Social status alters immune regulation and response to infection in macaques.

Social status is one of the strongest predictors of human disease risk and mortality, and it also influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined genomics with a social status manipulation in female rhesus macaques to investigate how status alters immune function. We demonstrate causal but largely plastic social status effects on immune cell proportions, cell type-specific gene expression levels, and the gene expression response to immune challenge. Further, we identify specific transcription factor signaling pathways that explain these differences, including low-status-associated polarization of the Toll-like receptor 4 signaling pathway toward a proinflammatory response. Our findings provide insight into the direct biological effects of social inequality on immune function, thus improving our understanding of social gradients in health.

Physical activity, sedentary behaviors, and Epstein-Barr virus antibodies in young adults.

This study aimed to elucidate the associations between physical activity, sedentary behaviors, and Epstein-Barr virus (EBV) antibody levels (as an indirect marker of cell-mediated immunity, CMI). This study made use of a 14-year longitudinal study with a representative sample of adolescents in the US. A total of 3361 participants (42.1% male) aged 11 to 21years at baseline who completed Wave I (1994-1995), Wave III (2001-2002), and Wave IV (2008) surveys of the National Longitudinal Study of Adolescent Health (Add Health) were analyzed. Physical activity and sedentary behaviors at Waves I and III were assessed using interviewer-administered questionnaire. EBV viral capsid antigen (VCA) IgG antibody levels at Wave IV were analyzed from dried blood spot assays. Adjusted for confounders, among males, one additional day spent per week on strenuous sports at Wave III were associated with a decrease of 4.09AU/ml in EBV antibody levels (p=0.012), while one additional hour spent per week viewing videos at Wave I was associated with an increase of 0.83AU/ml in EBV antibody levels (p=0.026). Among females, one additional day spent per week on individual sports at Wave III were associated with a decrease of 4.63AU/ml in EBV antibody levels (p=0.014), while sedentary behaviors were not associated with EBV antibody levels. To conclude, physical activity and sedentary behaviors were associated with CMI among males and physical activity was associated with CMI among females.

A quantitative assessment model of T-cell immune function for predicting risks of infection and rejection during the early stage after liver transplantation.

Although more and more clinical studies indicated that ImmuKnow assay could efficiently assess the immune status of recipients, it still has the challenge to predict the occurrence of clinical adverse events. This study aimed to establish a quantitative assessment model, which could more efficiently predict immune function of T lymphocytes after liver transplantation based on three indexes: CD4+ T lymphocyte count (C), CD4+/CD8+ ratio (R), and ImmuKnow adenosine triphosphate (ATP) value (A). We selected 194 recipients and measured the A, C, and R index every week, then obtained the Fisher linear discriminant functions by SPSS 16.0. Next, we divided the recipients into three groups: infection, stable, and rejection groups according to clinical status. After calculating, the discriminant function, 0.012A + 0.019C + 1.322R (simplified into T = 2A + 3C + 200R), was selected to represent the T-cell-mediated immune function. Based on the model, the optimal cutoff T values for infection and rejection were 1415 (sensitivity = 80%, specificity = 79.9%,AUC = 92.3%) and 1939.5 (sensitivity = 93.9%, specificity = 77.6%, AUC = 88.6%), relatively (p < 0.001). In conclusion, this model may be a more feasible way to evaluate the cellular immune function status in liver transplantation recipients.

Childhood adversity and cell-mediated immunity in young adulthood: does type and timing matter?

Childhood adversity can have powerful effects on health over the life course. Persistent changes in cell-mediated immune function may be one pathway linking adverse childhood experiences with later disease risk. However, limited research has examined childhood adversity in relation to cell-mediated immune function, and in particular, immune response to latent viruses in adulthood. The present study investigated the association of two types of childhood adversity, socioeconomic disadvantage during adolescence and abuse prior to age 18, with Epstein-Barr Virus (EBV) antibody titers in a large nationally representative sample of young adults aged 24-32years. Data were drawn from the National Longitudinal Study on Adolescent Health, Wave 4 (n=13,162). We examined the associations of three indicators of adolescent SES (parental education, household income, and occupational status) and frequency and timing of physical and sexual abuse with EBV antibodies, controlling for age, sex, race/ethnicity, and presence of a smoker in the household during adolescence. Lower parental occupational status and some categories of lower education were associated with elevated EBV antibodies (p<.05), and individuals who reported sexual abuse that occurred more than 10times had elevated EBV antibodies relative to individuals who were not sexually abused (p=0.03). Among individuals exposed to physical abuse, those who were first abused at age 3-5years had heightened EBV antibodies relative to those first abused during adolescence (p=0.004). This study extends prior research linking early adversity and immune function, and provides initial evidence that childhood adversity has a persistent influence on immune responses to latent infection in adulthood.

