Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

AIMS/HYPOTHESIS: Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(-)CD45RA(+/-); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV(+) and CMV(-) individuals. METHODS: A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27(-)CD45RA(-)) and CD45RA re-expressing effector memory (EMRA; CD27(-)CD45RA(+)) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. RESULTS: Among CMV(+) individuals (n = 400), elevated HbA(1c) was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV(-) individuals. CONCLUSIONS/INTERPRETATION: The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV(+) individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence.

Progenitor cells are mobilized by acute psychological stress but not beta-adrenergic receptor agonist infusion.

OBJECTIVES: Stimuli that activate the sympathetic nervous system, such as acute psychological stress, rapidly invoke a robust mobilization of lymphocytes into the circulation. Experimental animal studies suggest that bone marrow-derived progenitor cells (PCs) also mobilize in response to sympathetic stimulation. Here we tested the effects of acute psychological stress and brief pharmacological ß-adrenergic (ßAR) stimulation on peripheral PC numbers in humans. METHODS: In two studies, we investigated PC mobilization in response to an acute speech task (n=26) and ßAR-agonist (isoproterenol) infusion (n=20). A subset of 8 participants also underwent the infusion protocol with concomitant administration of the ßAR-antagonist propranolol. Flow cytometry was used to enumerate lymphocyte subsets, total progenitor cells, total haematopoietic stem cells (HSC), early HSC (multi-lineage potential), late HSC (lineage committed), and endothelial PCs (EPCs). RESULTS: Both psychological stress and ßAR-agonist infusion caused the expected mobilization of total monocytes and lymphocytes and CD8(+) T lymphocytes. Psychological stress also induced a modest, but significant, increase in total PCs, HSCs, and EPC numbers in peripheral blood. However, infusion of a ßAR-agonist did not result in a significant change in circulating PCs. CONCLUSION: PCs are rapidly mobilized by psychological stress via mechanisms independent of ßAR-stimulation, although the findings do not exclude ßAR-stimulation as a possible cofactor. Considering the clinical and physiological relevance, further research into the mechanisms involved in stress-induced PC mobilization seems warranted.

Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample.

Cytomegalovirus (CMV) is a herpes virus that has been implicated in biological aging and impaired health. Evidence, largely accrued from small-scale studies involving select populations, suggests that stress may promote non-clinical reactivation of this virus. However, absent is evidence from larger studies, which allow better statistical adjustment for confounding and mediating factors, in more representative samples. The present study involved a large occupational cohort (N=887, mean age=44, 88% male). Questionnaires assessed psychological (i.e., depression, anxiety, vital exhaustion, SF-12 mental health), demographic, socioeconomic (SES), and lifestyle variables. Plasma samples were analyzed for both the presence and level of CMV-specific IgG antibodies (CMV-IgG), used as markers for infection status and viral reactivation, respectively. Also assessed were potential biological mediators of stress-induced reactivation, such as inflammation (C-reactive protein) and HPA function (awakening and diurnal cortisol). Predictors of CMV infection and CMV-IgG among the infected individuals were analyzed using logistic and linear regression analyses, respectively. Confirming prior reports, lower SES (education and job status) was positively associated with infection status. Among those infected (N=329), higher CMV-IgG were associated with increased anxiety (ß=.14, p<.05), depression (ß=.11, p=.06), vital exhaustion (ß=.14, p<.05), and decreased SF-12 mental health (ß=-.14, p<.05), adjusting for a range of potential confounders. Exploratory analyses showed that these associations were generally stronger in low SES individuals. We found no evidence that elevated inflammation or HPA-function mediated any of the associations. In the largest study to date, we established associations between CMV-IgG levels and multiple indicators of psychological stress. These results demonstrate the robustness of prior findings, and extend these to a general working population. We propose that stress-induced CMV replication warrants further research as a psychobiological mechanism linking stress, aging and health.

A life-style physical activity intervention and the antibody response to pneumococcal vaccination in women.

