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Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019).

OBJECTIVE: To determine the effects of dietary consumption of Bifidobacterium lactis (strain HN019, DR10TM) on natural immunity. DESIGN: A randomized, double blind, placebo-controlled clinical trial. SETTING: Janeway Medical Centre, Memorial University, St Johns, Newfoundland. SUBJECTS: Twenty-five healthy elderly volunteers (median age 69 y; range 60-83 y). INTERVENTIONS: Twelve control subjects consumed 180 ml low-fat/low-lactose milk twice daily for a period of 6 weeks; 13 test subjects consumed milk supplemented with 1.5x1011 colony-forming units of B. lactis twice daily. Indices of natural immunity, including interferon production, phagocytic capacity and phagocyte-mediated bactericidal activity, were determined via peripheral blood at 0, 3, 6 and 12 weeks post-trial commencement. RESULTS: Subjects who consumed milk containing B. lactis for 6 weeks produced significantly enhanced levels of interferon-alpha, upon stimulation of their peripheral blood mononuclear cells in culture, in comparison to the placebo control group who received milk alone. There were also significant increases in polymorphonuclear cell phagocytic capacity among test group subjects, following consumption of milk supplemented with B. lactis, while individuals who consumed B. lactis-supplemented milk or milk alone showed enhanced phagocyte-mediated bactericidal activity. CONCLUSIONS: The results demonstrate that dietary consumption of B. lactis HN019 can enhance natural immunity in healthy elderly subjects, and that a relatively short-term dietary regime (6 weeks) is sufficient to impart measurable improvements in immunity that may offer significant health benefits to consumers. SPONSORS: Financial support for this project was provided by the New Zealand Dairy Board.

Aged↗

Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats.

Cells of the immune system and the cytokines they produce have been shown to function in the regulation of bone turnover. Incisors absent (ia) osteopetrotic rats demonstrate defects in natural immunity and bone resorption, even though they have excess numbers of both natural killer (NK) cells and osteoclasts. In an attempt to correct these defects, mutant (ia) and normal rats were infused with 3 x 10(4)U recombinant interleukin-2 (rIL-2)/day for 14 days using osmotic minipumps. The effects of IL-2 on natural immune function and bone resorption were evaluated after the infusion period. The percentage of NK cells in the spleen after treatment was quantitated by phenotypic analysis using monoclonal antibodies and flow cytometry. The elevated levels of NK cells normally seen in ia mutants were reduced to normal in the IL-2-infused rats. NK cell activity was evaluated by the 51Cr release assay and found to be enhanced to normal killing levels in the IL-2-treated mutants. The defects in NK function are corrected by IL-2 therapy. Likewise, the bone resorption defect appears to be corrected by the IL-2 infusions. The bone marrow cavity size was significantly increased in the IL-2-treated mutants compared with control mutants. Additionally, the percentage of osteoclasts exhibiting normal morphology was significantly increased in the IL-2-treated mutants. The bone density of the caudal vertebrae, evaluated by gray-scale analysis of x-rays, was found to be reduced in the IL-2-treated mutants. Interleukin-2 corrects both the bone resorption and natural immune defects in the ia mutation.

Animals↗

[Immunogenesis and nonspecific factors of natural resistance. XI. Further study of the depression mechanism of humoral reactions of natural immunity during the vaccinal process].

The mechanisms of depression of humoral reactions of natural immunity under the effect of vaccination were studied further. Experiments were carried out on albino rats tolerant to the horse serum protein. Administration of the antigen to the tolerant animals failed to cause formation of antibodies or to influence humoral factors of natural immunity. As to rats not immunized earlier, complement-fixing antibodies were revealed from the 7th to the 21st days after the administration of horse serum; simultaneously there was seen depression of the humoral mechanisms of natural resistance. The results obtained confirmed the hypothesis stating that there existed competitive relations between the specific and nonspecific immunological reaction in the fight for plastic provision of the corresponding reactions.

