Basic concepts of immunology and neuroimmunology

2000 ◽  
Vol 9 (6) ◽  
pp. 1-6 ◽  
Author(s):  
Anil Sehgal ◽  
Mitchel S. Berger
Keyword(s):  
T Cells ◽  
Immune System ◽  
Current Knowledge ◽  
Effective Means ◽  
Lymphatic Vessels ◽  
The Body ◽  
Activated T Cells ◽  
The Central Nervous System ◽  
System Review ◽  
The Brain

The immune system is a complex network of specialized cells and organs that defends the human body against attack from foreign pathogens. The major lymphocytes involved in protecting the body against potential infections are B and T cells, which also play an important role in combating tumor growth. The cells of the immune system patrol the tissues and organs through both blood and lymphatic vessels, but some organs—including cornea, testes, and brain—are usually not patrolled by these cells. The brain has been thought to be an immune-privileged site because of the tight blood–brain barrier (BBB) that protects it. Few cells migrate to the brain under normal circumstances, because the BBB permits only certain molecules to cross into brain tissue. Recently, however, studies have shown that activated T cells exposed to antigen can cross the intact BBB and migrate into brain. This finding opens the path to developing effective means of immunotherapy for lesions of the central nervous system. The authors discuss basic facets of the immune system, review the current knowledge about human neuroimmunology, and survey current strategies for developing immunotherapy-based treatments for human brain tumors.

scholarly journals The Role of Lymphatic Marker Prox-1 in Relation to Brain Tumours

2021 ◽  
Vol 65 (4) ◽  
pp. 72-78
Author(s):  
J. Teleky ◽  
J. Király
Keyword(s):  
Brain Tumours ◽  
Current Knowledge ◽  
Treatment Options ◽  
Lymphatic Vessels ◽  
Homeobox Gene ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
The Central Nervous System ◽  
The Brain

Abstract The homeobox gene, Prox-1 is a transcription factor essential for lymphatic development (lymphangiogenesis) during embryogenesis. It also performs different functions in various tissues such as: retina, lens, liver, pancreas and the central nervous system. Intense expression of Prox-1 has been demonstrated in the developing spinal cord and brain. In adulthood its expression continues in the hippocampus and cerebellum. In adult tissues the process of lymphatic vasculature formation is accompanied under certain pathological conditions such as inflammation, tissue repair and tumour growth. Prox-1 expression is typical for lymphatic vessels; thus it belongs to one of the most specific and widely used mammalian lymphatic endothelial marker in the detection of lymphangiogenesis and lymphatic vessel invasion in oncogenesis. It has been shown that Prox-1 is involved in cancer development and progression. It’s tumour suppressive and oncogenic properties are proven in several human cancers, including brain tumours. Among all body cancers the brain tumours represent the most feared tumours with very limited treatment options and a poor diagnosis. The aim of this paper was to show the current knowledge of the gene Prox-1 with an emphasis on brain tumours, especially in gliomas.

scholarly journals Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells

2019 ◽  
Vol 8 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Alexandra E. Turley ◽  
Joseph W. Zagorski ◽  
Rebekah C. Kennedy ◽  
Robert A. Freeborn ◽  
Jenna K. Bursley ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Low Dose ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Cadmium Exposure ◽  
Activated T Cells ◽  
Low Level

The purpose of this study was to determine the effect of subchronic, oral, low-dose cadmium exposure (32 ppm over 10 weeks) on the rat immune system. We found that cadmium exposure increased the induction of IFNγ and IL-10 in T cells activated ex vivo after cadmium exposure.

scholarly journals Vascular endothelial cell specification in health and disease

Angiogenesis ◽  
2021 ◽  
Author(s):  
Corina Marziano ◽  
Gael Genet ◽  
Karen K. Hirschi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Current Knowledge ◽  
Vascular Malformations ◽  
Immune Surveillance ◽  
Vascular Endothelial Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
The Body ◽  
Vascular Networks

AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

scholarly journals Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

2021 ◽  
Vol 22 (13) ◽  
pp. 6858
Author(s):  
Fanny Gaudel ◽  
Gaëlle Guiraudie-Capraz ◽  
François Féron
Keyword(s):  
G Proteins ◽  
The Body ◽  
Trace Amines ◽  
Chemical Senses ◽  
Brain Areas ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Human Brains ◽  
The Brain ◽  
Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

Introduction

2004 ◽  
Vol 8 (2_suppl) ◽  
pp. 1-2
Author(s):  
Daniel N. Sauder
Keyword(s):  
T Cells ◽  
Immune System ◽  
Ultraviolet A ◽  
Activated T Cells ◽  
Keratinocyte Proliferation ◽  
Memory T Cell ◽  
Immune Mediated ◽  
Selective Targeting ◽  
Traditional Therapies ◽  
Pathogenic Process

