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Invasive species have become a prolific environmental issue, second only to climate change, yet many of the phenomena that facilitate invasive success are not well understood (Phillip & Shine, Proc. Roy. Soc. B, 273, 1545‐1550). The combination of several generalist life‐history traits, certain physiological mechanisms, and environmental conditions is thought to play a significant role in invasion success. The ability to undergo fitness trade‐offs—to reallocate nutritional and energetic resources towards processes that increase reproduction, growth, and dispersal—is also thought to be an adaptive quality of many invasive species. Due to their inherent flexibility, phenotypically plastic traits in particular are often targeted for fitness reallocations. Immune function, for example, is determined by a highly plastic phenotype, which is crucial for combating a diverse array of pathogens. When active, immune function also demands extensive resources from the host. Laboratory and field studies suggest that certain aspects of the immune system are more costly than others, though, and that its components can be regulated independent of one another. In invasive species undergoing fitness trade‐offs, costly innate inflammatory responses are often downregulated, while antibody‐mediated responses may be enhanced. A combination of fixed physiological responses and environmentally induced trade‐offs are thought to regulate the immune system, though the relationship between these facets of regulation is still an area of active research. The field of ecoimmunology, then, has emerged in effort to understand the phenomena by which individual immune regulation can drive (and be driven by) species‐level ecology and evolution, and therefore be linked to invasive success (Downs et al., 2014. Integr. Compar. Biol., 54, 340–352). Research Highlights: Cross‐taxa studies suggest that selective regulation of immune system components ‐wherein more costly immune functions are down‐regulated in favor of up‐regulating more energetically‐efficient processes‐ may be contributing to invasive success. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Gallinarum causes a disease in chickens known as fowl typhoid. Interferon-gamma (IFN-γ) has been shown to be crucial in eliminating salmonellosis infection because of its strong association with T-cell responses. This study was undertaken to compare the expression of IFN-γ in chickens generated by different vaccine formulations. Eighty one-day-old Lohmann layer chicks were divided into four groups of 20 birds each for the experiment. This comprised an unvaccinated negative control group (NEG), a group vaccinated with the live 9R vaccine by the injection route (SC), a group vaccinated with alginate-coated chitosan microparticles encapsulating live plasmid-cured S. Gallinarum strain 9 (PC) by the oral route, and a group vaccinated with a weak attenuated live S. Gallinarum strain 9 encapsulated in alginate-coated chitosan microparticles (VM) given orally. Vaccinations were done at 10 and 14 weeks of age followed by challenge at 16 weeks of age. IgG was measured using ELISA. qRT-PCR was used to compare the mRNA fold expression of IFN-γ in the PC, VM and SC groups using the unvaccinated/unchallenged group as the control. There were significant differences in the IgG levels between each vaccinated group and the unvaccinated group (P < 0.05) after booster vaccination and post-challenge. There was 100% protection of the birds in SC and VM groups, 80% protection in PC group and 0% protection in the NEG group. Using 2−ΔΔCT calculation, IFN-γ was more highly expressed in the PC group than in the SC group or VM group. In conclusion, the IFN-γ was more highly expressed in the PC group (though not significantly higher) compared to the SC and VM groups and this could be attributed to the alginate-coated chitosan microparticles which acted as an adjuvant. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV)-infected persons are at a higher risk of severe influenza. Although we have shown that a standard-dose intradermal influenza vaccine versus a standard-dose intramuscular influenza vaccine does not result in differences in hemagglutination-inhibition titers in this population, a comprehensive examination of cell-mediated immune responses remains lacking.Methods: Serological, antigen-specific B-cell, and interleukin 2-, interferon γ-, and tumor necrosis factor α-secreting T-cell responses were assessed in 79 HIV-infected men and 79 HIV-uninfected men.Results: The route of vaccination did not affect the immunoglobulin A and immunoglobulin G (IgG) plasmablast or memory B-cell response, although these were severely impaired in the group with a CD4+ T-cell count of <200 cells/μL. The frequencies of IgG memory B cells measured on day 28 after vaccination were highest in the HIV-uninfected group, followed by the group with a CD4+ T-cell count of ≥200 cells/μL and the group with a CD4+ T-cell count of <200 cells/μL. The route of vaccination did not affect the CD4+ or CD8+ T-cell responses measured at various times after vaccination.Conclusions: The route of vaccination had no effect on antibody responses, antibody avidity, T-cell responses, or B-cell responses in HIV-infected or HIV-uninfected subjects. With the serological and cellular immune responses to influenza vaccination being impaired in HIV-infected individuals with a CD4+ T-cell count of <200 cells/μL, passive immunization strategies need to be explored to protect this population.Clinical Trials Registration: NCT01538940. [ABSTRACT FROM AUTHOR]