Animals↗

Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib).

Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 microg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0.15 microg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice.

Adolescent↗

[Stratum of the population of the Bashkir ASSR with natural immunity to hemorrhagic fever with renal syndrome].

Natural immunity to hemorrhagic fever with the renal syndrome (HFRS) in the human population of the Bashkir ASSR having the highest incidence of this infection was first studied using radioimmunoassay. The antigen was a suspension of lungs of rodents from natural foci containing high antigen titres. When 1726 human sera from 8 districts and 2 towns were examined, antibodies to HFRS were found in 20.1%, with variations from 6.9% to 41.5% in different territories. No relationship between the percentage of immune subjects and average incidence values for 17 years was found. In the immune population, men accounted for 21.3%, women for 19.3%. Among subjects under 40, the immune stratum was lower (17.5%) than among older subjects (26.2%). The percentage of immunity was found to depend on the occupation of the population. No significant difference in immunity could be found in persons with different blood groups. Antibody in HFRS convalescent was shown to persist in high titres for up to 20 years after the onset of the disease.

ABO Blood-Group System↗

Rubella epidemic in an institution: protective value of live rubella vaccine and serological behavior of vaccinated, revaccinated and naturally immune groups.

A rubella epidemic occurred in an institutional population composed of 189 susceptible, 37 naturally immune, 35 previously vaccinated and 38 serologically uncharacterized children and nursing staff. The epidemic lasted 3.5 months and showed more than 5 waves. Detailed clinical and serological examinations of these subjects were made. A rash appeared in 156 (52%) of 299 persons, including 145 (87%) of 166 unvaccinated and serologically uncharacterized subjects, but not in the 72 immune persons. In the middle of the 3rd wave urgent vaccination of 61 children aged 0 to 2 years of the susceptible group reduced the rate of appearance of a rash to 11 of the children (18%), as compared with 126 (98%) of 128 subjects in the unvaccinated non-immune group. The epidemic only reached a 4th wave in the vaccinated group, but it extended to a 5th wave or more in unvaccinated subjects. None of the 35 subjects in a previously vaccinated group developed rubella, although the rate of subclinical reinfection in this previously vaccinated group was higher (35%) than that in the naturally immune group (17%). Three cases of subclinical reinfection were detected even among 6 previously revaccinated subjects.

Adolescent↗

Construction and selection of the natural immune Fab antibody phage display library from patients with colorectal cancer.

AIM: To construct the natural immune Fab antibody phage display libraries of colorectal cancer and to select antibodies related with colorectal cancer. METHODS: Extract total RNA from tissue of local cancer metastasis lymph nodes of patients with colorectal cancer. RT-PCR was used to amplify the heavy chain Fd and light chain kappa and the amplification products were inserted successively into the vector pComb3 to construct the human libraries of Fab antibodies. They were then panned by phage display technology. By means of Dot immunoblotting and ELISA, the libraries were identified and the Fab phage antibodies binding with antigens of colorectal cancer were selected. RESULTS: The amplified fragments of Fd and kappa gained by RT-PCR were about 650 bp. Fd and kappa PCR products were subsequently inserted into the vector pComb3, resulting in a recombination rate of 40% and the volume of Fab phage display library reached 1.48 x 10(6). The libraries were enriched about 120-fold by 3 cycles of adsorption-elution-multiplication (panning). Dot immunoblotting showed Fab expressions on the phage libraries and ELISA showed 5 clones of Fab phage antibodies which had binding activities with antigens of colorectal cancer. CONCLUSION: The natural immune Fab antibody phage display libraries of colorectal cancer were constructed. They could be used to select the relative antibodies of colorectal cancer.

Antibodies↗

[Anti-Haemophilus influenzae b (Hib) natural immunity in children in Burkina Faso].