OBJECTIVE: To assess whether a life-style physical activity intervention improved antibody response to a pneumococcal vaccination in sedentary middle-aged women. METHODS: Eighty-nine sedentary women completed a 16-week exercise (physical activity consultation, pedometer, telephone/e-mail prompts; n = 44) or control (advisory leaflet; n = 45) intervention. Pneumococcal vaccination was administered at 12 weeks, and antibody titers (11 of the 23 contained in the pneumococcal vaccine) were determined before vaccination and 4 weeks and 6 months later. Physical activity, aerobic fitness, body composition, and psychological factors were measured before and after the intervention. RESULTS: The intervention group displayed a greater increase in walking behavior (from mean [standard deviation] = 82.16 [90.90] to 251.87 [202.13]) compared with the control condition (111.67 [94.64] to 165.16 [117.22]; time by group interaction: F(1,68) = 11.25, p = .001, η(2) = 0.14). Quality of life also improved in the intervention group (from 19.37 [3.22] to 16.70 [4.29]) compared with the control condition (19.97 [4.22] to 19.48 [5.37]; time by group interaction: F(1,66) = 4.44, p = .039, η(2) = 0.06). However, no significant effects of the intervention on antibody response were found (time by group η(2) for each of the 11 pneumococcal strains ranged from 0.001 to 0.018; p values all >.264). CONCLUSIONS: Participation in a life-style physical activity intervention increased subjective and objective physical activity levels and quality of life but did not affect antibody response to pneumococcal vaccination.

Vaccination response following aerobic exercise: can a brisk walk enhance antibody response to pneumococcal and influenza vaccinations?

High intensity acute exercise at the time of vaccination has been shown to enhance the subsequent antibody response. This study examines whether an acute moderate intensity aerobic intervention prior to vaccination can enhance antibody response to pneumonia and half dose influenza vaccination. Sixty young (age (SD)=22.0 (6.1) years) and 60 older (age (SD)=57.5 (6.5) years) adults attended the laboratory on two separate occasions. At the first session, baseline antibody titres were determined, before participants completed either a brisk walk around campus at >55% of their age-predicted heart rate maximum, or a resting control condition, for 45 min. After the intervention, all participants received a full-dose pneumococcal vaccination and a half-dose influenza vaccination. Four weeks later, participants returned for a follow up blood sample. Multivariate ANOVA revealed an increase in total antibody titres against the influenza vaccine (F((12,106))=25.76, p<.001, η(2)=.75) and both the IgM (F((12,106))=17.10, p<.001, η(2)=.66) and IgG (F((12,106))=25.76, p<.001, η(2)=.75) antibody titres against the pneumococcal vaccine. However, there were no significant Time×Group interactions (p's all >.15), indicating that a 45 min brisk walk prior to vaccination did not affect antibody response to either the influenza or pneumonia vaccine. The results suggest that higher intensity exercise is necessary to augment antibody response to vaccination.

Basic psychological need satisfaction, stress-related appraisals, and dancers' cortisol and anxiety responses.

Self-determination theory (Deci & Ryan, 2000) posits basic psychological need satisfaction (BPNS) as essential for optimal functioning and health. Grounded in this framework, the current study examined the role of BPNS in dancers' cognitive appraisals and hormonal and emotional responses to performance stress. Dancers reported their degree of BPNS 1 month before a solo performance. Threat and challenge appraisals of the solo were recorded 2 hr before the performance. Salivary cortisol and anxiety were measured 15 min before, and 15, 30, 45, and 60 min postperformance. Higher BPNS was associated with lower cortisol responses and anxiety intensity. Challenge appraisals mediated the association between BPNS and cortisol. Threat appraisals mediated the BPNS-anxiety intensity relationship. These findings point to the potential importance of performers' BPNS for optimal emotional and hormonal homeostasis in performance conditions.

Exercise intensity does not influence the efficacy of eccentric exercise as a behavioural adjuvant to vaccination.

