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Current explorations in psychoimmunology.

Psychoimmunology is a new discipline linking psychological and immunological events. Studies to date have shown parallels between animal studies which measure response to stress and human reaction to loss, such as bereavement. Stein et al., have studied T and B lymphocytes in a bereaved population, noting suppression of function for six months to one year after a loss. Bartrop has found similar correlations. Gottschalk reviewed leukocyte function in depressed patients, finding a correlation between degree of depression and suppressed chemiluminescence. Udelman attempted a correlation between immunity and psychological states. Correlations were found between hope and T- and B-cell counts. The importance of psychoimmunology is underscored by the measurable impact of emotions on the body's defenses. It would seem reasonable to assume that adequate psychological defenses would be of aid in reducing vulnerability to illness. Thus, the psychotherapist is confronted by a newly measurable challenge to aid in control of not only emotional, but also physical illness. The enhancement of immunocompetence is a truly essential goal in prevention of illness.

Antibody Formation↗

Autologous serologic responses in glioma patients. Correlation with tumor grade and survival.

The serologic responses of 42 patients with gliomas have been evaluated in a quantitative microcytotoxicity assay utilizing autologous cultured glioma cells. Forty-five percent of patients had detectable cytotoxic antibody apparently directed to their own cultured cells. When tumor grade was correlated with immune response, 15/20 patients with Grade I, II and III astrocytomas had antigens detectable in autologous sera whereas only 5/22 patients with Grade IV astrocytomas had such responses. None of the autologous fibroblasts from the 15 patients with paired gliomas and fibroblast lines had membrane antigens detectable using autologous sera and fibroblast absorption did not reduce antiglioma activity. Thus, the cytotoxicity observed in this assay appears to be restricted to tumor cells, suggesting reactivity against tumor-associated antigen. In addition, it appears that these immune responses are highly correlated with survival in primary malignant brain tumor patients.

Antibodies, Neoplasm↗

[HIV vaccines].

The devastation caused by the HIV pandemic will probably not be quelled until a safe and effective vaccine has been developed that is also affordable and available in the developing countries where the impact of this virus is most severe. Considerable progress has been made over the past several years in the search for a vaccine against HIV: roughly 30 different types are currently being investigated in phase I/II clinical trials. Major scientific challenges nonetheless still remain. An ideal vaccine would elicit both neutralizing antibodies and cytotoxic T lymphocytes (CTL) and, perhaps, mucosal immune response. The precise correlates of immunity have not been defined. Recombinant live vector-based vaccines, lipopeptides, and plasmid DNA have all been shown to induce CTL. The different forms of prime-boost vaccine strategies currently being tested in numerous clinical trials provide reasons for hope.

AIDS Vaccines↗

Influence of DNA encoding cytokines on systemic and mucosal immunity following genetic vaccination against herpes simplex virus.

The aim of our investigation was to improve the effectiveness of DNA vaccines against herpes simplex virus (HSV) infection. We chose coimmunization with DNA encoding cytokines known to emphasize components of immune defense that best correlate with immune protection. These include interferon-producing T and NK cells and the IgG2a isotype immunoglobulin. Our results show that the coadministration of plasmid DNA encoding IL-12 or IL-18 along with glycoprotein B (gB) DNA improves immune induction. Recipients of the coimmunization procedure had elevated humoral as well as IFN-gamma-producing T cell responses and showed greater resistance to vaginal challenge with a lethal dose of HSV-1. The adjuvant effects were observed when the vaccines were administered either systemically or mucosally. By most assays, the adjuvant effect of IL-18 was superior to IL-12, although gB DNA plus IL-18 failed to induce levels of immunity achieved by UV-inactivated HSV immunization. Mucosal immunization proved as an effective means of inducing systemic immunity, but was less effective than the systemic route for inducing protection from vaginal challenge. Our results also demonstrated that protection from such challenges was mainly a property of IFN-gamma. Thus, immunized IFN-gamma-/- mice remained susceptible to challenges even while generating readily measurable immune responses. The approach of using DNA vaccines combined with DNA encoding cytokines holds promise and represents a potentially useful approach for vaccines.