Specific immunotherapy in children: the evidence.

Specific immunotherapy (SIT) is the only treatment able to not only act on the symptoms of allergy but also act on the causes. At present, SIT may be administered in two forms: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). SCIT represents the standard modality of treatment while SLIT has recently been introduced into clinical practice and today represents an accepted alternative to SCIT. The main advantages of SIT that are lacking with drug treatment are long-lasting clinical effects and alteration of the natural course of the disease. This prevents the new onset of asthma in patients with allergic rhinitis and the onset of new sensitizations. The mechanism of action of both routes is similar; they modify peripheral and mucosal Th2-responses into a prevalent Th1-polarization with subsequent reduction of the allergic inflammatory reaction. Both have long-term effects for years after they have been discontinued, although for SLIT these evidences are insufficient. To date several guidelines have defined indications, controindications, side-effects, and clinical aspect for SCIT and SLIT. New forms of immunotherapy, allergen products and approaches to food allergy and atopic eczema represents the future of SIT.

Effort-reward imbalance, overcommitment, and cellular immune measures among white-collar employees.

We investigated whether chronic job stress, i.e., effort-reward imbalance (ERI) and overcommitment is associated with cellular immunity among 190 male and 157 female white-collar daytime employees (mean age 38; range 22-69 years). Participants provided a blood sample for the measurement of circulating immune (natural killer (NK), B, and T) cell counts and NK cell cytotoxicity (NKCC) and completed a questionnaire survey during April to June 2002. Stepwise multiple linear regression analyses revealed that NK cells were associated with effort (ß=-.230; p=.013), reward (ß=.169; p=.047), and ERI (ß=-.182; p=.047) scores but not with overcommitment in men; reward score was positively associated with NKCC (ß=.167; p=.049) and inversely associated with B cells (ß=-.181; p=.030). No significant associations were found in women. Although the picture remains less clear in women, our findings suggest a potential immunological pathway linking adverse working conditions and stress-related disorders in men.

Varicella zoster virus vaccines: effective, but concerns linger.

Both varicella and herpes zoster (HZ) can cause severe disease in certain age groups. The cell-mediated immune (CMI) response to the varicella zoster virus (VZV) is critical in preventing a recurrence of VZV. The varicella vaccine has markedly decreased the morbidity and mortality associated with varicella, but concerns linger about the cost and frequency of vaccine administration and the long-term effects on both adult varicella and HZ epidemiology in the individual and in the population. Therapy for HZ with an antiviral is only partially effective. A zoster vaccine is now available that boosts the CMI immune reaction to VZV in individuals and has proven safe and partially effective in preventing both HZ and post-herpetic neuralgia. Concerns about the zoster vaccine include the costs of administration, the overall health-care costs to society, and the acceptance and implementation of the vaccine in the elderly. Because of altered immune responses to VZV as a result of universal varicella vaccination it becomes even more compelling in the future to have a zoster vaccine ready to boost the CMI response to a sufficient level to prevent HZ. The 2 vaccines are intertwined in the future epidemiology of VZV disease.

Antioxidant protection, carotenoids and the costs of immune challenge in greenfinches.

Costs accompanying immune challenges are believed to play an important role in life-history trade-offs and warranting the honesty of signal traits. We performed an experiment in captive greenfinches (Carduelis chloris L.) in order to test whether and how humoral immune challenge with non-pathogenic antigen [sheep red blood cells (SRBC)] affects parameters of individual condition including intensity of coccidian infection, estimates of total antioxidant protection, plasma carotenoids and ability to mount a cell-mediated immune response. We also asked whether the potential costs of immune challenge can be alleviated by dietary carotenoid supplementation. None of the treatments affected intensity of coccidiosis. Humoral immune challenge suppressed the cell-mediated response to phytohemagglutinin (PHA), suggesting a trade-off between the uses of different arms of the immune system. Immune challenge reduced body-mass gain, but only among the carotenoid-depleted birds, indicating that certain somatic costs associated with immune system activation can be alleviated by carotenoids. No evidence for oxidative stress-induced immunopathological damages could be found because immune activation did not affect total antioxidant protection or carotenoid levels. Carotenoid supplementation inclined birds to fattening, indicating that lutein interfered with lipid metabolism. Altogether, our results support the hypotheses of biological importance of carotenoids and exemplify the overwhelming complexity of their integrated ecophysiological functions.

