scholarly journals A ROLE FOR CELLULAR IMMUNITY IN EARLY POSTPARTUM PERIOD

2021 ◽  
Vol 23 (4) ◽  
pp. 853-858
Author(s):  
N. A. Panova ◽  
V. G. Skopichev
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cellular Immunity ◽  
Wide Spectrum ◽  
Active Form ◽  
Lymphoid Cells ◽  
Intestinal Lumen ◽  
Immune Memory ◽  
Epithelial Layer ◽  
Sex Chromatin

The functioning of the secretory organs is closely related to the activity of the immune system. As is well known, this participation is manifested in the fact that at certain stages of activity, the lymphoid cells migrating to the organ can be involved in the regulation of secretion. In addition, the products of the immune system and even its cellular elements can become components of a number of secrets. Colostrum and milk contain a large number of cells of a wide spectrum (up to 1/3 of the volume), of which the number of lymphocytes is up to 16% of leukocytes. Lymphocytes, in an immunologically active form, entering the newborn’s body with colostrum, activate the cellular immunity system. The transport of lymphokinin mediators plays a certain role in this process. Microphages, T- and B-lymphocytes, penetrating through the intercellular spaces into the lymphoid layer of the intestine, transmit immunoreceptors to the prolymphocytes of the newborn, "armed" with their activity to recognize genetically foreign ones. The lymphocytes contained in colostrum are the cells of the immune system that provide cellular and humoral immunity. They are mainly represented by T-cells, B-cells and killer cells. Milk T-cells produce a full spectrum of immune regulatory proteins such as interferon, tumor necrosis factor alpha. These cells are the cells of the immune memory. Newborns who received the first portion of colostrum no later than an hour after birth are characterized by an increased number of leukocytes, more pronounced phagocytosis, which indicates the stimulation of hemo- and lymphocytosis. When carrying out transmission and scanning electron microscopy in the epithelial layer of the intestine, cellular elements were found that got there from the intestinal lumen. Microsections show how cells of a lymphoid nature, pushing apart the structures of the epithelial layer, bypass natural barriers and, at the same time, retain their physiological usefulness. The possibility of penetration of immunocompetent cells of the mother’s colostrum into the bloodstream of the young is proved using the natural label of the female’s cells – sex chromatin. Naturally, sex chromatin-labeled cells were sought in male newborns. The detection of colostrum cells in the intestinal wall and bloodstream of the young is approximately 25% in the blood, 1% in the lymph, and about 70% in the intestine. There is no doubt that the leukocytes of colostrum are of exceptional importance in creating immunity in newborn animals. 

scholarly journals Analysis of the Long-Term Impact on Cellular Immunity in COVID-19-Recovered Individuals Reveals a Profound NKT Cell Impairment

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Jia Liu ◽  
Xuecheng Yang ◽  
Hua Wang ◽  
Ziwei Li ◽  
Hui Deng ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Cellular Immunity ◽  
Cd8 T Cells ◽  
Nkt Cell ◽  
Cellular Immune System ◽  
Long Term Impact ◽  
Cellular Immune

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19-convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2-unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of annexin V and 7-aminoactinomycin D (7-AAD) double-positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies and TIM-3 expression on CD4 and CD8 T cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by granzyme B (GzmB) expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully able to proliferate and produce effector cytokines upon T cell receptor (TCR) stimulation. Collectively, we provide a comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease. IMPORTANCE Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here. This enabled us to investigate the “immunological scar” left by SARS-CoV-2 on cellular immunity after recovery from the disease. In this study, we characterized the long-term impact of SARS-CoV-2 infection on the immune system and provide a comprehensive picture of cellular immunity of a convalescent COVID-19 patient cohort with the longest recovery time. We revealed that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease; in particular, a profound NKT cell impairment was found in the convalescent phase of COVID-19.

scholarly journals NK Cell Memory to Cytomegalovirus: Implications for Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 394
Author(s):  
Calum Forrest ◽  
Ariane Gomes ◽  
Matthew Reeves ◽  
Victoria Male
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Vaccine Development ◽  
Nk Cell ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Murine Cytomegalovirus ◽  
Immune Memory ◽  
Cell Memory