Acute exercise prior to vaccination can improve the antibody response to influenza vaccination. However, both the optimal exercise protocol and the mechanisms underpinning this adjuvant effect remain unclear. The aim of the current study was to determine whether exercise intensity influenced the efficacy of the intervention. One hundred and sixty healthy young adults were randomly assigned to a resting control group or one of three intervention groups, who exercised at an intensity of 60%, 85%, or 110% of their pre-determined concentric one repetition maxima. The exercise groups performed 50 repetitions of the eccentric portion of both bicep curl and lateral raise movements. All participants then immediately received a reduced dose (50% recommended dose) influenza vaccine. Antibody titres to the three viral strains contained in the vaccine were measured at baseline and at 28 days post-vaccination. Compared to the control group, exercise enhanced the antibody response to the least immunogenic of the three strains (B/Florida). In addition, the exercise groups showed an augmented response to the A/Uruguay strain compared to control; however, this effect was observed only in men. The intervention had no effect on the antibody responses to the most immunogenic strain, A/Brisbane. Finally, antibody responses were unrelated to the intensity of the exercise bout. In conclusion, our findings provide further evidence of exercise as an adjuvant to enhance vaccination responses. The results further show that responses to the low-immunogenic antigens are particularly responsive to augmentation by acute eccentric exercise.

Phenotypic characterization of gammadelta T cells mobilized in response to acute psychological stress.

Gamma-delta (gammadelta) T lymphocytes are versatile cells that play key roles in bacterial clearance, wound repair, and delayed-type hypersensitivity reactions. Recently we showed that these cells are mobilized into the blood during acute psychological stress. gammadelta T lymphocytes are a heterogeneous population of cells, and the current study aimed to characterize the effects of stress on distinct gammadelta T cell populations. Twenty-nine healthy participants completed a 12min speech task. Blood samples were taken after a resting baseline, during the last two minutes of the task, and after a 15min recovery period. Flow cytometry was used to investigate the response of memory phenotypes (i.e. Naïve, Central memory, Effector Memory, and CD45RA(+) Effector Memory (EMRA)) within the delta1 and delta2 gammadelta T cell populations. Cells were further analysed on expression of adhesion molecules (CD11a, CD62L) and the NK-receptor CD94. Both the delta1 and delta2 subsets were mobilized during stress, and for both subsets, EMRA cells were mobilized to a much greater extent than the other memory phenotypes. Analysis of migration markers revealed that mobilized cells had a predominantly tissue migrating phenotype (CD11a(hi)CD62L(lo/neg)) and expressed high levels of the NK-receptor CD94. The current findings indicate that stress primarily mobilizes gammadelta memory cells that have high cytotoxic capability, tissue homing potential, and the capacity for rapid, innate-like target recognition. This selective mobilization possibly provides protection in contexts when tissue damage and antigen exposure are more likely to occur.

The effects of vaccine timing on the efficacy of an acute eccentric exercise intervention on the immune response to an influenza vaccine in young adults.

An acute bout of exercise prior to vaccination can improve the antibody and cell-mediated responses to influenza vaccination. The mechanisms underpinning this adjuvant effect remain unclear, and further investigation to determine the optimal exercise protocol is warranted. The aim of the current study was to determine whether exercise augmented the immune response to vaccination, and whether the timing of exercise relative to vaccination affected the efficacy of the intervention. One hundred and fifty-six (76 men) healthy participants were randomly assigned to a control group or one of three intervention groups who exercised immediately, 6h or 48 h prior to administration of a standard trivalent influenza vaccine. The exercise groups performed 50 repetitions of the eccentric portion of both the bicep curl and lateral raise movements at an intensity eliciting 85% of each participant's pre-determined concentric one repetition maxima. Antigen-specific serum antibody titres were measured at baseline and 28 days post-vaccination as indicators of the humoral response. All three viral strains elicited strong antibody responses; however, eccentric exercise did not further augment any antibody responses compared to the control group. Cell-mediated immunity at 28 days post-vaccination was determined by measuring the IFN-gamma response to in vitro stimulation of the blood with whole vaccine. There were no differences in cell-mediated immunity among the groups. Although these null findings were unexpected, they are consistent with previous research showing that exercise-induced immunoenhancement was only observed when the control group had relatively poor responses. In conclusion, it is likely that the robust immune responses to the vaccine observed in this study may have limited any further immune enhancement by exercise.

