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Haemophilus influenzae type b vaccine in India: need and timing, immunogenecity and tolerance.

OBJECTIVE: (i) To assess the natural immunity and susceptibility to Haemophilus influenzae type b (Hib) infections in children in India. (ii) To study the immunogenecity and tolerance of Hib vaccine (ACTHIB) in young infants. DESIGNS: (i) Cross sectional study. (ii) Prospective trial. SETTING: Well baby and immunization clinics. METHODS: (i) PRP antibody titers against Hib estimated in 172 healthy infants and children aged 1 month to 10 years. (ii) Antibody titres estimated before and after ACTHIB vaccine given with primary immunization (age group 6 to 8 weeks) in 50 babies. RESULTS: (i) Naturally protective levels of Hib antibodies found in less than 20% of infants under one year, but in over 80% above 4 years. (ii) Seroconversion after ACTHIB vaccination was 100% with very high protective levels. There were no significant adverse reactions. CONCLUSIONS: ACTHIB vaccine proved to be safe and highly immunogenic. As susceptibility to Hib is highest in the first year of life, the vaccine should be recommended in the primary immunization schedule (combined with DPT). The very high titers achieved suggest the possibility of decreasing the number of doses or the amount of antigen to reduce the prevalent high cost.

Child↗

Human cytomegalovirus downregulates complement receptors (CR3, CR4) and decreases phagocytosis by macrophages.

Human cytomegalovirus (HCMV) infection is associated with an increased susceptibility to opportunistic infections. Although the subversion of adaptive immune responses has been extensively studied, the consequences of HCMV infection on natural immune responses are not well documented. A striking selective downmodulation of CD11b/CD18 (CR3) or CD11c/CD18 (CR4) was found upon HCMV infection, on two models, the monocytic THP-1 cell line and monocyte- derived macrophages. HCMV-infected macrophages have an altered adhesion/phagocytic capacity to Candida albicans, a pathogen responsible for some opportunistic infections in immunocompromised patients. These results suggest a new mechanism implicated in the augmentation of opportunistic infections in HCMV patients.

Candida albicans↗

Induction of Haemophilus influenzae type b capsular antibody in neonatal rabbits by gastrointestinal colonization with cross-reacting Escherichia coli.

In two separate experiments, newborn rabbits were fed a live suspension of either of two Escherichia coli strains which possess a "K" antigen cross-reactive with the capsular polysaccharide of Haemophilus influenzae type b. Both feedings were harmless and resulted in fecal excretion of the fed E. coli in most animals as well as active immunization of fed animals toward H. influenzae type b. Feeding non-enteropathogenic, cross-reacting E coli to newborns may be a method for inducing active immunity toward H. influenzae type b diseases by accelerating the acquisition of "natural" immunity.

Animals↗

Suppressed cell-mediated immunity and monocyte and natural killer cell activity following allogeneic immunization of women with spontaneous recurrent abortion.

Spontaneous recurrent abortion (SRA) has been treated by means of immunization with paternal or third-party white blood cells, yet the immunological basis for SRA and for the role of immunization protocols in pregnancy outcome remains controversial. To elucidate this question, nine women with SRA were immunized with paternal mononuclear cells and studied before and 2 weeks after immunization. Seven women who became pregnant gave birth to live newborns. Secretion of the T helper 1 cytokines IL-2 and interferon-gamma by patients, mononuclear cells decreased, while production of IL-10 increased. The levels of natural killer and lymphokine-activated killer cell-mediated cytotoxicity were markedly decreased. Monocyte functions such as secretion of IL-1 alpha, tumor necrosis factor alpha, IL-6, and cytotoxic activity decreased concurrently with elevations in IL-10 and transforming growth factor beta secretion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downregulated. This resulted in a decrease in monocyte costimulatory activity of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunization may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.

Abortion, Habitual↗

In vitro exposure to peptidic delta opioid receptor antagonists results in limited immunosuppression.

