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Effects of aztreonam on natural immunity in mice.

The influence of the dose and the duration of treatment with aztreonam, a monocyclic beta-lactam antibiotic, on the natural immune response of mice has been investigated. The results show the effects induced by the antibiotic on several immune parameters were affected by the duration of treatment. Thus, treatment with 28 mg/kg per day of aztreonam over 14 days increased every immune parameter tested, while treatment with 57 mg/kg per day of aztreonam for 7 days only enhanced the natural killer (NK) activity of splenocytes. Since aztreonam does not apparently impair the innate immune response, it might be a suitable therapy for the treatment of patients who are immunosuppressed.

Animals↗

Natural immunity to dust mites in adults with chronic asthma. I. Mite-specific serum IgG and IgE.

Natural immunity to dust mite (Dermatophagoides farinae) antigen was assessed in a population of 63 adults with a clinical diagnosis of chronic asthma. Immunity was determined by measuring immediate hypersensitivity to an intracutaneous injection of dust mite antigen, mite-specific serum IgG concentrations using a double antibody ELISA, and mite-specific serum IgE concentrations by RAST. Using these tests, 68% of the asthmatic patients exhibited a positive skin test; 38% had elevated concentrations of mite-specific IgE, and 63% had elevated concentrations of mite-specific IgG. In contrast, when analyzed individually, these tests were positive in only 10 to 11% of normal subjects or patients with chronic obstructive pulmonary disease. Only 10% of asthmatics had elevated serum concentrations of mite-specific antibodies of the IgG4 subclass. The asthmatic patients could be subdivided into 4 groups based on their immunologic reactivity to dust mites; 24% of the patients had elevated concentrations of mite-specific IgG in the absence of allergic reactivity to mites (skin test). A second subgroup (27%) exhibited allergic reactivity in the absence of elevated concentrations of mite-specific serum IgG. A third subgroup (41%) consisted of patients who exhibited both allergic reactivity and elevated IgG concentrations. The smallest subgroup (8%) consisted of patients with no measurable immunity to mites. In total, 94% of the asthmatic group exhibited a positive immune response to at least one of the dust-mite-specific tests, whereas only 26% of the normal subjects could be considered to be immune using the criteria of a positive reaction in at least 1 of the 3 tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The changes and significance of red cell nature-immune-adhesion function in liver diseases at different stages].

OBJECTIVE: To study the changes of red cells nature immune adhesion function (RNIAF) in liver diseases at different stages, and the feasibility of RNIAF in evaluating the severity of liver diseases. METHODS: Venous blood was extracted from 682 patients with liver disease, including cirrhosis, chronic hepatitis, acute hepatitis, hepatitis gravis, and 50 healthy blood donors as controls. Suspension of red cells in self-plasma was mixed with solution of mouse ascites carcinoma cells. A tumor cell attached with 5 red cells or 2 lymphocytes/granulocytes was counted as one rosette. The adhesion rate was calculated. Serum soluble complement receptor 1 (sCR1) was measured with a newly established sandwich enzyme-linked immunosorbent assay (ELISA). The CR1 expressed on erythrocytes has assayed by cell-ELISA. RESULTS: The expression of CR1 on erythrocytes was lower among the patients with liver diseases. Compared with that in healthy controls, RNIAF decreased among the patients with various liver diseases (all P < 0.01) in the order of acute hepatitis, chronic hepatitis, cirrhosis Child's A, cirrhosis Child's B, cirrhosis Child's C, and hepatitis gravis. CHE and PTA decreased and PT increased among the patients with cirrhosis and hepatitis gravis (all P < 0.05 or P < 0.01). RNIAF was positively correlated with CHE, PT, and PTA in patents with cirrhosis. CHE, PT and PTA remained at low levels while RNIAF almost returned to its normal level in the convalescents of hepatitis gravis. CR1 expressed on erythrocytes and sCR1 in serum in various liver diseases were decreased at different degrees, however, they changed significantly later than RNIAF. Serum sCR1 significantly increased in the patients with cirrhosis, particularly in those in grades Child's A to C. CONCLUSION: Low-cost, easy to operate and with early change and stable results, RNIAF may be used as an important indicator to evaluate the severity of liver diseases. of CHE, PT/PTA. It is an important to evaluate the severity of liver function in clinic.