Administration, Intranasal↗

Factors affecting influenza vaccine uptake among health care workers.

BACKGROUND: In 2000, the UK Departments of Health recommended influenza immunization to employees directly involved in patient care. Uptake of this immunization had tended to be variable and usually low. AIMS: To assess personal and organizational factors associated with influenza immunization uptake among Health Care Workers (HCWs). METHODS: A cross-sectional survey of all HCWs within the Health and Social Care Trusts in Northern Ireland and a parallel-group study of nursing staff within Elderly Care using self-administered questionnaires. RESULTS: Of 203 nurses working in elderly care units 76(37%) were immunized and 127(63%) declined. Almost 70% of those not immunized perceived themselves to be 'healthy' and gave this reason for declining immunization. Nurses were more likely to be immunized by a factor of four if they believed there was benefit for healthy HCWs, three if they felt at-risk of contracting influenza and nine on a recommendation from the occupational health (OH) unit. Fifteen OH units participated in a survey of HCWs at the time of immunization. Five thousand two hundred and thirty (9.7%) HCWs were immunized. Increased uptake was correlated with immunization in area of work (r=0.74, P=0.02) and when provided out of hours (r=0.83; P<0.001) and by a factor of two with individual targeting of availability (P<0.001) and when individuals had been previously immunized (P<0.001). CONCLUSION: Uptake of influenza immunization is low. Attitudes to one's health and to the value of influenza immunization affect the uptake as does the delivery of the immunization programme.

Adult↗

[Immunity to and incidence of measles in a population of Parisian children].

BACKGROUND: Measles remains prevalent in France despite the development of nationwide vaccination program. This study evaluates measles immunity and correlates it with active immunization. MATERIAL AND METHODS: A total of 250 (131 boys and 119 girls) French children, aged 2 to 15 years, seen as outpatients in our hospital, were studied from 1.01.90 to 1.06.91; 133 had received live measles vaccine during the 2nd year of life, the 117 others were not vaccine-protected. Evaluation included medical records, specially those concerning past-history of measles or measles-like diseases and immunizations. Measles IgG and IgM antibodies (ELISA) were looked for in all 250 children. RESULTS: 102 of the 117 children who were not vaccine-protected had a detectable antibody titer. 42 of these 102 had a history of measles, before the age of 5 years in 30, between 5 and 10 years in 9 and after the age of 10 years in 3. Only 4 of the 70 children aged over 10 years and not vaccine-protected had no detectable antibodies. 131 of the 133 actively immunized children had detectable antibodies. CONCLUSIONS: Measles is probably more frequently subclinical than was believed until now. Its relative frequency in France in children who had not received the live vaccine explains the high percentage of those aged over 10 years who had detectable antibodies and the relatively low incidence of the disease in teenagers and young adults.

Adolescent↗

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection.

T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV. In this report we correlate improvements in markers of immune function with a decrease in apoptosis, and changes in its regulation. Therapy with nelfinavir plus saquinavir in combination with two nucleoside analogue inhibitors of reverse transcriptase dramatically reduces plasma viremia and increases CD4 T cell counts. Coincident with these improvements, CD38 and HLA-DR coexpression on both CD4 and CD8 T cells decrease, and CD45RA and CD62L coexpression increase. Furthermore, spontaneous apoptosis decreases in both CD4 and CD8 T cells (CD4 apoptosis 17.4 vs 2.6%, P=0.005; CD8 apoptosis 15.0 vs 1.0%, P<0.001), as does both Fas mediated apoptosis (CD4 apoptosis 19.0 vs 3.5%, P=0.03; CD8 apoptosis 13.7 vs 1.5%, P=0.002) and CD3 induced AICD (CD4 apoptosis 13.7 vs 3.2%, P=0.001; CD8 apoptosis 29 vs 2.2%, P=0.08). Changes in apoptosis are not associated with changes in Fas receptor expression, but are significantly correlated with changes in activation marker profiles. Although this suggests a possible regulatory role for the apoptosis inhibitory protein FLIP, direct assessment did not reveal quantitative differences in FLIP expression between apoptosis resistant PBL's from HIV negative patients, and apoptosis sensitive PBL's from HIV positive patients. These findings support the hypothesis that apoptosis mediates HIV induced CD4 T cell depletion, but indicate the need for further studies into the molecular regulation of HIV induced apoptosis.