Natural killer (NK) cells are innate lymphoid cells that recognize and eliminate virally-infected and cancerous cells. Members of the innate immune system are not usually considered to mediate immune memory, but over the past decade evidence has emerged that NK cells can do this in several contexts. Of these, the best understood and most widely accepted is the response to cytomegaloviruses, with strong evidence for memory to murine cytomegalovirus (MCMV) and several lines of evidence suggesting that the same is likely to be true of human cytomegalovirus (HCMV). The importance of NK cells in the context of HCMV infection is underscored by the armory of NK immune evasion genes encoded by HCMV aimed at subverting the NK cell immune response. As such, ongoing studies that have utilized HCMV to investigate NK cell diversity and function have proven instructive. Here, we discuss our current understanding of NK cell memory to viral infection with a focus on the response to cytomegaloviruses. We will then discuss the implications that this will have for the development of a vaccine against HCMV with particular emphasis on how a strategy that can harness the innate immune system and NK cells could be crucial for the development of a vaccine against this high-priority pathogen.

scholarly journals Vitamin D3and the immune system: maintaining the balance in health and disease

2007 ◽  
Vol 20 (1) ◽  
pp. 106-118 ◽  
Author(s):  
Femke Baeke ◽  
Evelyne Van Etten ◽  
Lut Overbergh ◽  
Chantal Mathieu
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Immune System ◽  
Animal Models ◽  
Autoimmune Diseases ◽  
Active Form ◽  
Epidemiological Data ◽  
Cell Types ◽  
Dihydroxyvitamin D

1,25-Dihydroxyvitamin D3(1,25(OH)2D3), the active form of vitamin D3, is a central player in Ca and bone metabolism. More recently, important immunomodulatory effects have been attributed to this hormone. By binding to its receptor, the vitamin D receptor, 1,25(OH)2D3regulates the expression of various genes and consequently affects the behaviour of different cell types within the immune system. 1,25(OH)2D3can potently inhibit pathogenic T cells and gives rise to elevated numbers of regulatory T cells via the induction of tolerogenic dendritic cells. These immunomodulatory activities of 1,25(OH)2D3have also been proven usefulin vivo: administration of 1,25(OH)2D3in several animal models can prevent or cure different autoimmune diseases and graft rejection. To overcome the dose-limiting side effects of 1,25(OH)2D3on Ca and bone, less calcaemic structural analogues (alone or in combination with synergistically acting drugs or bone-resorption inhibitors) have been successfully used in animal models. Furthermore, as 1,25(OH)2D3also contributes to host defence against infectious agents by the induction of antimicrobial responses, this molecule might provide a new strategy to deal with drug-resistant infections. According to the pleiotropic effects of 1,25(OH)2D3in the immune system, increasing epidemiological data underline the importance of adequate vitamin D intakes in reducing the risk of several autoimmune diseases and infections such as tuberculosis.

scholarly journals Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nikos E. Papaioannou ◽  
Natallia Salei ◽  
Stephan Rambichler ◽  
Kaushikk Ravi ◽  
Jelena Popovic ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Early Life ◽  
Adult Life ◽  
Lymphoid Cells ◽  
Environmental Signals ◽  
Cell Responses ◽  
Adult Mice

AbstractConventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.

scholarly journals A NOVEL LANGERIN EXPRESSING TYPE 2-CONVENTIONAL DENDRITIC CELL IS SIGNIFICANTLY DECREASED IN CROHN’S DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S32-S33
Author(s):  
Chloe Doyle ◽  
Kirstie Bertram ◽  
Jake Rhodes ◽  
Anthony Cunningham ◽  
Grahame Ctercteko ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
Immune System ◽  
Dendritic Cell ◽  
Crohn's Disease ◽  
Mononuclear Phagocytes ◽  
Lymphoid Cells ◽  
T Helper 17 ◽  
Intestinal Immune System

Abstract Crohn’s disease is a chronic relapsing auto-inflammatory condition of the gastrointestinal tract that primarily affects young individuals with an increasing incidence rate. There is still no cure for Crohn’s disease and current treatment-options are limited to controlling inflammatory molecules such as TNF. Unfortunately, these biologics can produce significant side effects and not all patients respond to anti-TNF treatment. New treatments are therefore urgently needed. Targeting the cells and molecules of the immune system still represents the most promising approach which is why we have conducted an in-depth study of the immune cells and molecules associated with a healthy intestinal immune system and compared that to what is happening in Crohn’s disease. Our group has privileged access to large human ileum explants as well as draining lymph node samples isolated from patients undergoing colorectal surgery to remove Crohn’s affected tissue. We have designed and optimised enzymatic tissue digestion protocols to isolate these cells in an immature state with minimal receptor cleavage. We have also developed high-parameter flow and mass cytometry panels to comprehensively identify and characterise all known subsets of mononuclear phagocytes (MNP), innate lymphoid cells, mucosal-associated invariant T cells, natural killer cells and T and B lymphocytes. We have discovered that the newly described Langerin+ type 2-conventional dendritic cell (cDC2) is significantly decreased in Crohn’s affected ileum compared to healthy ileum. Furthermore, we have shown this decrease corresponds with lower TGF-b levels, a known driver of Langerin expression. After 7 days of co-culture, sorted Langerin+ cDC2 induced significantly higher levels of IL-17 and IL-22 in allogenic naïve CD4+ T cells compared to other MNP subsets, including cDC2 which did not express Langerin. These differentiated T cells expressed high levels of RORt and aryl hydrocarbon receptor (AHR) – transcription factors that are associated with CD4+ T helper 17 cells, implying that they may play a crucial role in intestinal barrier repair and regeneration that is absent in Crohn’s disease. Together these results suggest that Langerin+ cDC2 may have an anti-inflammatory role in human tissue and their reduction in Crohn’s disease may contribute to the pathogenesis of this disease, highlighting a potential therapeutic target for Crohn’s disease.

