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PubMedDate not supplied

Biological markers of host susceptibility to air pollutants in epidemiologic studies on chronic airways obstruction.

Measuring the variations in risk among individuals or populations of environmentally induced chronic airways obstruction is necessary to develop rational policy to reduce the incidence of those diseases in a given population. Before being able to formulate this policy, however, one must know how to detect those individuals who are susceptible to ari pollutants since they are at increased risk of disease. In the paper the authors discussed several monitoring techniques to detect markers of early biological events relevant to host susceptibility and disease progression. The biological markers are based on genetic traits, pulmonary function tests, biochemical and immune changes. The authors discuss merits and demerits of particular approaches in identifying persons prone to chronic airways obstruction. They stress the point that more research is needed on biochemical and immunological markers of lung injury to assess their usefulness in identifying individuals at higher risk.

Air Pollutants↗
PubMed1994

HIV-1 immunogen induction of HIV-1-specific delayed-type hypersensitivity: results of a double-blind, adjuvant-controlled, dose-ranging trial.

OBJECTIVE: To investigate the capacity of an HIV-1 immunogen to induce or augment HIV-1-specific delayed-type hypersensitivity (DTH) over a range of doses in asymptomatic HIV-1-seropositive adults. DESIGN: A single center, double-blind, adjuvant-controlled, dose-ranging trial involving 48 HIV-1-seropositive asymptomatic patients. Each dose group consisted of 12 subjects, eight receiving HIV-1 immunogen and four incomplete Freund's adjuvant (IFA). The doses studied were 50, 100, 200, or 400 micrograms (total protein). The HIV-1 immunogen was administered intramuscularly every 4 weeks for 36 weeks, with dosing contingent on the lack of an HIV-1 immunogen DTH response. A maximum of six doses was permitted. METHODS: Immunogenicity was assessed every 4 weeks by DTH skin testing to the inactivated HIV-1 antigen in saline with > 9 mm induration representing a response to immunization. Changes in p24-antibody levels were determined by endpoint titration using an enzyme-linked immunosorbent assay and Western blot. RESULTS: At doses of > or = 100 micrograms, all treated patients demonstrated significant differences in the ability to mount an HIV-1-specific cell-mediated response relative to adjuvant controls. Dose-related response patterns were observed in the period between doses and the occurrence of rises in HIV-1 DTH. Treatment appeared to increase p24-antibody titers as well as reactivities to other HIV-1 antigens as determined by Western blots. The HIV-1 immunogen was well tolerated. CONCLUSIONS: The minimum dose of the HIV-1 immunogen in IFA required to induce HIV-1 DTH relative to the IFA control group was 100 micrograms in this patient population.

Adult↗
PubMed1993

[Macrophage activation syndrome in lupus].

A patient with systemic lupus erythematosus developed unexplained fever, nonregenerative anemia, leukopenia, and elevations in serum triglyceride and ferritin levels. Bone marrow studies established the diagnosis of macrophage activation syndrome with active hemophagocytosis. No infectious cause was found but pulmonary nocardiosis developed during the course of the disease. Intravenous gammaglobulin therapy was followed by a transient remission. Cyclophosphamide was given subsequently. In lupus patients, macrophage activation syndrome is exceedingly rare and has the same clinical, laboratory, and histologic features as those seen in patients with hemopathies, infections, or immune deficiencies. Investigations for an underlying infection are often negative, suggesting that the macrophage activation syndrome is due to lupus-related immune changes. Treatment is not standardized and relapses are common. This diagnosis should be considered in lupus patients with febrile pancytopenia.

Adult↗
PubMedDate not supplied

[Parameters of cellular and humoral immunity in patients with diabetes mellitus in the early stages of disease development; experience in treatment with the immunosuppressant azathioprine].