Adolescent↗

Vaginal lactobacilli in adolescents: presence and relationship to local and systemic immunity, and to bacterial vaginosis.

OBJECTIVE: The objective of this study was to survey middle adolescents for the presence of vaginal lactobacilli, lactobacilli-specific immune sensitization, and correlates of vaginal immunity with lactobacilli and bacterial vaginosis (BV). METHODS: A cohort of 89 female adolescents were evaluated for the presence of vaginal lactobacilli species, H2O2-producing species, and the prevalence of BV. Cytokines and antibodies in cervicovaginal lavages were detected and peripheral blood lymphocyte (PBL) responses to Lactobacillus crispatus were evaluated. RESULTS: The majority of lactobacillus species were H2O2-producing and predominated by Lactobacillus acidophilus. PBL responses to lactobacilli were detectable in 50% of the cohort. BV was present in 36% of adolescents and negatively correlated with the presence of vaginal lactobacilli. The majority of locally associated cytokines and antibodies were similar in those with or without BV or lactobacilli. CONCLUSIONS: Adolescents harbor vaginal lactobacilli with relationships to BV along with lactobacilli-specific immune sensitization, but with few correlates of local immunity to lactobacilli or BV.

Adolescent↗

Depressed immune response in malnourished rats correlates with increased thymic noradrenaline level.

Depressed immune response is well documented in protein-calorie malnutrition (PCM). Also, central and peripheral noradrenaline (NA) activities have been reported to be increased in malnourished animals. Since increases in central and peripheral NA may inhibit immune function, it is possible that malnutrition-induced immunodepression could be mediated by noradrenergic hyperactivity. To address this hypothesis the effect of malnutrition on cell-mediated immune response, as well as on NA levels of the median eminence, spleen and thymus was studied in PCM rats. Decreased lymphoproliferative response and IL-1 production by mononuclear macrophages was observed in PCM. Besides, increased NA concentration was detected in thymuses of PCM rats, while unchanged levels of this neurotransmitter were observed in median eminence and spleen. These data suggest a positive correlation between malnutrition-induced immunodepression and sympathetic noradrenergic activity in thymus, an organ implicated in immune cell differentiation during early development.

Animals↗

The L1210 assay for immune complexes: application in cancer patients and correlation with disease progress.

Immune complexes (ICs) were determined by the non-complement-dependent L1210 radioimmune assay on 132 serum samples collected from 53 patients with a variety of cancers. Both the mean IC levels and frequency of positive tests were significantly greater in cancer patients (mean = 96 +/- 100 microgram/ml, 46% positive) than in a control group of 67 normal healthy blood donors (mean = 39 +/- 15, 3% positive). When cancer patients were assorted into groups by disease progress, those with large or progressing tumors had significantly higher mean values (136 +/- 129) and frequency of positives (75%) than those with small or regressing tumors (58 +/- 18, 22% positive). In lung cancer patients, IC levels showed a strong inverse correlation (rs = -0.903) with survival time in patients who died, and appeared to be a better prognostic indicator than performance status (Karnofsky scale) at time of diagnosis. Serial IC measurements taken on several patients showed a decrease in levels concomitant with a favorable response to cytoreductive therapy, sustained normal levels during periods of prolonged remission, and a rise to elevated levels with (and sometimes preceding) documentation of new metastases.

Animals↗

Differential epitope positioning within the germline antibody paratope enhances promiscuity in the primary immune response.