Induction of Th1 (cell-mediated) immunity and associated production of IFN-γ by CD4+ T cells has been widely used as a marker of protective immunity against tuberculosis (TB). This is based on two assumptions. The first is the widely accepted view that Mycobacterium tuberculosis (Mtb), the causative agent of TB is an obligate intracellular pathogen, and the second is based on the Th1/Th2 paradigm, which posits that polarization of CD4+ T cells into type1 (cell-mediated) and type 2 (humoral) is central for proper induction of protective immunity against pathogens. However, almost all licensed vaccines currently in use are primarily anti-body based whether intracellular or extra-cellular. In addition, converging data from both animal models and humans indicate that the production of IFN-γ alone is not sufficient to confer protection against TB. In addition, a substantial body of the literature suggests that, in addition to Th1 cells, antibody classes and sub-classes are protective against TB. In a recent study, we have shown that there is a synergy between IFN-γ (cell-mediated) and IgA (humoral) in human population in an endemic setting. In this review, current data from both animal and human studies that support mixed Th1 and Th2 responses that are protective against Mtb and other pathogens are presented. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the immunomodulatory activity of aqueous extract of Nyctanthes arbor-tristis flowers (NAFE) with particular reference to splenocytes proliferation and induction of cytokines. Materials and Methods: Antibody titer was determined by tube agglutination and indirect ELISA assay in four groups of mice-control, antigen alone, and NAFE-treated (400 and 800 mg/kg for 21 days) after immunization with Salmonella antigen while cellular immunity was studied in three groups of rats (control and NAFE-treated - 400 and 800 mg/kg) following DNCB application. Splenocytes from untreated and NAFE-treated rats were stimulated using concanavalin-A (Con-A) and optical density (OD) and stimulation index were determined. Splenocytes from control rats were also treated in vitro with NAFE (50-1600 µg/ml) and Con-A to determine the effect on splenocytes proliferation. Interleukin-2 (IL-2) and IL-6 levels in splenocytes supernatant from control and NAFE-treated rats and following in vitro treatment of splenocytes with NAFE (50-1600 µg/ml) were determined using ELISA kits. Results: Marked to a significant increase in antibody titer by both the methods in NAFE-treated mice and a significant increase in skin thickness in rats after challenge with DNCB, respectively suggested humoral and cell-mediated immunostimulant potential of NAFE. Significant increase in OD and stimulation index following ex vivo and in vitro exposure of splenocytes and sensitization with Con-A and significant elevation in IL-2 and IL-6 levels in splenocytes supernantant was also observed after their ex vivo and in vitro exposure to NAFE. Conclusion: Humoral and cell-mediated immunostimulant activity of NAFE seems to be mediated through splenocytes proliferation and increased production of cytokines, especially IL-2 and IL-6. [ABSTRACT FROM AUTHOR]

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 naive 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, particularly males, and a greater difference between primary and secondary responses. Adult microbial killing of Escherichia coli decreased as parents moved from incubation to nestling rearing for both nest treatments; however, killing of Candida 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 exposure to microorganisms in the environment affects the adaptive immune system in nesting birds, with exposure upregulating the antibody response in adult birds. [ABSTRACT FROM AUTHOR]

