Toll like receptors play a role in general immunity, eye infection and inflammation : TLRs for nanodelivery

Dendritic cells [DCs] are potent antigen presenting cells [APC], which plays a vital role in immune system by detecting and capturing pathogens in the body. DCs perform a pivotal role in induction of T cell response. Regulation of immune response can be achieved by specific antigen [Ag] delivery to DCs. A delivery system that can efficiently target and present Ags to DCs for the purpose of anti-tumour activity is currently a topic of significant research interest. DCs are receiving attention due to their key role in anti cancer host response and due to their adjuvanic property in tumour vaccines. Role of toll like receptors [TLR] in innate immune system and their part in eventual stimulation of adaptive immunity is exploited to develop vaccines. TLR agonists in conjugation with vaccines are shown to increase therapeutic efficacy in some cases. TLRs also play a vital role in protecting the cornea from invading pathogens. Due to adverse effects in the treatment of ocular inflammations, cancer and in viral infections, an alternate approach such as the use of TLRs will solve the inquisitive question regarding side effects. The intended delivery is attained by the use of nanoparticles which in turn leads to prolonged half-life in the body. Co-delivery of Ags, TLRs and immunomodulators using nanoparticles has been demonstrated to elicit potent cellular immune responses and are currently under development of clinically applicable immunisations and vaccines.

An immunological approach to raising alarms in video surveillance

Inspired by the human immune system, and in particular the negative selection algorithm, we propose a learning mechanism that enables the detection of abnormal activities. Three detectors for detecting abnormal activity are generated using negative selection. Tracks gathered by people’s movements in a room are used for experimentation and results have shown that the classifier is able to discriminate abnormal from normal activities in terms of both trajectory and time spent at a location.

Effect of selenium-saturated bovine lactoferrin (Se-bLF) on antioxidant enzyme activities in human gut epithelial cells under oxidative stress

Cancer and many chronic inflammatory diseases are associated with increased amounts of reactive oxygen species (ROS). The potential cellular and tissue damage created by ROS has significant impact on many disease and cancer states and natural therapeutics are becoming essential in regulating altered redox states. We have shown recently that iron content is a critical determinant in the antitumour activity of bovine milk lactoferrin (bLF). We found that 100% iron-saturated bLF (Fe-bLF) acts as a potent natural adjuvant and fortifying agent for augmenting cancer chemotherapy and thus has a broad utility in the treatment of cancer. Furthermore, we also studied the effects of iron saturated bLF's ability as an antioxidant in the human epithelial colon cancer cell line HT29, giving insights into the potential of bLF in its different states. Thus, metal saturated bLF could be implemented as anti-cancer neutraceutical. In this regard, we have recently been able to prepare a selenium (Se) saturated form of bLF, being up to 98% saturated. Therefore, the objectives of this study were to determine how oxidative stress induced by hydrogen peroxide (H₂O₂) alters antioxidant enzyme activity within HT29 epithelial colon cancer cells, and observe changes in this activity by treatments with different antioxidants ascorbic acid (AA), Apo (iron free)-bLF and selenium (Se)-bLF. The states of all antioxidant enzymes (glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GsT), catalase and superoxide dismutase (SOD)) demonstrated high levels within untreated HT29 cells compared to the majority of other treatments being used, even prior to H₂O₂ exposure. All enzymes showed significant alterations in activity when cells were treated with antioxidants AA, Apo-bLF or Se-bLF, with and/or without H₂O₂ exposure. Obvious indications that the Se content of the bLF potentially interacted with the glutathione (GSH)/GPx/GR/GsT associated redox system could be observed immediately, showing capability of Se-bLF being highly beneficial in helping to maintain a balance between the oxidant/antioxidant systems within cells and tissues, especially in selenium deficient systems. In conclusion, the antioxidative defence activity of Se-bLf, investigated in this study for the first time, shows dynamic adaptations that may allow for essential protection from the imbalanced oxidative conditions. Because of its lack of toxicity and the availability of both selenium and bLF in whole milk, Se-bLF offers a promise for a prospective natural dietary supplement, in addition to being an immune system enhancement, or a potential chemopreventive agent for cancers.

An immunological approach to raising alarms in video surveillance

Inspired by the human immune system, and in particular the negative selection algorithm, we propose a learning mechanism that enables the detection of abnormal activities. Three types of detectors for detecting abnormal activity are developed using negative selection. Tracks gathered by people's movements in a room are used for experimentation and results have shown that the classifier is able to discriminate abnormal from normal activities in terms of both trajectory and time spent at a location.

Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction

Background: Contact hypersensitivity (CS) reaction in the skin is T-cell mediated immune reaction which plays a major role in the pathogenesis and chronicity of various inflammatory skin disorders and, like other delayed-type hypersensitivity (DTH) reactions, affords immunity against tumor cells and microbes. CS response is a self-limiting reaction, and interleukin (IL)-10 is considered to be a natural suppressant of cutaneous inflammatory response. Recently, it has been demonstrated that major depression is related to activation of the inflammatory response and elevation of some parameters of cell-mediated immunity. It has been suggested that such activation of the immune system may play a role in etiology of depression. If this immunoactivation is involved in etiology of depression, one would expect that antidepressant agents may have negative immunoregulatory effects. To the best of our knowledge, the effect of antidepressants on contact hypersensitivity has not been studied.

