scholarly journals “An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

2021 ◽  
Vol 2 ◽  
Author(s):  
Susan L. Swain ◽  
Olivia Kugler-Umana ◽  
Susan L. Tonkonogy
Keyword(s):  
B Cell ◽  
Adaptive Immune System ◽  
Housing Conditions ◽  
Germ Free ◽  
Cell Responses ◽  
Adaptive Immune ◽  
B Cell Subsets ◽  
Poor Efficacy ◽  
Normal Laboratory ◽  
Intrinsic Program

As mice age their adaptive immune system changes dramatically, leading to weakened responses to newly encountered antigens and poor efficacy of vaccines. A shared pattern emerges in the aged, with both CD4 T and B cell responses requiring higher levels of pathogen recognition. Moreover, in aged germ-free mice we find accumulation of the same novel age-associated T and B cell subsets that we and others have previously identified using mice maintained in normal laboratory animal housing conditions, suggesting that their development follows an intrinsic program.

scholarly journals Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mauro Di Pilato ◽  
Miguel Palomino-Segura ◽  
Ernesto Mejías-Pérez ◽  
Carmen E. Gómez ◽  
Andrea Rubio-Ponce ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immune System ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Adaptive Immune

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

scholarly journals Mansonella perstans microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses

2018 ◽  
Vol 12 (1) ◽  
pp. e0006184 ◽  
Author(s):  
Manuel Ritter ◽  
Winston Patrick Chounna Ndongmo ◽  
Abdel Jelil Njouendou ◽  
Nora Nganyewo Nghochuzie ◽  
Lucy Cho Nchang ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Mansonella Perstans ◽  
B Cell Subsets

Cellular side of acquired immunity (B cells)

2013 ◽  
pp. 371-378
Author(s):  
Thomas Dörner ◽  
Peter E. Lipsky
Keyword(s):  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Plasma Cells ◽  
Adaptive Immune System ◽  
Adaptive Immune ◽  
B Cell Homeostasis ◽  
Anti Cd20 ◽  
Antigen Presenting

B cells have gained interest in rheumatoid arthritis (RA) beyond being the precursors of antibody-producing plasma cells since they are also a broader component of the adaptive immune system. They are capable of functioning as antigen-presenting cells for T-cell activation and can produce an array of cytokines. Disturbances of peripheral B-cell homeostasis together with the formation of ectopic lymphoid neogenesis within the inflamed synovium appears to be a characteristic of patients with RA. Enhanced generation of memory B cells and autoreactive plasma cells producing IgM-RF and ACPA-IgG antibodies together with formation of immune complexes contribute to the maintenance of RA, whereas treatment with B-cell-directed anti-CD20 and CLTA4-Ig therapy provides clinical benefit.

scholarly journals Immune outcomes and safety of high-dose oral insulin as a primary prevention immunotherapy in young autoantibody-negative children at high genetic risk for type 1 diabetes

2020 ◽  
Author(s):  
Robin Assfalg ◽  
Jan Knoop ◽  
Kristi L. Hoffman ◽  
Markus Pfirrmann ◽  
Jose Maria Zapardiel-Gonzalo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Primary Prevention ◽  
Genetic Risk ◽  
Adaptive Immune System ◽  
Oral Insulin ◽  
Dependent Manner ◽  
Cell Responses ◽  
Adaptive Immune

AbstractBackgroundOral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes with insulin autoimmunity often appearing in the first years of life. The aim of this study was to assess the safety and immunological effects of oral insulin immunotherapy as a primary prevention.MethodsA phase I/II randomized controlled trial (Clinicaltrials.govNCT02547519) was performed in 44 islet autoantibody-negative children aged 6 months to 2 years with familial and additional genetic risk for type 1 diabetes. Children were randomized 1:1 to daily insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months. Hypoglycemia was a major safety measure. The primary immune efficacy outcome was an induction of antibody or T cell responses to oral insulin.ResultsOral insulin was well tolerated with no changes in metabolic variables. The primary immune outcome did not differ between treatment groups and responses were observed in both children who received insulin (55%) or placebo (67%). Responses were, however, modified by the type 1 diabetes INSULIN gene. Among children with a susceptible genotype, antibody responses to insulin were more frequent in insulin-treated (cumulative response, 75.8%) as compared to placebo-treated children (18.2%; P = 0.0085). Mechanistic studies identified microbiome changes that were related to INSULIN genotype and frequent treatment-independent inflammatory episodes that modified the in vitro T cell responses to insulin in children with susceptible INSULIN genotypes.ConclusionThe study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe and engaged the adaptive immune system in an INSULIN genotype-dependent manner, and linked inflammatory episodes to the activation of insulin-responsive T cells.One Sentence SummaryOral insulin given daily to very young children was safe and may engage the adaptive immune system in an INSULIN genotype-dependent manner.

scholarly journals Fierce selection and interference in B-cell repertoire response to chronic HIV-1

2018 ◽  
Author(s):  
Armita Nourmohammad ◽  
Jakub Otwinowski ◽  
Marta Łuksza ◽  
Thierry Mora ◽  
Aleksandra M Walczak
Keyword(s):  
Immune Response ◽  
Population Genetics ◽  
Immune System ◽  
B Cell ◽  
Adaptive Immune System ◽  
Clonal Interference ◽  
Cell Repertoire ◽  
Beneficial Mutations ◽  
Adaptive Immune ◽  
Hiv 1