A total of 40 patients with type I diabetes mellitus, in whom the disease was diagnosed 1 to 12 months previously, were examined. An imbalance between the T and B cellular components of the immunity was found in the patients with the early stages of the disease, as was an elevated titer of the complement C1 component as against the reference group. The degree of the immunologic shifts was in direct correlation with the HLA A9 antigen expression, this relationship being the most marked in cases with the HLA DR3 and DR4. The incidence of these antigens expression was significantly higher in the patients with marked immunity shifts, than in those with negligible immunity changes. Therapy with an immunosuppressant azathioprine was associated with a noticeable reduction of the initially elevated cellular immunity parameters (total T and B lymphocyte counts, T helpers-inductors, DR carriers) and a trend towards a reduction of all the components and total activity of the classical route of the complement activation predominantly at the expense of the C1 and C5 components. The efficacy of this drug in therapy of new cases of insulin-dependent diabetes mellitus was confirmed, and the indisputable relationship between the efficacy of immunity suppression, that helped achieve a clinical remission, and the disease duration, was demonstrated. Monitoring of the cellular and humoral immunity parameters, of the activity of the classical route of the complement activation permitted an indirect judgement on the usefulness of immunity suppression for the correction of immunity disorders as factors contributing to the development of microvascular disturbances in insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1993

European isolation and confinement study. Confinement and immune function.

During spaceflight, several unusual factors act on the physiology of the astronaut: weightlessness, radiation, confinement, isolation, living and working in a small group, workload, and anxiety. The resulting physiological changes are known to include alterations of the immune system. It is difficult to determine from observations on astronauts which space-related factor(s) are responsible for the immune changes. Studies of analogous environments on Earth have supplied only scarce information. Dedicated simulation studies provide a better tool, where some space-related stress factors (weightlessness, radiation) are absent, but others are or can be present: isolation and confinement, small group living, workload, and anxiety. A reduction in immune activity was found in bed rest studies and in long-term Soviet confinement experiments (after 90 days). In the ISEMSI confinement experiment (28 days), a tendency to immune activation (PHA-reactivity and interleukin-2 production) was observed in two out of six subjects. There is a need for further experiments, in which a large number of immunological parameters can be analyzed.

Humans↗
PubMed1994

Specific and nonspecific aspects of humoral immune response in leprosy.

1. We have studied some generic and specific aspects of the humoral immune response in 96 patients with leprosy (29 paucibacillary and 67 multibacillary individuals). We determined serum immunoglobulins (IgM, IgG and IgA), CH50, C1q, C3 and C4, circulating immune complexes (CIC), C-reactive protein (CRP), rheumatoid factor (RF) and antinuclear antibodies. No specific pattern of general humoral immune changes could be observed. 2. The specific immune response was studied by the detection of specific IgM anti-M. leprae antibodies. An immunoradiometric assay (IRMA) and an ELISA were compared for clinical effectiveness. IRMA showed greater sensitivity for the serodiagnosis of leprosy as compared to ELISA (88.1% vs 58.2% for multibacillary patients and 20.7% vs 10.3% for paucibacillary leprosy patients). Specificity was 96% for IRMA and 97% for ELISA. 3. Our results indicate that nonspecific changes in the humoral immune response are of little value in assessing leprosy patients and that immune assays for the detection of specific anti-M. leprae antibodies may be of value in the diagnosis, study and follow-up of these patients.

Adolescent↗
PubMedDate not supplied

[Antiendomysial antibodies: current role in the diagnosis of celiac disease compared to antigliadin antibodies].

We evaluated in parallel the action of antigliadin (AGA-IgA) and anti-endomysium (EmA) antibodies in a group of 144 coeliac patients during the various diagnostic procedures, and in 277 controls (206 affected by other gastroenterological diseases and 71 healthy or affected by non-gastroenterological diseases, not causing any immune changes). Little difference was observed between the two tests both during the initial phase of the disease and during gluten-free diet. No EmA positivity was observed in controls; AGA-IgA resulted positive in 6.3% of gastroenterological controls and in 5.6% of non-gastroenterological controls. Finally, the sensitivity, specificity and predictability of the two tests were evaluated in a sample of 92 subjects undergoing intestinal biopsy. The results show that the tests have the same sensitivity, but only for EmA 100% specificity was found.

Adolescent↗
PubMed1993

Immunologic changes occurring at kindergarten entry predict respiratory illnesses after the Loma Prieta earthquake.