Mobilization of gammadelta T lymphocytes in response to psychological stress, exercise, and beta-agonist infusion.

The mobilization of cytotoxic lymphocytes, such Natural Killer (NK) cells and CD8(+) T cells, during stress and exercise is well documented in humans. However, humans have another cytotoxic lymphocyte subset that has not been studied in this context: the Gamma Delta (gammadelta) T lymphocyte. These cells play key roles in immune processes including the elimination of bacterial infection, wound repair and delayed-type hypersensitivity reactions. The current study investigated the effects of stress, exercise, and beta-agonist infusion on the mobilization of gammadelta T lymphocytes. Three separate studies compared lymphocytosis in response to an acute speech stress task (n=29), high (85%W(max)) and low (35%W(max)) intensity concentric exercise (n=11), and isoproterenol infusion at 20 and 40 ng/kg/min (n=12). Flow cytometric analysis was used to examine lymphocyte subsets. gammadelta T lymphocytes were mobilized in response to all three tasks in a dose-dependent manner; the extent of mobilization during the speech task correlated with concomitant cardiac activation, and was greater during higher intensity exercise and increased dose of beta-agonist infusion. The mobilization of gammadelta T lymphocytes was greater (in terms of % change from baseline) than that of CD8(+) T lymphocytes and less than NK cells. This study is the first to demonstrate that gammadelta T cells are stress-responsive lymphocytes which are mobilized during psychological stress, exercise, and beta-agonist infusion. The mobilization of these versatile cytotoxic cells may provide protection in the context of situations in which antigen exposure is more likely to occur.

Acute exercise mobilises CD8+ T lymphocytes exhibiting an effector-memory phenotype.

An acute bout of exercise evokes mobilisation of lymphocytes into the bloodstream, which can be largely attributed to increases in CD8+ T lymphocytes (CD8TLs) and natural killer (NK) cells. Evidence further suggests that, even within these lymphocyte subsets, there is preferential mobilisation of cells that share certain functional and phenotypic characteristics, such as high cytotoxicity, low proliferative ability, and high tissue-migrating potential. These features are characteristic of effector-memory CD8TL subsets. The current study therefore investigated the effect of exercise on these newly-identified subsets. Thirteen healthy and physically active males (mean+/-SD: age 20.9+/-1.5 yr) attended three sessions: a control session (no exercise); cycling at 35% Watt(max) (low intensity exercise); and 85% Watt(max) (high intensity exercise). Each bout lasted 20 min. Blood samples were obtained before exercise, during the final min of exercise, and +15, and +60 min post-exercise. CD8TLs were classified into naïve, central memory (CM), effector-memory (EM), and CD45RA+ effector-memory (RAEM) using combinations of the cell surface markers CCR7, CD27, CD62L, CD57, and CD45RA. In parallel, the phenotypically distinct CD56(bright) 'regulatory' and CD56(dim) 'cytotoxic' NK subsets were quantified. The results show a strong differential mobilisation of CD8TL subsets (RAEM>EM>CM>naïve); during high intensity exercise the greatest increase was observed for RAEM CD8Tls (+450%) and the smallest for naïve cells (+84%). Similarly, CD56(dim) NK cells (+995%) were mobilised to a greater extent than CD56(bright) (+153%) NK cells. In conclusion, memory CD8TL that exhibit a high effector and tissue-migrating potential are preferentially mobilised during exercise. This finding unifies a range of independent observations regarding exercise-induced phenotypic and functional changes in circulating lymphocytes. The selective mobilisation of cytotoxic tissue-migrating subsets, both within the NK and CD8TL population, may enhance immune-surveillance during exercise.