AbstractDuring chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host’s adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape the immune response are still unknown. Traditional population genetics methods fail to distinguish chronic immune response from healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell repertoires and identify complex dynamics with a constant production of better B-cell receptor mutants that compete, maintaining large clonal diversity and potentially slowing down adaptation. A substantial fraction of mutations that rise to high frequencies in pathogen engaging CDRs of B-cell receptors (BCRs) are beneficial, in contrast to many such changes in structurally relevant frameworks that are deleterious and circulate by hitchhiking. We identify a pattern where BCRs in patients who experience larger viral expansions undergo stronger selection with a rapid turnover of beneficial mutations due to clonal interference in their CDR3 regions. Using population genetics modeling, we show that the extinction of these beneficial mutations can be attributed to the rise of competing beneficial alleles and clonal interference. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix.

Graphene Oxide Modulates B Cell Surface Phenotype and Impairs Immunoglobulin Secretion in Plasma Cell

2016 ◽  
Vol 16 (4) ◽  
pp. 4205-4215 ◽  
Author(s):  
Shaohai Xu ◽  
Shengmin Xu ◽  
Shaopeng Chen ◽  
Huadong Fan ◽  
Xun Luo ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Graphene Oxide ◽  
Immune System ◽  
Cell Surface ◽  
B Cell ◽  
Plasma Cell ◽  
Adaptive Immune System ◽  
Surface Phenotype ◽  
Adaptive Immune

Since discovery, graphene oxide (GO) has been used in all aspects of human life and revealed promising applications in biomedicine. Nevertheless, the potential risks of GO were always being revealed. Although GO was found to induce immune cell death and innate immune response, little is known regarding its toxicity to the specific adaptive immune system that is crucial for protecting against exotic invasion. The B-cell mediated adaptive immune system, which composed of highly specialized cells (B and plasma cell) and specific immune response (antibody response) is the focus in our present study. Using diverse standard immunological techniques, we found that GO modulated B cell surface phenotype, both costimulatory molecules (CD80, CD86 and especially CD40) and antigen presenting molecules (both classical and nonclassical) under the condition without causing cell death. Meanwhile, the terminal differentiated immunoglobulin (Ig) secreting plasma cell was affected by GO, which displayed a less secretion of Ig and more severe ER stress caused by the retention of the secreted form of Ig in cell compartment. The combined data reveal that GO has a particular adverse effect to B cell and the humoral immunity, directly demonstrating the potential risk of GO to the specific adaptive immunity.

scholarly journals Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets

Blood ◽  
2013 ◽  
Vol 121 (3) ◽  
pp. 459-467 ◽  
Author(s):  
Jurjen Tel ◽  
Gerty Schreibelt ◽  
Simone P. Sittig ◽  
Till S. M. Mathan ◽  
Sonja I. Buschow ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Adaptive Immune System ◽  
Plasmacytoid Dendritic Cells ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antitumor Immunotherapy

Abstract In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16+, CD1c+, and BDCA-3+ myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8+ T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c+ and BDCA3+ mDCs, pDCs induce potent Ag-specific CD4+ and CD8+ T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4+ and CD8+ T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3+ mDCs. These findings, and the fact that pDCs outnumber BDCA3+ mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8+ T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.

scholarly journals Fierce Selection and Interference in B-Cell Repertoire Response to Chronic HIV-1

2019 ◽  
Vol 36 (10) ◽  
pp. 2184-2194 ◽  
Author(s):  
Armita Nourmohammad ◽  
Jakub Otwinowski ◽  
Marta Łuksza ◽  
Thierry Mora ◽  
Aleksandra M Walczak
Keyword(s):  
Immune Response ◽  
Population Genetics ◽  
Immune System ◽  
B Cell ◽  
Adaptive Immune System ◽  
Clonal Interference ◽  
Cell Repertoire ◽  
Beneficial Mutations ◽  
Adaptive Immune ◽  
Hiv 1

Abstract During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host’s adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape the immune response are still unknown. Traditional population genetics methods fail to distinguish chronic immune response from healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell repertoires and identify complex dynamics with a constant production of better B-cell receptor (BCR) mutants that compete, maintaining large clonal diversity and potentially slowing down adaptation. A substantial fraction of mutations that rise to high frequencies in pathogen-engaging CDRs of BCRs are beneficial, in contrast to many such changes in structurally relevant frameworks that are deleterious and circulate by hitchhiking. We identify a pattern where BCRs in patients who experience larger viral expansions undergo stronger selection with a rapid turnover of beneficial mutations due to clonal interference in their CDR3 regions. Using population genetics modeling, we show that the extinction of these beneficial mutations can be attributed to the rise of competing beneficial alleles and clonal interference. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix.

scholarly journals Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model

2020 ◽  
Author(s):  
Ami Patel ◽  
Jewell Walters ◽  
Emma L. Reuschel ◽  
Katherine Schultheis ◽  
Elizabeth Parzych ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Adaptive Immune System ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Viral Loads ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Nasal Clearance

SummaryCoronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess immunogenicity and anamnestic protective efficacy in rhesus macaques of the intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800. INO-4800 is an ID-delivered DNA vaccine currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and neutralizing antibody responses against both the D614 and G614 SARS-CoV-2 spike proteins. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T and B cell responses. These responses were associated with lower viral loads in the lung and with faster nasal clearance of virus. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease.

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