scholarly journals Active Modulation of Memory CD8+T cells Through a Photothermal-Metbolism Based Tumor Vaccine for Cancer Prevention and Treatment

2020 ◽  
Author(s):  
Lihua Luo ◽  
Xiang Li ◽  
Junlei Zhang ◽  
Chunqi Zhu ◽  
Mengshi Jiang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cancer Prevention ◽  
Cd8 T Cells ◽  
Tumor Vaccine ◽  
Effector T Cells ◽  
Immune Memory ◽  
Photothermal Effect ◽  
Memory Cd8 T Cells ◽  
Prevention And Therapy

Tumor vaccine inducing effective and perdurable antitumor immunity has a great potential for cancer prevention and therapy. The key indicator for a successful tumor vaccine is to boost the immune system to produce more memory T cells. Although many tumor vaccines have been designed in the past two decades, few of them involve actively regulating immune memory CD8+T cells. The behavior of tumor-associated antigens (TAA) in stimulating the immune system is related to the formation of immune memory. At the same time, the metabolic pattern of memory CD8+T cells changed significantly compared to effector T cells. Here we present a tumor vaccine vector (TA-Met@MS) by encapsulating tumor antigen (TA, the whole tumor cell antigen induced with photothermal-therapy (PTT) as a TAA model), metformin (Met, an activator of AMP-activated protein kinase (AMPK)) and Hollow gold nanospheres (HAuNS, with photothermal conversion effect in the near infrared (NIR) region) into poly (lactic-co-glycolic acid) (PLGA) microspheres. TA via the treatment with PTT showed high immunogenicity and immune-adjuvant effectiveness. We found that NIR light-mediated photothermal effect lead to a pulsed-release behavior of TA and Met from the microspheres, based on their sustained release. The released TA regulated primary T cell expansion and contraction, and stimulated the production of effector T cells at the early immunization stage. The metabolic behavior of the cells was then intervened from glycolysis into fatty acids oxidation (FAO) through the activation of AMPK mediated by the released Met, which enhanced cell survival and facilitated the differentiation of memory CD8+T cells. Our study may present a valuable insight to design tumor vaccine for enhanced cancer prevention and therapy.

Adaptive Immune System in Fish

2021 ◽  
Vol 22 (4) ◽  
Author(s):  
Adef Othan Kordon ◽  
Lesya Pinchuk ◽  
Attila Karsi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Teleost Fish ◽  
Cytotoxic T Cells ◽  
Adaptive Immune System ◽  
Immune Memory ◽  
Cellular Cytotoxicity ◽  
Th Cells ◽  
Adaptive Immune

The immune system of all jawed vertebrates is composed of two major subsystems, the innate (non-specific) and adaptive (specific) immune system. The innate immune system is the first to respond to infectious agents; however, it does not provide longlasting protection. The adaptive immune system is activated later and responds to pathogens with specificity and memory. The main components of the adaptive immune system, including T cell receptors (TCRs), major histocompatibility complex (MHC), immunoglobulins (Igs), and recombination-activating gene (RAG) arose in the first jawed fish (cartilaginous and teleost fish). This review explores and discusses components of the adaptive immune system in teleost fish and recent developments in comparative immunology. Similar to mammals, the adaptive immune system in teleost fish is divided into two components: cellular-mediated responses and humoralmediated responses. T cells, the principal elements of cellular-mediated adaptive immune responses, differentiate into effector helper T (Th) cells or effector cytotoxic T cells (CTLs). The central elements involved in the differentiation of Th subsets in mammals, cytokines and master transcription factors, have also been identified in teleost fish. In addition, each subset of Th cells, defined with a particular cytokine to control the immune responses, has been described in teleost fish. Similarly, to mammals, CTLs contribute to cellular cytotoxicity in teleost fish. B cells act as a central player in humoral-mediated adaptive immunity by producing opsonizing, neutralizing and complement-binding antibodies and inducing antibody-dependent cellular cytotoxicity (ADCC). Three classes of antibodies named IgM, IgD, and IgT/Z have been characterized in teleost fish. The presence of an adaptive immune system and consequent immune memory in teleost fish allows vaccination, the most appropriate method for disease control in aquaculture. Immunological studies in fish provide a comprehensive assessment of the fish immune system, which is crucial for understanding the evolution of the mammalian immune system.