Cell Adhesion↗

Induction of TH1 and TH2 responses: a key role for the 'natural' immune response?

What pushes a T-cell response towards a predominantly TH1 or TH2 phenotype? Several factors have been proposed, including the properties of antigens, dose of antigen, site of exposure and ongoing immune response in the host. Here, Sergio Romagnani presents new evidence to indicate a determining role for the 'natural' immune response, including NK cells and cells of the mast cell/basophil lineage, in the subsequent 'specific' T-cell response.

Animals↗

Augmentation of natural immunity and regulation of tumor growth by conditioning.

We have reported the effect of classical (Pavlovian) conditioning of natural immunity on survival of tumor-bearing mice. In the first study, we have observed that mice conditioned, transplanted with tumor, and re-exposed to conditioned stimulus (camphor odor) had an increase in median survival (day 43, as compared to days 34, 38, and 37 of various control groups). Two of these conditioned mice lived more than 120 days and showed early tumor growth, but were free of disease at day 97. We report the observations of a repeat study. Two groups of conditioned mice were used for these studies. One group was re-exposed to the conditioning stimulus following transplantation with tumor (CND) and the second group was not re-exposed to odor of camphor (CNDo). Statistically significant delay in growth of MOPC 104E in the CND group was observed when compared with the CNDo group. The survival data supports the observations of tumor IgM values. In an independent study, we investigated the possible mechanisms of MOPC 104E regulation in vitro. Plastic adherent spleen cells (macrophage cells) from mice primed in vivo with MOPC 104E tumor cells suppressed tumor IgM production by MOPC cells by 98% and also reduced colony formation by MOPC cells. The possible mechanism(s) of regulation of tumor growth in conditioned mice might be mediated by plastic adherent activated macrophages.

Animals↗

Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1.

We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen.

Adolescent↗

[Activity of certain mechanisms of natural immunity in white rats provided with different amounts of vitamin D].

In rats with D avitaminosis some mechanisms of natural immunity were shown to be unaltered (complement, unspecific bactericidal activity of blood serum, content of normal antibodies to Vi-antigen, lysozyme). Pronounced D hypervitaminosis led to an increase in the unspecific bactericidal activity of blood serum, accompanied by the increase in complement and lysozyme in blood serum, whereas content f lysozyme in leukocytes was decreased. The D hypervitaminosis was also accompanied by distinct atrophy of thymus and by inhibition of T-lymphocyte activity.

Animals↗

Interferons antagonize gamma-ray-induced depression of natural immunity.

PURPOSE: The aim of this study was to determine the inhibitory effects of in vitro radiation on the number and function of natural killer (NK) cells and to investigate the capability of interferons (IFNs) to restore the activity of NK, depressed by gamma-rays. METHODS AND MATERIALS: Mononuclear cells (MNC) were obtained from intact or in vitro irradiated (20 Gy) peripheral blood collected from healthy donors. Alternatively, MNC were irradiated (20 Gy) after separation from intact whole blood. The in vitro treatment of MNC with IFNs (alpha, beta, or gamma, 200 UI/ml) was performed at different times after or before radiation. The NK activity (4 h-51Cr release test), the percentage of CD16+/CD56+ cells and apoptosis (cytometric analysis), and binding (microscopic observation) were evaluated on Days 0, 1, 2, and 5 from gamma-ray exposure and IFNs treatment. RESULTS: The in vitro treatment of irradiated MNC with betaIFN after radiation completely reverses the inhibitory effects of gamma-rays on human NK activity. BetaIFN do not reduce the apoptosis induction by radiation and don't modify the number of CD16- or CD56-positive cells. The binding between irradiated effectors and tumor cells (K562) appears partially increased in betaIFN-treated MNC. CONCLUSIONS: The results of the present investigation suggest a possible role of betaIFN in reversing the detrimental effect of radiation on human natural immunity and provide a rational basis for in vivo use of betaIFN in cancer radiotherapy.

Gamma Rays↗

Natural immunity in mice to the envelope glycoprotein of endogenous ecotropic type C viruses: neutralization of virus infectivity.

