1,721,043 research outputs found
Microbial antigenic pressure and evolution of the immune response: toward a better understanding of the human immune system in health and disease and therapeutic interventions
No full textThe continuous antigenic triggering has greatly contributed to the evolution of the immune system and, therefore, animals have developed cells able to cope with a broad variety of microbial antigens and or their toxins, e.g., endotoxins. At the same time, intestinal commensals have evolved along with human progress and introduction of new foods, thus empowering both regional and systemic immune response. In this review, some important steps in the evolution of the immune system will be analyzed such as organization of lymphoid organs, formation of germinal centers, leukocyte attraction to tissue, function of Toll like receptors and role of antimicrobial peptides. In particular, the major phylogenetic acquisitions of living organisms in the assessment of the immune machinery will be emphasized. Finally, fish will be taken into consideration as animal models of human diseases also in view of drug design strategies. Special attention will be focused on vaccinated salmon and zebrafish model
Anti-inflammatory and anti-allergic properties of donkey's and goat's milk.
No full textNowadays, donkey's and goat's milk consumption has been reevaluated for its potential benefits to human health. For example, in infants with intolerance to cow's milk, donkey's milk represents a good alternative due to its chemical characteristics similar to those of human milk. On the other hand, goat's milk in virtue of its higher content in short chain, medium chain, mono and polyunsaturated fatty acids than that of cow's milk, is more digestible than the bovine counterpart. From an immunological point of view, donkey's milk is able to induce release of inflammatory and anti-inflammatory cytokines from normal human peripheral blood lymphomononuclear cells, thus maintaining a condition of immune homeostasis. Similarly, goat's milk has been shown to trigger innate and adaptive immune responses in an in vitro human system, also inhibiting the endotoxin-induced activation of monocytes. Finally, in these milks the presence of their own microbiota may normalize the human intestinal microbiota with a cascade of protective effects at intestinal mucosal sites, even including triggering of intestinal T regulatory cells. In the light of the above considerations, donkey's and goat's milk should be recommended as a dietary supplement in individuals with inflammatory and allergic conditions, even including elderly people
The new era of nutraceuticals: Beneficial effects of polyphenols in various experimental and clinical settings
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Update on Mechanisms of Adaptive Resistance to Immune Check Point Blockers in Malignancies: A Short Commentary
No full textNo abstract availabl
The Impact of Bacterial Lipolysaccharides on the Endothelial System: Pathological Consequences and Therapeutic Countermeasures.
No full textEndothelial cells (ECs) express on their membrane Toll like receptor (TLR)-4 and, therefore, are able to interact with lipopolysaccharides (LPS) or endotoxins, major constituents of the Gram-negative bacteria outer membrane. The impact of LPS on ECs can be either direct or mediated via release of cytokines and/or chemokines originated from monocytes/macrophages. In this review, the effect of the interaction between LPS and ECs on the outcome of various human diseases such as preeclampsia, hereditary haemorrhagic teleangiectasia, atherosclerosis and sepsis will be illustrated. Finally, the major therapeutic attempts aimed at neutralizing LPS and, therefore, their influence on ECs will be discusse
Mechanisms of neutrophil-mediated disease: innovative therapeutic interventions
No full textOver recent years, neutrophil functions have extensively been reevaluted. For instance, it has been found that extracellular traps generated by activated neutrophils are able to perform a very effective antimicrobial activity against a plethora of microorganisms. In addition, neutrophils possess the ability to interact with monocytes/macrophages either via release of their granule content or via efferocytosis. Efferocytosis is based on neutrophil clearance by macrophages, which, in turn, exert pro- or antinflammatory effects. Furthermore, alarmins released by neutrophils have been shown to mobilize and activate dendritic cells as well as macrophages for antigen-presentation to occur. Finally, other researchers have demonstrated that neutrophils act as suppressor cells by deprivation of arginine in T cells. From a clinical point of view, it is well known that neutrophils are present as activated effector cells in a number of diseases such as infectious disease, sepsis, autoimmune disease, cardiovascular disease and tumors. They play pro-inflammatory and angiogenetic effects in some cases, while in other cases they depress host immune response. In this review, also emphasis will be placed on neutrophil functional deficits which seem to participate to the pathogenesis of various diseases, e.g., viral hepatitis C infection and inflammatory bowel disease. Finally, novel therapeutic measures able to modulate neutrophil functions will be described with special reference to both immune agents and natural product
The Interleukin-17/Interleukin-22 Innate Axis in the Gut as a New Drug Target in Allergic-Inflammatory and Autoimmune Diseases. A Working Hypothesis.