scholarly journals Preclinical evaluation of NF-κB-triggered dendritic cells expressing the viral oncogenic driver of Merkel cell carcinoma for therapeutic vaccination

2017 ◽  
Vol 9 (7) ◽  
pp. 451-464 ◽  
Author(s):  
Kerstin F. Gerer ◽  
Michael Erdmann ◽  
Sine R. Hadrup ◽  
Rikke Lyngaa ◽  
Lena-Marie Martin ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Active Form ◽  
T Antigen ◽  
Therapeutic Vaccination ◽  
Merkel Cell ◽  
Healthy Donors

Background: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host’s genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. Methods: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT. To permit major histocompatibility complex (MHC) class II next to class I presentation, we used an RNA construct in which the antigen was fused to a DCLamp sequence in addition to the unmodified antigen. To further improve their immunogenicity, the DCs were additionally activated by co-transfection with the constitutively active nuclear factor (NF)-κB activator caIKK. These DCs were used to stimulate autologous CD8+ T-cells or a mixture of CD4+ and CD8+ T-cells. Then the percentage of T-cells, specific for the truncLT, was quantified by interferon (IFN)γ ELISpot assays. Results: Both the truncLT and its DCLamp-fusion were detected within the DCs by flow cytometry, albeit the latter required blocking of the proteasome. The transfection with caIKK upregulated maturation markers and induced cytokine production. After 2–3 rounds of stimulation, the T-cells from 11 out of 13 healthy donors recognized the antigen. DCs without caIKK appeared in comparison less potent in inducing such responses. When using cells derived from MCC patients, we could induce responses for 3 out of 5 patients; however, here the caIKK-transfected DCs did not display their superiority. Conclusion: These results show that optimized DCs are able to induce MCV-antigen-specific T-cell responses. Therapeutic vaccination with such transfected DCs could direct the immune system against MCC.

scholarly journals Antigen presentation by type 3 innate lymphoid cells instructs the differentiation of gut microbiota-specific regulatory T cells

2021 ◽  
Author(s):  
Ranit Kedmi ◽  
Tariq Najar ◽  
Kailin R. Mesa ◽  
Allyssa Grayson ◽  
Lina Kroehling ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Differentiation ◽  
Antigen Presentation ◽  
Th17 Cells ◽  
Immune Cell ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Host Immune System ◽  
Type 3

The mutualistic relationship of gut-resident microbiota and cells of the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a poised, but largely non-aggressive, immune cell compartment1,2. Consequences of disturbing this balance, by environmental or genetic factors, include proximal inflammatory conditions, like Crohn's disease, and systemic illnesses, both metabolic and autoimmune. One of the means by which this equilibrium is achieved is through induction of both effector and suppressor or regulatory arms of the adaptive immune system. In mice, Helicobacter species induce regulatory (iTreg) and follicular helper (Tfh) T cells in the colon-draining mesenteric lymph nodes under homeostatic conditions, but can instead induce inflammatory Th17 cells and colitis when iTreg cells are compromised3,4. How Helicobacter hepaticus and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here, we investigated which cells and molecular components are required to convey the microbial instruction for the iTreg differentiation program. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was both required and sufficient for iTreg induction. These RORγt+ cells, likely to be type 3 innate lymphoid cells (ILC3), require the MHC class II antigen presentation machinery, the chemokine receptor CCR7, and αv integrin, which activates TGF-β, for iTreg cell differentiation. In the absence of any of these, instead of iTreg cells there was expansion of microbiota-specific pathogenic Th17 cells, which were induced by other antigen presenting cells (APCs) that did not require CCR7. Thus, intestinal commensal microbes and their products target multiple APCs with pre-determined features suited to directing appropriate T cell differentiation programs, rather than a common APC that they endow with appropriate functions. Our results illustrate the ability of microbiota to exploit specialized functions of distinct innate immune system cells, targeting them to achieve the desired composition of equipoised T cells, thus maintaining tolerance.

Sign in / Sign up

Export Citation Format

Share Document