorithm is a hybridization of self-organization antibody network (soAbNet) and immune operator. There are two phases in immune operator. One is vaccination, and the other is immune selection. In the process of vaccination, vaccines were obtained from training dataset by using consistency-preservingK-means algorithm (K-means-CP algorithm) and were taken as the initial antibodies for soAbNet. After the soAbNet was trained, immune selection was applied to optimize the memory antibodies in the trained soAbNet. The effectiveness of the proposed algorithm is verified using benchmark classification dataset and real-world transformer fault dataset. For comparison purpose, three transformer diagnosis methods such as the IEC criteria, back propagation neural network (BPNN), and soAbNet are utilized. The experimental results indicate that the proposed approach can extract the dataset characteristics efficiently and the diagnostic accuracy is higher than that obtained with other individual methods.

CXCR5+CD4+ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity

Although many relevant immune reactions are initiated in the lymph nodes, this compartment has not been systematically studied in humans. Analyses have been performed on immune cells derived from tonsils, but as this tissue is most often inflamed, generalization of these data is difficult. Here, we analyzed the phenotype and function of the human CD4(+) T-cell subsets and lineages in paired resting lymph node and peripheral blood samples. Naive, central memory cells and effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally represented in both compartments. On the other hand, cytotoxic CD4(+) T cells were strikingly absent in the lymph nodes. CXCR5(+)CD4(+) T cells, representing putative follicular Th (Tfh) cells were over-represented in lymph nodes and expressed higher levels of Tfh markers than their peripheral blood counterparts. Compared with the circulating pool, lymph-node-derived CXCR5(+)CD4(+) T cells were superior in providing help to B cells. Thus, functionally competent Tfh cells accumulate in resting human lymph nodes, providing a swift induction of naive and memory antibody responses upon antigenic challenge.

Backtracking clonal selection algorithm for multi-modal function optimization

To solve some existing problems in multi-modal function optimization,an improved Clonal Selection Algorithm(CSA) based on the backtracking mechanism,Backtracking Clonal Selection Algorithm(BCSA),was proposed in this paper.The global search capability could be enhanced by using the improved backtracking mechanism and the restraining operation of memory antibodies,which maintained the diversity of antibodies.In addition,in order to improve the convergence speed,the improved dynamic mutation,selection and crossover operation were adopted.The results tested on typical multi-modal functions show that BCSA has a powerful performance in global search.

THU0034 CD19 Distinguishes Memory and Pre-Memory Antibody Secreting Cells

BackgroundPlasma cells (PC), are differentiated B cells that play a major role in humoral immunity as they actively secrete antibodies which identify and neutralize foreign antigens. Normally, plasma cells develop...

SP0112 Lymphoid tissue inducer cells are sufficient for memory CD4 T cell survival

Maintaining memory T cells is critical to the success of vaccination and T cell survival is heavily influenced by costimulatory molecules, amongst which, the tumour necrosis factor super family members...

Preliminary safety, product parameters, and immune response assessments from a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy (ACI), in patients (pts) with surgically resected HER2+ urothelial cancer (UC) at high risk for recurrence.

4547^ Background: DN24-02 is a HER2-targeted ACI, consisting of antigen presenting cells (APC) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to GM-CSF; DN24-02 is based on the same manufacturing platform as sipuleucel-T, approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. NeuACT (N10E1; NCT01353222) is an open-label, randomized phase 2 trial comparing adjuvant DN24E02 to surveillance in HER2+ UC pts at high risk of relapse following cystectomy or nephroureterectomy. The primary endpoint is overall survival. Here we report preliminary evaluation of adverse events (AE), product potency, and immune response. Methods: Pts randomized to DN24-02 underwent leukapheresis followed by infusion of DN24-02 (total of 3 infusions with 2 wk intervals). AEs were assessed at each visit. Product potency was assessed for each infusion by measuring CD54 upregulation on APCs, a marker of APC activation. Antigen-specific immune responses were evaluated by ELISA to HER500 and BA7072. Results: As of November 2012, 13 pts had received ≥1 DN24-02 infusion. The most commonly reported AEs within 1 day after DN24-02 infusion were mild–moderate chills (54%), nausea (31%) and fatigue (23%). Ten pts completed all DN24-02 infusions and were assessed for product potency. Increased median APC activation at infusions 2 and 3 compared with infusion 1 was indicative of an immunological prime-boost effect; this effect was also seen in the 7/10 pts with prior neoadjuvant chemotherapy. Median anti-BA7072 and anti-HER500 titers (IgM) were 128- and 256-fold higher at week 6 vs baseline, respectively. The emergence of IgG indicated a memory antibody phenotype. Conclusions: Preliminary data indicate that DN24-02 product potency (CD54 upregulation) is comparable to sipuleucel-T. DN24-02 appears to be well tolerated in UC. Favorable immune responses were observed, including in pts with prior neoadjuvant chemotherapy. Updated results, including preliminary T-cell immune response data, will be presented. Clinical trial information: NCT01353222.

