Evolution of JAK-STAT pathway components : mechanisms and role in immune system development

Background
Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK) – Signal transducer and activator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a diverse range of organisms.

Results
Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components.

Conclusion
Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

Malicious code detection architecture inspired by human immune system

Malicious code is a threat to computer systems globally. In this paper, we outline the evolution of malicious code attacks. The threat is evolving, leaving challenges for attackers to improve attack techniques and for researchers and security specialists to improve detection accuracy. We present a novel architecture for an effective defense against malicious code attack, inspired by the human immune system. We introduce two phases of program execution: Adolescent and Mature Phase. The first phase uses a malware profile matching mechanism, whereas the second phase uses a program profile matching mechanism. Both mechanisms are analogous to the innate immune system

Impact of nest sanitation on the immune system of parents and nestlings in a passerine bird

Bacterial communities are thought to have fundamental effects on the growth and development of nestling birds. The antigen exposure hypothesis suggests that, for both nestlings and adult birds, exposure to a diverse range of bacteria would select for stronger immune defences. However, there are relatively few studies that have tested the immune/bacterial relationships outside of domestic poultry. We therefore sought to examine indices of immunity (microbial killing ability in naïve birds, which is a measure of innate immunity and the antibody response to sheep red blood cells, which measures adaptive immunity) in both adult and nestling zebra finches (Taeniopygia guttata). We did this throughout breeding and between reproductive attempts in nests that were experimentally manipulated to change the intensity of bacterial exposure. Our results suggest that nest sanitation and bacterial load affected measures of the adaptive immune system, but not the innate immune parameters tested. Adult finches breeding in clean nests had a lower primary antibody response to sheep red blood cells (SRBC), particularly males, and a greater difference between primary and secondary responses. Adult microbial killing of E.coli decreased as parents moved from incubation to nestling rearing for both nest treatments; however, killing of C.albicans remained consistent throughout. In nestlings, both innate microbial killing and the adaptive antibody response did not differ between nest environments. Together, these results suggest that the exposure to microorganisms in the environment affect the adaptive immune system in nesting birds, with exposure upregulating the antibody response in adult birds.

An immune network approach for web document clustering

The human immune system provides inspiration for solving a wide range of innovative problems. In this paper, we propse an immune network based approach for web document clustering. All the immune cells in the network competitively recognize the antigens (web documents) which are presented to the network one by one. The interaction between immune cells and an antigen leads to an augment of the network through the clonal selection and somatic mutation of the stimulated immune cells, while the interaction among immune cells results in a network compression. The structure of the immune network is well maintained by learning and self-regularity. We use a public web document data set to test the effectiveness of our method and compare it with other approaches. The experimental results demonstrate that the most striking advantage of immune-based data clustering is its adaptation in dynamic environment and the capability of finding new clusters automatically.

Learning to detect texture objects by artificial immune approaches

This paper introduces a novel method to detect texture objects from satellite images. First, a hierarchical strategy is developed to extract texture objects according to their roughness. Then, an artificial immune approach is presented to automatically generate segmentation thresholds and texture filters, which are used in the hierarchical strategy. In this approach, texture objects are regarded as antigens, and texture object filters and segmentation thresholds are regarded as antibodies. The clonal selection algorithm inspired by human immune system is employed to evolve antibodies. The population of antibodies is iteratively evaluated according to a statistical performance index corresponding to object detection ability, and evolves into the optimal antibody using the evolution principles of the clonal selection. Experimental results of texture object detection on satellite images are presented to illustrate the merit and feasibility of the proposed method.

Using immune genetic algorithm to optimize the reactive power

A novel algorithm, immune genetic algorithm (IGA) is proposed for reactive power optimization of power system. While retaining excellent characteristics of genetic algorithm (GA), through imitating the biological immune system, the algorithm evaluates and selects the optimal solutions by the affinities between antigens and antibodies. With the regulation of the activating and suppressing of antibodies, IGA can achieve the dynamic balance between individual diversity and population convergence, and avoid getting into the local optimal solution. The proposed IGA is applied to the IEEE 30-bus system, and the results show that it is superior to the GA with good population convergence and fast computing speed.

Effect of zinc supplementation on the immune status of healthy older individuals aged 55–70 years : the ZENITH Study

Aging is associated with alterations in the immune system, effects which may be exacerbated by inadequate zinc (Zn) status. We examined the relationship between Zn status and markers of immunity and the effect of supplementation with 15 mg or 30 mg Zn/d for 6 months on immune status in healthy individuals. Zn status was assessed by dietary intake and biochemical indices. Immune status was assessed by multiple flow cytometric methods. At baseline, Zn concentration was positively associated with lymphocyte subpopulation counts and T-lymphocyte activation. Zn supplementation of 30 mg/d significantly lowered B-lymphocyte count, albeit at month 3 only. Lower doses of Zn (15 mg Zn/d) significantly increased the ratio of CD4 to CD8 T lymphocytes at month 6. Overall, these findings suggest that total Zn intake (diet plus supplementation) of up to 40 mg Zn/d do not have significant long-term effects on immune status in apparently healthy persons aged 55–70 years.

Optimal immune responses : immunocompetence revisited

The function of the immune system of an animal is to provide defence against infection, in order to maximize fitness. Understanding this and, particularly, how limiting resources are traded off between costly immune responses and other physiological demands, is central to properly understanding life-history traits and their evolution. Here, we propose that functional (rather than immunological) measures of immune responses should be used when investigating this. We further suggest that optimal immune responses are context specific, rather than generic; that is, a maximum immune response is not necessarily optimal. The nature of an optimal immune response will depend on the specific circumstances and infection status of the animal. Identifying and understanding such optimality requires that the effects of different immune strategies on fitness be considered.

