Nutrition and Immunity with Emphasis on Infection and Autoimmune Disease

1996 ◽  
Vol 10 (4) ◽  
pp. 285-312 ◽  
Author(s):  
Laurence S. Harbige
Keyword(s):  
Immune System ◽  
Vitamin E ◽  
T Cell ◽  
Autoimmune Disease ◽  
Vitamin A ◽  
Protein Energy Malnutrition ◽  
Dietary Lipids ◽  
Substantial Impact ◽  
Cell Functions ◽  
Immunological Mechanisms

Nutrition and nutritional status can have profound effects on immune functions, resistance to infection and autoimmunity in man and other animals. Nutrients enhance or depress immune function depending on the nutrient and level of its intake. Protein-energy malnutrition and vitamin A deficiency are strongly associated with impaired immunity and infectious disease. The essential role vitamin A plays in infection and maintenance of mucosal surfaces has long been known. Recent evidence shows that T-cell subpopulations, cytokines and antibody subclasses are all affected by vitamin A. In animal studies supplementation with vitamin E protects against infection and is linked to stimulatory effects on the immune system. In man vitamin E and other anti-oxidants increase the number of CD4+ cells. Dietary lipids and zinc have a substantial impact on autoimmunity from protective to potentiation of immunopathological processes in animals. There is considerable potential to modify human autoimmune disease by manipulation of lipid nutrition. Deficiency of pyridoxine induces atrophy of lymphoid organs, marked reduction in lymphocyte numbers, impairs antibody responses and IL-2 production. Dietary copper is important in the prevention of infection in some animal species and T-cell function is defective under deficiency states due to an inability to produce IL-2. Selenium has been linked to viral infection, enhanced T-cell functions and TNFß induced increase in natural killer cell activity. Understanding the molecular and cellular immunological mechanisms involved in nutrient-immune interactions will increase our applications for nutrition of the immune system in health and in disease.

scholarly journals Lifting the innate immune barriers to antitumor immunity

2020 ◽  
Vol 8 (1) ◽  
pp. e000695 ◽  
Author(s):  
Carla V Rothlin ◽  
Sourav Ghosh
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
T Cell ◽  
Time Course ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Innate Immune ◽  
Cell Functions

The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response. Tumor cells often escape immune surveillance and killing. Therefore, disrupting the brakes built into the immune system should effectively boost the anticancer immune response. The success of anti-CTLA4, anti-PD-1 and anti-PD-L1 have firmly established this proof of concept. Since the response rate of anti-CTLA4, anti-PD-1 and anti-PD-L1 is still limited, there is an intense effort for the identification of new targets and development of approaches that can expand the benefits of immunotherapy to a larger patient pool. Additional T cell checkpoints are obvious targets; however, here we focus on the unusual suspects—cells that function to initiate and guide T cell activity. Innate immunity is both an obligate prerequisite for the initiation of adaptive immune responses and a requirement for the recruitment of activated T cells to the site of action. We discuss some of the molecules present in innate immune cells, including natural killer cells, dendritic cells, macrophages, myeloid-derived suppressor cells, endothelial cells and stromal cells, that can activate or enhance innate immune cell functions, and more importantly, the inhibitors or checkpoints present in these cells that restrain their functions. Boosting innate immunity, either by enhancing activator functions or, preferably, by blocking the inhibitors, may represent a new anticancer treatment modality or at least function as adjuvants to T cell checkpoint inhibitors.

scholarly journals Autoimmune Disorders & COVID-19

Medicines ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 55
Author(s):  
Leonardo Freire-de-Lima ◽  
Aline Miranda Scovino ◽  
Camilla Cristie Barreto Menezes ◽  
Leonardo Marques da Fonseca ◽  
Jhenifer Santos dos Reis ◽  
...  
Keyword(s):  
Immune System ◽  
Respiratory Failure ◽  
Autoimmune Disease ◽  
Severe Pneumonia ◽  
Type I ◽  
Cytokine Storm ◽  
Immunological Mechanisms ◽  
The World ◽  
Inflammatory Syndrome

Coronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. Since 2019, several studies regarding the interplay between autoimmune diseases and COVID-19 infections is increasing all over the world. In addition, thanks to new scientific findings, we actually know better why certain conditions are considered a higher risk in both situations. There are instances when having an autoimmune disease increases susceptibility to COVID-19 complications, such as when autoantibodies capable of neutralizing type I IFN are present, and other situations in which having COVID-19 infection precedes the appearance of various autoimmune and autoinflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C), Guillain-Barré syndrome, and Autoimmune haemolytic anaemia (AIHA), thus, adding to the growing mystery surrounding the SARS-CoV-2 virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae. Herein, we discuss the role of host and virus genetics and some possible immunological mechanisms that might lead to the disease aggravation.

scholarly journals CRISPR/Cas9-mediated TGFβRII disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Khadijeh Alishah ◽  
Matthias Birtel ◽  
Elham Masoumi ◽  
Leila Jafarzadeh ◽  
Hamid Reza Mirzaee ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Solid Tumors ◽  
Target Cells ◽  
Cell Functions ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract Background CAR T-cell therapy has been recently unveiled as one of the most promising cancer therapies in hematological malignancies. However, solid tumors mount a profound line of defense to escape immunosurveillance by CAR T-cells. Among them, cytokines with an inhibitory impact on the immune system such as IL-10 and TGFβ are of great importance: TGFβ is a pleiotropic cytokine, which potently suppresses the immune system and is secreted by a couple of TME resident and tumor cells. Methods In this study, we hypothesized that knocking out the TGFβ receptor II gene, could improve CAR T-cell functions in vitro and in vivo. Hereby, we used the CRISPR/Cas9 system, to knockout the TGFβRII gene in T-cells and could monitor the efficient gene knock out by genome analysis techniques. Next, Mesothelin or Claudin 6 specific CAR constructs were overexpressed via IVT-RNA electroporation or retroviral transduction and the poly-functionality of these TGFβRII KO CAR T-cells in terms of proliferation, cytokine secretion and cytotoxicity were assessed and compared with parental CAR T-cells. Results Our experiments demonstrated that TGFβRII KO CAR T-cells fully retained their capabilities in killing tumor antigen positive target cells and more intriguingly, could resist the anti-proliferative effect of exogenous TGFβ in vitro outperforming wild type CAR T-cells. Noteworthy, no antigen or growth factor-independent proliferation of these TGFβRII KO CAR T-cells has been recorded. TGFβRII KO CAR T-cells also resisted the suppressive effect of induced regulatory T-cells in vitro to a larger extent. Repetitive antigen stimulation demonstrated that these TGFβRII KO CAR T-cells will experience less activation induced exhaustion in comparison to the WT counterpart. Conclusion The TGFβRII KO approach may become an indispensable tool in immunotherapy of solid tumors, as it may surmount one of the key negative regulatory signaling pathways in T-cells.

scholarly journals Immune System Dysfunction and Autoimmune Disease in Mice Lacking Emk (Par-1) Protein Kinase

2001 ◽  
Vol 21 (9) ◽  
pp. 3206-3219 ◽  
Author(s):  
Jonathan B. Hurov ◽  
Thaddeus S. Stappenbeck ◽  
Christian M. Zmasek ◽  
Lynn S. White ◽  
Sheila H. Ranganath ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
Protein Kinase ◽  
Autoimmune Disease ◽  
Immune Cell ◽  
Interleukin 4 ◽  
Parotid Glands ◽  
Immune System Dysfunction

