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PubMedDate not supplied

A natural immunity-activating plant lectin, Viscum album agglutinin-I, induces apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine thymocytes.

A galactoside-specific plant lectin, Viscum album agglutinin-I (VAA-I) with protein synthesis-inhibiting properties, has been shown to be cytotoxic in various eukaryotic cells, in vitro above a 10 ng/ml concentration. Noncytotoxic concentrations of VAA-I induced mRNA expression and enhanced secretion of proinflammatory cytokines in cultures of human peripheral blood mononuclear cells. In an animal model VAA-I has been shown to stimulate natural killer cells and granulocytes. In this study, human peripheral blood lymphocytes (PBL), human peripheral blood monocytes (PBM), murine thymocytes and human monocytic THP-1 cells were incubated for 24 h in the presence of various concentrations of VAA-I. The apoptotic effect of VAA-I was analyzed by flow cytometry following staining of the apoptotic nuclei in the cells with PI in hypotonic buffer and quantitative detection of DNA breaks were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. In cultures of all types of investigated cells, a dose-dependent VAA-I concentrations above 10 ng/ml in PBL and at 1 ng/ml VAA-I concentration in PBM, thymocytes and THP-1 cells, a lectin-induced increase of the apoptotic nuclei was observed. In 24-hour cultures of PBL and thymocytes, the ratios between apoptotic and nonapoptotic cells were enhanced 10 times and 8 times, respectively, by 100 ng/ml VAA-I compared to the negative control. The concentration of 100 micrograms/ml VAA-I only caused necrosis. The isolated A chain of the VAA-I induced apoptosis in PBL and thymocytes. In the culture of PBL the isolated B chain of the VAA-I was not effective indicating that cytokine induction by VAA-I is probably not involved in its apoptotic effect. On CD4+8+ thymocytes, VAA-I resulted in a reduced expression of CD8+ molecules that could be related to a loss of volume and increase of density, both characteristic features of apoptosis.

Animals↗
PubMed2003

Mammalian antibiotic peptides.

The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus creating a strong need to develop new antimicrobial agents. These new antibiotics should possess novel mechanisms of action and different cellular targets compared with existing antimicrobials. Recent discoveries and isolations of so-called animal antibiotics, mostly small cationic peptides, which represent a potent branch of natural immunity, offered the possibility to acquire new and effective antibiotics of this provenance. To this date, more than 500 antibiotic peptides have been distinguished and defined. Their antimicrobial properties present new opportunities for their use as antibiotics or for construction of their more effective derivatives, but much research is still required to pave the way to their practical use. This is a survey of substances forming an armamentarium of natural immunity of mammals.

Animals↗
PubMed1977

Rubella in Orkney: seroepidemiology and vaccination.

Rubella haemagglutination inhibiting (HAI) antibody titres were determined in 54 seronegative women and 31 naturally immune women after vaccination and revaccination with Wistar RA27/3 strain rubella vaccine administered by the intranasal or subcutaneous routes or revaccination with the Cendehill strain administered subcutaneously. In addition, HAI antibody titres were determined in 46 seronegative schoolgirls after vaccination with the Cendehill strain and revaccination with the RA27/3 strain.All seronegative women vaccinated with the RA27/3 strain developed antibody, peak titres being reached 6 weeks after vaccination. Six months after vaccination with the Cendehill strain, 45 (98%) of the 46 seronegative girls had developed antibody, but 11 (24%) had not reached their peak titre by 6 weeks, suggesting a slower response than that elicited by the RA27/3 strain. Revaccination did not induce significant antibody responses in the seronegative women vaccinated 6 months previously with RA27/3 but 4 naturally immune women developed an eightfold increase in antibody. In 10 (22%) of 46 schoolgirls previously vaccinated with the Cendehill strain a significant rise in antibody followed revaccination with RA27/3. These results provide further evidence of the more rapid antibody responses elicited by the RA27/3 vaccine in comparison with the Cendehill vaccine.An outbreak of natural rubella occurred in 1972 and 97 cases were confirmed serologically. The clinical disease was more common in older school-children and in adults. More males than females were affected in the 11-15 age group, the sex ratio being 18:12; this may be explained by the routine vaccination of girls of this age group as part of the national programme which began in 1970. The significance of the persistence of high HAI antibody titres after natural infection and the effect of the epidemic on the serological status of the population are discussed.