The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. [ABSTRACT FROM AUTHOR]

Abstract: A traditional approach used to assess whether immune defense is costly is to explore the existence of trade-offs between immunity and other functions; however, quantitative studies of the energetic costs associated with the activation of the immune system are scarce. We assessed the magnitude of a PHA-triggered immune response and the associated energetic costs in 60-day old Ctenomys talarum. We expected that the magnitude of the macroscopic inflammatory response to PHA is lower in young tuco-tucos compared with that of adults, given the allocation of substantial energy to growth, and that the magnitude of the inflammation is lower in male pups compared to females, due to the higher investment in growth of the larger sex. Concomitantly, we expected that the pups challenged with PHA show an increase in oxygen consumption compared to control animals and that a positive association exists between magnitude of the PHA-induced inflammation and oxygen consumption. Contrary to what was expected, young tuco-tucos mounted a higher inflammatory response compared with adults and there were no differences in the magnitude of this response between sexes. The inflammatory response induced by a PHA injection did not represent a significant energetic cost for young tuco-tucos. There were no differences in oxygen consumption between PHA-injected and control animals, and tuco-tucos that mounted a higher inflammatory response to PHA did not show higher oxygen consumption. Energy expenditure, however, is not the only physiological cost involved in trade-offs between immune response and various functions of the organism, and other currencies are discussed. [Copyright &y& Elsevier]

As habitats become more fragmented, population densities and diets of wildlife can change dramatically, contributing to increased stress and incidence of infections and disease. To better understand effects of human disturbance on immunocompetence of wild mammals, we studied individual and combined effects of social and nutritional stress on the health of wild-captured adult male white-footed mice ( Peromyscus leucopus (Rafinesque, 1818)), a species that commonly occurs in close proximity to humans. Paired mice had reduced body mass and circulating monocytes, higher serum corticosterone level, and a significantly weaker humoral immune response compared with mice housed individually. Mice fed a 5% protein diet had reduced body mass and circulating monocytes, but no differences in humoral or cellular immune responses compared with mice fed a 30% protein diet. The only interactive effect of the two stresses on immune-related parameters was on mass of the spleen. We hypothesize that reduced humoral immunocompetence in response to acute and chronic social stress likely contributes to increases in disease transmission in high-density populations associated with fragments of habitat. In addition, anthropogenic impacts that limit food availability may be of greater importance to immune function than impacts on food quality. [ABSTRACT FROM AUTHOR]

Abstract: In March 2009 a novel swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the Western United States. Vaccination with conventional influenza vaccine (CIV) does not result in cross-reactive antibodies, however, the disproportionate number of cases (37%) occurring among persons younger than 50 years old suggested that adaptive immune memory might be responsible for the relative lack of virulence in older, healthy adults. Using EpiMatrix, a T-cell epitope prediction and comparison tool, we compared the sequences of the three hemagglutinin (HA) and neuraminidase (NA) proteins contained in 2008–2009 CIV to their counterparts in A/California/04/2009 (H1N1) looking for cross-conserved T-cell epitope sequences. We found greater than 50% conservation of T helper and CTL epitopes between novel S-OIV and CIV HA for selected HLA. Conservation was lower among NA epitopes. Sixteen promiscuous helper T-cell epitopes are contained in the S-OIV H1N1 HA sequence, of which nine (56%) were 100% conserved in the 2008–2009 influenza vaccine strain; 81% were either identical or had one conservative amino acid substitution. Fifty percent of predicted CTL epitopes found in S-OIV H1N1 HA were also found in CIV HA sequences. Based on historical performance, we expect these epitope predictions to be 93–99% accurate. This in silico analysis supports the proposition that T-cell response to cross-reactive T-cell epitopes, due to vaccination or exposure, may have the capacity to attenuate the course of S-OIV H1N1 induced disease—in the absence of cross-reactive antibody response. The value of the CIV or live-attenuated influenza vaccine containing the 2008–2009 vaccine strains, as defense against H1N1, could be further tested by evaluating human immune responses to the conserved T-cell epitopes using PBMC from individuals infected with H1N1 and from CIV vaccinees. [Copyright &y& Elsevier]