ABSTRACT Emk is a serine/threonine protein kinase implicated in regulating polarity, cell cycle progression, and microtubule dynamics. To delineate the role of Emk in development and adult tissues, mice lacking Emk were generated by targeted gene disruption.Emk −/− mice displayed growth retardation and immune cell dysfunction. Although B- and T-cell development were normal, CD4+T cells lacking Emk exhibited a marked upregulation of the memory marker CD44/pgp-1 and produced more gamma interferon and interleukin-4 on stimulation through the T-cell receptor in vitro. In addition, B-cell responses to T-cell-dependent and -independent antigen challenge were altered in vivo. AsEmk −/− animals aged, they developed splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Taken together, these results demonstrate that the Emk protein kinase is essential for maintaining immune system homeostasis and that loss of Emk may contribute to autoimmune disease in mammals.

scholarly journals Lymphocyte Deficiencies Increase Susceptibility to Friend Virus-Induced Erythroleukemia in Fv-2 Genetically Resistant Mice

1999 ◽  
Vol 73 (8) ◽  
pp. 6468-6473 ◽  
Author(s):  
Kim J. Hasenkrug
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
B Cells ◽  
Virus Replication ◽  
Genetic Resistance ◽  
Early Infection ◽  
Virus Spread ◽  
Friend Virus ◽  
Immunological Mechanisms

ABSTRACT The study of genetic resistance to retroviral diseases provides insights into the mechanisms by which organisms overcome potentially lethal infections. Fv-2 resistance to Friend virus-induced erythroleukemia acts through nonimmunological mechanisms to prevent early virus spread, but it does not completely block infection. The current experiments were done to determine whether Fv-2 alone could provide resistance or whether immunological mechanisms were also required to bring infection under control. Fv-2-resistant mice that were CD4+ T-cell deficient were able to restrict early virus replication and spread as well as normalFv-2-resistant mice, but they could not maintain control and developed severe Friend virus-induced splenomegaly and erythroleukemia by 6 to 8 weeks postinfection. Mice deficient in CD8+ T cells and, to a lesser extent, B cells were also susceptible to late Friend virus-induced disease. Thus,Fv-2 resistance does not independently prevent FV-induced erythroleukemia but works in concert with the immune system by limiting early infection long enough to allow virus-specific immunity time to develop and facilitate recovery.

scholarly journals Desensitization with Self-Antigen dsDNA Inhibits B and T-cell Functions by Modulating Treg as Regulator Immune System in Pristane-induced Lupus Mice Model

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Saiful Arifin
Keyword(s):  
Immune System ◽  
T Cell ◽  
Th17 Cells ◽  
Positive Control ◽  
Control Group ◽  
Mice Model ◽  
Cell Functions ◽  
Single Intraperitoneal Injection ◽  
Immune System Regulation ◽  
Self Antigen

The aim of this study was to develop a novel therapeutic method for improving immune system regulation in SLE using escalating dose self-antigen dsDNA immunotherapy. Methods: Female Balb/c mice were given a single intraperitoneal injection of  0.5 ml pristane.. Starting at 12 weeks after injection,. the mice were evaluated for clinical and serological manifestations. Mice with lupus signs (PIL mice) were divided into four groups; positive control group, PIL A (0.01 μg/ml, 0.1 μg/ml, 1 μg/ml ) EDI dsDNA, PIL B (0.1 μg/ml, 1 μg/ml, 10 μg/ml ) EDI dsDNA, and PIL C(1 μg/ml, 10 μg/ml, 100 μg/ml). EDI dsDNA were administered once every week in consecutively. The doses would increase every week. dsDNA were complexed with the cationic polyethylenimine (PEI) before injection. Samples  were analyzed for autoantibodies levels (dsDNA, ANA) and ,TGF-β cytokine  from serum using ELISA and T-Reg, mature dendritic cells  from spleen using flowcytometry.. Results: Escalating dose antigen spesific immunotherapy with self-antigen dsDNA significantly decreased ANA (p=0.02), anti-dsDNA (p=0.03), dendritic cell mature  (p=0.02) compare to positive control, and not significantly decreases Th17 cells (p=0,18) but the result tend to get lower. Desensitization using self-antigen dsDNA was increased T-reg proliferation (p=0.00) and level of TGF-β (p=0.03) significantly compare to positive control. Conclusion: Desensitization using self-antigen dsDNA coupled to PEI was able to modulate T-Reg as a regulator immune respon and inhibit B and T cell functions in lupus mice model.