BACKGROUND: Natural immunity to Haemophilus infection type b that is acquired by the mothers and passively transmitted to their newborns is not well-known in developing countries, where the frequency of Haemophilus meningitis in infancy is high. POPULATION AND METHODS: Blood samples (5 ml) were taken from 89 women at the time of delivery and from the cord of their babies. Blood samples were also taken from 290 infants and children, distributed into nine subgroups as a function of their age. Children with protein-calorie malnutrition and immune deficiency were excluded from the study. Antibodies against Haemophilus influenzae were measured by Elisa and radioimmunologic methods. Blood concentrations of 0.15 pg/ml or more were considered to be protective. RESULTS: All the blood samples of mothers and cords contained protective levels of antibodies, as did the samples from 30% of those infants aged 0-60 days (all the infants were less than 1 month). No infant in the subgroup 12-23 months had protective levels of antibodies. The incidence of Haemophilus meningitis was correlated with the absence of antibodies. CONCLUSION: Maternal immunity is gradually lost by babies during their first 2 months of life, earlier than in developed countries. Early vaccination, at 3 months of age, is mandatory.

Adolescent↗

Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children.

Children putatively immune to the large roundworm Ascaris lumbricoides were identified in an area of Nigeria where infection is hyperendemic. Immunity was associated with higher levels of serum ferritin, C-reactive protein, and eosinophil cationic protein, indicating ongoing acute phase or inflammatory processes. In contrast, children who were susceptible to the infection had little serological evidence of inflammation despite their high parasite burdens. Immunoglobulin G (IgG) antibody activity in all subclasses was present in high titer in most children but appeared to have no protective function. Despite exceptionally high total IgE levels, there was no evidence that atopic responses to local common allergens was associated with natural immunity to Ascaris. Among those individuals who produced IgG antibody to recombinant ABA-1 allergen of Ascaris, the naturally immune group had significantly more IgE antibody to the allergen than did those susceptible to the infection. IgE antibody responses in conjunction with innate inflammatory processes therefore appear to associate with natural immunity to ascariasis.

Adolescent↗

The role of glycosphingolipids in natural immunity. Gangliosides modulate the cytotoxicity of natural killer cells.

Incubation of gangliosides with natural killer (NK) cells from various sources was found to inhibit NK activity in vitro whereas incubation of the same gangliosides with human or mouse lymphoma cells prior to their exposure to NK effectors resulted in a sharp increase in the NK sensitivity of the tumor cells. These effects depended on the oligosaccharide structure of the gangliosides and on the origin of the NK effector cells. The lysis of YAC cells by mouse splenocytes or of MOLT-4 cells by NK cells isolated from the peripheral blood of Syrian hamsters or humans was inhibited most strongly by pre-incubation of the effector cells with gangliosides GM3 and GD3 which are known to be elevated in the serum of tumor-bearing hosts. It is suggested that target cell-associated gangliosides may function as target structures recognized by NK cells while serum gangliosides may contribute to the inhibition of NK cells during tumor development and thus help the tumor to escape NK surveillance.

Animals↗

The immunosenescent phenotype in mice and humans can be defined by alterations in the natural immunity reversal by immunomodulation with oral AM3.

The reactivities of monocyte/macrophages and natural killer (NK) cells (natural immunity) were evaluated following the administration of the biological response modifier AM3. The lower number of macrophages and NK cells in middle-aged mice (MAM) compared to young adult mice (YAM) were significantly elevated following AM3 treatment to equal or greater than YAM values. Both macrophage and NK cell cytotoxicity peaked at two days following AM3 treatment and remained elevated over control values for up to 8 days following a four days treatment regimen by the oral route. Of particular interest was the clinical effect of AM3 treatment in chronic bronchitis (CB) patients and various aged volunteers. In middle-aged patients with chronic bronchitis (MACBpts) AM3 treatment resulted in significant increases in the number of monocytes as well as their phagocytic and chemotactic activity. Differential NK cell cytotoxicities were observed in MACBpts compared to middle-aged healthy adults (MAHA) and young healthy adults (YHA). Cytotoxicity in YHA was 2-fold higher than MAHA and 5-fold higher than MACBpts. The depressed number of NK cells in MACBpts was reversed following the AM3 treatment to near NK cell levels in YHA. These observations help to explain how AM3 aids in the restoration of natural cellular immunity and its possible application as an adjuvant to bacterial & viral vaccines as well as in the treatment CB.