No full textThe innate lymphoid cells (ILCs) have been grouped into three main categories: ILC1s [T helper (h)1-like cells], ILC2s (Th2-like cells) and ILC3s (Th17-like cells), respectively. In particular, ILC3s are responsible for the secretion of both interleukin (IL)-17 and IL-22, which play either protective (antimicrobial and repairing activities) or harmful (inflammation and tumor growth) roles into the host. Here, some putative interventional studies will be hypothesized, taking into account that activation of innate cell receptors, arylhydrocarbon receptor and gut microbiota, respectively, contribute to both differentiation and function of ILC3s. A series of biological and natural compounds may represent putative regulators of these cells in the gut. In this respect, the modulating effects of agonist and antagonists of Toll-like receptors and nucleotide binding oligomerization domain-like receptors, polyphenols and probiotics will be described in detail
The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis.
No full textGut immune system is daily exposed to a plethora of antigens contained in the environment as well as in food. Both secondary lymphoid tissue, such as Peyer's patches, and lymphoid follicles (tertiary lymphoid tissue) are able to respond to antigenic stimuli releasing cytokines or producing antibodies (secretory IgA). Intestinal epithelial cells are in close cooperation with intraepithelial lymphocytes and possess Toll-like receptors on their surface and Nod-like receptors (NLRs) which sense pathogens or pathogen-associated molecular patterns. Intestinal microbiota, mainly composed of Bacteroidetes and Firmicutes, generates tolerogenic response acting on gut dendritic cells and inhibiting the T helper (h)-17 cell anti-inflammatory pathway. This is the case of Bacteroides fragilis which leads to the production of interleukin-10, an anti-inflammatory cytokine, from both T regulatory cells and lamina propria macrophages. Conversely, segmented filamentous bacteria rather induce Th17 cells, thus promoting intestinal inflammation. Intestinal microbiota and its toxic components have been shown to act on both Nod1 and Nod2 receptors and their defective signaling accounts for the development of inflammatory bowel disease (IBD). In IBD a loss of normal tolerance to intestinal microbiota seems to be the main trigger of mucosal damage. In addition, intestinal microbiota thanks to its regulatory function of gut immune response can prevent or retard neoplastic growth. In fact, chronic exposure to environmental microorganisms seems to be associated with low frequency of cancer risk. Major nutraceuticals or functional foods employed in the modulation of intestinal microbiota are represented by prebiotics, probiotics, polyunsaturated fatty acids, amino acids and polyphenols. The cellular and molecular effects performed by these natural products in terms of modulation of the intestinal microbiota and mostly attenuation of the inflammatory pathway are described
Disorders of Innate Immunity in Human ageing and effects of Nutraceutical Administration
No full textImmune decline with ageing accounts for the increased risk of infections, inflammatory chronic disease,
autoimmunity and cancer in humans. Both innate and adaptive immune functions are compromised in aged people and,
therefore, attempts to correct these dysfunctions represent a major goal of modern medicine. In this review, special
emphasis will be placed on the aged innate immunity with special reference to polymorphonuclear cell, monocyte/
macrophage, dendritic cell and natural killer cell functions. As potential modifiers of the impaired innate immunity, some
principal nutraceuticals will be illustrated, such as micronutrients, pre-probiotics and polyphenols. In elderly, clinical trials
with the above products are scanty, however, some encouraging effects on the recovery of innate immune cells have been
reported. In addition, our own results obtained with symbiotics and polyphenols extracted from red wine or fermented
grape marc suggest the potential ability of these substances to modulate the innate immune response in ageing, thus
reducing the inflammaging which characterizes immune senescence
Immunity to Tuberculosis and Novel Therapeutic Strategies
No full textBoth innate and adaptive immunity is involved in the cellular immune response against Mycobacterium tuberculosis (Mtb). Alveolar macrophages (Mθ) actively participate to the engulfment and killing of Mtb, while dendritic cells (DCs) act as antigen presenting cells. Also, neutrophils and natural killer cells protect the host against Mtb. Adaptive immunity is based on the DC-mediated activation of Th1 cells, that produce interferon-γ and enhance the microbicidal activity
of Mθ. Moreover, T regulatory (Treg) and Th17 cells seem to play antithetic roles in which the former are able to exert anti-inflammatory functions and the latter contribute to the exacerbation of inflammation. Despite such a defensive armamentarium, Mtb has been shown to escape from the host immunity adopting different strategies. Intradermal vaccination with Bacille Calmette Guerin (BCG) has been replaced by the intranasal route using viral-vectored tuberculosis (TB) vaccines which better boost BCG immunization. Also, Mtb filtrate proteins, mucosal adjuvants and IgA monoclonal antibodies
have been experimented in the immunotherapy against TB. Vitamin D has been shown to be protective in the course of TB in view of its receptors present on Mθ and Treg cells. Finally, polyphenols have been demonstrated to restore Mtb mediated depression of Mθ function as well as to directly act on Mtb, thus arresting its growth. From our own studies with red grape polyphenols, it emerges that these compounds may support Th1 responses, especially in elderly patients, also exerting Treg cell-mediated anti-inflammatory activity via IL-10 release. Therefore, polyphenol supplementation may contribute to reinforce anti-Mtb defences and mitigate excessive inflammation
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