Previous studies by our group have demonstrated that in vitro exposure to delta-opioid receptor agonists results in a significant immunostimulation, whereas in vitro exposure to non-peptidic delta-opioid receptor antagonists results in significant suppression of various immune functions. The present study assessed potential immunomodulation by the peptidic delta-opioid receptor antagonists TIPP, D-TIPP, and ICI 174864 using a panel of in vitro immune function assays. Splenocytes from female B6C3F1 mice were cultured with the peptides at concentrations of 0.00001-10 microM. B cell proliferation was quantified following cellular activation, T cell function was assessed by cytokine production following stimulation with anti-CD3 monoclonal antibody, natural immunity was assessed by quantitating natural killer (NK) cell activity following a 24-h exposure, and macrophage function was assessed by quantification of interleukin-6 (IL-6) production. None of the peptides examined significantly affected B cell proliferation. Production of IL-2 by T cells was not consistently affected by exposure to either TIPP or D-TIPP, but was significantly suppressed at 10 microM ICI 174864. Production of IL-4, however, was significantly suppressed by low concentrations of either TIPP or D-TIPP, and by 10 microM ICI 174864. IL-6 production by macrophages was unaffected except for sporadic incidents of enhanced production in cells exposed to ICI 174864. NK cell function exhibited a differential pattern of suppression, with the greatest degree of suppression observed following exposure to TIPP and only slight suppression in cells exposed to either D-TIPP or ICI 174864. These data suggest that peptidic delta-opioid receptor antagonists do not exhibit the same pattern or degree of immunosuppressive activity as the non-peptidic antagonists at equivalent in vitro concentrations.

Animals↗

Natural antibodies and the autoimmunity of atherosclerosis.

In recent years, the subject of natural antibodies has been revisited and the immunobiological roles of these humoral factors are being better defined. These antibodies are secreted by distinct sets of innate-like B cells, B-1 cells and marginal zone B cells, which arise early in development to become the sources of "natural immune memory". Due to their interactions with a variety of self-determinants, natural antibodies have previously been postulated to play roles in the maintenance of host homeostasis. A central paradigm has recently been developed from the demonstration that oxidation derived epitopes on apoptotic cells and oxidized low-density lipoproteins are recognized by the phosphorylcholine-specific germline encoded B-1 cell natural antibody, T15, which has provided important insights into possible "house-keeping" functions under both normal and pathological conditions. In this review, the potential functions of natural antibodies in the pathogenesis and progression of the chronic inflammatory condition of atherosclerosis are discussed, as well as their capacities for apoptotic cell binding and clearance. These interactions of natural antibodies and oxidation-epitopes from phospholipids appear to provide a dynamic immunobiological connection linking host responses in infection, autoimmunity and atherosclerosis.

Animals↗

Immunochemical relationship between natural haemagglutinins and immune antibodies in the toad (Bufo paracnemis).

Natural and induced antibodies from serum of Bufo paracnemis were isolated by specific immunoadsorption (natural antibodies and specific induced antibodies, respectively). Natural agglutinins specific to rabbit red blood cells (RRBC) showed, by immunodiffusion (ID) and by immunoelectrophoresis (IEP) against rabbit anti-B, paracnemis serum, at least three precipitation lines. Similar patterns were obtained with the specific induced antibodies. Immunochemical identity between natural and induced antibodies was observed by ID test. These results were assessed by repeatedly absorbing rabbit anti-Bufo serum with natural antibodies: these natural antibodies totally exhausted the activity of rabbit immune serum against specific anti-bovine serumalbumine and vice-versa. These reactions were studied using a very sensitive radioimmunodiffusion test. The heterogeneity of natural haemagglutinins and their identity with induced antibodies are discussed in relation with these experimental data.

Agglutinins↗

Genital tract infection with Chlamydia trachomatis fails to induce protective immunity in gamma interferon receptor-deficient mice despite a strong local immunoglobulin A response.