Peran Beberapa Zat Gizi Mikro Untuk Meningkatkan Sistem Imunitas Tubuh Dalam Pencegahan COVID-19

2021 ◽  
Vol 1 (1) ◽  
pp. 16-23
Author(s):  
Nur Amaliah ◽  
Fery
Keyword(s):  
Candida Albicans ◽  
Immune System ◽  
Vitamin E ◽  
Epithelial Cells ◽  
Vitamin A ◽  
Vitamin C ◽  
The Body ◽  
Ivig Treatment ◽  
Plasma Vitamin ◽  
Tract Infections

Abstract: The emergence of the novel coronavirus in Wuhan, China, wich  causes severe respiratory tract infections in humans (COVID-19), has become a global health concerm. Most coronavirus infect animals but can evolve into strains that can also infect humans. Recently, we showed that intravenous immunoglobin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates evergrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut in association with downregulation of proinflammatory mediators combined with upregulation of anti- inflammatory cytokines. Micronutrients are vitamins and minerals. One of the roles of vitamins and minerals is as an antioxidant that can strengthen the human immune system. The role of vitamin A is more in the maintenance of epithelial cells, which is one of the epithelial cells of the body tissues involved in the non-specific immune system. Vitamin E or α-tocopherol has an important role in erythrocyte membranes and plasma lipoproteins, they are able to maintain the integrity of the cell  membrane because vitamin E has a phenol ring capable of providing hydrogen ions to free radicals. Vitamin C as an electron donor that can break the chain reaction of Reactive Oxygen Species and Reactive Nitrogen Species. Selenium is a trace mineral that is essential for protein synthesis and enzyme activity of glutathione peroxidase (GSH - PX). Selenium has a role as a catalyst in the breakdown of peroxide produced by the body to become a bond that is not toxic. Therefore, the adequacy of nutrients, especially vitamins and minerals, are necessary in maintaining optimal immune system as a preventive health efforts.   Abstrak: Munculnya coronavirus baru di Wuhan, Cina, yang menyebabkan infeksi saluran pernapasan parah pada manusia (COVID-19), telah menjadi masalah kesehatan global. Sebagian besar virus corona menginfeksi hewan tetapi dapat berevolusi menjadi strain yang juga dapat menginfeksi manusia. Baru-baru ini, kami menunjukkan bahwa pengobatan imunoglobulin intravena (IVIg) mengurangi peradangan sel epitel usus dan menghilangkan pertumbuhan berlebih dari patogen jamur manusia oportunistik Candida albicans di usus murine dalam hubungannya dengan downregulasi mediator proinflamasi yang dikombinasikan dengan upregulasi sitokin anti-inflamasi. Zat gizi mikro adalah vitamin dan mineral. Salah satu peran vitamin dan mineral adalah sebagai antioksidan yang mampu memperkuat sistem daya tahan tubuh manusia (sistem imun). Peran vitamin A banyak pada pemeliharaan sel epitel, dimana sel epitel merupakan salah satu jaringan tubuh yang terlibat di dalam fungsi imunitas non-spesifik. Vitamin E atau α-tokoferol mempunyai peran penting di membran eritrosit dan lipoprotein plasma, vitamin ini mampu mempertahankan integritas membran sel karena vitamin E mempunyai cincin fenol yang mampu memberikan ion hidrogennya kepada radikal bebas. Demikian pula dengan vitamin C sebagai donor elektron sehingga cepat memutus rantai reaksi SOR (Spesies Oksigen Reaktif) dan SNR (Spesies Nitrogen Reaktif). Selenium merupakan mineral kelumit yang penting untuk sintesis protein dan aktivitas enzim glutation peroksidase (GSH-PX). Selenium mempunyai peranan sebagai katalisator dalam pemecahan peroksida yang terbentuk di dalam tubuh menjadi ikatan yang tidak bersifat toksik. Maka karena itu kecukupan zat gizi terutama vitamin dan mineral sangat diperlukan dalam mempertahankan sistem kekebalan tubuh yang  optimal sebagai upaya preventif agar selalu sehat.