Previous studies in adult populations have demonstrated alterations in immune function after psychologically stressful events, and pediatric research has shown significant associations between stress and various childhood morbidities. However, no previous work has examined stress-related immune changes in children and subsequent illness experience. Twenty children were enrolled in a study on immunologic changes after kindergarten entry and their prospective relationship to respiratory illness (RI) experience. Midway through a 12-week RI data collection period, the October 17, 1989 Loma Prieta earthquake occurred. The timing of this event created a natural experiment enabling us to study possible associations between immunologic changes at kindergarten entry, the intensity of earthquake-related stress for children and parents, and changes in RI incidence over the 6 weeks after the earthquake. Immunologic changes were measured using helper (CD4+)-suppressor (CD8+) cell ratios, lymphocyte responses to pokeweed mitogen, and type-specific antibody responses to Pneumovax, in blood sampled 1 week before and 1 week after school entry. RI incidence was assessed using home health diaries and telephone interviews completed every 2 weeks. RIs per child varied from none to six. Six children showed an increase in RI incidence after the earthquake; five experienced a decline. Changes in helper-suppressor cell ratios and pokeweed mitogen response predicted changes in RI incidence in the postearthquake period (r = .43, .46; p < .05). Children showing upregulation of immune parameters at school entry sustained a significant increase in RI incidence after the earthquake.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation↗
PubMedDate not supplied

Evidence that CRH microinfused into the locus coeruleus decreases cell-mediated immune response in rats.

Rat/human-corticotropin-releasing hormone (CRH) microinfused unilaterally into the locus coeruleus (LC) of awake, chronically cannulated rats produced intense behavioral stimulation accompanied by a marked decrease of the proliferative response of splenocytes to Con A and LPS and natural killer activity. These effects were specifically prevented by prior administration into the same site of the CRH antagonist (alpha-helical CRH [9-41]). The present results confirm that a strict relationship exists between the CNS and cell-mediated immunity; in addition, they also indicate that CRH produces its behavioral and immune changes by an interaction with specific receptors and that one of the main sites through which CRH exerts these effects is represented by the LC.

Animals↗
PubMed1995

[Correlation between HLA antigens and immune status in dust-induced lung diseases in workers of machine-building industry].

Simultaneous study of immune state and HLA-testing was conducted for 73 patients with pneumoconiosis and 52 sufferers from dust bronchitis. The HLA antigens appeared to correlate with immune disorders in those diseases. The study revealed differences in the HLA antigens causing immune changes in pneumoconiosis and dust bronchitis. Those differences corresponded to differences between the markers of propensity to those diseases. Thus, the authors assume that formation of pneumoconiosis or dust bronchitis could depend on genetically determined variants of immune disorders.

B-Lymphocytes↗
PubMedDate not supplied

Immune effects of preoperative immunotherapy with high-dose subcutaneous interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the neurohormone melatonin in gastrointestinal tract tumor patients.

Surgery-induced immunosuppression could influence tumor/host interactions in surgically treated cancer patients. Previous studies have shown that high-dose IL-2 preoperative therapy may neutralize surgery-induced lymphocytopenia. Moreover, experimental studies have demonstrated that the immunomodulating neurohormone melatonin (MLT) may amplify IL-2 activity and reduce its dose required to activate the immune system. On this basis, we have compared the immune effects of presurgical therapy with high-dose IL-2 with respect to those obtained with preoperative neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study included 30 patients with gastrointestinal tract tumors, who were randomized to undergo surgery alone, or surgery plus a preoperative biotherapy with high-dose IL-2 (18 million IU/day subcutaneously for 3 days) or low-dose IL-2 (6 million IU/day subcutaneously for 5 days) plus MLT (40 mg/day orally). Patients underwent surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to prevent surgery-induced lymphocytopenia. However, mean number of lymphocytes, T lymphocytes and T helper lymphocytes observed on day 1 of postoperative period was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. Moreover, toxicity was less in patients treated with IL-2 and MLT. This biological study shows that both immunotherapy with high-dose IL-2 or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively are tolerated biotherapies, capable of neutralizing surgery-induced lymphocytopenia in cancer patients. Moreover, the study would suggest that the neuroimmunotherapy may induce a more rapid effect on postoperative immune changes with respect to IL-2 alone.

Adult↗
PubMedDate not supplied

[Historical aspects of the risk factors of Schistosoma intercalatum schistosomiasis].

