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PubMed1977

[Disruption of the mechanisms of natural immunity in the initial stage of adjuvant disease in rats and guinea pigs].

Similar changes in the nonspecific immunity indices were noted in experiments on rats and guinea pigs with adjuvant disease: depression of blood serum bactericidal activity and increase of the lysozyme and complement level, as well as inhibition of the phagocytic activity of leukocytes and production of normal antibodies to O- and Vi-antigens of typhoid bacilli in rats. Changes in disturbances of natural immunity factors in adjuvant disease correlated with the severity of the process in both animal species.

Animals↗
PubMed2006

Functional defect of natural immune system in an apparent immunocompetent patient with pulmonary cryptococcosis.

We report a case of pulmonary cryptococcosis in a 21-year-old Italian female smoker with no apparent immune disorder. In this study we demonstrated that: (i) patient's neutrophils and monocytes manifested a significant reduction of killing activity against Cryptococcus neoformans as well as Candida albicans; (ii) the suppression was more pronounced in monocytes than in neutrophils; (iii) neutrophils and monocytes showed a significant impairment of TNF-alpha, IL-1beta, and nitric oxide production. These results suggest that the apparent immunocompetent host with pulmonary cryptococcosis could have specific defects in natural immune system mechanisms.

Adult↗
PubMed2002

Interspecific neisserial high molecular weight proteins able to induce natural immunity responses are strongly correlated with in vitro bactericidal activity.

Human sera from healthy volunteers and patients convalescent from meningitis were used to search for widely cross-reactive antigens implicated in vivo protective responses. Using the type strain Neisseria meningitidis B16B6 and a wide variety of both N. meningitidis and N. lactamica strains, several cross-reactive antigens and bactericidal sera were found, although the cross-reactivity patterns did not correlate with bactericidal activity, a total correlation was found between bactericidal activity and reaction with one or two high molecular weight proteins (162 and 138 kDa), and a mouse serum against the purified proteins showed a high bactericidal activity. Our results suggest that the high molecular weight proteins found are immunogenic and cross-reactive, eliciting bactericidal responses during infection and as a result of natural immunity. These proteins should be taken into account in studies for future vaccine formulations.

Animals↗
PubMed2000

Evaluation of the natural immunity in pups inoculated with a modified-live canine parvovirus type 2b (CPV-2b) strain.

Three pups 2-4 months old were vaccinated subcutaneously with the modified live canine parvovirus, CPV-2b/29-97 strain. During an observation period of two weeks pups remained clinically health, exhibiting a vigorous post-vaccinal active serological response (haemoagglutinating inhibiting antibody titers for CPV-2 ranging from 1:2560 to 1:5120 at 21 days post inoculation). Phagocytosis and killing of Candida albicans exerted by polymorphonuclear cells and monocytes did not undergo significant modifications 3-6 days post vaccination up to 30 days. Antibacterial activity mediated by peripheral blood lymphocytes (Salmonella typhi was used as a target) was slightly, but not significantly decreased 3 days post vaccination. Conclusively, in pups the CPV type 2b vaccine seems to be safe as far as natural immune responses are concerned, while its immunogenicity is preserved.

Animals↗
PubMed1999

Augmentation of natural immunity to a pro-inflammatory cytokine (TNF-alpha) by targeted DNA vaccine confers long-lasting resistance to experimental autoimmune encephalomyelitis.

TNF-alpha is thought to be a key pro-inflammatory cytokine in T cell-mediated autoimmune diseases, particularly in rheumatoid arthritis (RA) and multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) serves as an animal model for MS. The current study observes a notable TNF-alpha-specific antibody titer generated during the course of EAE, apparently not sufficient to prevent the development of disease. Administration of TNF-alpha-naked DNA vaccine enhanced the production of TNF-alpha-specific antibody titer and conferred EAE resistance. These antibodies were found to be neutralizing in vitro and capable of inhibiting the development of disease when transferred to other EAE rats. Thus, modulation of EAE with TNF-alpha DNA vaccines enhances the regulation of natural immunity to a self pro-inflammatory cytokine and provides a tool by which the immune system is encouraged to elicit anti-self protective immunity to restrain its own harmful reactivity when such a response is needed.

Animals↗
PubMed1994

Functional overlap in the src gene family: inactivation of hck and fgr impairs natural immunity.

We have generated mice with targeted disruptions of the src-like genes hck and fgr to assess the role of these kinases in myeloid cell development and function. Hematopoiesis appears to proceed normally in both hck-l- and fgr-l- animals, and in hck-l(-)-fgr-l- double homozygotes, but phagocytosis is impaired in hck-l- macrophages. Macrophages cultured from doubly homozygous, hck-l(-)-fgr-l- animals retain many other normal functional properties, suggesting that the deficiency of these kinases is complemented by other src family members. The specific activity of the Lyn protein kinase is increased in hck-l- macrophages, implying that Lyn may compensate for a deficiency in Hck. Doubly mutant animals, however, have a novel immunodeficiency characterized by an increased susceptibility to infection with Listeria monocytogenes, indicating that either hck or fgr is required to maintain a normal natural immune response. These data provide the first direct example of genetic interactions between src gene family members.