In most species, sexes differ in levels of parasitism. These differences have traditionally been believed to be static, but a capacity for adjusting anti-parasite investments would allow sexes to allocate resources adaptively contingent on environmental conditions. During stressful periods, such as a food shortage, allocation decisions would be mandated in males and females, but the biasing of resources may differ depending on the value of various physiological alternatives to the fitness of each sex. To determine whether sexes sacrifice immune or reproductive capacity when stressed, male and female Siberian hamsters ( Phodopus sungorus) were pharmacologically deprived of glucose. Glucose deprivation was expected to compromise immune activity (delayed-type hypersensitivity) more than reproductive capacity in males because male fitness is limited by reproductive opportunities. The opposite was predicted for females because of the greater value of surviving to breed in favorable conditions. Contrary to expectations, glucoprivation compromised immune activity in female, but not male, hamsters. Conversely, glucoprivation reduced male, but not female, reproductive organ masses. These results may reflect the adjustments made by wild hamsters during food shortages, or they may be influenced by the study design; neither sex was permitted to incur other behavioral and physiological costs, such as lactation and parental care. Regardless, our results indicate that sex differences in parasitism are likely to be plastic in many circumstances, but further work in free-living animals is critical to ascertain whether results of the present study are naturally representative. [ABSTRACT FROM AUTHOR]

Abstract: In developing countries, hepatitis E (HEV) and hepatitis A (HAV) are the major causes of acute viral hepatitis with similar feco-oral modes of transmission. In contrast to the high seroprevalence of hepatitis A infection, a low seroprevalence of HEV among children in endemic areas has been reported. These data suggest the possibility that silent HEV infection is undiagnosed by the current available methods. Many of the serological tests used for HEV diagnosis have poor specificity and are unable to differentiate among different genotypes of HEV. Moreover, the RT-PCR used for HEV isolation is only valid for a brief period during the acute stage of infection. Cell-mediated immune (CMI) responses are highly sensitive, and long lasting after sub-clinical infections as shown in HCV and HIV. Our objective was to develop a quantitative assay for cell-mediated immune (CMI) responses in HEV infection as a surrogate marker for HEV exposure in silent infection. Quantitative assessment of the CMI responses in HEV will also help us to evaluate the role of CMI in HEV morbidity. In this study, an HEV-specific interferon-gamma (IFN-γ) ELISPOT assay was optimized to analyze HEV-specific CMI responses. We used peripheral blood mononuclear cells (PBMC) and sera from experimentally infected chimpanzees and from seroconverted and control human subjects to validate the assay. The HEV-specific IFN-γ ELISPOT responses correlated strongly and significantly with anti-HEV ELISA positive/negative results (rho=0.73, p =0.02). Moreover, fine specificities of HEV-specific T cell responses could be identified using overlapping HEV ORF2 peptides. [Copyright &y& Elsevier]

Abstract: Immune deficiency can be part of CHARGE syndrome but often receives only limited attention. We present two patients with CHARGE syndrome confirmed CHD7 mutations who had severe T-cell deficiency, and review 15 CHARGE patients from the literature with immunological problems. Most of them had severe T-cell deficiency, although the spectrum also included mild T-cell deficiency and isolated humoral immune deficiency. We conclude that immunodeficiency can form an important symptom in CHARGE syndrome although the frequency and exact nature are still insufficiently known. We propose to evaluate immune functions in all CHARGE syndrome patients, to estimate the frequency and nature of the accompanying immunodeficiency, and to obtain better data regarding prognosis and management. [Copyright &y& Elsevier]