CD4+ T cells have been found to play a critical role in immune protection against Chlamydia trachomatis infection. Since both humoral and cell-mediated antichlamydial immunity have been implicated in host protection, the crucial effector functions provided by the CD4+ T cells may rely on Th1 or Th2 functions or both. In the present study, we evaluated the development of natural immunity following vaginal infection with C. trachomatis serovar D in female gamma interferon receptor-deficient (IFN-gammaR-/-) mice with a disrupted Th1 effector system. We found that in comparison with wild-type mice, the IFN-gammaR-/- mice exhibited a severe ascending primary infection of prolonged duration which stimulated almost 10-fold-stronger specific local immunoglobulin A (IgA) and IgG responses in the genital tract. Following resolution of the primary infection and despite the augmented antibody responses to chlamydiae, the IFN-gammaR-/- mice were completely unprotected against reinfection, suggesting that local antibodies play a subordinate role in host protection against chlamydial infection. Immunohistochemical analysis of frozen sections of the genital tract revealed many CD4+ T cells in the IFN-gammaR-/- mice, with a dominance of interleukin 4-containing cells in mice following resolution of the secondary infection. However, in contrast to the findings with wild-type mice, the typical clusters of CD4+ T cells were not found in the IFN-gammaR-/- mice. Few and similarly distributed CD8+ T cells were observed in IFN-gammaR-/- and wild-type mice. Whereas chlamydia-infected macrophages from wild-type mice had no inclusion bodies (IB) and produced significant amounts of nitric oxide (NO) in the presence of IFN-gamma, macrophages from IFN-gammaR-/- mice contained many IB but no NO. These results indicate that CD4+ Th1 cells and IFN-gamma, rather than local antibodies, are critical elements in host immune protection stimulated by a natural ascending C. trachomatis infection in the female genital tract.

Animals↗

Neutrophil granule proteins as targets of leukemia-specific immune responses.

PURPOSE OF REVIEW: Recent progress in the identification of leukemia antigens has stimulated the development of vaccines to treat hematological malignancies. Here we review the identification and characterization of the myeloid leukemia-specific antigens proteinase 3 and neutrophil elastase found in the primary (azurophil) granule proteins of granulocytes and their precursors. A peptide 'PR1' derived from these proteins induces powerful HLA-A0201-restricted CD8 T-cell proliferation. PR1-specific T cells are cytotoxic to leukemia and myelodysplastic syndrome progenitors, and occur at low frequencies in normal individuals. Frequencies are higher in patients with myeloid leukemias, and highest in patients with chronic myeloid leukemia entering molecular remission after allogeneic stem cell transplantation. RECENT FINDINGS: These observations, together with the known association of autoimmunity to proteinase 3 and neutrophil elastase in Wegener's granulomatosis, support the concept that there is a natural immunity to primary granule proteins which can be boosted to enhance immunity to leukemia. Preliminary reports indicate that PR1 peptide vaccination induces significant increases in PR1-specific cytotoxic T cells with rapid and durable remissions in some patients with advanced myeloid leukemias. SUMMARY: These promising developments in antileukemia vaccines have stimulated research to optimize vaccine delivery and modify regulation of natural T-cell immunity to primary granule proteins to improve treatment of otherwise refractory myeloid leukemias and myelodysplastic syndrome.

Animals↗

Vaccine therapy for HIV: a historical review of the treatment of infectious diseases by active specific immunization with microbe-derived antigens.

A review of the history of 'vaccine therapy' for infectious diseases is presented. The concept originated when Auzias-Turenne introduced 'syphilitic vaccination' or 'syphilization' as a treatment for syphilis in Paris in the mid-1800s; his clinical studies probably influenced Pasteur's successful rabies postexposure vaccine trials. Robert Koch in Berlin in the 1890s observed that inoculation of tuberculin into patients with tuberculosis induced an inflammatory response in affected tissues, and advocated 'tuberculin therapy'. Sir Almroth Wright in London in the early 20th century devised methods to measure changes in serum 'opsonizing' activity in response to therapeutic inoculations with microbe-derived vaccines. Since the advent of antibiotics, active specific immunization with microbe-derived antigens (vaccine therapy) has been largely forgotten as a strategy for treatment of infectious diseases. Advances in antigen production and in molecular immunology now permit new tactics to probe, analyse and selectively alter in vivo human immune responses to infectious microbes. Our recent demonstration that vaccine therapy can boost natural immunity to HIV in infected patients should rekindle interest in this approach.

AIDS Vaccines↗

Modulatory effect of prostaglandin E2 on the immune response in mice, with special reference to anti-sperm immunity.