Bilharziosis is a considerable public health problem. It is caused by many species of schistosoma, four of which have wide geographical distribution: Schistosoma mansoni, S. haematobium, S. japonicum and S. intercalatum. The recently discovered S. intercalatum is limited to central and west Africa. Its spread is progressive and its pathogenicity is not completely known. S. intercalatum bilharziosis is usually manifested in the form of dysentery. The physiopathologic explanation of this clinical manifestation is less clear. Immunopathologically, the formation of an inflammatory granuloma constitutes the origin of its symptoms. This is due to many biological factors including delayed hypersensitivity reactions. All cellular immunity changes will facilitate the appearance of symptoms. Our aim has been to show the importance of malnutrition as a pathogenic factor of S. intercalatum bilharziosis. The initial research hypothesis was as follows: malnutrition plays a role in the evolution of a patient from an asymptomatic state of infection to a symptomatic state of illness. We carried out the study in the suburbs of Bata, in Equatorial Guinea. The inhabitants of Ncolombong, essentially rural immigrants, comprised our study population. Following their consent, we recruited individuals less than 45 years of age who had not taken praziquantel during the last 12 months. We included a total of 297 patients. Our study was a case-control, matching on sex and age. A case was defined as an infected patient with acute or chronic diarrhea occurring within the last month' preceding the stool sample analysis. All cases were retained after exhaustive screening of the study population. Each case (group 1) was matched with one or several asymptomatic infected patients (group 2) and two or several asymptomatic noninfected patients chosen at random (group 3). The definition of malnutrition was as follows: weight/height < or = 90% for children less than 15 years of age or weight/height < or = 90% with a corporal mass index < or = 20 for children more than 15 years of age. Two logistical regression models were performed in order to distinguish pathogenic from infection factors. Among the confusion bias identified, none of the helminthiasis in Bata are risk factors. The risk factors of the infection have been searched with an interrogatory. The bias caused by the interviewer is minimized because all the team staff were trained for a week before the beginning of the study. Apart from malnutrition, the other causes of cellular immunodeficiency do not seem to have any relationship with the development of symptoms. The logistical model of infection identified the classical risk factors of infection: river leisures (OR = 3.97, CI 95%: 1.86-8.47), poor or average quality of walls of the house (OR = 2.53, CI 95%: 1.15-5.58), lack of water well (OR = 2.08, CI 95%: 1.08-4). Our study could not show any relationship between malnutrition and bilharziosis. The nutritional state does not play a significative role in the infection or development of the disease. Nevertheless, the nutritional state of the host probably influences other host or parasite factors. As a result, we still don't know its influence on ADCC (Antibody Dependent Cellular Mediated Cytotoxicity) mechanisms, on adult parasite adaptation and the efficiency of laying of eggs which affects the parasitological charge. We haven't found any relationship between parasitological load and appearance of symptoms. The parasitological load indirectly reflects the efficiency of the laying and nothing proves that it is correlated with the intensity of delayed type hypersensibility reactions. In the logistical model of the disease, a stay of more than 2 months in an endemic area (OR = 0.14, CI 95%: 0.03-0.76) and a poor or average quality of walls of the house decreased the risk (OR = 0.31, CI 95%: 0.11-0.85). This result permits us to suppose that there is a tolerance to schistosomian antigens by cellular immunity

Acute Disease↗
PubMed1977

[Alteration of the natural humoral immunity in experimental diphtheritic infection induced by different doses of the agent].

The authors carried out a complex study of natural humoral immunity factors in rabbits experimentally infected with various doses of diphtheria bacillus (500, 200, 100, 50 and 1 million, 10 000 and 1000 microorganisms). Natural protection factors--the complement, properdin, and lysozyme proved to undergo similar dynamic changes with each infection dose. The extent and direction of the changes depended on the infection dose. No significant natural immunity changes were caused by a low dose. A dose of 10 000 microbes caused stimulation of properdin and lysozyme activity. Dose of 1, 5, and 50 million suppressed the activity of all the components, the most pronounced with the later dose. Changes occurring with the doses of 200 and 100 million microbes were phasic in character.

Animals↗
PubMed1996

Long-term assessment of interferon responses in the HIV+ and AIDS patients.

Impairment of interferon (IFN) system in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) became a basis for searching IFN responses to monitor the disease progression. For detailed investigations 16 HIV+/AIDS patients with at least 4 successively taken blood samples available for IFN determinations were selected. IFN responses were tested in two ways. Firstly, IFN level in plasma was measured. Secondly, capacity of IFN production by leukocytes was evaluated. The latter was determined in the whole blood assay, in which Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as IFN-alpha and IFN-gamma inducers, respectively. The levels of IFN induced in whole blood leukocytes varied considerably in all individuals that had been tested. Nevertheless, two patterns of IFN responses were observed. In pattern I, patients had low levels of IFN in plasma and high levels of induced IFN-alpha and IFN-gamma. It was characteristic for 8 patients in good clinical condition. On the contrary, severe disease found in 2 patients was correlated with high levels of IFN in plasma and low levels of induced IFNs (pattern II). In 6 patients IFN responses were classified as intermediate pattern I/II suggesting transition from pattern I to pattern II. A variation of pattern I was found in the case of a patient defined as long-term survivor having relatively low levels of all IFN tested. The results suggested that interferon measurements reflected clinical condition of HIV+ patients showing not only past but also current immune changes.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Diurnal rhythmicity of human cytokine production: a dynamic disequilibrium in T helper cell type 1/T helper cell type 2 balance?