B cell intrinsic and extrinsic roles of ADP-ribosyltransferase, PARP14 in regulation of IgA and IgE responses (P1078)

Abstract Immunological memory, including both persistent and recall antibody (Ab) responses, enables more efficient and effective protection against infection, but key molecular mechanisms regulating emergence and persistence of memory B cells and plasma cells remain unclear. Poly-ADP-Ribose Polymerase14 (PARP14) is highly expressed in B cells and identified as a Stat6-interacting protein with intrinsic mono-ADP-ribosyltransferase (mART) activity. Although there are 17 PARP family members, the physiological function of most PARPs are not known well. Here we show that recall IgA and IgE production are impaired in PARP14-deficient mice. Further analysis revealed that, although PARP14 regulation of IgE involves B cell intrinsic function, IgA regulation by PARP14 was predominantly B cell extrinsic. Of note, PARP14 regulates the levels of CD103+ dendritic cells and T helper 17 (Th17) cells which might influence IgA generation in B cells. Moreover, PARP14 regulates the expression of RORα, Runx1 and Smad3 during Th17 differentiation, and mART activity of PARP plays a critical role in Th17 differentiation. Collectively, these results shed new light on differential mechanisms of Ig regulation, provide evidence that an endogenous mono ADP-ribosyltransferase regulates recall Ab production, and may have important implications for a new therapeutic target.

The B-cell response to a primary and booster course of MenACWY-CRM197 vaccine administered at 2, 4 and 12 months of age

A quadrivalent meningococcal vaccine conjugated to CRM197 (MenACWY-CRM197) is immunogenic in young infants. We assessed the memory B-cell and antibody responses after a primary and booster course of MenACWY-CRM197 in children. At 5 months of age, following primary immunisation, serogroup-specific memory B-cells were detectable in fewer than 25% of children, although protective antibody titres (hSBA≥4) were detectable in 69% of children against serogroup A and more than 95% against the other serogroups. At 12 months, before booster immunisation the percentages with hSBA≥4 were 5% for serogroup A, and between 44 and 70% for the other serogroups. One month after booster immunisation with MenACWY-CRM197 over 50% of children had detectable memory B-cells, and 91% had hSBA≥4 against serogroup A and more than 99% against the other serogroups. These data show that few antigen-specific anticapsular memory B-cells can be detected after two-doses priming with MenACWY-CRM197. For MenC and CRM197, the antigens with the highest number of B-cells at 5 months, there was a definite (p≤0.02) but weak correlation with antibody persistence at 12 months. Although previous studies suggest that measuring memory B-cell responses after priming immunisations in infancy can be used to predict antibody persistence and memory responses, this may not be suitable for all antigens in young children.

Immunogenicity and Contraceptive Efficacy ofEscherichia coli-Expressed Recombinant Porcine Zona Pellucida Proteins

To overcome availability of the purified native zona pellucida (ZP) glycoproteins for immunocontraception, porcine ZP3, and ZP4 were expressed in E.coli. Purified recombinant proteins were characterized by SDS-PAGE and Western blot, and immunogenicity and contraceptive efficacy determined in FvB/J female mice. Purified ZP3, ZP3 with promiscuous T-cell epitope of tetanus toxoid, ZP4 and ZP4 incorporating promiscuous T-cell epitope of bovine RNase revealed ~44-, ~49-, ~53-, and ~55-kDa bands by SDS-PAGE and Western blot, respectively. Immunization of female mice with recombinant proteins elicited high antibody titers as well as T-cell responses. Immune sera recognized mouse oocyte ZP and also inhibited in vitro fertilization. Immunized mice showed significant decrease in fertility. Recombinant proteins were able to recall memory antibody response in female mice primed with porcine native ZP. Availability of recombinant porcine proteins will be useful in the development of contraceptive vaccine.

Chaotic Immune Genetic Hybrid Algorithms and Its Application

To solve the shortage in genetic algorithms, such as slow convergence speed, poor local searching capability and easy prematurity, firstly,the immune memory recognition function was introduced, to speed up the searching speed and improve the overall searching capabilities of genetic algorithm. Secondly,the Henon chaotic map was introduced into the generation of the initial population, made the generated initial population uniformly distributed in the solution space, to reduce data redundancy, increase the diversity of antibody population and the search range of initial population manipulation , prevent the defect of falling into local optimum. Finally, Logistic map was introduced into manipulation of crossover and mutation, meanwhile the map was used to produce the chaotic disturbance strategy on the memory and populations antibodies , to improve the quality of optimal solution and the searching speed of the algorithm, increase efficient of searching. It was proved that the above hybrid algorithm is convergence by mathematics method. The results of function optimization show that the above hybrid algorithm is valid and has better performance than other algorithms. DOI: http://dx.doi.org/10.11591/telkomnika.v11i2.2063 Full Text: PDF

Malaria infection alters the expression of B-cell activating factor resulting in diminished memory antibody responses and survival.

Malaria is a major cause of morbidity worldwide with reports of over 200-500 million infected individuals and nearly 1 million deaths each year. Antibodies have been shown to play a critical role in controlling the blood stage of this disease; however, in malaria-endemic areas antibody immunity is slow to develop despite years of exposure to Plasmodium spp. the causative parasite. Using rodent Plasmodium yoelii YM, we provide evidence that malarial infections result in a decrease in the proportion of DCs that express the B-cell survival factor, BAFF, resulting in a decreased ability of these DCs to support memory B-cell differentiation into antibody secreting cells (ASCs) and/or the survival of ASCs. Further, compared with infected WT mice, ASC numbers were significantly increased in malaria-infected transgenic mice that either overexpressed BAFF or mice with BAFF-independent B-cell survival (B-cell-restricted TRAF3 deletion). Remarkably, BAFF-overexpressing mice were protected from lethal malaria infections, indicating the significance of the role BAFF plays in determining the outcome of malaria infections. These findings describe a previously unappreciated mechanism by which Plasmodium spp. can depress the generation of protective antibody responses.