The intraperitoneal administration of prostaglandin E2 (PgE2) considerably delayed the rejection of allogeneic skin grafts, both in the primary (first set) and secondary (second set) reaction, and inhibited the production of plaque-forming cells after antigenic stimulation with sheep red blood cells. In addition, the treatment of mice with PgE2 during their immunization with allogeneic epididymal spermatozoa resulted in a markedly slower rejection of the following skin grafts from the donor's strain in comparison with the animals injected with spermatozoa only. Evidence was also found concerning the immunosuppressive effect of PgE2 on the humoral immune response against sperm antigens. The possible immunoregulatory role of PgE2 in the natural immune tolerance to sperm antigens is discussed.

Animals↗

[Physiological autoimmunity].

The serum of normal individuals contains antibodies directed against their own antigens (autoantigens). These autoantibodies are the main and the best known component of normal autoimmunity. They mostly involve polyreactive (one antibody recognising several antigens) IgM, but also IgG, usually having low affinity for antigens. The role of natural autoimmunity is becoming better understood. It participates in the equilibrium of the immune system, contributing to controlled production of antibodies, accelerated elimination of external antigens or aged autoantigens, and to triggering of a specific immune response. Some data suggest that the action of autoantibodies in homeostasis can extend beyond the immune system. Many pathological states, of immune nature or not, are associated with an increase or diminution of the titre of natural autoantibodies. The mechanisms and consequences of these changes remain to be elucidated.

Animals↗

Measles virus haemagglutination-inhibition antibodies among pregnant and non-pregnant women in the vaccine era in Harare, Zimbabwe.

OBJECTIVES: To determine the prevalence of measles virus haemagglutination-inhibitive antibodies among pregnant and non-pregnant women born before 1963 (pre-vaccine era) and those born after 1963 (vaccine era) in Harare. DESIGN: Prospective study of serum samples collected from pregnant and non-pregnant women born during the pre-vaccine era and vaccine era in Harare. SETTING: A laboratory based study at the Virology Laboratory, Department of Medical Microbiology, University of Zimbabwe using serum samples of women from different communities in Harare. SUBJECTS: 546 pregnant and non-pregnant women. MAIN OUTCOME MEASURES: Age, pregnant or not pregnant and the use of measles virus haemagglutination-inhibition antibody tests to determine prevalence rates or levels of antibodies to the measles virus. RESULTS: The results showed that 158 (28.9pc) out of a total of 546 pregnant and non-pregnant women screened were positive for measles virus haemagglutination-inhibition antibodies (MVHIA) at titers ranging from 1:10 to 1:80.39.8pc and 18pc of pregnant women born before 1963 and after 1963 were respectively positive whereas 49pc and 27.3pc of non-pregnant women born before 1963 and after 1963 were also positive for MVHIA respectively. The mean age of women born before 1963 was 38 + 2 years (range 34 to 60 years, median 42 years) while those born after 1963 had a mean age of 22 + 2 years (range 10 to 28 years; median 23 years). Higher antibody titers (1:40 and 1:80) were most commonly observed in both pregnant and non-pregnant women born during the pre-vaccine era than those born during the vaccine era and the difference was of statistical significance (p < 0.01). CONCLUSION: Finally results suggest that immunity acquired by exposure to wild measles virus (pre-vaccine era or natural immunity) is higher than immunity acquired following immunisation (vaccine era) and this may affect the duration of maternally derived immunity by children of mothers born during the different eras. Consequently, while we expect that this finding will be of value in immunisation schedules, we suggest a titer of 1:40 and above as the likely screening titer for routine identification of protected women in Zimbabwe.

Adolescent↗

Molluscan immune defenses.