Diurnal rhythmicity is a characteristic of neuroendocrine pathways but is less understood in relation to immune function. We asked whether cellular (type 1) or humoral (type 2) immune responses or type 1/type 2 balance exhibit diurnal rhythmicity in healthy humans, and, if so, whether this is related to plasma levels of cortisol or melatonin, two hormones with immunomodulatory actions. LPS- or tetanus-stimulated human whole blood IFN-gamma and IL-10 production, and the IFN-gamma/IL10 ratio exhibited significant diurnal rhythmicity. The IFN-gamma/IL-10 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma melatonin. IFN-gamma and, to a lesser extent, IL-10 production was sensitive to inhibition by exogenous cortisone; the IFN-gamma/IL-10 ratio decreased by >70% after the administration of oral cortisone acetate (25 mg). Our findings support the concept that plasma cortisol and possibly melatonin regulate diurnal variation in the IFN-gamma/IL-10 ratio. As IFN-gamma and IL-10 have opposing effects on cellular immunity, changes in their balance would be anticipated to impose diurnal rhythmicity on cellular immunity. This implies that the nature of an immune response, e.g., to vaccination, may be modified by the time of day of Ag presentation and could be therapeutically manipulated by the administration of cortisol or melatonin.

Antigen Presentation↗
PubMedDate not supplied

Individual susceptibility to inhaled pollutants--identification, mechanisms and public health policy implications.

In every community, there are individuals whose chances of illness or accident are greater than those of others. In susceptible persons, adverse health effects occur at a lower exposure than in the majority of population. The reason for this, though often weak, can usually be ascertained. The paper focuses primarily on host factors that may increase an individual's susceptibility to air pollutants present in the general environment. These factors include genetic background, age, gender, nutritional status, physiological status, presence of coexisting lung disease, and lifestyle. They relate to various mechanisms of individual susceptibility to air pollutants from the environment into the body, to alterations in detoxification and immunological reactions, and to variations in the responsiveness of lung tissues. Several epidemiological techniques to detect biological events relevant to host susceptibility and disease progression are mentioned. They are mainly based on genetic traits, host characteristics, pulmonary function tests, biochemical and immune changes. Measuring the variations in risk among susceptible individuals is necessary to assess correctly respiratory health risk due to inhaled pollutants at the population level, and subsequently to develop rational public health policy to reduce the incidence of those diseases in a given population. Before being able to formulate this policy, however, one must know how to detect those individuals who are susceptible to air pollutants.

Age Factors↗
PubMed1991

HIV-2-induced immunosuppression among asymptomatic West African prostitutes: evidence that HIV-2 is pathogenic, but less so than HIV-1.

Two hundred and forty-one prostitutes working in The Gambia were tested for retroviral infections and their immune system evaluated. Sixty-three were seropositive for HIV-2 only, five for HIV-1 only and six for both HIV-1 and HIV-2 (26.1, 2.1 and 2.5%, respectively). When compared to seronegative individuals, the 63 women infected with HIV-2 clearly had an abnormal immune system, with significantly lower CD4+ and higher CD8+ lymphocyte counts and percentages, lower CD4+:CD8+ ratios, lower CD25+ (activated) lymphocyte counts, and lower lymphocyte proliferation responses after stimulation with phytohaemagglutinin, purified protein derivative (PPD), Candida or pokeweed mitogen, and higher levels of neopterin and beta 2-microglobulin. However, when the HIV-2-seropositive prostitutes were compared with the five women infected with HIV-1, the former were less abnormal, with significantly higher CD4+ percentages and CD4+:CD8+ ratios and lower CD8+ percentages and counts. Immunological anomalies were seen in five women known to have been infected with HIV-2 for less than 17 months. Coinfection with HTLV-1 resulted in more severe immunological alterations than infection with HIV-2 alone.

Acquired Immunodeficiency Syndrome↗