Abstract: The immune response to vaccination in animals can be enhanced by exposure to acute stress at the time of vaccination. The efficacy of this adjuvant strategy for vaccination in humans requires investigation. The current study employed a randomised controlled trial design to examine the effects of eccentric exercise prior to influenza vaccination on the antibody and cell-mediated responses. Sixty young healthy adults (29 men, 31 women) performed eccentric contractions of the deltoid and biceps brachii muscles of the non-dominant arm (exercise group) or rested quietly (control group), and were vaccinated 6h later in the non-dominant arm. Change in arm circumference and pain were measured to assess the physiological response to exercise. Antibody titres were measured pre-vaccination and at 6- and 20-week follow-ups. Interferon-γ in response to in vitro stimulation by the whole vaccine, an index of the cell-mediated response, was measured 8 weeks post-vaccination. Interferon-γ responses were enhanced by exercise in men, whereas antibody titres were enhanced by eccentric exercise in women but not in men. Men showed greater increase in arm circumference after eccentric exercise than women but there was no difference in reported pain. The interferon-γ response was positively associated with the percentage increase in arm circumference among the exercise group. Eccentric exercise exerted differential effects on the response to vaccination in men and women, with enhancement of the antibody response in women, but enhancement of the cell-mediated response in men. Eccentric exercise of the muscle at the site of vaccine administration should be explored further as a possible behavioural adjuvant to vaccination. [Copyright &y& Elsevier]

Immune system components differ in their functions and costs, and immune defense profiles are likely to vary among species with differing ecologies. We compared adaptive immune defenses in two closely related species that have contrasting inflammatory immune responses, the widespread and abundant house sparrow ( Passer domesticus) and the less abundant tree sparrow ( Passer montanus). We found that the house sparrow, which we have previously shown mounts weaker inflammatory responses, exhibits stronger adaptive immune defenses, including antibody responses, natural antibody titers, and specific T-cell memory, than the tree sparrow. Conversely, tree sparrows, which mount strong inflammatory responses, also mount stronger nonspecific inflammatory T-cell responses but weaker specific adaptive responses. Prevalence of avian malaria parasite infections, which are controlled by adaptive immune defenses, was higher in the geographically restricted tree sparrow than in the ubiquitous house sparrow. Together these data describe distinct immune defense profiles between two closely related species that differ greatly in numbers and distributions. We suggest that these immunological differences could affect fitness in ways that contribute to the contrasting abundances of the two species in North American and Western Europe. [ABSTRACT FROM AUTHOR]

1. Measurements of phytohemagglutinin (PHA)-induced tissue swelling are arguably the most popular surrogates for immunocompetence in wild birds. It is largely unresolved, however, whether the basic assumption underlying these measures is valid, particularly whether more swelling represents a ‘better’ or ‘stronger’ cell-mediated immune response. 2. In this study we took a first step towards such validation by characterizing immune cell infiltration over time into the wing-webs (patagia) of PHA-challenged House Sparrows ( Passer domesticus). Relative to saline-injected wing-webs, PHA-injected wing-webs displayed intensive infiltration of many immune cell types, including basophils, eosinophils, heterophils, lymphocytes, macrophages and thrombocytes. The abundance of most of these cell types changed over the course of the swelling response (6–48 h post-injection). Peak infiltration time varied depending on cell type. At several time points, significant correlations between the numbers of some cell types (particularly heterophils) and the degree of swelling were detected. 3. Together, these data indicate that PHA-induced swelling is related to heightened immune cell activity in House Sparrows, but also that the PHA swelling response in this species is dynamic and involves both innate and adaptive components of the immune system. We thus caution against interpreting larger swellings as ‘greater cell-mediated immunocompetence’, given the complex nature of this immune response. [ABSTRACT FROM AUTHOR]

