Ecological and life-history factors influencing the evolution of maternal antibody allocation : a phylogenetic comparison

Maternally derived yolk antibodies provide neonates with immune protection in early life at negligible cost to mothers. However, developmental effects on the neonate's future immunity are potentially costly and thus could limit yolk antibody deposition. The benefits to neonatal immunity must be balanced against costs, which may depend on neonate vulnerability to pathogens, developmental trajectories and the immunological strategies best suited to a species' pace of life. We measured yolk antibodies and life-history features of 23 species of small Neotropical birds and assessed the evidence for each of several hypotheses for life history and ecological effects on the evolution of yolk antibody levels. Developmental period and yolk antibodies are negatively related, which possibly reflect the importance of humoral immune priming through antigen exposure, and selection to avoid autoimmunity, in species with a slower pace of life. There is also a strong relationship between body size and yolk antibody concentration, suggesting that larger species are architecturally equipped to produce and transfer higher concentrations of antibodies. These results suggest that developmental effects of maternally derived antibodies, such as imprinting effects on B-cell diversity or autoimmune effects, are important and deserve more consideration in future research.

Does timing matter? How priority effects influence the outcome of parasite interactions within hosts

In nature, hosts are exposed to an assemblage of parasite species that collectively form a complex community within the host. To date, however, our understanding of how within-host–parasite communities assemble and interact remains limited. Using a larval amphibian host (Pacific chorus frog, Pseudacris regilla) and two common trematode parasites (Ribeiroia ondatrae and Echinostoma trivolvis), we experimentally examined how the sequence of host exposure influenced parasite interactions within hosts. While there was no evidence that the parasites interacted when hosts were exposed to both parasites simultaneously, we detected evidence of both intraspecific and interspecific competition when exposures were temporally staggered. However, the strength and outcome of these priority effects depended on the sequence of addition, even after accounting for the fact that parasites added early in host development were more likely to encyst compared to parasites added later. Ribeiroia infection success was reduced by 14 % when Echinostoma was added prior to Ribeiroia, whereas no such effect was noted for Echinostoma when Ribeiroia was added first. Using a novel fluorescent-labeling technique that allowed us to track Ribeiroia infections from different exposure events, we also discovered that, similar to the interspecific interactions, early encysting parasites reduced the encystment success of later arriving parasites by 41 %, which could be mediated by host immune responses and/or competition for space. These results suggest that parasite identity interacts with host immune responses to mediate parasite interactions within the host, such that priority effects may play an important role in structuring parasite communities within hosts. This knowledge can be used to assess host–parasite interactions within natural communities in which environmental conditions can lead to heterogeneity in the timing and composition of host exposure to parasites.

Plant-pathogen interactions: toward development of next-generation disease-resistant plants

Briskly evolving phytopathogens are dire threats to our food supplies and threaten global food security. From the recent advances made toward high-throughput sequencing technologies, understanding of pathogenesis and effector biology, and plant innate immunity, translation of these means into new control tools is being introduced to develop durable disease resistance. Effectoromics as a powerful genetic tool for uncovering effector-target genes, both susceptibility genes and executor resistance genes in effector-assisted breeding, open up new avenues to improve resistance. TALENs (Transcription Activator-Like Effector Nucleases), engineered nucleases and CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats)/Cas9 systems are breakthrough and powerful techniques for genome editing, providing efficient mechanisms for targeted crop protection strategies in disease resistance programs. In this review, major advances in plant disease management to confer durable disease resistance and novel strategies for boosting plant innate immunity are highlighted.

Do maternally derived antibodies and early immune experience shape the adult immune response?

1. Immunological imprinting by maternally derived antibodies has been proposed to have both positive and negative consequences for offspring immunity in early and adult life. However, few studies of maternal effects on immunity have followed individuals past the juvenile stages.

2. Using laboratory Japanese quail, we developed a novel method of directly manipulating yolk antibodies of neonates, and then followed individuals through a series of immune challenges until they were of reproductive age.