Adolescent↗
PubMed2006

Immune protection, natural products, and skin cancer: is there anything new under the sun?

Non-melanoma skin cancers such as squamous cell carcinoma and basal cell carcinoma are the most common types of human neoplasms, representing one third of all new malignancies diagnosed in the US. The number of new cases diagnosed per year in the US alone is approaching one million and continues to rise. Ultraviolet (UV) radiation from the sun is a major cause of non-melanoma skin cancer in humans. Aside from the mutagenic effects of UV radiation, there are suggestions from clinical studies and evidence in animal models that the immune system plays an important role in preventing skin cancer development and progression, and is suppressed by cutaneous exposure to UV radiation. In this article, we review the research on new and existing agents that are being developed to protect the skin immune response from suppression by UV radiation. We also discuss the current state of knowledge regarding their mechanism of action in humans as well as animal models of photosuppression, and their efficacy in cancer prevention.

Aloe↗
PubMed1982

Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes.

By comparing natural immunity to Aspergillus fumigatus (AF) in vivo with the action of human or mouse phagocytes against AF in vitro, we delineated two sequential lines of defense against AF. The first line of defense was formed by macrophages and directed against spores. Macrophages prevented germination and killed spores in vitro and rapidly eradicated conidia in vivo, even in neutropenic and athymic mice. The second was the neutrophilic granulocyte (PMN), which protected against the hyphal form of AF. Human and mouse PMN killed mycelia in vitro. Normal, but not neutropenic mice, stopped hyphal growth, and eradicated mycelia. Either line of defense acting alone protected mice from high challenge doses. Natural immunity collapsed only when both the reticuloendothelial system and PMN were impaired. These findings are in keeping with the clinical observation that high doses of cortisone and neutropenia are the main risk factors for invasive aspergillosis. Cortisone inhibited the conidiacidal activity of mouse macrophages in vivo and of human or mouse mononuclear phagocytes in vitro. Cortisone damaged this first line of defense directly and not through the influence of T lymphocytes or other systems modifying macrophage function as shown in athymic mice and in vitro. In addition, daily high doses of cortisone in mice reduced the mobilization of PMN so that the second line of defense was also impaired. Thus, cortisone can break down natural resistance on its own. Myelosuppression rendered mice susceptible only when the first line of defense was overpowered by high challenge doses, by activated spores that cannot be killed by macrophages, or by cortisone suppression of the conidiacidal activity of macrophages. The host, thus, can call upon two independent phagocytic cell lines that form graded defense systems against aspergillus. These lines of defense function in the absence of a specific immune response, which seems superfluous in the control and elimination of this fungus.

Animals↗
PubMed2005

Post-transplant lymphoproliferative disorder with supraglottic involvement.

OBJECTIVE: Transplant patients with primary Epstein-Barr virus (EBV) infection may develop post-transplant lymphoproliferative disorder (PTLD). Since many infants are seronegative at the time of transplantation, PTLD is a major concern for paediatric transplant centres. First manifestations of PTLD are frequently observed in the ENT area with adenoidal and/or tonsillar involvement. DESIGN: Retrospective study of two cases of PTLD with confirmed supraglottic involvement, their management and outcome. Only patients with pathologically and immunologically demonstrated B-cell proliferation were diagnosed as PTLD. RESULT: Two infants developed an acute stridor during PTLD respectively 8 and 10 months after orthotopic liver transplantation (OLT). These infants were seronegative for EBV at the time of transplantation. IgM anti-EBV and/or detection of EBV genome by polymerase chain reaction were positive. Laryngeal examination revealed hypopharyngeal and/or supraglottic mucosal hyperplasia. Immunostaining of laryngeal biopsy was positive for latent membrane protein-1 (LMP1). Patients were treated by a reduction in immunosuppression as far as tolerated with the intent to recover natural immune response by the patient over the proliferation of EBV-infected cells. Complete remission of PTLD was observed in these two cases. CONCLUSION: Tonsillar hypertrophy and adenoid enlargement are the most encountered features of PTLD in OLT occurring in the ENT area. Acute stridor with supraglottic involvement may also be observed in PTLD and must be promptly diagnosed as the prognosis of this disorder is related to rapid reduction in immunosuppression and consequently to the recovering of a natural immune response against the EBV infection.