As a paradigm for the development of a vaccine against human schistosomiasis, the radiation-attenuated (RA) vaccine has enabled the dissection of different immune responses as putative effector mechanisms. This review considers advances made in the past, and updates our knowledge with reference to recent studies that have provided new information relevant particularly to the early innate events after vaccination, and to the nature of the protective effector mechanism. Priming of a protective response by RA larvae is a highly co-ordinated series of events starting in the skin, draining lymph nodes and lungs, leading to the development of various effector responses, ranging from Th1-associated cell-mediated activity, to anti-parasitic antibodies, all of which contribute to the elimination of challenge larvae to varying extents. In this respect, the RA vaccine elicits a multifaceted immune response, from which we can derive valuable insights relevant to the future design of novel delivery systems and adjuvants for recombinant and subunit vaccines. [ABSTRACT FROM AUTHOR]

One of the primary assumptions of the immunocompetence hypothesis is that testosterone is immunosuppressive. Although many studies in birds and mammals have supported this assumption, conflicting results have been reported in a variety of species. We investigated the effects of testosterone manipulation on both cell-mediated and humoral immunity in adult songbirds, European starlings (Sturnus vulgaris). Male and female starlings were wild-caught, housed in the laboratory, and implanted with either empty silastic capsules or capsules containing testosterone. Six weeks after implantation, humoral immunity was assessed by injecting the birds with a novel antigen, keyhole limpet hemocyanin, and measuring specific antibody responses 10 and 15 days later via an enzyme-linked immunosorbant assay. Cell-mediated immunity was assessed 7 weeks after implantation via intradermal injection of the T-cell mitogen phytohemagglutinin into the wing web and measuring the degree of swelling 24 h later. Antibody responses to antigenic challenge were significantly suppressed in testosterone-treated females 10 days post-injection and in both sexes 15 days post-injection. Furthermore, there was a significant inverse relationship between individual variability in antibody responsiveness and plasma testosterone concentrations. Cell-mediated responses to phytohemagglutinin stimulation were also significantly suppressed in testosterone-treated males compared to same-sex controls. Testosterone treatment significantly increased plasma corticosterone concentrations compared to controls, and the possibility of this effect mediating the immunosuppressive effects of testosterone is discussed. The present study is among the first to demonstrate testosterone-induced suppression of both cell-mediated and humoral immunity in a species of songbird. [ABSTRACT FROM PUBLISHER]

Simple Summary: Hempseed meal (HSM) is a byproduct of hemp oil production and is high in protein, fiber, and fat. With hempseed having an ideal omega 6:3 ratios for human health, a similar ratio is observed in HSM. Currently, HSM is not approved for use in animal feed as there are several safety concerns for both the animal and consumer. In this study, we evaluated the effect of HSM supplementation for goats on their humoral, cell-mediated immune responses and select cytokine expression and serum concentration. Supplementation of HSM improved the cell mediated immune response but decreased the antibody response in goats. Including HSM in the diet of goats could improve the cell-mediated immune response. The objective of this study was to evaluate the effect of varying levels of hempseed meal supplementation on antibody and cell-mediated immune responses, as well as the expression of some of the important immunoregulatory cytokines. Treatments consisted of hempseed meal supplementation at 0 (control), 10, 20, and 30% of the total diet. Goats were randomly assigned to one of the four treatments n = 10. Cell-mediated immune response was evaluated on day 59 of the feeding period by measuring skinfold thickness at 24 h following intradermal injection of phytohemagglutinin. A significant increase in skinfold thickness was observed with increasing levels of supplementation as compared to that of the control group. Serum antibody titers to chicken ovalbumin were not significantly different between treatment groups. Cytokine concentrations of IL-6 increased linearly with increasing level of supplementation (p < 0.05), contrarily to the linear decrease that was observed for TNF-α (p < 0.05). Although IL-2 tended to increase with the 10 and 30% levels of supplementation (p < 0.07), the result was not significant, and no significant differences were obtained with respect to IL-4 concentrations. Cytokine gene expression values measured by RT-PCR, however, demonstrated some significant differences. HSM supplementation had no significant effect on the expression of IL-2 or IL-6. However, significant differences were observed with the 30% supplementation for IL-4 and TNF-α as compared to that of the control group (p < 0.05). IL-4 was down regulated for the 10 and 20% treatment groups but was upregulated for the 30% treatment group. TNF-α was downregulated in the 10% but upregulated for the 20 and 30% treatment groups. No significant differences were observed for the serum cortisol concentration or white blood cell counts. These results suggested that hempseed meal supplementation may improve cell-mediated immune response while having no effect on antibody-mediated immune response. However, more research needs to be conducted to determine the most efficacious inclusion rate. [ABSTRACT FROM AUTHOR]