3. Our method of directly injecting purified antibodies into the yolk sac of newly hatched chicks successfully elevated the plasma titres of specific anti-KLH IgY in neonates. This allows us to test whether differences in neonatal anti-KLH IgY affect immunity at the juvenile and adult stages of life.

4. We found little evidence for an effect of maternal antibodies on juvenile stage immune response, in contrast to results from previous studies. Adult immune response depended largely on the magnitude of the juvenile immune response regardless of the identity of the antigen in the juvenile immune challenge, and did not depend on neonatal IgY titres. Our results are consistent with a priming effect of early immune experience on adult stage immune responsiveness, but we found no evidence of carryover effects of yolk-derived antibodies on adult immunity.

5. This study employs new methodology for investigation of maternal antibodies and presents results suggesting that further studies of maternal effects on immunity will require careful consideration of the numerous ways maternally derived yolk components can impact the different types of immune response.

Vascular attack by 5,6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci

The promise of cancer immunotherapy is that it will not only eradicate primary tumors but will generate systemic antitumor immunity capable of destroying distant metastases. A major problem that must first be surmounted relates to the immune resistance of large tumors. Here we reveal that immune resistance can be overcome by combining immunotherapy with a concerted attack on the tumor vasculature. The functionally related antitumor drugs 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone acetic acid (FAA), which cause tumor vasculature collapse and tumor necrosis, were used to attack the tumor vasculature, whereas the T-cell costimulator B7.1 (CD80), which costimulates T-cell proliferation via the CD28 pathway, was used to stimulate antitumor immunity. The injection of cDNA (60–180 µg) encoding B7.1 into large EL-4 tumors (0.8 cm in diameter) established in C57BL/6 mice, followed 24 h later by i.p. administration of either DMXAA (25 mg/kg) or FAA (300 mg/kg), resulted in complete tumor eradication within 2–6 weeks. In contrast, monotherapies were ineffective. Both vascular attack and B7.1 immunotherapy led to up-regulation of heat shock protein 70 on stressed and dying tumor cells, potentially augmenting immunotherapy. Remarkably, large tumors took on the appearance of a wound that rapidly ameliorated, leaving perfectly healed skin. Combined therapy was mediated by CD8+ T cells and natural killer cells, accompanied by heightened and prolonged antitumor cytolytic activity (P < 0.001), and by a marked increase in tumor cell apoptosis. Cured animals completely rejected a challenge of 1 x 107 parental EL-4 tumor cells but not a challenge of 1 x 104 Lewis lung carcinoma cells, demonstrating that antitumor immunity was tumor specific. Adoptive transfer of 2 x 108 splenocytes from treated mice into recipients bearing established (0.8 cm in diameter) tumors resulted in rapid and complete tumor rejection within 3 weeks. Although DMXAA and B7.1 monotherapies are complicated by a narrow range of effective doses, combined therapy was less dosage dependent. Thus, a broad range of amounts of B7.1 cDNA were effective in combination with 25 mg/kg DMXAA. In contrast, DMXAA, which has a very narrow range of high active doses, was effective at a low dose (18 mg/kg) when administered with a large amount (180 µg) of B7.1 cDNA. Importantly, combinational therapy generated heightened antitumor immunity, such that gene transfer of B7.1 into one tumor, followed by systemic DMXAA treatment, led to the complete rejection of multiple untreated tumor nodules established in the opposing flank. These findings have important implications for the future direction and utility of cancer immunotherapies aimed at harnessing patients’ immune responses to their own tumors.

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.

Monitoring of immune responses to a herbal immuno-modulator in patients with advanced colorectal cancer.