Adjuvants, Immunologic↗

Natural immunity and HIV disease progression.

OBJECTIVE: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1. DESIGN: Data used were from 172 individuals with an estimated measure of NK cell activity and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.0 years. METHODS: The lytic activity of NK cells and LAK cells, the CD4 T lymphocyte count, and the concentration of CD16/CD56 NK cells were measured at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis was performed considering three main endpoints: CD4 cell counts below 100 x 10(6) cells/l, clinical AIDS, and death. RESULTS: In unadjusted analysis and after adjustment for age, CD4 T lymphocyte count and plasma HIV RNA at enrolment, low LAK cell activity was significantly associated with higher risk of progression to a CD4 T lymphocyte count < 100 x 10(6) cells/l (crude P = 0.001; adjusted P = 0.04) and to death (crude P = 0.0002; adjusted P = 0.02). Patients with low NK cell responsiveness to interferon-alpha tended to be at higher risk of death (crude P = 0.04; adjusted P = 0.13) whereas unstimulated NK cell activity and the concentration of NK cells were of no prognostic value for patients in this cohort. CONCLUSIONS: The present study suggests that low LAK cell activity and low NK cell responsiveness to interferon-alpha may be important in the pathogenesis of HIV infection.

CD4 Lymphocyte Count↗

Enhancement of natural immunity seen after voluntary exercise in rats. Role of central opioid receptors.

Chronic voluntary exercise in wheels for 5 weeks in spontaneously hypertensive rats (SHR) augments in vivo natural killer (NK) cell cytotoxicity. Endogenous beta-endorphin is increased in cerebrospinal fluid after voluntary exercise in rats and we have recently shown that beta-endorphin administered i.c.v. augments NK cell mediated cytotoxicity in vivo in a similar way as chronic voluntary exercise. We have now further investigated the involvement of central opioid systems in the exercise-induced augmentation in natural immunity. Exercise consisted of voluntary running in wheels for 5 weeks. In vivo cytotoxicity was measured as clearance of injected 51Cr-labeled YAC-1 lymphoma cells from the lungs. The clearance of YAC-1 cells in vivo was significantly increased in runners as compared to sedentary controls. Selective delta, kappa, or mu-opioid receptor antagonists were administered i.c.v. with osmotic minipumps during the last 6 days of the 5 weeks of running. The delta-receptor antagonist naltrindole (40-50 microg/day) significantly but not completely inhibited the enhanced NK-cell cytotoxicity seen after 5 weeks of exercise. Neither the kappa-receptor antagonist nor-BNI or the mu-receptor antagonist beta-FNA influenced the augmentation in NK cell cytotoxicity. Nor-BNI per se significantly augments in vivo cytotoxicity, indicating some inhibiting effect on natural immunity that could be mediated through the kappa-opioid receptor. Our data suggest the involvement of central delta-opioid receptors in the enhancement of natural cytotoxicity seen after chronic voluntary exercise.

Animals↗

Tick-borne encephalitis virus transmission between ticks cofeeding on specific immune natural rodent hosts.