Human intestinal intraepithelial lymphocytes (IEL) demonstrate target cell-restricted spontaneous cytotoxic (SC) activity that is due to CD2+CD3+CD8+CD16- CD56- effector cells: they kill epithelial ceil (EC) tumours (such as DLD-1 colon cancer cells), but not natural killer (NK)-sensitive K-562 cells. The present study shows that the measured levels of SC activities by IEL correlated with those of autologous lamina propria lymphocytes (LPL), but not with those of peripheral blood lymphocytes (PBL). Also, the susceptibilities of DLD-1 cell clones to lysis by IEL and PBL effector cells did not correlate, suggesting different mechanisms of lysis. Antibody blocking experiments showed that the main surface molecules involved in lysis depended on the effector cell type: αEβ7 (HML-1) on IEL and CD16 on PBL. No antibody-dependent cell-mediated cytotoxicity (ADCC) was demonstrated by IEL, even after stimulation with interferon-gamma (IFN-γ). Few IEL expressed Fc receptors for IgG. This study describes further differences between the SC activities of IEL and PBL. [ABSTRACT FROM AUTHOR]

The lymphokine, interleukin 2 (IL-2), is an important modulator of cell-mediated immune (CMI) responses. We report here the detection of an inhibitor of IL-2 in normal sera by measuring the inhibition of thymidine incorporation in IL-2 dependent murine CTLL cells. The inhibitor, partially purified by Sephacryl S-200 gel filtration, eluted with the 60,000-70,000 mol. wt fraction. The factor was destroyed at 56 °C for 30 min and did not bind to Protein A Sepharose, suggesting that it is not an immunoglobulin G. Of 26 normal sera tested, 23 had significant levels of the inhibitor. Since connective tissue diseases are often associated with deficient CMI responses, we examined the levels of IL-2 inhibitor in 26 systemic lupus erythematosus (SLE) and 22 rheumatoid arthritis (RA) patients. Only 8 SLE and 12 RA patients had normal levels of the inhibitor. Of the 18 SLE patients with low or undetectable levels, 15 had clinically defined active disease and of the eight with normal levels, three had active disease. The decrease In the IL-2 inhibitor level did not correlate either with steroid or cyctophosphamide treatment or with serum levels of DNA binding and C3. These data suggest that the function of the inhibitor is to control IL-2 activity under normal conditions. Decreased levels of the IL-2 inhibitor in these patients might be explained either as a reduced requirement of this regulatory protein secondary to decreased IL-2 production or a defect of the cells responsible for the production of both IL-2 and its inhibitor. [ABSTRACT FROM AUTHOR]

The depressed cell-mediated immunity in rheumatoid arthritis was investigated in vivo by cutaneous hypersensitivity responses to seven antigens including tuberculin PPD, and in vitro by lymphocyte transformation to the latter antigen. In vivo 40% of rheumatoid patients were anergic compared to 2% of controls (P < 0001) with an associated reduction ill sum score(59 ±6 5 o 15 3 ± 8 7, P < 0 001). In vitro lymphocyte proliferation to PPD was also significantly depressed (P< 0 001) and could not be reversed by indomethacin. A significant correlation between the in vivo sum scored (induration in mm) and in vitro thymidine incorporation (d/min) (r=0-59, P<0001) was found. In an attempt to overcome the depressed in vitro response the addition of a crude supernatant from a mixed lymphocyte reaction was found to return the PPD stimulated lymphocyte proliferation to the normal range. This effect was mimicked by purified IL-2 but not purified IL-1. The implications of this finding are are discussed. [ABSTRACT FROM AUTHOR]