The interest of marine invertebrates as food resources provides a major interest to study molluscan immunity for better understanding of the host response to pathogens. Molluscs possess a natural immunity formed by anatomical and chemical protective barriers that prevent damage of the underlying tissues, body fluid losses and the infections of pathogenic microorganisms and parasites. The main physical barrier is shell and mucus which cover the soft body of molluscs. The integrity of body coverings is supported by blood clotting and wound healing. The internal defense mechanisms of molluscs involve such cellular reactions as: phagocytosis, nodule formation, encapsulation, pearl formation, atrophy, necrosis and tissue liquefaction. Granular hemocytes are the most numerous cell type of molluscan blood active in cellular defenses. Invaders small in size are eliminated by phagocytosis in which participate lectins and products of prophenyloxidase system activation. Numerous and large intruders are eliminated by nodule formation or encapsulation, either cellular or humoral. Humoral components of molluscan immunity are formed by lysozyme activity, lectins and the phenyloxidase system. Up to now the role of mercenenes, paolins, acute phase reactants, alpha 2-macroglobulins and multifunctional binding proteins with anti-protease activity is not well clarified yet. Research prospects on the field of molluscan immunology should essentially be devoted to study cellular defense functions and humoral effectors to select pathogen-resistant molluscs. This aim could also be achieved by the identification and characterization of immune genes which are candidates for molluscs genetic transformation.

Animals↗

Clinical trial with inactivated hepatitis A vaccine and recommendations for its use.

OBJECTIVE: To compare the reactogenicity and immunogenicity of an inactivated hepatitis A vaccine in two different immunisation schedules. DESIGN: Randomised trial. SETTING: One London teaching hospital. SUBJECTS: 104 healthy adult volunteers (71 men, 33 women aged 19-60). INTERVENTIONS: Hepatitis A vaccine to group 1 (54 volunteers) at 0, 1, and 2 months and to group 2 (50) at 0, 1, and 6 months. MAIN OUTCOME MEASURES: Symptoms at and after each dose; liver function, hepatitis A virus specific serum immune response; and responses in saliva and parotid fluid in immunised volunteers and subjects with natural immunity. RESULTS: The vaccine was well tolerated; 97% (96/99) and 100% of those immunised developed serum antibody after one and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose and were significantly higher in men but not women in group 2 after the third dose (ratio between geometric mean titres 0.265, 95% confidence interval 0.18 to 0.39; p less than 0.001). At one year this group-sex interaction was absent; geometric mean titres for both sexes were significantly higher in group 2 (ratio 0.330, 0.227 to 0.478; p less than 0.0001). Antibody responses were not significantly different between the groups at two years. Compared with naturally infected subjects immunised volunteers developed poor or undetectable virus specific IgG and IgA responses in saliva and parotid fluid. CONCLUSIONS: The vaccine was safe and highly immunogenic, and the differences in the immune responses in saliva and parotid fluid are unlikely to affect its efficacy.

Adult↗

Naturally acquired measles immunity in Nepal and Sri Lanka.

Serological surveys of naturally acquired measles antibodies in children 6--72 months of age were done in Nepal and Sri Lanka. The prevalences of naturally acquired measles immunity are compared by age groups with serological studies done in other countries. Suggestions are made regarding age ranges for measles vaccination programs.

Humans↗

The flip-side of Cytoadherence: immune selection, antigenic variation and the var Genes of Plasmodium falciparum.

In areas where Plasmodium falciparum is endemic, the natural immunity acquired by people exposed to frequent malaria infection is likely to have a differential selective impact upon different parasite genotypes. It has been suggested that the immune response directed against the variant antigen PfEMP1, which is expressed on the infected erythrocyte surface, is a crucial determinant of parasite population structure and favours the existence of distinct strains, or Varotypes. Here, Colin Sutherland summarizes current knowledge of the var multigene family, which encodes the PfEMP1 variants, and suggests that this information may allow certain predictions of the strain hypothesis to be tested directly.

Journal Article↗

Recovery of the immune system after exercise.

In the recovery phase after intense exercise is found suppressed blood concentration of lymphocytes, suppressed natural immunity of blood lymphocytes, decreased concentration of secretory IgA in mucosa, but increased blood concentration of neutrophils and increased levels in the blood of inflammatory cytokines. Thus, after intense long-term exercise, the immune system is characterized by concomitant inflammation and temporary suppression of the cellular immune system, the most pronounced findings being 2-4 h after the exercise. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. High levels of cytokines, especially interleukin-6, are found in the recovery period after eccentric exercise, and it has been demonstrated that a close association exists between muscle damage and increased levels of interleukin-6.

Humans↗