Correlation between the promiscuity of the primary antibody response and conformational flexibility in a germline antibody was addressed by using germline antibody 36-65. Crystallographic analyses of the 36-65 Fab with three independent dodecapeptides provided mechanistic insights into the generation of antibody diversity. While four antigen-free Fab molecules provided a quantitative description of the conformational repertoire of the antibody CDRs, three Fab molecules bound to structurally diverse peptide epitopes exhibited a common paratope conformation. Each peptide revealed spatially different footprints within the antigen-combining site. However, a conformation-specific lock involving two shared residues, which were also associated with hapten binding, was discernible. Unlike the hapten, the peptides interacted with residues that undergo somatic mutations, suggesting a possible mechanism for excluding "nonspecific" antigens during affinity maturation. The observed multiple binding modes of diverse epitopes within a common paratope conformation of a germline antibody reveal a simple, yet elegant, mechanism for expanding the primary antibody repertoire.

Animals↗

Correlation of in vitro immune response with clinical course of malignant neoplasia in dogs.

An attempt was made to quantify the host antitumor immune response in 16 dogs with progressively growing tumors by evaluating the in vitro reactivity of their lymph node or peripheral blood lymphocytes to their own tumor cells. Serum from dogs with the same histologic type of neoplasm inhibited allogenic lymphocyte cytotoxicity, whereas serum from normal dogs, and a dog clinically free of osteosarcoma 17 months after limb amputation, did not significantly block cell-mediated reactivity. Low ratios of sensitized lymphocytes to tumor cells often stimulated tumor cell growth in vitro. Autologous serum from dogs with progressively growing neoplasms appeared to potentiate the stimulation of tumor growth above a simple blocking of lymphocyte-mediated cytotoxicity. An attempt was made to correlate the in vitro immune reactivity of the dog to the clinical behavior of its neoplasm. There was fair to good correlation in 12 dogs and no correlation in the remaining 4 dogs.

Animals↗

Effects of organochlorine contaminants on loggerhead sea turtle immunity: comparison of a correlative field study and in vitro exposure experiments.

Several laboratory and field studies indicate that organochlorine contaminants (OCs), such as polychlorinated biphenyls (PCBs) and pesticides, modulate immune responses in rodents, wildlife, and humans. In the present study we examined the effects of OCs on immunity in free-ranging loggerhead sea turtles (Caretta caretta). Mitogen-induced lymphocyte proliferation responses, lysozyme activity, and OC concentrations were measured from blood samples. Mitogens chosen in the lymphocyte proliferation assay were phytohemagglutinin (PHA) and concanavalin A (ConA) for T-lymphocyte stimulation, and lipopolysaccharide (LPS) and phorbol 12,13-dibutyrate (PDB) for B-lymphocyte stimulation. Lysozyme activity was significantly and negatively correlated with whole-blood concentrations of 4,4 -dichlorodiphenyldichloroethylene (4,4 -DDE) and the sum of chlordanes. Lymphocyte proliferation responses stimulated by PHA, LPS, and PDB were significantly and positively correlated with concentrations of the sum of PCBs measured in whole blood. LPS- and PDB-induced proliferation were also significantly and positively correlated with 4,4 -DDE blood concentrations. These correlative observations in free-ranging turtles suggest that current, chronic exposure to OCs may suppress innate immunity and enhance certain lymphocyte functions of loggerhead sea turtles. To further test this hypothesis, lymphocyte proliferation was measured after in vitro exposure of peripheral blood leukocytes from 16 turtles to Aroclor 1254 (0-13.5 microg/mL) or 4,4 -DDE (0-13.4 microg/mL). Both contaminants increased PHA- and PDB-induced proliferation at concentrations below those that affected cell viability. Moreover, the concentrations that enhanced PDB-induced proliferation in vitro were similar to concentrations measured in turtles with the highest proliferative responses. The similarities between the in vitro experiments and the correlative field study suggest that OC exposure modulates immunity in loggerhead turtles.