Animals↗
PubMed1986

[Natural immunity of the pupils in a secondary vocational and technical school for rubber and plastics].

In connection with the reconstruction of the educational system and occupational training of the youths, the problem of the effect of the occupational factors on the organism of the juveniles is of exceptional importance. The search of early changes by the application of immunological tests in that aspect is very rational. The state of microflora of the deep layers of the skin, the microbic contamination of nasal mucosa have been studied as well as the content of complement in serum and serum immunoglobulins G, A and M and the phagocytosis in the students from SPTS. The experimental subjects have exposed to a complex of toxic-chemical substances with different intensity during their occupational training and practice. It has been established that the training under the specific conditions for mastering the specialty has led to a slight decrease of the antimicrobic resistance and reduction of the phagocytic function of leukocytes, not affecting the humoral factors of natural immunity.

Adolescent↗
PubMed1996

Identification of T-cell determinants in natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in an adult population exposed to malaria.

AMA-1 of Plasmodium falciparum is a promising candidate antigen in malaria vaccine development. In this study, we have mapped the immunodominant T-cell determinants in this antigen by using synthetic peptides. From the amphipathic scores, 17 putative T-cell determinants were identified. Nine of the 17 peptides complementary to the putative T-cell determinants induced proliferation of peripheral blood mononuclear cells (PBMC) from Kenyan residents who had lifelong exposure to malaria; none of these peptides induced proliferation of PBMC from donors who were not previously exposed to malaria. This indicates that AMA-1 peptides were stimulating T cells that were previously primed by prior exposure to P. falciparum. Many positive responders showed reactivity to more than one peptide, and some of the potent proliferative T epitopes were found to be localized in the highly conserved regions of AMA-1, suggesting that it may be possible to induce T-cell memory that can recognize different variant forms of the parasite. This information on the natural immune responses against the AMA-1 vaccine antigen in clinically immune adults will be helpful in the development of an AMA-1 antigen-based malaria vaccine and may also guide testing of AMA-1-based vaccine formulations.

Adult↗
PubMed1991

Development of natural immunity in Plasmodium falciparum malaria: study of antibody response by Western immunoblotting.

A longitudinal study was carried out in Burkina Faso to investigate the natural development of the immune response to Plasmodium falciparum malaria. Three bleedings were carried out before, during, and after the seasonal peak of transmission. Detailed antigen mapping and antibody prevalence of the 248 collected serum samples were established by immunoblotting on the basis of several epidemiological and biological parameters. An improved Western immunoblotting system was used to analyze up to 67 serum samples on each nitrocellulose sheet. This system allowed us to perform the entire study with strictly comparable conditions. Two different blood-stage antigens (exoantigens and somatic antigens) were used to analyze the distribution of different classes and subclasses of immunoglobulins according to the age of the individuals, the presence or absence of a malarial attack, the transmission period, the origin of parasite isolates, and the response to intraerythrocytic stages. Although this analysis emphasizes strong individual variations, reactions with two major antigens of 115 and 103 kDa were especially noted. These antigens induced high antibody levels and prevalences but were probably not involved in protection. The prevalence of immunoglobulin G (IgG) antibodies differed by isotype. Most of antigens stimulating IgG production were also responsible for the IgM antibody response. The role played by these antibodies in the development of natural immunity against malaria is discussed.

Adolescent↗
PubMedDate not supplied

[Natural immunity and herpes infection].

The review details natural immunological factors that are the first-line protection from herpes simplex virus. These reactions may be conventionally divided into 3 active phases. In Phase 1, the virus is attacked by proteins, such as complement of precursors of natural class M (IgM) antibodies and antimicrobial peptides. In Phase 2, the interferons produced by infected epithelial and resident dendritic cells go into action. And, finally, in Phase 3, effector cells, such as neutrophils, macrophages, and natural killer cells, show antiviral activity.

Animals↗
PubMed1986

Natural immunity against ovarian tumors.

We have analysed natural killer (NK) cytotoxic activity in peripheral blood and ascitic fluids of patients with advanced stage of ovarian epithelial carcinoma. All patients displayed low NK activity in peripheral blood and virtually no cytotoxicity in ascitic fluids. NK activity in ascitic fluids could be substantially augmented after regional administration of virus-modified tumor cell extracts (VMTE), and that in peripheral blood after culture of effector cells with interleukin-2 (IL-2) in vitro. Activated NK cells displayed cytotoxic activity against NK-sensitive and NK-resistant tumor cell lines as well as against fresh ovarian tumors. Parallelism was found between regional NK augmentation and regression of malignant ascites. The latter observation suggests possible NK cell role in defense against ovarian tumors.

Ascitic Fluid↗
PubMed2004

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis.