Female↗
PubMed1998

Immunization against natural Helicobacter pylori infection in nonhuman primates.

Helicobacter pylori infection is widespread in some breeding groups of a rhesus monkey colony (71% H. pylori positive by 1 year), and the rate of seroconversion is also high. As a result, these groups can be used to test the safety and efficacy of an anti-H. pylori vaccine. Nine-month-old female animals were randomized to receive either 8 mg of recombinant urease (rUre) plus 25 microg of Escherichia coli heat-labile enterotoxin (LT) (n = 26) or placebo plus LT (n = 29), given four times at 1-week intervals followed by a booster 1 month later. Ten months after the start of the immunization, the animals were subjected to endoscopy and biopsy samples were obtained. H. pylori negativity was defined as no H. pylori growth by culture and no H. pylori observed at histology. By this criterion, 2 (7%) of 29 animals receiving placebo and 8 (31%) of 26 immunized animals were H. pylori negative (P < 0.035). In addition, antral gastritis score was significantly less in H. pylori-negative immunized monkeys than in H. pylori-positive animals, whether they were given rUre plus LT or placebo plus LT (P < 0.02 or P < 0.01, respectively). Interestingly, antral gastritis was also significantly less in H. pylori-positive animals given rUre plus LT than in H. pylori-positive animals given placebo plus LT (P < 0.02). However, quantitative cultures did not demonstrate significant differences between the two latter groups. It is concluded that oral administration of rUre vaccine plus LT significantly protects nonhuman primates against H. pylori infection while not causing undesirable side effects.

Animals↗
PubMed1976

Natural mechanisms of controlling lymphotropic herpesvirus infection (Marek's disease) in the chicken.

Four categories of natural resistance phenomena against Mareks disease in chickens, i.e., maternal antibody, age resistance, genetic resistance, and natural immunization, are described. In nature, these forms of resistance probably act in concert through comlex interrelationships. The mechanisms are not well understood but include humoral immunity (maternal antibody), cell-mediated immunity, and possibly other mechanisms. The possible role of newly discovered tumor-specific antigens in cell-mediated immunity against Marek's disease lymphomas is discussed.

Age Factors↗
PubMed1992

Studies on naturally acquired immunity to African ticks. II. Observations on cattle exposed to Rhipicephalus appendiculatus under varying periods of repeated infestations.

Groups of Friesian cattle were infested repeatedly with Rhipicephalus appendiculatus at weekly intervals (eight infestations) and at intervals of 3 weeks (seven infestations) and 6 weeks (seven infestations). The engorgement weight of adults, nymphs and larvae decreased significantly initially, from the second infestation, but rose significantly at later infestations. This rise was more dramatic with larval instars than with any other. A new method for quantifying the resistance status of animals was introduced; this method showed that the resistance acquired by cattle during 6-weekly reinfestations was more stable than that acquired by cattle during weekly and 3-weekly reinfestations. The criteria for assessing natural resistance to ticks was reappraised. These are classified into those serving long- and short-term purposes, and those which have direct and indirect effects. Criteria which could serve long- and short-term purposes include a reduced number of engorged ticks, an increased number of dead male and female ticks, a decreased number of ticks which fed above the critical engorgement weight and an increased number which fed within the pre-mating weight and decreased the number of copulations. The criterion of reduced engorgement weight can serve the short-term purpose only. A new manifestation of resistance to ticks, i.e. decreased moulting weights of nymphs and adults, together with the criterion of decreased egg hatchability, were classified as indirect effects because they were manifested after the ticks had dropped off the resistant cattle.

Animals↗
PubMed1980

Cellular immunity in natural and experimental infections caused by Mycobacterium tuberculosis and Mycobacterium kansasii.