House sparrows (Passer domesticus) adjust their social status position to their physiological costs.

For group-living animals, the maintenance of a position in the social hierarchy may be associated with physiological costs such as increased stress and energy expenditure or suppressed immune functions. In this study, we experimentally manipulated the social status of house sparrows so that each bird experienced two social environments in random sequence: being dominant and subordinate. For 14 males, we investigated how corticosterone concentrations, energy expenditure and immune functions were affected by these changes in social status position. We found that the cost of maintaining a social status position differed between individuals and were related to individual body size. Birds with small body size had increased costs in terms of increased stress responses and reduced cell-mediated immune responses while being experimentally kept as dominants, while birds with large body size had increased costs while they were subordinates. We also found that birds with increased energetic and immunological costs as dominants obtained a low status position in the large group, while birds with increased costs as subordinates obtained a high status position in the large group. In summary, we found that the costs associated with the maintenance of social status position differed between individuals and was related to the individuals' body size. Furthermore, in a large group, individuals maintained a social status position that minimized energetic and immunological costs.

Serologic assessment of type 1 and type 2 immunity in healthy Japanese adults.

We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti-human T-cell lymphotrophic virus I and anti-hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guérin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with "normal" antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults.

Competitive coexistence in antiviral immunity.

Adaptive immunity to viruses in vertebrates is mediated by two distinct but complementary branches of the immune system: the cellular response, which eliminates infected cells, and the humoral response, which eliminates infectious virus. This leads to an interesting contest, since the two responses compete, albeit indirectly, for proliferative stimuli. How can a host mount a coordinated antiviral campaign? Here we show that competition may lead to a state of "competitive coexistence" in which, counterintuitively, each branch complements the other, with clinical benefit to the host. The principle is similar to free-market economics, in which firms compete, but the consumer benefits. Experimental evidence suggests this is a useful paradigm in antiviral immunity.

Cell mediated immune status in malignancy--pretherapy and post-therapy assessment.

Twenty-eight cases of malignancies of different kinds were studied to assess T-cell activity and population before and after institution of therapy. Fifteen cases were diagnosed as non-metastasising squamous cell carcinoma of larynx, pharynx, laryngopharynx, hypopharynx and tonsils. Seven cases were non-metastasising infiltrating duct carcinoma of breast and 6 cases were non-Hodgkin's lymphoma (NHL). It was observed that 3 out of 15 cases (20%) of squamous cell carcinoma cases were Mantoux test (MT) negative with a T-cell population of less than 40%, 2 out of 7 cases (28.6%) of infiltrating duct carcinoma of breast were MT negative with a T-cell population of less than 40% and 3 out of 6 cases (50%) of NHL were MT negative with a T-cell population of less than 40%. The normal controls, consisting of apparently normal healthy adults, had a T-cell population of more than 40% and were all MT positive. The patients who showed a negative skin test and a T-cell population less than 40% were further subjected to assessment of T-cell population and activity after appropriate therapy, and clinical cure of the disease. It was observed that 2 out of 3 cases (66.66%) of squamous cell carcinomas, 2 out of 2 cases (100%) of adenocarcinomas and one out of 3 cases (33.33%) of NHL showed positive conversion with a T-cell population of more than 40%.

Utilidad clínica de multitest en la evaluación de inmunidad celular / Usefulness of multitest in the assessment of cell immunity

The aim of this work was to assess cellular immunity using the Multitest CMI and relate its results with lymphocyte counts and lymphocyte subpopulations determined using monoclonal antibodies against CD4 and CD8 and fluorescence microscopy. We studied 51 patients (31 males), 20 infected with HIV, 18 with recurring infections, 5 with cancer, 2 with tuberculosis and 6 with miscellaneous diagnoses. According to Multitest results, patients were classified as normal, hypoergic or anergic. Twenty five percent of patients were normal, 65 percent hypoergic and 10 percent anergic. Eighty percent of anergic patients were infected with HIV. No differences in total lymphocyte count were observed between the 3 groups. CD4 lymphocyte count was lower in anergic patients when compared with the other groups. All patients with CD4 counts below 200 cells/mmü were anergic. It is cincluded that Multitest CMI is useful for the assessment of cellular immunity and complements the determination of lymphocyte subpopulations