scholarly journals African Trypanosomosis Obliterates DTPa Vaccine-Induced Functional Memory So That Post-Treatment Bordetella pertussis Challenge Fails to Trigger a Protective Recall Response

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 603
Author(s):  
Magdalena Radwanska ◽  
Hang Thi Thu Nguyen ◽  
Stefan Magez
Keyword(s):  
Immune Cell ◽  
Early Stage ◽  
Adaptive Immune System ◽  
Vaccine Failure ◽  
Recall Response ◽  
Zoonotic Infections ◽  
Adaptive Immune ◽  
Single Field ◽  
Antibody Ratio ◽  
Trypanosomosis Control

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination is considered the only sustainable method for global trypanosomosis control. Unfortunately, no single field applicable vaccine solution has been successful so far. The active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here, we show that Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and a diminazene diaceturate anti-parasite treatment scheme, our results demonstrate that while the latter ensured full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-B. pertussis vaccine recall response. The DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-B. pertussis antibody ratio in favor of IgG2a, and a striking impact on all of the spleen immune cell populations. Interestingly, an increased plasma IFNγ level in DTPa-vaccinated trypanosome-infected mice coincided with a temporary antibody-independent improvement in early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome-inflicted immune damage is not restored by successful anti-parasite treatment.

scholarly journals Evolution during primary HIV infection does not require adaptive immune selection

2020 ◽  
Author(s):  
David A Swan ◽  
Morgane Rolland ◽  
Joshua Herbeck ◽  
Joshua T Schiffer ◽  
Daniel B Reeves
Keyword(s):  
Viral Load ◽  
Immune System ◽  
Hiv Infection ◽  
Evolutionary Dynamics ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Viral Fitness ◽  
Immune Cell Population ◽  
Adaptive Immune

AbstractModern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic (wi-phy) models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The most parsimonious and accurate model required no positive selection, suggesting that the host adaptive immune system reduces viral load, but does not drive observed viral evolution. Rather, random genetic drift primarily dictates fitness changes. These results hold during early infection, and even during chronic infection when selection has been observed, viral fitness distributions are not largely different from in vitro distributions that emerge without adaptive immunity. These results highlight how phylogenetic inference must consider complex viral and immune-cell population dynamics to gain accurate mechanistic insights.One sentence summaryThrough the lens of a unified population and phylodynamic model, current data show the first wave of HIV mutations are not driven by selection by the adaptive immune system.

scholarly journals IL-2–dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells

2013 ◽  
Vol 210 (6) ◽  
pp. 1167-1178 ◽  
Author(s):  
Georg Gasteiger ◽  
Saskia Hemmers ◽  
Matthew A. Firth ◽  
Audrey Le Floc’h ◽  
Morgan Huse ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Adaptive Immune System ◽  
Target Cells ◽  
Cell Reactivity ◽  
Adaptive Immune ◽  
Missing Self

The emergence of the adaptive immune system took a toll in the form of pathologies mediated by self-reactive cells. Regulatory T cells (T reg cells) exert a critical brake on responses of T and B lymphocytes to self- and foreign antigens. Here, we asked whether T reg cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. Although depletion of T reg cells led to systemic fatal autoimmunity, NK cell tolerance and reactivity to strong activating self- and non-self–ligands remained largely intact. In contrast, missing-self responses were increased in the absence of T reg cells as the result of heightened IL-2 availability. We found that IL-2 rapidly boosted the capacity of NK cells to productively engage target cells and enabled NK cell responses to weak stimulation. Our results suggest that IL-2–dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2.

scholarly journals Inflammation and Cell Death of the Innate and Adaptive Immune System during Sepsis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1011
Author(s):  
Christina Nedeva
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Immune Activation ◽  
Immune Cell ◽  
Medical Condition ◽  
Treatment Options ◽  
Disease Onset ◽  
Adaptive Immune System ◽  
Comprehensive Overview ◽  
Adaptive Immune