In rabbits sensitized with M. tuberculosis and M. kansasii the of macrophage migration inhibition from the spleen due to antigens of both types of mycobacteria was evaluated. In parallel experiments the release of MIF the indirect migration inhibition was evaluated, using antigens added to lymphocyte suspensions from popliteal nodes of sensitized animals. As an indicator system spleen fragments of intact rabbits were used. In patients excreting M. tuberculosis and M. kansasii (groups of 31 subjects) the release of MIF from lymphocytes in venous blood was investigated, using the same antigens; migration inhibition was also tested on spleen fragments of intact rabbits. Rabbits sensitized with M. kansasii responded by marked migration inhibition induced by both antigens in the direct as well as the indirect test. Marked differences were, however, manifested in animals sensitized with M. tuberculosis: in the homologous system a high reactivity was preserved, however, the heterologous antigen of M. kansasii influenced the migration in the direct and indirect test much less. These differences of reactivity were statistically significant at the 1% and 5% level of significance resp. Similar results as in model experiments were recorded also in patients naturally infected with M. tuberculosis and M. kansasii. In subjects with M. kansasii migration inhibition induced by both antigens was recorded and the differences were not statistically significant. In patients with M. tuberculosis the reactivity to the homologous antigen was more marked than to the heterologous antigen of M. kansasii and this difference was significant at the 1% level of significance.

Animals↗
PubMed1988

Boosting of transmission-blocking immunity during natural Plasmodium vivax infections in humans depends upon frequent reinfection.

The infectivity to mosquitoes of 31 acute Plasmodium vivax patients was measured by permitting mosquitoes to feed directly on the patients. The infectivity of these patients correlated closely with titers of antibodies in their serum as measured by indirect immunofluorescence against air-dried female gametes of P. vivax. Infectivity by direct feeding was also closely parallel to the transmission-blocking activity of the sera of patients as measured by the suppression of infectivity of parasitized blood by autologous serum relative to normal (nonmalarial) human serum when fed to mosquitoes through a membrane. These results are consistent with serum antibodies in human P. vivax infections as major factors determining the infectivity of an infected individual to mosquitoes. It was further noted that individuals having a second attack of P. vivax within less than 4 months were considerably less infectious to mosquitoes than first-attack patients were. This "boosting" of transmission-blocking immunity was much less if longer intervals intervened between attacks. We discuss the immunological implications and possible epidemiological significance of this short-term boosting of transmission-blocking immunity by successive P. vivax infections.

Acute Disease↗
PubMed2004

Seroepidemiology of varicella-zoster virus antibodies among health-care workers and day-care-centre workers.

Inclusion of live varicella vaccine in the routine occupational health vaccination schedule requires knowledge of the natural immunity to varicella zoster virus (VZV) among high-risk occupations. This study aims were to evaluate VZV antibody positivity among health-care workers (HCWs) and day-care-centre workers (DCWs) and to assess its association with potential risk factors. Three groups of workers were tested for VZV antibody positivity: hospitals and community clinic HCWs (n = 335), DCWs (n = 117) and blue-collar workers as controls (n = 121). The total VZV antibody positivity was 94.4%. There was no significant difference in VZV antibody positivity among study groups. DCWs had the lowest VZV seroprevalence (90.9%, 95% CI 85.7-96.1) and controls the highest (96.6%, 95% CI 93.2-99.9). This high VZV antibody positivity suggests that no special occupational measures are indicated in health-care or day-care occupational settings in Israel. On-going monitoring of the natural immunity to VZV is necessary to detect trends over time.

Adult↗
PubMed1999

Should adolescents be vaccinated against hepatitis A: the Hong Kong experience.

