1,721,076 research outputs found
The tolerant immune system: Biological significance and clinical implications of T cell tolerance
No full textBackground: T cell tolerance both at thymic and peripheral levels is a mechanism of protection finalized to eradicate autoreactive T cell clones and/or to maintain immune homeostasis, especially, postnatally. Central tolerance occurs in the thymic medulla via a mechanism of negative selection which leads to the eradication of autoreactive T cell clones.Mechanisms of Action: Such a tolerogenic event relies on Fas-mediated apoptosis of autoreactive T cell clones operated by thymic dendritic cells (DCs), on the one hand. On the other hand, activated thymic T regulatory (Treg) cells in cooperation with medullary thymic epithelial cells and DCs suppress autoreactive T cell clones. Peripherally, different types of Treg cells exert the so-called peripheral tolerance towards autoreactive T cell clones which may have escaped from negative selection mechanisms. At the same time, peripheral Treg cells activated by tolerogenic DC have anti-inflammatory activities, especially in the intestine towards food and microbial antigens.Drug Targeting: Various natural and dietary products, such as vitamins (A, C, D), lactobacilli and polyphenols will be described for their tolerogenic capacity to attenuate the inflammatory pathway, as observed in preclinical and clinical studies
Impact of heavy metals on host cells: Special focus on nickel-mediated pathologies and novel interventional approaches
No full textBackground: Heavy metals [arsenic, aluminium, cadmium, chromium, cobalt, lead, nickel (Ni), palladium and titanium] are environmental contaminants able to impact with host human cells, thus, leading to severe damage. Objective: In this review, the detrimental effects of several heavy metals on human organs will be discussed and special emphasis will be placed on Ni. In particular, Ni is able to interact with Toll-like receptor-4 on immune and non-immune cells, thus, triggering the cascade of pro-inflammatory cytokines. Then, inflammatory and allergic reactions mediated by Ni will be illustrated within different organs, even including the central nervous system, airways and the gastrointestinal system. Discussion: Different therapeutic strategies have been adopted to mitigate Ni-induced inflammatoryallergic reactions. In this context, the ability of polyphenols to counteract the inflammatory pathway induced by Ni on peripheral blood leukocytes from Ni-sensitized patients will be outlined. In particular, polyphenols are able to decrease serum levels of interleukin (IL)-17, while increasing levels of IL10. These data suggest that the equilibrium between T regulatory cells and T helper 17 cells is recovered with IL-10 acting as an anti-inflammatory cytokine. In the same context, polyphenols reduced elevated serum levels of nitric oxide, thus, expressing their anti-oxidant potential. Finally, the carcinogenic potential of heavy metals, even including Ni, will be highlighted. Conclusion: Heavy metals, particularly Ni, are spread in the environment. Nutritional approaches seem to represent a novel option in the treatment of Ni-induced damage and, among them, polyphenols should be taken into consideration for their anti-oxidant and anti-inflammatory activities
Mast cells as a double-edged sword in immunity: Their function in health and disease. first of two parts
No full textBackground: Mast cells (MCs) have recently been re-interpreted in the context of the immune scenario in the sense that their pro-allergic role is no longer exclusive. In fact, MCs even in steady state conditions maintain homeostatic functions, producing mediators and intensively crosstalking with other immune cells. MCs Function: Here, emphasis will be placed on the array of receptors expressed by MCs and the variety of cytokines they produce. Then, the bulk of data discussed will provide readers with a wealth of information on the dual ability of MCs not only to defend but also to offend the host. This double attitude of MCs relies on many variables, such as their subsets, tissues of residency and type of stimuli ranging from microbes to allergens and food antigens. Interaction with other Cells: Finally, the relationship between MCs with basophils and eosinophils will be discussed
A point of view: The need to identify an antigen in psyconeuroimmunological disorders.
No full textSeveral lines of evidence support a mutual relationship between the nervous system and the immune system. Therefore, it is not surprising that some neuropsychiatric disorders are also characterized by immune abnormalities. In patients with phobic disorders and in patients with migraine without aura some common immune abnormalities have been detected and, in particular, natural immunity deficits, exaggerated release of proinflammatory cytokines and circulating bacterial endotoxins have been found. In other neurological disease, some etiologic factors have been detected as in the case of Guillain-Barre syndrome in which molecular mimicry between Campylobacter jejuni endotoxin and GM1 ganglioside may cause an acute inflammatory polyneuropathy. On the other hand, attempts to identify an antigen have been made in patients with Alzheimer's disease and schizophrenia. Finally, the chronic fatigue syndrome, an old illness in search for an antigen, risk factors and precipitating agents have b..
Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective
No full textCoronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5. With regard to pathogenicity, S proteins are essential for viral entry into host cells. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) , which accounts for complete binding to ACE2. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV. The sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host. Resveratrol (RES) is able to activate sirtuin (Sirt)1. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation. Then, RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols
Sepsis: From historical aspects to novel vistas. Pathogenic and therapeutic considerations
No full textBackground: Sepsis is a clinical condition due to an infectious event which leads to an early hyper-inflammatory phase followed by a status of tolerance or immune paralysis. Hyper-inflammation derives from a massive activation of immune (neutrophils, monocytesimacrophages, dendritic cells and lymphocytes) and non-immune cells (platelets and endothelial cells) in response to Cram-negative and Cram-positive bacteria and fungi.Discussion: A storm of pro-intlammatory cytokines and reactive oxygen species accounts fur the systemic inflammatory response syndrome. In this phase, bacterial clearance may he associated with a scvcrc organ failure development. Tolerance or compensatory anti-inflammatory response syndrome (CARS) depends on the production of anti-inflammatory mediators, such as interleukin-10, secreted by T regulatory cells. However, once triggered. CARS, if prolonged, may also be detrimental to the host, thus reducing bacterial clearance.Conclusion: In this review, the description of pathogenic mechanisms of sepsis is propaedeutic to the illustration of novel therapeutic attempts for the prevention or attenuation of experimental sepsis as well as of clinical trials. In this direction, inhibitors of NF-KB pathway, cell therapy and use of dietary products in sepsis will be described in detail
Mast cells as a double edged sword in immunity: Disorders of mast cell activation and therapeutic management. second of two parts
No full textBackground: Mast cells (MCs) bear many receptors that allow them to respond to a variety of exogenous and endogenous stimuli. However, MC function is dual since they can initiate pathological events or protect the host against infectious challenges. Involvement of Mast Cells in Various Diseases: The role of MCs in disease will be analyzed in a broad sense, describing cellular and molecular mechanisms related to their involvement in autoinflammatory diseases, asthma, autoimmune diseases and cancer. On the other hand, their protective role in the course of bacterial, fungal and parasitic infections will also be illustrated. Therapeutic Approaches: As far as treatment of MC-derived diseases is concerned, allergen immunotherapy as well as other attempts to reduce MC-activation will be outlined according to the recent data. Finally, in agreement with current literature and our own data polyphenols have been demonstrated to attenuate type I allergic reactions and contact dermatitis in response to nickel. The use of polyphenols in these diseases will be discussed also in view of MC involvement
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