Methods: The aim of the present study was to establish the effect of prolonged desipramine or fluoxetine treatment on CS reaction to picryl chloride.

Results: Antidepressants significantly suppressed CS reaction, fluoxetine by 53% whereas desipramine by 47% compared to positive control. Moreover, desipramine and fluoxetine decreased relative weight of auxillary lymph nodes. Desipramine decreased also relative weight of inguinal lymph nodes and spleens whereas desipramine and fluoxetine increased production of IL-10 in comparison to positive control.

Conclusion: The observed effect of antidepressant drugs on CS reaction is consistent with the hypothesis that T-cell mediated immunity is targeted by antidepressants.

Personality and the emergence of the pace-of-life syndrome concept at the population level

The pace-of-life syndrome (POLS) hypothesis specifies that closely related species or populations experiencing different ecological conditions should differ in a suite of metabolic, hormonal and immunity traits that have coevolved with the life-history particularities related to these conditions. Surprisingly, two important dimensions of the POLS concept have been neglected: (i) despite increasing evidence for numerous connections between behavioural, physiological and life-history traits, behaviours have rarely been considered in the POLS yet; (ii) the POLS could easily be applied to the study of covariation among traits between individuals within a population. In this paper, we propose that consistent behavioural differences among individuals, or personality, covary with life history and physiological differences at the within-population, interpopulation and interspecific levels. We discuss how the POLS provides a heuristic framework in which personality studies can be integrated to address how variation in personality traits is maintained within populations.

Recent advances in immunology to target cancer, inflammation and infections

Immunology is the branch of biomedical sciences to study of the immune system physiology both in healthy and diseased states. Some aspects of autoimmunity draws our attention to the fact that it is not always associated with pathology. For instance, autoimmune reactions are highly useful in clearing off the excess, unwanted or aged tissues from the body. Also, generation of autoimmunity occurs after the exposure to the non-self antigen that is structurally similar to the self, aided by the stimulatory molecules like the cytokines. Thus, a narrow margin differentiates immunity from auto-immunity as already discussed. Hence, finding answers for how the physiologic immunity turns to pathologic autoimmunity always remains a question of intense interest. However, this margin could be cut down only if the physiology of the immune system is better understood. The individual chapters included in this book will cover all the possible aspects of immunology and pathologies associated with it. The authors have taken strenuous effort in elaborating the concepts that are lucid and will be of reader's interest.

A novel model of sensitization and oral tolerance to peanut protein

The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens.

Identification of natural killer cell receptor genes in the genome of the marsupial Tasmanian devil (Sarcophilus harrisii)

Within the mammalian immune system, natural killer (NK) cells contribute to the first line of defence against infectious agents and tumours. Their activity is regulated, in part, by cell surface NK cell receptors. NK receptors can be divided into two unrelated, but functionally analogous superfamilies based on the structure of their extracellular ligand-binding domains. Receptors belonging to the C-type lectin superfamily are predominantly encoded in the natural killer complex (NKC), while receptors belonging to the immunoglobulin superfamily are predominantly encoded in the leukocyte receptor complex (LRC). Natural killer cell receptors are emerging as a rapidly evolving gene family which can display significant intra- and interspecific variation. To date, most studies have focused on eutherian mammals, with significantly less known about the evolution of these receptors in marsupials. Here, we describe the identification of 43 immunoglobulin domain-containing LRC genes in the genome of the Tasmanian devil (Sarcophilus harrisii), the largest remaining marsupial carnivore and only the second marsupial species to be studied. We also identify orthologs of NKC genesKLRK1, CD69, CLEC4E, CLEC1B, CLEC1A and an ortholog of an opossum NKC receptor. Characterisation of these regions in a second, distantly related marsupial provides new insights into the dynamic evolutionary histories of these receptors in mammals. Understanding the functional role of these genes is also important for the development of therapeutic agents against Devil Facial Tumour Disease, a contagious cancer that threatens the Tasmanian devil with extinction.

Future health implications of prenatal and early-life vitamin D status

Current or recent low vitamin D status (or proxy measures such as dietary intake or ambient ultraviolet radiation) is linked to several chronic diseases, including osteoporosis, cancers, and cardiovascular and autoimmune diseases. Low prenatal vitamin D status may also increase susceptibility to such diseases in later life via specific target organ effects and/or through changes to the developing immune system. Maternal vitamin D supplementation during pregnancy could be an important public health measure to decrease risk of a range of chronic diseases, but further research is required to clarify beneficial and adverse effects of high prenatal vitamin D.

Characterisation of an ancient S100 protein with multiple functions

 This project focused on the novel S100A19 protein, expressed exclusively in marsupials and monotremes, identifying it as an important component of the innate immune system. Data showed that S100A19 is differentially regulated in the pouch and mammary gland of the wallaby to protect the infant when most susceptible to infection.

The gut microbiome and diet in psychiatry: focus on depression.

With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. A rapidly emerging field of research suggests that the microbiome-gut-brain axis is of substantial relevance to mood and behaviour. Similarly, unhealthy diet has recently emerged as a significant correlate of and risk factor for depression. This review provides evidence for the gut microbiota as a key factor mediating the link between diet and depressive illness.