Psoriasis is an immune-mediated skin disease in which T cells initiate and maintain the pathogenic process.1 T cells become activated, migrate into the skin, and induce the keratinocyte proliferation associated with the psoriatic phenotype. The activated T cells that infiltrate the skin express the memory phenotype (CD45RO+).2,3 Both CD4+ and CD8+ memory T-cell subtypes are believed to play a role in the pathogenesis of psoriasis. The effectiveness of many traditional therapies for psoriasis (e.g., cyclosporine, methotrexate, psoralen/ultraviolet A light) can be attributed, at least in part, to the potent immunosuppressive effects of these treatments.4,5 Unfortunately, a lack of selective targeting of the immune system by these therapies may result in treatment-limiting side effects.

scholarly journals Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabien Pifferi ◽  
Benoit Laurent ◽  
Mélanie Plourde
Keyword(s):  
Fatty Acids ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Lipid Transport ◽  
Omega 3 ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

scholarly journals Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

2021 ◽  
Author(s):  
Anna H.E. Roukens ◽  
Marion König ◽  
Tim Dalebout ◽  
Tamar Tak ◽  
Shohreh Azimi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Nasal Mucosa ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Upper Airway ◽  
Effector Memory ◽  
Long Term Effects ◽  
Activated T Cells

AbstractThe immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.

The Ouroboros of Inflammatory Signaling to the Brain for the Control of Neuroendocrine Function

2021 ◽  
Author(s):  
Georgia E. Hodes
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Immune Regulation ◽  
The Body ◽  
Immune Disorders ◽  
Inflammatory Signaling ◽  
Late 20Th Century ◽  
Immune Systems ◽  
Neuroendocrine Function ◽  
The Brain

In the late 20th century, the discovery that the immune system and central nervous system were not autonomous revolutionized exploration of the mechanisms by which stress contributes to immune disorders and immune regulation contributes to mental illness. There is increasing evidence of stress as integrated across the brain and body. The immune system acts in concert with the peripheral nervous system to shape the brain’s perception of the environment. The brain in turn communicates with the endocrine and immune systems to guide their responses to that environment. Examining the groundwork of mechanisms governing communication between the body and brain will hopefully provide a better understanding of the ontogeny and symptomology of some mood disorders.

EXTH-82. T CELL HITCHHIKING AS A MECHANISM OF DRUG DELIVERY TO THE BRAIN

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi182-vi182
Author(s):  
Kirit Singh ◽  
Patrick Gedeon ◽  
Teilo Schaller ◽  
David Snyder ◽  
Mustafa Khasraw ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Median Survival ◽  
Mass Spectroscopy ◽  
Ct Imaging ◽  
Spectroscopy Analysis ◽  
Activated T Cells ◽  
Pet Ct ◽  
The Brain ◽  
Mass Spectroscopy Analysis

Abstract INTRODUCTION The blood-brain barrier (BBB) restricts access to the central nervous system (CNS). Our brain bispecific T cell engager (hEGFRvIII:CD3 BRiTE) treats subcutaneous syngeneic tumor (CT2AvIII) but not intracranial CT2AvIII. CD3 engaging molecules such as nanoparticles can be carried into the brain by binding to activated T cells. We therefore sought to determine if co-administration of larger molecules (BRiTE, approx. 55kDa) with activated T cells could cross the BBB, enhancing survival. METHODS We implanted 8–10-week-old transgenic hCD3 mice (n=7-8 per group) with 30,000 CT2AvIII cells. Tumors were established for 6 days. Mice were administered either (1) autologous lymphocyte transfer (ALT) alone (single intravenous (IV) injection, 1 x 107 activated T cells), (2) serial IV BRiTE doses (50ug, 10 days) (3) BRiTE and ALT or (4) no treatment. Mice were followed for survival using Kaplan-Meier curves and compared via log rank test. Targeted mass spectroscopy analysis as well as PET/CT imaging of mice administered Iodine-124 radiolabelled BRiTE was performed to assess for intracranial accumulation. RESULTS Mice who received BRiTE and ALT demonstrated significantly enhanced survival compared to controls (median survival 29 vs 21 days, p=0.0135). Mice who received only BRiTE or ALT exhibited median survival comparable to controls (p=0.192, p=0.944 respectively). Mass spectroscopy analysis revealed that mice had a 7-fold increased peak area ratio of BRiTE in the CNS when co-treated with activated T cells compared to BRiTE alone (0.14, 0.02 respectively) while PET/CT imaging demonstrated increased radioactive signal over background localized to coordinates within the brain where tumors were injected. CONCLUSIONS Giving activated T cells alongside BRiTE allows better access to the intracranial compartment and is required to achieve efficacy in mice with syngeneic orthotopic glioma. Future work will determine the optimal dose and schedule for this approach, as well as defining the precise mechanism by which this occurs.

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