Animals↗

Differentiation of entamoeba histolytica/entamoeba dispar by PCR and their correlation with humoral and cellular immunity in individuals with clinical variants of amoebiasis.

To correlate a particular state of immunity with Entamoeba spp., we used colorimetric PCR to differentiate E. histolytica from E. dispar in individuals with amoebiasis and to associate its presence with the clinical profile, including humoral and cellular immune responses to E. histolytica. Our results showed high levels of antibody in acute amoebiasis and elevation of IL-4 production, a cytokine related to Th2 profile, associated with E. histolytica. In chronic amoebiasis, even with anti-E. histolytica seropositivity, intestinal symptoms were associated with E. dispar in all the cases, without differences in level of antibodies, BTI, CD4+/CD8+ ratio, INF-gamma, and IL-4. Among asymptomatic carriers, E. dispar was more frequently found; however, identification of E. histolytica in two asymptomatic carriers associated with high levels of INF-gamma, a cytokine related to Th1 profile, demonstrate the importance of making specific diagnosis of Entamoeba spp., to establish the clinical and epidemiological behavior in both intestinal and extra-intestinal amoebiasis.

Acute Disease↗

Immune complexes in uveitis.

We determined the incidence of immune complex increases, the nature of immune complexes, and the correlation between the immune complex level and clinical uveitis status in patients with chronic iridocyclitis and chronic diffuse uveitis. Ten of 16 patients with chronic iridocyclitis had increased levels of immune complexes, and this correlated with disease activity. Immune complexes were detected in ten of 12 patients with chronic diffuse uveitis. These complexes have a molecular weight of approximately 2 X 10(6) daltons. The antibody component of immune complex is IgG; however; the antigenic component of the immune complexes is unclear.

Adolescent↗

Cell mediated immune response in patients with Chagas. Correlation with the presence of Chagasic cardiomyopathy.

We are reporting data from a series of studies undertaken to evaluate if there was any correlation between the cell mediated immune response and the presence of Chagasic cardiomyopathy. Infected patients without evidence of heart pathology (INF), infected patients with Chagasic cardiomyopathy (CDM) and healthy controls, were studied. We evaluated: a) the correlation of the immune response with the presence of parasitemia; b) the suppression induced by Trypanosoma cruzi antigens using a costimulation assay; c) their production of IL2 when stimulated with antigens and mitogen; and d) the response of variable proportion of T cells subpopulations to parasite antigens. The immune response of INF was lower when parasitemia could be demonstrated. The negative regulation of the cell mediated immune response was higher in INF. The production of IL2 was lower in patients than in controls. CDM patients showed a tendency to produce less IL2 than INF. The outline of the response of variable proportions of subsets of T cells had a high concordance in CDM and no concordance in INF. These results show that there are differences in the cell mediated immune response of INF and CDM. The high concordance of the response of variable proportions of T cells, from CDM, suggests that this test could have a prognostic value.

Animals↗

[Correlation between the indices of immunity and virus elimination in cytomegalovirus infection].

Correlations between titres of complement-fixing antibody, levels of E-RFC, Ea-RFC, EAC-RFC, EA-RFC, and the intensity of virus excretion in the saliva and urine of women with chronic form of cytomegaly, as well as the effect of decaris in vitro on the level of E-RFC were studied. The highest antibody titres were found in subjects with generalized infection (virus excretion in the saliva and urine) and in cases where high concentrations of the virus were found in the salivary gland cells. In these subjects, total levels of E-RFC and their active subpopulations were decreased. The lowest antibody titres were found in women excreting no virus in the study period. Relative amounts of E-RFC and Ea-RFC in them were within normal ranges. No correlation between the levels of EAC-RFC, EA-RFC, and virus excretion was found. Decaris in vitro normalized the reduced values of E-RFC. Theoretical substantiation of the possibility of using this drug for treatment of patients with cytomegalovirus infection is presented.

Antibodies, Viral↗