Complement cascade activation after an acute psychological stress task.

OBJECTIVE: To examine complement cascade activation after an acute psychological stress task. Psychological stress has been implicated in the exacerbation of inflammatory disorders. Although the complement cascade is a key component of these inflammatory processes, there has been little research regarding its susceptibility to stress. METHODS: In experiment 1, 38 healthy participants completed an 8-minute psychological stress task. Complement components were assessed from blood samples taken by venipuncture, at rest and immediately post task. In experiment 2, 40 participants undertook a similar task; blood samples were collected from a cannula at rest, immediately post task, and after 30 and 60 minutes of recovery. In experiment 3, 40 participants were exposed to both a stress and a control session. Session order was counterbalanced and, on both occasions, we received blood samples from half the participants via a cannula and the other half by repeated venipuncture. RESULTS: In experiment 1, C3a levels increased significantly from rest to task, indicating complement cascade activation. In experiment 2, we found that both C3a and Factor Bb increased significantly from rest to task and recovered by 30 and 60 minutes. C5a rose significantly 30 minutes after completion of the stress task. In experiment 3, C3a increased in response to the mental stress task, whereas it decreased slightly during the control session. There was no significant effect of blood taking method. CONCLUSIONS: These experiments demonstrate that the complement cascade is susceptible to acute psychological stress and suggest a potential mechanism for stress-induced inflammatory activation in individuals with inflammatory disorders.

Meningococcal A vaccination response is enhanced by acute stress in men.

OBJECTIVE: To determine if acute stress experienced at the time of antigenic challenge augments the subsequent immune response. METHODS: Sixty healthy young adults were randomized to exercise (n = 20), mental stress (n = 20) or control (n = 20) before meningococcal A+C vaccination. Antibody concentration was measured by microsphere-based antibody quantification assay at prevaccination, 4 and 20 weeks post vaccination. RESULTS: Meningococcal serogroup A antibody responses were enhanced by exercise and mental stress in men but not women (F(2,51) = 4.00, p = .02, eta(2) = 0.135). CONCLUSIONS: Stress-induced immune enhancement has now been demonstrated in the antibody response to thymus-independent as well as thymus-dependent vaccines. These findings indicate that this effect is not specific to T-cell involvement.

Sex differences in the interleukin-6 response to acute psychological stress.

Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory response, may mediate inflammatory disease exacerbation associated with stress. Twenty men and twenty women completed a single session, comprising baseline (20 min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken at baseline, immediately after the task, and at +30 and +60 min recovery were analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60 min recovery, and a sex difference was found in the IL-6 response, with men peaking earlier than women. These findings confirm a small delayed IL-6 increase after acute laboratory stress, and reveal sex differences in the profile of the IL-6 response.

Reductions in secretory immunoglobulin A to cold pressor stress are not influenced by timing of saliva sampling.

Acute psychological stress has been shown to alter secretory immunity, principally secretory immunoglobulin A (S-IgA). Most acute stress tasks result in increases in S-IgA, but decreases have been reported in response to the cold pressor. However, the evidence is mixed, with increases and no changes in S-IgA in response to the cold pressor also being reported. It was hypothesised that differences in the timing of saliva sampling may provide an explanation for these discrepant results. Participants completed two 4-min cold pressor tasks, each preceded by a rest period in which baseline S-IgA was measured. In one condition, S-IgA was assessed during the final 2 min of the cold pressor; in the other, it was measured immediately after completion of the task. S-IgA decreased from baseline to task, regardless of timing of saliva sampling. It was concluded that differences in timing of sampling do not account for the mixed reports in the literature.

Life events, perceived stress and antibody response to influenza vaccination in young, healthy adults.