Hong Kong is a well developed city in the center of an endemic region for hepatitis A. The age at which hepatitis A occurs has shifted from childhood and adolescence to adults like many western countries. There is a high chance of outbreaks with the introduction of infection from neighbouring countries. Reducing the susceptibility of a population by vaccination can eliminate the diseases but updated sero-epidemiological data is needed to analyse the level of natural immunity, and identify those susceptible to infection for preventive measures. This study conducted amongst secondary school children seeks to identify those who are at risk and to obtain data on the present sero-prevalence of anti-HAV. Overall prevalence of anti-HAV in this age group was 7% increasing with age. Analysed by multiple regression model, those students living in mainland China over 3 years had odds ratio of 31.6 (95% c. i. 17.4-57.3) compared with those born in Hong Kong. Students with a father in a skilled occupation and an education level of secondary school or above, and both parents with secondary education or above, had an odds ratio of 0.22 (95% c.i. 0.07-0.7) and 0.35 (95% c.i. 0. 17-0.72) associated with presence of anti-HAV, respectively. Improved socio-economic state exposes higher proportion of the population at risk. Immunisation is worthwhile to be considered for the adolescents in Hong Kong. Prevaccination screening is cost effective only for those adolescents who are most likely to have natural immunity.

Adolescent↗
PubMed2004

Neisseria meningitidis, Neisseria lactamica and Moraxella catarrhalis share cross-reactive carbohydrate antigens.

Carriage of commensal bacteria species is associated with the development of natural immunity to meningococcal disease, with lipo-oligosaccharides (LOS) of meningococci being one of the main virulence factors associated with severity of meningococcal disease. Meningococcal reference strains and isolates from the commensal species Neisseria lactamica and Moraxella catarrhalis were assessed for the presence of cross-reactive glycoconjugate antigens. Binding of human blood group antibodies of the P and Ii system to meningococcal immunotype reference strains were in accordance with the presence of known LOS carbohydrate structures. Binding studies with meningococcal immunotyping antibodies and blood group phenotyping antibodies to N. lactamica strains from different European countries showed, that a greater number of isolates obtained from native Greek and Scottish adults and children bound anti-meningococcal L(3, 7, 9) immunotyping (P < 0.001), pK (P = 0.035) and paragloboside (P < 0.001) blood group typing antibodies compared to isolates obtained from children of Russian immigrants in Greece. A greater number of M. catarrhalis strains isolated from children in Scotland bound anti-L(3, 7, 9) antibodies (38.2%) compared to strains isolated from adults (22.2%) (P = 0.017). These findings provide evidence that blood group like glycoconjugate antigens found on the commensal species N. lactamica and M. catarrhalis might be involved in the development of natural immunity to meningococcal endotoxins during childhood, and might be exploited as anti-meningococcal vaccine candidates.

Adolescent↗
PubMed1998

HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B.

BACKGROUND/AIMS: Hepatitis B virus specific T cell responses are crucial for viral elimination but their nature is not fully understood. METHODS: We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection. Proliferation and production of interferon-gamma, IL-10 and tumor necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. RESULTS: Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5). Both interferon-gamma (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected. Proliferative or cytokine responses to HBsAg were very weak or absent. Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-gamma to more than 200 IU/ml in all patients and slightly increased the production of IL-10. Neutralization of IL-10 increased the HBeAg-induced interferon-gamma production but had no effect on tumor necrosis factor-alpha production. Addition of anti-IL-4 or anti-tumor necrosis factor-alpha had no significant influence on proliferation or cytokine release. Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated with HBsAg. CONCLUSIONS: Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not upon HBsAg stimulation. IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-gamma production in HBsAg-stimulated cultures.

Cryopreservation↗
PubMed2002

Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau, west Africa.

To study the natural history of rotavirus infection and to determine the protection it confers against reinfection and diarrhea, 200 newborns in Guinea-Bissau were prospectively followed for up to 2 years. Rotavirus was detected in stool specimens collected weekly. By age 2 years, the incidence of primary rotavirus infection was 74%. In the first 3 months of life, 17% of the infections were diarrhea associated, compared with 60% at 9-11 months; after age 18 months, all infections were asymptomatic. A primary infection conferred 52% (95% confidence interval [CI], 16% to 73%) and 70% (95% CI, 29% to 87%) protection against subsequent rotavirus infection and rotavirus diarrhea, respectively. The protection was 66% (95% CI, 24% to 85%) against reinfection within the same epidemic, compared with 34% (95% CI, -29% to 67%) against reinfection in any subsequent epidemic. The high level of protection against symptomatic rotavirus infection provides an important incentive for development of a rotavirus vaccine.

Cohort Studies↗