To determine whether the portion of a vertebrate host population having specific immunity to tick-borne encephalitis (TBE) virus can participate in the TBE virus transmission cycle, natural hosts immunized against TBE virus were challenged with infected and uninfected ticks. Yellow-necked field mice (Apodemus flavicollis) and bank voles (Clethrionomys glareolus) were either immunized with TBE virus by subcutaneous inoculation of the virus, or they were exposed to virus-infected Ixodes ricinus ticks. One month later, when serum neutralizing antibody was detectable, the animals were infested with infected (donor) adult female ticks and uninfected (recipient) nymphal ticks; recipients were allowed to feed either in close contact (chamber 1) or physically separated (chamber 2) from the infected donor ticks. Following challenge with infected (and uninfected) ticks, viremia developed in all the control, nonimmune animals, whereas viremia was undetectable in all those animals naturally immunized by previous exposure to infected ticks. Despite the presence of neutralizing antibodies in all the immunized animals, 89% (24/ 27) immune animals supported virus transmission between infected and uninfected cofeeding ticks. Most transmission was localized, occurring within chamber 1; disseminated transmission from chamber 1 to chamber 2 was reduced. Immunization by tick bite was more effective than immunization by syringe inoculation in blocking cofeeding virus transmission. Nevertheless 76% (9/12) animals with "natural" immunity still supported transmission. The results demonstrate that natural hosts having neutralizing antibodies to TBE virus (and no detectable viremia) can still support virus transmission between infected and uninfected ticks feeding closely together on the same animal. These observations have important epidemiological implications relating to the survival of TBE virus in Nature.

Animals↗

Natural immunity to dust mites in patients with chronic rhinosinusitis.

Chronic rhinosinusitis is an extremely common clinical problem of which the etiology is poorly understood. To understand the role of common environmental antigens in this disease, natural immunity to antigens derived from the house dust mite was evaluated in 22 adults with chronic rhinosinusitis and compared to a carefully matched group of patients with chronic asthma or to a group of normal individuals. Allergic reactivity to dust mites was very common in patients with chronic rhinosinusitis, with 68% exhibiting a positive immediate skin test reaction and 41% exhibiting elevated levels of mite-specific serum IgE; 72% of patients with rhinosinusitis also exhibited markedly elevated levels of mite-specific serum IgG, which were present in both mite-allergic and nonallergic patients. IgG titers were much higher in the group with rhinosinusitis than in patients with asthma, whereas allergic reactivity to dust mites was significantly higher in the patients with asthma. Mite-specific immunity was low or absent in the group of normal individuals. These findings demonstrate that natural immunity to dust mites is very common in patients with chronic rhinosinusitis and suggest that immunity to mites may be involved in this syndrome. Furthermore, the data indicate that there may be significant differences in the ability of patients with rhinosinusitis or asthma to produce mite-specific antibodies of the IgG class.

Adult↗

Development of natural immunity to Neisseria meningitidis.

Although meningococcal disease is rare in industrialized nations, Neisseria meningitidis holds a prominent position amongst pediatric infections because of the dramatic clinical presentation of the disease, high mortality, epidemic potential and the recent disappearance of many other important infectious diseases in developed countries through improvements in public health and vaccination. The precise nature of natural immunity to meningococci remains unknown, although a complex interaction between the organism and nasopharyngeal mucosal barrier, innate immune mechanisms and acquired immunity is involved. Study of the mechanisms of natural immunity may provide the key to development of vaccines that can reduce the burden of disease in early childhood.

Antibodies, Bacterial↗

Differential susceptibility of metastatic lymphoma cells to natural immunity.

The susceptibility of metastatic variant lymphoma cells to natural immunity was studied using a low malignant/metastatic parental RAW117-P cell line and its liver colonizing highly malignant/metastatic RAW117-H10 cell line. The metastatic variant RAW117-H10 cells express a significantly lower amount of laminin-like and fibronectin-like molecules as determined by flow cytometry using monospecific polyclonal antibodies to laminin and fibronectin. Our studies indicated that the RAW117-H10 cells are resistant to natural killer (NK) cell-mediated cytotoxicity. In vitro activation of the effector cells with interferon-gamma increased the susceptibility of these cells to NK-mediated cytotoxicity while maintaining the difference between the two cell lines. However, when recombinant interleukin-2 was used to activate the effector cells, the cytotoxicity of the lymphokine-activated effector cells to both parental low metastatic RAW117-P cells and highly metastatic RAW117-H10 cells was similar.

Animals↗