OBJECTIVES: Chronic stress has been associated with impaired response to influenza vaccination in the elderly. This study investigated whether mild, intermittent stress experienced by young, healthy adults has a similar effect. METHODS: Antibody and psychological status were determined prevaccination and 5 weeks and 5 months later; a fourfold increase in antibody to at least one viral strain was considered protective. RESULTS: At 5 months, unprotected participants reported significantly more life events and tended to report more perceived stress than those who were protected. CONCLUSIONS: Psychological stress is detrimental to long-term maintenance of antibody levels following vaccination in young, healthy adults.

Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults.

Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process results in an accumulation of differentiated 'effector' phenotype memory T cells, predominantly driven by Cytomegalovirus (CMV) infection. Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (mean ± SD; age 21 ± 3 years, body mass index 22.7 ± 2.7 kg m(2)) were assessed for CMV serostatus, the numbers/proportions of CD4(+) and CD8(+) late differentiated/effector memory cells (i.e. CD27(-)CD28(-)/CD45RA(+)), plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV(+). A higher lymphocyte and CD8(+) count (both p < 0.01) and a lower CD4/CD8 ratio (p < 0.03) were observed in CMV(+) people. Eight percent (4/58) of CMV(+) individuals exhibited a CD4/CD8 ratio <1.0, whereas no CMV(-) donor showed an inverted ratio (p < 0.001). The numbers of CD4(+) and CD8(+)CD27(-)CD28(-)/CD45RA(+) cells were ~ fourfold higher in CMV(+) people (p < 0.001). Plasma IL-6 was higher in CMV(+) donors (p < 0.05) and showed a positive association with the numbers of CD8(+)CD28(-) cells (p < 0.03). Finally, there was a significant negative correlation between vaccine-induced antibody responses to the A/Brisbane influenza strain and CMV-specific immunoglobulin G titres (p < 0.05). This reduced vaccination response was associated with greater numbers of total CD8(+) and CD4(+) and CD8(+)CD27(-)CD28(-)/CD45RA(+) cells (p < 0.05). This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population.

Using vaccinations to assess in vivo immune function in psychoneuroimmunology.

Finding clinically relevant measures of immune function is an important challenge in psychoneuroimmunological research. Here, we discuss the advantages of the vaccination model, and provide guidance on the methodological decisions that are important to consider in the use of this technique. These include the choice of vaccination, timing of assessments, and the available outcome measures.

Antibody response to vaccination as a marker of in vivo immune function in psychophysiological research.

The hunt for novel tools to investigate empirical questions is ever present in psychophysiological research. Antibody response to vaccination has received increasing attention over recent years as a useful measure of in vivo immune function. There is now considerable evidence that the magnitude of the antibody response to vaccination is associated with a wide range of psychosocial factors. Further, there are preliminary indications that manipulating psychosocial variables, using both chronic and acute interventions, can also alter the efficacy of the vaccination. This review will discuss the theoretical and clinical relevance of the vaccine model in this context, and will address key methodological considerations for researchers considering adopting this approach. The review will also address how the strategic use of this model could help researchers further elucidate some of the remaining theoretical issues.

Cardiovascular activity and the antibody response to vaccination.

OBJECTIVE: To examine the relationship between cardiovascular activity in response to acute psychological stress and the antibody response to vaccination. METHODS: Fifty-seven healthy participants were vaccinated with the trivalent influenza vaccine and meningococcal A+C polysaccharides. Antibody levels were measured at baseline and 5-weeks post-vaccination. Cardiovascular activity was measured at rest, during, and following a mental arithmetic stress task in 54 participants. RESULTS: Participants demonstrating a fourfold increase in antibody titre to the A/Panama and B/Shangdong influenza strains and to meningococcal A showed greater blood pressure reactions toward the end of the acute stress task. In addition, there was some evidence of delayed diastolic blood pressure recovery in those who were responders to A/Panama and B/Shangdong influenza strains. CONCLUSION: The present results suggest that heightened cardiovascular reactivity to stress and delayed recovery may not necessarily be detrimental to all aspects of health and may be associated with an enhanced immune response to antigen challenge.