During atherogenesis, LDL is oxidized, generating various oxidation-specific neoepitopes, such as malondialdehyde-modified (MDA-modified) LDL (MDA-LDL) or the phosphorylcholine (PC) headgroup of oxidized phospholipids (OxPLs). These epitopes are recognized by both adaptive T cell-dependent (TD) and innate T cell-independent type 2 (TI-2) immune responses. We previously showed that immunization of mice with MDA-LDL induces a TD response and atheroprotection. In addition, a PC-based immunization strategy that leads to a TI-2 expansion of innate B-1 cells and secretion of T15/EO6 clonotype natural IgM antibodies, which bind the PC of OxPLs within oxidized LDL (OxLDL), also reduces atherogenesis. T15/EO6 antibodies inhibit OxLDL uptake by macrophages. We now report that immunization with MDA-LDL, which does not contain OxPL, unexpectedly led to the expansion of T15/EO6 antibodies. MDA-LDL immunization caused a preferential expansion of MDA-LDL-specific Th2 cells that prominently secreted IL-5. In turn, IL-5 provided noncognate stimulation to innate B-1 cells, leading to increased secretion of T15/EO6 IgM. Using a bone marrow transplant model, we also demonstrated that IL-5 deficiency led to decreased titers of T15/EO6 and accelerated atherosclerosis. Thus, IL-5 links adaptive and natural immunity specific to epitopes of OxLDL and protects from atherosclerosis, in part by stimulating the expansion of atheroprotective natural IgM specific for OxLDL.

Animals↗
PubMedDate not supplied

Effects of B4 Coxsackievirus infection on cell-mediated immunity, natural cytotoxicity and interleukin-1 production by spleen cells, in mice.

By using CBA inbred mice as responders, the influence of in vivo B4 Coxsackievirus infection (in two separate experimental procedures) on anti-virus cell-mediated immunity (CMI), natural killer (NK) cell activity and lipopolysaccharide (LPS) induced interleukin-1 (IL-1) production in spleen cells were studied. Both experimental infection schedules were able to induce a "positive" CMI response. NK cell activity was also significantly stimulated, especially by the administration of high virus amounts/inoculum, with frequent injections. On the contrary, LPS-dependent IL-1 synthesis increased particularly following application of the other experimental schedule (low virus amounts, few injections). Some aspects concerning CMI, NK and IL-1 relationships, during several enteroviral diseases, are discussed.

Animals↗
PubMed1993

Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice.

This study investigated the influence of 9 wk of chronic exercise on natural cytotoxicity in male C3H mice. Both in vivo cytotoxicity (pulmonary vasculature) and in vitro cytotoxicity (spleen) were determined for voluntary (wheel running; n = 30) and forced (treadmill running, 15 m/min, 30 min/day; n = 30) exercise protocols. A sedentary control group (n = 30) and a treadmill control group (5 m/min, 5 min/day; n = 30) were also included. After 9 wk of chronic exercise, submaximal exercise O2 uptake was reduced in the wheel-running group relative to that in sedentary or treadmill-trained mice. Maximal citrate synthase activity of soleus muscle was higher in treadmill-trained group compared with that in sedentary or wheel-running mice. Chronic exercise consistently reduced percent retention of CIRAS 3 tumor cells in the lungs of treadmill- (15.3 +/- 1.4) and wheel- (17.9 +/- 1.4) trained mice below that of sedentary (29.5 +/- 2.7) and treadmill control (25.8 +/- 1.8) groups (P < 0.001). Injection of anti-asialo GM1 (ASGM1) antibody increased tumor cell retention in the lungs for all groups but did not alter the differences between activity conditions. In vitro cytotoxicity was enhanced in treadmill- and wheel-trained mice relative to that in sedentary controls but was not elevated in the treadmill control group. Anti-ASGM1 injection eliminated in vitro cytotoxicity for all groups. Chronic exercise slightly increased the frequency of ASGM1-positive splenocytes in treadmill-trained mice only. These results indicate that chronic exercise enhances natural cytotoxic mechanisms in vivo and in vitro and that this enhancement is present for both forced and voluntary exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Changes in natural immunity during the course of HIV-1 infection.

The role of natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxicity in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV-1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC-0) subjects and HIV-1+ individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC-2) or symptomatic (CDC-4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL-2 and their cytolysis of K562 and U-937 targets was determined using chromium release assays. The role of CD8+ lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell-mediated cytotoxicities in HIV-1-infected individuals were reduced compared with seronegative controls without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8+ subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI-/CDC-2 seropositive population. No corresponding changes in LAK activities in seronegative control or HIV+/OI+/CDC-4 groups were observed. Levels of LAK activity against K562 targets in CDC-0/HIV- and CDC-4/HIV+ groups correlated with the percentage of CD56+ LAK cells; corresponding LAK activity in the CDC-2/HIV+ group correlated with the percentage of both CD56+ and CD8+ subsets. These findings suggest that adaptive changes in non-MHC restricted cytotoxic responses occur in HIV-1 individuals at early stages post-HIV infection, before the onset of opportunistic infection.

Acquired Immunodeficiency Syndrome↗