scholarly journals A fundamental bimodal role for neuropeptide Y1 receptor in the immune system

2005 ◽  
Vol 202 (11) ◽  
pp. 1527-1538 ◽  
Author(s):  
Julie Wheway ◽  
Charles R. Mackay ◽  
Rebecca A. Newton ◽  
Amanda Sainsbury ◽  
Dana Boey ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Molecular Mechanism ◽  
T Cell Activation ◽  
Negative Regulator ◽  
Interleukin 12 ◽  
Th1 Cell ◽  
Cell Functions ◽  
Y1 Receptor

Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y (NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors (Y1, Y2, Y4, Y5, and y6). Using Y1-deficient (Y1−/−) mice, we showed that Y1−/− T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1−/− mice were resistant to T helper type 1 (Th1) cell–mediated inflammatory responses and showed reduced levels of the Th1 cell–promoting cytokine interleukin 12 and reduced interferon γ production. This defect was due to functionally impaired antigen-presenting cells (APCs), and consequently, Y1−/− mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress-induced immunosuppression.

scholarly journals CRISPR/Cas9-mediated TGFβRII Disruption Enhances Anti-tumor Efficacy of Human Chimeric Antigen Receptor T Cells in Vitro

2021 ◽  
Author(s):  
Khadijeh Alishah ◽  
Matthias Birtel ◽  
Elham Masoumi ◽  
Leila Jafarzadeh ◽  
Hamid Reza Mirzaee ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Solid Tumors ◽  
Target Cells ◽  
Cell Functions ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract Background: CAR T-cell therapy has been recently unveiled as one of the most promising cancer therapies in hematological malignancies. However, solid tumors mount a profound line of defense to escape immunosurveillance by CAR T-cells. Among them, cytokines with an inhibitory impact on the immune system such as IL-10 and TGFβ are of great importance: TGFβ is a pleiotropic cytokine, which potently suppresses the immune system and is secreted by a couple of TME resident and tumor cells. Methods: In this study, we hypothesized that knocking out the TGFβ receptor II gene, could improve CAR T-cell functions in vitro and in vivo. Hereby, we used the CRISPR/Cas9 system, to knockout the TGFβRII gene in T-cells and could monitor the efficient gene knock out by genome analysis techniques. Next, Mesothelin or Claudin 6 specific CAR constructs were overexpressed via IVT-RNA electroporation or retroviral transduction and the poly-functionality of these TGFβRII KO CAR T-cells in terms of proliferation, cytokine secretion and cytotoxicity were assessed and compared with parental CAR T-cells.Results: Our experiments demonstrated that TGFβRII KO CAR T-cells fully retained their capabilities in killing tumor antigen positive target cells and more intriguingly, could resist the anti-proliferative effect of exogenous TGFβ in vitro outperforming wild type CAR T-cells. Noteworthy, no antigen or growth factor-independent proliferation of these TGFβRII KO CAR T-cells has been recorded. TGFβRII KO CAR T-cells also resisted the suppressive effect of induced regulatory T-cells in vitro to a larger extent. Repetitive antigen stimulation demonstrated that these TGFβRII KO CAR T-cells will experience less activation induced exhaustion in comparison to the WT counterpart. Conclusion: The TGFβRII KO approach may become an indispensable tool in immunotherapy of solid tumors, as it may surmount one of the key negative regulatory signaling pathways in T-cells.

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