Sepsis is a life-threatening medical condition that occurs when the host has an uncontrolled or abnormal immune response to overwhelming infection. It is now widely accepted that sepsis occurs in two concurrent phases, which consist of an initial immune activation phase followed by a chronic immunosuppressive phase, leading to immune cell death. Depending on the severity of the disease and the pathogen involved, the hosts immune system may not fully recover, leading to ongoing complications proceeding the initial infection. As such, sepsis remains one of the leading causes of morbidity and mortality world-wide, with treatment options limited to general treatment in intensive care units (ICU). Lack of specific treatments available for sepsis is mostly due to our limited knowledge of the immuno-physiology associated with the disease. This review will provide a comprehensive overview of the mechanisms and cell types involved in eliciting infection-induced immune activation from both the innate and adaptive immune system during sepsis. In addition, the mechanisms leading to immune cell death following hyperactivation of immune cells will be explored. The evaluation and better understanding of the cellular and systemic responses leading to disease onset could eventuate into the development of much needed therapies to combat this unrelenting disease.

scholarly journals FB5P-seq: FACS-based 5-prime end single-cell RNAseq for integrative analysis of transcriptome and antigen receptor repertoire in B and T cells

2019 ◽  
Author(s):  
Noudjoud Attaf-Bouabdallah ◽  
Iñaki Cervera-Marzal ◽  
Chuang Dong ◽  
Laurine Gil ◽  
Amédée Renand ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Immune Cell ◽  
Antigen Receptor ◽  
Adaptive Immune System ◽  
Integrative Analysis ◽  
T Cell Subsets ◽  
Bioinformatics Pipeline ◽  
Human Tonsil ◽  
Adaptive Immune

AbstractSingle-cell RNA sequencing (scRNA-seq) allows the identification, characterization, and quantification of cell types in a tissue. When focused on B and T cells of the adaptive immune system, scRNA-seq carries the potential to track the clonal lineage of each analyzed cell through the unique rearranged sequence of its antigen receptor (BCR or TCR, respectively), and link it to the functional state inferred from transcriptome analysis. Here we introduce FB5P-seq, a FACS-based 5’-end scRNA-seq method for cost-effective integrative analysis of transcriptome and paired BCR or TCR repertoire in phenotypically defined B and T cell subsets. We describe in details the experimental workflow and provide a robust bioinformatics pipeline for computing gene count matrices and reconstructing repertoire sequences from FB5P-seq data. We further present two applications of FB5P-seq for the analysis of human tonsil B cell subsets and peripheral blood antigen-specific CD4 T cells. We believe our novel integrative scRNA-seq method will be a valuable option to study rare adaptive immune cell subsets in immunology research.

scholarly journals Bacterial toxins and the immune system

2005 ◽  
Vol 201 (3) ◽  
pp. 321-323 ◽  
Author(s):  
Jorge E. Galán
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Persistent Infection ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Bacterial Toxins ◽  
Cell Functions ◽  
Adaptive Immune

Microorganisms that cause persistent infection often exhibit specific adaptations that allow them to avoid the adaptive immune response. Recently, several bacterial toxins have been shown in vitro to disrupt immune cell functions. However, it remains to be established whether these activities are relevant during infection and whether these toxins have specifically evolved to disrupt the adaptive immune system.

scholarly journals Hippo Pathway in Mammalian Adaptive Immune System

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 398 ◽  
Author(s):  
Takayoshi Yamauchi ◽  
Toshiro Moroishi
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cell ◽  
Hippo Pathway ◽  
Adaptive Immune System ◽  
Signaling Mechanism ◽  
Adaptive Immune ◽  
Adaptive Immune Cell ◽  
Cancer Pathogenesis ◽  
The Hippo Pathway