The ability of naturally immune mouse sera to neutralize ecotropic AKR murine leukemia virus (MuLV) was examined by using unfrozen virus preparations harvested for 1 h. In this assay several mouse sera significantly and consistently neutralized MuLV infectivity. The ability of these sera to neutralize was correlated with the presence of antibodies against MuLV detectable in a radioimmune precipitation assay using radioactively labeled intact virions. This neutralization was specific, in that either N- or B-tropic viruses, but not Friend MuLV, were neutralized. In addition, neutralization could be abrogated with purified AKR MuLV gp71 at concentrations that do not interfere with virus infectivity but could not be abrogated with Rauscher MuLV gp71. Neutralizing activity could be removed by absorption with intact AKR MuLV, but not by absorption with Friend MuLV, a BALB/c xenotropic virus, or with NZB xenotropic virus. All the neutralizing activity of (B6C3)F1 mouse sera was associated with the immunoglobulin G fraction.

AKR murine leukemia virus↗

Effects of 1,25-dihydroxyvitamin D3 on bone resorption and natural immunity in osteopetrotic (ia) rats.

Osteopetrois is an inherited bone disease characterized by an excessive accumulation of bone throughout the skeleton. The disease in the ia (incisors absent) rat is the result of reduced bone resorption caused by defective, although numerous osteoclasts. In addition to the bone defects, ia rats have suppressed natural immunity, even though these animals have excessive numbers of natural killer (NK) cells. The osteopetrotic condition also appears to have an associated abnormality in vitamin D metabolism. Because 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] stimulates bone resorption and has a role in the immunoregulation of NK cells, mutant and normal rats were infused with 1,25-(OH)2D3 for 14 days in an attempt to correct the defects in this mutant. Serum levels of osteocalcin, 25-OHD3, and 1,25-(OH)2D3, as well as NK function and parameters of bone resorption, were evaluated after the infusion period. Serum levels of osteocalcin and 1,25-(OH)2D3 were elevated in both ia and normal rats treated with 1,25-(OH)2D3. Serum 25-OHD3 levels were significantly reduced in the treated animals. The elevated percentage of NK cells normally found in ia rats was reduced to normal in the treated mutants, and NK cell function was elevated to normal levels of lytic activity. The percentage of NK cells and NK function remained unchanged in the treated normal rats. The bone marrow cavity size was significantly increased in the 1,25-(OH)2D3-treated mutants, as was the percentage of osteoclasts exhibiting normal morphology. Radiographically, the mutant bones were less dense.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Action of plant extracts on the natural immunity indices of animals].

The influence of extracts from oak bark, St. John's-wort leaves and pine buds on natural immunity characteristics of mice has been studied. The injection of these extracts into mice has been found to enhance their resistance to infection with Staphylococcus aureus and Bordetella pertussis virulent cultures, to decrease the enzymatic activity of 5'-nucleotidase in the peritoneal exudate macrophages of mice and to increase the level of lysozyme in their blood. The action of these extracts has proved to depend on their dosage and the time of observation.

5'-Nucleotidase↗

Increased IL-12 P40 homodimer secretion by spleen cells during in vivo growth of the BW-19 T cell hybridoma accompanies suppression of natural immunity.

The high capacity of the T cell hybridoma BW-19 to metastasize to the spleen, despite its high and moderate sensitivity to lysis by macrophages and natural killer (NK) cells, respectively, appears to be linked to its capacity to suppress local resident NK cell and macrophage activity. Such suppression of splenic NK cell and macrophage activity is accompanied by an increased production of the p40 subunit of interleukin-12 (IL-12) by spleen cells. Closer examination revealed that most of the p40 subunit is present under the form of the homodimer (p40)2, whereas the heterodimeric form of IL-12 is present only in small amounts. Since (p40)2 is known to be a strong antagonist of IL-12-mediated effects, i.e., NK cell activation and interferon-gamma (IFN-gamma) secretion, the increased production of (p40)2 after BW-19 cell inoculation may contribute to the suppression of NK cell and macrophage activity. In addition, we found that the high production of (p40)2 in our tumor model was accompanied by a drastic decrease in IL-2 and IFN-gamma production by spleen cells, further favoring the possibility that (p40)2 plays a role in the suppression of NK cell and macrophage cytotoxicity. Our results show that normal spleen cells can produce (p40)2 in response to cancer cell growth in vivo and are highly suggestive of a role for (p40)2 in the suppression of natural immunity.