The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response

The immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birdsʼ humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.

Hospital malnutrition : prevalence, identification and impact on patients and the healthcare system

Malnutrition is a debilitating and highly prevalent condition in the acute hospital setting, with Australian and international studies reporting rates of approximately 40%. Malnutrition is associated with many adverse outcomes including depression of the immune system, impaired wound healing, muscle wasting, longer lengths of hospital stay, higher treatment costs and increased mortality. Referral rates for dietetic assessment and treatment of malnourished patients have proven to be suboptimal, thereby increasing the likelihood of developing such aforementioned complications. Nutrition risk screening using a validated tool is a simple technique to rapidly identify patients at risk of malnutrition, and provides a basis for prompt dietetic referrals. In Australia, nutrition screening upon hospital admission is not mandatory, which is of concern knowing that malnutrition remains under-reported and often poorly documented. Unidentified malnutrition not only heightens the risk of adverse complications for patients, but can potentially result in foregone reimbursements to the hospital through casemix-based funding schemes. It is strongly recommended that mandatory nutrition screening be widely adopted in line with published best-practice guidelines to effectively target and reduce the incidence of hospital malnutrition.

Functional similarities between pigeon 'milk' and mammalian milk : induction of immune gene expression and modification of the microbiota

Pigeon ‘milk’ and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon ‘milk’. Therefore, using a chicken model, we investigated the effect of pigeon ‘milk’ on immune gene expression in the Gut Associated Lymphoid Tissue (GALT) and on the composition of the caecal microbiota. Chickens fed pigeon ‘milk’ had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon ‘milk’-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon ‘milk’-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon ‘milk’, as well as being directly seeded by bacteria present in pigeon ‘milk’. Our results demonstrate that pigeon ‘milk’ has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon ‘lactation’ and mammalian lactation evolved independently but resulted in similarly functional products.

The Glutathione System: a new drug target in neuroimmune disorders

Glutathione (GSH) has a crucial role in cellular signaling and antioxidant defenses either by reacting directly with reactive oxygen or nitrogen species or by acting as an essential cofactor for GSH S-transferases and glutathione peroxidases. GSH acting in concert with its dependent enzymes, known as the glutathione system, is responsible for the detoxification of reactive oxygen and nitrogen species (ROS/RNS) and electrophiles produced by xenobiotics. Adequate levels of GSH are essential for the optimal functioning of the immune system in general and T cell activation and differentiation in particular. GSH is a ubiquitous regulator of the cell cycle per se. GSH also has crucial functions in the brain as an antioxidant, neuromodulator, neurotransmitter, and enabler of neuron survival. Depletion of GSH leads to exacerbation of damage by oxidative and nitrosative stress; hypernitrosylation; increased levels of proinflammatory mediators and inflammatory potential; dysfunctions of intracellular signaling networks, e.g., p53, nuclear factor-κB, and Janus kinases; decreased cell proliferation and DNA synthesis; inactivation of complex I of the electron transport chain; activation of cytochrome c and the apoptotic machinery; blockade of the methionine cycle; and compromised epigenetic regulation of gene expression. As such, GSH depletion has marked consequences for the homeostatic control of the immune system, oxidative and nitrosative stress (O&NS) pathways, regulation of energy production, and mitochondrial survival as well. GSH depletion and concomitant increase in O&NS and mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson’s disease, suggesting that depleted GSH is an integral part of these diseases. Therapeutical interventions that aim to increase GSH concentrations in vivo include N-acetyl cysteine; Nrf-2 activation via hyperbaric oxygen therapy; dimethyl fumarate; phytochemicals, including curcumin, resveratrol, and cinnamon; and folate supplementation.

Immune-microbiota interactions: dysbiosis as a global health issue

Throughout evolution, microbial genes and metabolites have become integral to virtually all aspects of host physiology, metabolism and even behaviour. New technologies are revealing sophisticated ways in which microbial communities interface with the immune system, and how modern environmental changes may be contributing to the rapid rise of inflammatory noncommunicable diseases (NCDs) through declining biodiversity. The implications of the microbiome extend to virtually every branch of medicine, biopsychosocial and environmental sciences. Similarly, the impact of changes at the immune-microbiota interface are directly relevant to broader discussions concerning rapid urbanization, antibiotics, agricultural practices, environmental pollutants, highly processed foods/beverages and socioeconomic disparities--all implicated in the NCD pandemic. Here, we make the argument that dysbiosis (life in distress) is ongoing at a micro- and macro-scale and that as a central conduit of health and disease, the immune system and its interface with microbiota is a critical target in overcoming the health challenges of the twenty-first century.

Applying both positive and negative selection to supervised learning for anomaly detection

This paper presents a novel approach of applying both positive selection and negative selection to supervised learning for anomaly detection. It first learns the patterns of the normal class via co-evolutionary genetic algorithm, which is inspired from the positive selection, and then generates synthetic samples of the anomaly class, which is based on the negative selection in the immune system. Two algorithms about synthetic generation of the anomaly class are proposed. One deals with data sets containing a few anomalous samples; while the other deals with data sets containing no anomalous samples at all. The experimental results on some benchmark data sets from UCI data set repertory show that the detection rate is improved evidently, accompanied by a slight increase in false alarm rate via introducing novel synthetic samples of the anomaly class. The advantages of our method are the increased ability of classifiers in identifying both previously known and innovative anomalies, and the maximal degradation of overfitting phenomenon.