The Hippo pathway was originally identified as an evolutionarily-conserved signaling mechanism that contributes to the control of organ size. It was then rapidly expanded as a key pathway in the regulation of tissue development, regeneration, and cancer pathogenesis. The increasing amount of evidence in recent years has also connected this pathway to the regulation of innate and adaptive immune responses. Notably, the Hippo pathway has been revealed to play a pivotal role in adaptive immune cell lineages, as represented by the patients with T- and B-cell lymphopenia exhibiting defective expressions of the pathway component. The complex regulatory mechanisms of and by the Hippo pathway have also been evident as alternative signal transductions are employed in some immune cell types. In this review article, we summarize the current understanding of the emerging roles of the Hippo pathway in adaptive immune cell development and differentiation. We also highlight the recent findings concerning the dual functions of the Hippo pathway in autoimmunity and anti-cancer immune responses and discuss the key open questions in the interplay between the Hippo pathway and the mammalian immune system.

scholarly journals Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity

2021 ◽  
Vol 9 ◽  
Author(s):  
Kelly Z. Miao ◽  
Grace Y. Kim ◽  
Grace K. Meara ◽  
Xiaodan Qin ◽  
Hui Feng
Keyword(s):  
Immune System ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Driving Forces ◽  
Adaptive Immune System ◽  
Experimental System ◽  
Dynamic Interactions ◽  
Adaptive Immune ◽  
Anti Cancer ◽  
New Frontier

The future of improved immunotherapy against cancer depends on an in-depth understanding of the dynamic interactions between the immune system and tumors. Over the past two decades, the zebrafish has served as a valuable model system to provide fresh insights into both the development of the immune system and the etiologies of many different cancers. This well-established foundation of knowledge combined with the imaging and genetic capacities of the zebrafish provides a new frontier in cancer immunology research. In this review, we provide an overview of the development of the zebrafish immune system along with a side-by-side comparison of its human counterpart. We then introduce components of the adaptive immune system with a focus on their roles in the tumor microenvironment (TME) of teleosts. In addition, we summarize zebrafish models developed for the study of cancer and adaptive immunity along with other available tools and technology afforded by this experimental system. Finally, we discuss some recent research conducted using the zebrafish to investigate adaptive immune cell-tumor interactions. Without a doubt, the zebrafish will arise as one of the driving forces to help expand the knowledge of tumor immunity and facilitate the development of improved anti-cancer immunotherapy in the foreseeable future.

scholarly journals Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease

2021 ◽  
Vol 8 (5) ◽  
pp. e1036
Author(s):  
Zhaoqi Yan ◽  
Wei Yang ◽  
Hairong Wei ◽  
Marissa N. Dean ◽  
David G. Standaert ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Parkinson Disease ◽  
Peripheral Blood ◽  
Cytokine Production ◽  
Early Stage ◽  
Adaptive Immune System ◽  
Th2 Cells ◽  
Adaptive Immune

ObjectiveTo determine the activation status and cytokine profiles of CD4+ T cells, CD8+ T cells, and CD19+ B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs).MethodsPeripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed.ResultsAdaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4+ and naive CD8+ T cells are significantly decreased in patients with PD, whereas central memory CD4+ T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4+ Th17 cells, IL-4–producing CD4+ Th2 cells, and IFN-γ–producing CD8+ T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19+ B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4+ T cells and B cells were associated with clinical motor disease severity.ConclusionsThese findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4+ T cells, CD8+ T cells, and CD19+ B cells in patients with PD.

scholarly journals The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

2016 ◽  
Vol 113 (9) ◽  
pp. E1316-E1325 ◽  
Author(s):  
Samuel E. Marsh ◽  
Edsel M. Abud ◽  
Anita Lakatos ◽  
Alborz Karimzadeh ◽  
Stephen T. Yeung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
B Cells ◽  
Adaptive Immunity ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Phagocytic Capacity ◽  
Adaptive Immune ◽  
5Xfad Mice

The innate immune system is strongly implicated in the pathogenesis of Alzheimer’s disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting “Rag-5xfAD” mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive–innate immunity cross talk and accelerated disease progression.

scholarly journals The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1280 ◽  
Author(s):  
Alessandro Maglione ◽  
Simona Rolla ◽  
Stefania Federica De Mercanti ◽  
Santina Cutrupi ◽  
Marinella Clerico
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Cell Types ◽  
Point Of View ◽  
Adaptive Immune ◽  
Future Path

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS.

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