A model for hapten- induced cell-mediated immunity (CMI) in the oral mucosa of the spraque-Dawley rat is presented. Sensitization was performed with 0.1 ml of a hapten (DNCB 2%, in acetone solution) administered five times on shaved dorsal skin. Ten days after completed sensitization eliciting doses of 0.1-0.02% of the hapten were applied in the buccal mucosa one of several times giving rise to an inflammation dominated by lymphocytes. The development of the reaction was studied in a times sequence study. also sensitization through the buccal mucosa was attempted, with three or more of the eliciting doses applied directly in the buccal mucosa. Light microscpically, the reaction was identical to the one seen in previously sensitized rats. The effects of DNCB and DNFB on sensitized animal with eliciting doses of 24μl 2% or 0.002% in acetone/olive oil were compared. No differences were seen in the low concentration range, but in the high concentration range, DNFB showed a more potent effect giving rinse to ulcers, not observed with DNCB. [ABSTRACT FROM AUTHOR]

Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  P54 Table 1 Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  Total number of patients who had rituximab  10  Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months)  7  Number of patients on rituximab monotherapy  2  Number of patients who are 6 months post-treatment  1  Number of patients with other risk factors for PCP  1 (hypogammaglobulinaemia)  Number of patients who are eligible for prophylaxis, as per the guideline  8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia)  Number of patients on cotrimoxazole  7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole  We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Mycobacterium avium subsp. paratuberculosis (MAP) is responsible for Johne's disease (JD) or paratuberculosis. Diagnosis of MAP infection by measuring host cell-mediated and humoral immune responses has been a major focus in MAP research. For this purpose, several MAP antigens such as secreted protein, cell envelope protein, cell-mediated immune and lipoprotein antigens have been identified and tested to measure their diagnostic utility with varying degree of success. Identifying the optimal antigen or antigen combinations for diagnosis of infected animals is hindered by the complex nature of the disease, prolonged subclinical infection, the differential expression of antigens and scarcity of well characterized MAP-specific epitopes making selection of a single MAP antigen very difficult. Thus, multiplexing of antigens with larger scale and longitudinal studies may lead to development of cost-effective next generation serodiagnostics. This mini review focuses on the role of different MAP antigens in the diagnosis of JD. [ABSTRACT FROM AUTHOR]

Objective: Infection of chickens with low pathogenic avian influenza virus, such as H9N2 virus, culminates in decreased egg production and increased mortality and morbidity if co-infection with other respiratory pathogens occurs. We have previously observed the induction of antibody- and cell-mediated immune responses after intramuscular administration of an H9N2 beta-propiolactone inactivated virus vaccine to chickens. Given the fact that in ovo vaccination represents a practical option for vaccination against H9N2 AIV in chickens, in the current study, we set out to characterize immune responses in chickens against a beta-propiolactone inactivated H9N2 virus vaccine after primary vaccination in ovo on embryonic day 18, and secondary intramuscular vaccination on day 14 post-hatch. We also included the Toll-like receptor 21 ligand, CpG ODN 2007, and an oil emulsion adjuvant, AddaVax™, as adjuvants for the vaccines. Results: Antibody-mediated immune responses were observed after administering the secondary intramuscular vaccine. Cell-mediated immune responses were observed in chickens that received the beta-propiolactone inactivated H9N2 virus combined with AddaVax™. Our results demonstrate that adaptive immune responses can be induced in chickens after a primary in ovo vaccination and secondary intramuscular vaccination. [ABSTRACT FROM AUTHOR]

The orofacial manifestations of 10 non-HIV-infected children with primary defects of cell mediated immunity are reported. Oral candidiasis was observed in 80% of patients, with oral ulceration present in 50%. Other oral manifestations included enamel hypoplasia, angular stomatitis, oral purpura and recurrent herpetic infection. [ABSTRACT FROM AUTHOR]