Animals↗

Evaluation of in vivo and in vitro effectivity of immune defense against a spontaneously arising, nonlymphoid rat tumor. I. Analysis of natural immune defense.

Possible mechanisms of natural defense against a nonimmunogenic, nonlymphoid rat tumor were evaluated in vitro and examined for effectivity in vivo, using BSp6S, the subcutaneously grown transplantation line of a spontaneously arising fibrosarcoma in the BDX rat strain, which is highly susceptible to natural killer (NK) cells and macrophages (Mø). The role of nonspecific immune defense in vivo was demonstrated by eliminating NK cells by irradiation and Mø by silica treatment. Especially after depletion of NK cells a significant acceleration of tumor growth and a reduction in the number of cells required for tumor takes was observed. Activation of Mø by Corynebacterium parvum (CP) did lead to retardation of tumor growth; prevention of tumor growth was only achieved after inoculation of a marginal dose of tumor cells. Activation of NK cells was of minor influence. It is concluded that NK cells and Mø are the main influences on survival time, the effectiveness of NK cells being limited to early periods of tumor growth.

Animals↗

[The effect of ionizing radiation on various factors of natural immunity of hamsters under normal conditions and during invasion with the cestode, Hymenolepis diminuta].

Effect of single and chronic irradiation on factors of hamsters natural immunity such as complement, lysozyme and antibodies in norm and in the cestode invasion has been investigated. Significant phase changes in the complement activity level, lysozyme content and specific antibodies titre have been shown to occur in hamster blood under the influence of ionizing radiation. Cestode invasion in irradiated host organism increases the negative effect of ionizing radiation on the hamster immune system.

Animals↗

Analysis of Neisseria lactamica antigens putatively implicated in acquisition of natural immunity to Neisseria meningitidis.

Sera from healthy human volunteers, patients convalescent from meningococcal meningitis, and mice immunized with outer membrane proteins from Neisseria meningitidis and Neisseria lactamica strains were used to analyze and identify antigens cross-reactive to both neisserial species. All classes of meningococcal proteins except class 1 (PorA) and class 5 cross-reacted with N. lactamica proteins and two other proteins of 65 and 55 kDa (an iron-regulated protein). Results obtained with the mouse sera demonstrate that cross-reactive antibodies can be elicited by either N. meningitidis or N. lactamica. These results support the suggestion that N. lactamica contributes to the development of natural immunity against N. meningitidis during the first years of life. The use of vaccines containing proteins other than PorA could interfere in colonization of mucosal surfaces by N. lactamica, hampering the natural mechanisms of immunity acquisition in humans. Only convalescent sera reacted with the 55 and 65 kDa proteins, which suggests that they might be relevant for pathogenicity.

Animals↗

Modification of natural immunity in mice by imipenem/cilastatin.

The imipenem/cilastatin constitutes a broad spectrum beta-lactam antibiotic formulation, especially used in pre and post-operatory treatments for transplanted or drug-immunosuppresed patients. The effect of the dose and the duration of the treatment with imipenem/cilastatin on some parameters of natural immunity in BALB/c mice were examined. The treatment by intraperitoneal route with 1 or 2 g/70 kg/day during 7 days did not alter significantly the parameters tested, whereas the greater dose used (4 g/70 kg/day) had an inhibitory effect on peritoneal cell counts and phagocytic activity, as well as it caused an increase on IL-1 production and natural killer activity. The greater stimulating effect of innate immunity was obtained with the lowest imipenem/cilastatin dose used (0.5 g/70 kg/day). Since this antibiotic apparently does not impair the studied innate immune responses at 1 or 2 g/70 kg/day, it seems to be especially suited for the therapy of systemic bacterial infections in immunocompromised patients.

Animals↗

A new theory on the common evolutionary origin of natural immunity, inflammation and stress response: the invertebrate phagocytic immunocyte as an eye-witness.

Data in favor of the hypothesis of the common evolutionary origin of natural immunity inflammation and stress response are presented. These phenomena seem to be mediated by a common pool of molecules (POMC-derived peptides, cytokines, biogenic amines, glucocorticoids, and nitric oxide). Macrophages are able to release all the above mentioned molecules. They play a primary role in defence mechanisms. Thus, we argue that this cell can be considered the eye-witness of the common evolutionary origin of the immune and neuroendocrine systems.

Animals↗