Many herbal medicines are widely used as immuno-modulators in Asian countries. Ganoderma lucidum (Lingzhi) is one of the most commonly used herbs in Asia and preclinical studies have established that the polysaccharide fractions of G. lucidum have potent immuno-modulating effects. However, clinical evidence for this is scanty. The present open-labeled study aimed to evaluate the effects of G. lucidum polysaccharides on selected immune functions in patients with advanced colorectal cancer. Forty-seven patients were enrolled and treated with oral G. lucidum at 5.4 g/day for 12 weeks. Selected immune parameters were monitored using various immunological methods throughout the study. In 41 assessable cancer patients, treatment with G. lucidum tended to increase mitogenic reactivity to phytohemagglutinin, counts of CD3, CD4, CD8 and CD56 lymphocytes, plasma concentrations of interleukin (IL)-2, IL-6 and interferon (IFN)-γ, and NK activity, whereas plasma concentrations of IL-1 and tumor necrosis factor (TNF)-α were decreased. For all of these parameters, no statistical significance was observed when a comparison was conducted between baseline and those values after a 12-week treatment with G. lucidum. The changes of IL-1 were correlated with those for IL-6, IFN-γ, CD3, CD4, CD8 and NK activity (p < 0.05) and IL-2 changes were correlated with those for IL-6, CD8 and NK activity. The results indicate that G. lucidum may have potential immuno-modulating effect in patients with advanced colorectal cancer. Further studies are needed to explore the benefits and safety of G. lucidum in cancer patients.

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.

Priming vs. rhyming : orthographic and phonological representations in the left and right hemispheres

The right cerebral hemisphere has long been argued to lack phonological processing capacity. Recently, however, a sex difference in the cortical representation of phonology has been proposed, suggesting discrete left hemisphere lateralization in males and more distributed, bilateral representation of function in females. To evaluate this hypothesis and shed light on sex differences in the phonological processing capabilities of the left and right hemispheres, we conducted two experiments. Experiment 1 assessed phonological activation implicitly (masked homophone priming), testing 52 (M = 25, F = 27; mean age 19.23 years, SD 1.64 years) strongly right-handed participants. Experiment 2 subsequently assessed the explicit recruitment of phonology (rhyme judgement), testing 50 (M = 25, F = 25; mean age 19.67 years, SD 2.05 years) strongly right-handed participants. In both experiments the orthographic overlap between stimulus pairs was strictly controlled using DICE [Brew, C., & McKelvie, D. (1996). Word-pair extraction for lexicography. In K. Oflazer & H. Somers (Eds.), Proceedings of the second international conference on new methods in language processing (pp. 45–55). Ankara: VCH], such that pairs shared (a) high orthographic and phonological similarity (e.g., not–KNOT); (b) high orthographic and low phonological similarity (e.g., pint–HINT); (c) low orthographic and high phonological similarity (e.g., use–EWES); or (d) low orthographic and low phonological similarity (e.g., kind–DONE). As anticipated, high orthographic similarity facilitated both left and right hemisphere performance, whereas the left hemisphere showed greater facility when phonological similarity was high. This difference in hemispheric processing of phonological representations was especially pronounced in males, whereas female performance was far less sensitive to visual field of presentation across both implicit and explicit phonological tasks. As such, the findings offer behavioural evidence indicating that though both hemispheres are capable of orthographic analysis, phonological processing is discretely lateralised to the left hemisphere in males, but available in both the left and right hemisphere in females.

Protein kinase C isozymes as potential therapeutic targets in immune disorders

Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.

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.

Absolute versus relative difference measures of priming: Which is appropriate when baseline scores change with age?

It is often of theoretical interest to know if implicit memory (repetition priming) develops across childhood under a given circumstance. Methodologically, however, it is difficult to determine whether development is present when baseline performance for unstudied items improves with age. Calculation of priming in absolute (priming=studied - unstudied) or relative-to-baseline terms can lead to different conclusions. In first noting this problem, Parkin (1993) suggested using the Snodgrass (1989a) calculation of relative priming [priming=(studied - unstudied)/(maximum - unstudied)], and most developmental studies have since adopted this procedure. Here, we question the Snodgrass method because the Snodgrass method's results are not replicated in the picture identification task when baselines are equated experimentally across age groups. Instead, results support an absolute measure of priming. Theoretically, we argue against its core assumption; namely, that children and adults always lie on the same learning curve, with an equal maximum performance level and equal rate of learning.

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.