'Towards a Conceptual Framework for Innate Immunity'

Innate immunity now occupies a central role in immunology. However, artificial immune system models have largely been inspired by adaptive not innate immunity. This paper reviews the biological principles and properties of innate immunity and, adopting a conceptual framework, asks how these can be incorporated into artificial models. The aim is to outline a meta-framework for models of innate immunity

Intestinal macromolecular transport supporting adaptive immunity

The gastrointestinal tract performs opposing functions of nutrient absorption, barrier maintenance, and the delivery of luminal substances for the appropriate induction of tolerogenic or protective adaptive immunity. The single-layer epithelium lining the gastrointestinal tract is central to each of these functions by facilitating the uptake and processing of nutrients, providing a physical and chemical barrier to potential pathogens, and delivering macromolecular substances to the immune system to initiate adaptive immune responses. Specific transport mechanisms allow nutrient uptake and the delivery of macromolecules to the immune system while maintaining the epithelial barrier. This review examines historical observations supporting macromolecular transport by the intestinal epithelium, recent insights into the transport of luminal macromolecules to promote adaptive immunity, and how this process is regulated to promote appropriate immune responses. Understanding how luminal macromolecules are delivered to the immune system and how this is regulated may provide insight into the pathophysiology of inflammatory diseases of the gastrointestinal tract and potential preventative or therapeutic strategies. Keywords: Antigen Transport, Mucosal Tolerance, Goblet Cell

In the eye of the storm: T cell behavior in the inflammatory microenvironment.

Coordinated unfolding of innate and adaptive immunity is key to the development of protective immune responses. This functional integration occurs within the inflamed tissue, a microenvironment enriched with factors released by innate and subsequently adaptive immune cells and the injured tissue itself. T lymphocytes are key players in the ensuing adaptive immunity and their proper function is instrumental to a successful outcome of immune protection. The site of inflammation is a "harsh" environment in which T cells are exposed to numerous factors that might influence their behavior. Low pH and oxygen concentration, high lactate and organic acid content as well as free fatty acids and reactive oxygen species are found in the inflammatory microenvironment. All these components affect T cells as well as other immune cells during the immune response and impact on the development of chronic inflammation. We here overview the effects of a number of factors present in the inflammatory microenvironment on T cell function and migration and discuss the potential relevance of these components as targets for therapeutic intervention in autoimmune and chronic inflammatory diseases

Livestock abundance predicts vampire bat demography, immune profiles, and bacterial infection risk

Human activities create novel food resources that can alter wildlife–pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria. We predicted that abundant livestock could reduce starvation and foraging effort, allowing for greater investments in immunity. Bats from high-livestock sites had higher microbicidal activity and proportions of neutrophils but lower immunoglobulin G and proportions of lymphocytes, suggesting more investment in innate relative to adaptive immunity and either greater chronic stress or pathogen exposure. This relationship was most pronounced in reproductive bats, which were also more common in high-livestock sites, suggesting feedbacks between demographic correlates of provisioning and immunity. Infection with both Bartonella and haemoplasmas were correlated with similar immune profiles, and both pathogens tended to be less prevalent in high-livestock sites, although effects were weaker for haemoplasmas. These differing responses to provisioning might therefore reflect distinct transmission processes. Predicting how provisioning alters host–pathogen interactions requires considering how both within-host processes and transmission modes respond to resource shifts

Adaptive immunity in cancer immunology and therapeutics.

Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The vast genetic alterations characteristic of tumours produce a number of tumour antigens that enable the immune system to differentiate tumour cells from normal cells. Counter to this, tumour cells have developed mechanisms by which to evade host immunity in their constant quest for growth and survival. Tumour-associated antigens (TAAs) are one of the fundamental triggers of the immune response. They are important because they activate, via major histocompatibility complex (MHC), the T cell response, an important line of defense against tumourigenesis. However, the persistence of tumours despite host immunity implies that tumour cells develop immune avoidance. An example of this is the up-regulation of inhibitory immune checkpoint proteins, by tumours, which induces a form of self-tolerance. The majority of monoclonal antibodies in clinical practice have been developed to target tumour-specific antigens. More recently there has been research in the down-regulation of immune checkpoint proteins as a way of increasing anti-tumour immunity

Molecular Mechanisms Used by Salmonella to Evade the Immune System

Human and animal pathogens are able to circumvent, at least temporarily, the sophisticated immune defenses of their hosts. Several serovars of the Gram-negative bacterium Salmonella enterica have been used as models for the study of pathogen-host interactions. In this review we discuss the strategies used by Salmonella to evade or manipulate three levels of host immune defenses: physical barriers, innate immunity and adaptive immunity. During its passage through the digestive system, Salmonella has to face the acidic pH of the stomach, bile and antimicrobial peptides in the intestine, as well as the competition with resident microbiota. After host cell invasion, Salmonella manipulates inflammatory pathways and the autophagy process. Finally, Salmonella evades the adaptive immune system by interacting with dendritic cells, and T and B lymphocytes. Mechanisms allowing the establishment of persistent infections are also discussed.European Regional Development Fund SAF2013-46229-R, SAF2016-75365-

Reviewing the effects of food provisioning on wildlife immunity

While urban expansion increasingly encroaches on natural habitats, many wildlife species capitalize on anthropogenic food resources, which have the potential to both positively and negatively influence their responses to infection. Here we examine how food availability and key nutrients have been reported to shape innate and adaptive immunity in wildlife by drawing from field-based studies, as well as captive and food restriction studies with wildlife species. Examples of food provisioning and key nutrients enhancing immune function were seen across the three study type distinctions, as were cases of trace metals and pharmaceuticals impairing the immunity of wildlife species. More generally, food provisioning in field studies tended to increase innate and adaptive responses to certain immune challenges, whereas patterns were less clear in captive studies. Mild food restriction often enhanced, whereas severe food restriction frequently impaired immunity. However, to enable stronger conclusions we stress a need for further research, especially field studies, and highlight the importance of integrating nutritional manipulation, immune challenge, and functional outcomes. Despite current gaps in research on this topic, modern high throughput molecular approaches are increasingly feasible for wildlife studies and offer great opportunities to better understand human influences on wildlife health.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'

Retinoic acid as a modulator of T cell immunity

Indexación: Scopus. DOAJ.Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity.http://www.mdpi.com/2072-6643/8/6/34