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PubMed1994

Long-term follow-up study of rubella antibodies in naturally immune and vaccinated young adults.

Selective rubella vaccination of 12-year-old schoolgirls was introduced in Sweden in 1973 and at the same time a long-term follow-up cohort study was initiated. In 1982, a two-dose programme with a combined vaccine against measles, mumps and rubella (MMR) was introduced and vaccinations were given at the ages of 18 months and 12 years to both boys and girls. The cohort initially comprised 486 girls. It was followed for between 8 and 16 years. All the girls enrolled were seronegative before vaccination and had seroconverted to a haemagglutination-inhibition (HAI) titre of at least 1:16. On the last test occasion 16 years later, 22% had titre values below 1:16, and 6% lacked detectable antibodies against rubella (< 1:8). A fourfold or greater rise in titre was seen in 36% of the girls during the first 8 years of observation, whereas during the following 8 years only 1% showed a significant increase of titre values. The geometric mean titre declined from 1:110 to 1:34 during the first 8 years and further to 1:18 during the following 8 years. From 1982 to 1990, the seroimmunity to rubella of 18-year-old girls and boys was studied yearly. The number studied was 3308 18-year-old schoolgirls and 6347 18-year-old recruits born between 1964 and 1972. The recruits were divided into two groups, 4610 unvaccinated and born in 1964-1969 and 1737 vaccinated and born in 1970-1972. Seropositive recruits in the first group were thus naturally immune only, while the second group had a mixture of natural and vaccine-induced immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

In vitro combined effects of a triazene compound and interferon-beta on natural immunity against lymphoblastoid cells: studies at effector and target cell level.

It was shown that Dacarbazine and other triazene compounds render murine leukemias highly immunogenic and susceptible to natural immunity (NI). In addition a pilot clinical study revealed that Dacarbazine can be cytotoxic for bone marrow blasts in patients with acute non-lymphoblastic leukemias through a mechanism that could be, at least in part, of immunological origin. However triazenes depress antigen-dependent responses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex interaction between triazenes and IFN on NI effector (i.e. NK) lymphocytes and human target lymphoblastoid cells has been investigated. The results show that: (a) IFN increases NK activity and antagonizes the depressive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the NK function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased growth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regulates the susceptibility of lymphoblastoid cells to NK effectors; (d) however a net "therapeutic gain" was found if the overall influence of MTBA+IFN on target and effector cells is considered.

Antibodies, Monoclonal↗
PubMed1990

Specific expression of human c-fgr in natural immunity effector cells.

The c-fgr gene product was shown by immune complex protein kinase assay with specific antibodies to be a 58-kilodalton protein (p58c-fgr) with tyrosine-specific autophosphorylating activity. On examination of peripheral blood cells by immunoblotting with anti-c-fgr antibodies, p58c-fgr was found only in the fractions of monocytes, granulocytes, and natural killer cells. On the other hand, histochemical studies of hybridization demonstrated accumulation of c-fgr transcripts on most monocytes and large lymphocytes. In hematopoietic cell lines, p58c-fgr was detected in differentiated granulocytic cells as well as in differentiated monocytic cells of HL-60-cell origin. These data suggest a specific role for p58c-fgr in natural immunity effector cells.

Animals↗
PubMed2001

A syndrome characterized by psychiatric disorders, recurrent mucosal infections and natural immunity deficits: clinical approach.

The authors summarize their own previous work on the identification of a subset of patients characterized by psychiatric disorders, recurrency of mucosal infections and impaired natural immunity. The diagnostic approach to these patients based on the close collaboration between infectivologists, immunologists and psychiatrists is described with the aim to find out combined treatments for the amelioration of clinical manifestations.

Humans↗
PubMed1999

[A new possibility for enhancing natural immunity: a radiation-detoxified endotoxin].

Using ionizing radiation the author and co-workers produced a detoxified endotoxin preparation (Tolerin) which seems to be a suitable product for the increase of natural immunity (nonspecific resistance)-including activation of bone marrow in immunosuppressions, immunodeficiencies-protection against various types of shocks-radiation injury, septic/endotoxic shock, etc.- and increase of immunogen effect of antigens (e.g. inactivated virus vaccines) as an immunoadjuvant in human beings and experimental animals.

Adjuvants, Immunologic↗
PubMedDate not supplied

[Alterations in natural immunity and risk of infection in patients with diabetes mellitus].

This review addresses the recent litterature devoted to the risk of severe infections in patients with diabetes and to the potential influence of diabetes on the function of natural immunity. Although much controversy still exists regarding the incidence of infections in diabetic patients, several studies confirm that diabetes mellitus is associated with an increased severity and mortality in community acquired pneumonia. Furthermore, the risk of severe bacteremia (especially associated with Streptococcus pneumoniae) is higher in diabetic patients. Polynuclear neutrophils are clearly influenced by the diabetic state. On the one hand, their antimicrobial function is inhibited by hyperglycaemia, due to inhibition of G6PD or diversion of NADPH in the polyol pathway; on the other hand, the AGE/RAGE/NF-kappaB pathway involved in the pathogenesis of chronic complications of diabetes could also amplify inflammatory systemic manifestations associated with infections and play a role in the higher mortality rate observed in diabetic subjects with severe infections. These observations argue for the systematic vaccination of all diabetic patients against influenza and Streptococcus pneumoniae, for the reappraisal of diabetes as a significant pejorative risk factor in community acquired pneumonia and for intensive insulin therapy in all diabetic patients with severe infection.

Diabetes Complications↗
PubMedDate not supplied

[Some natural immunity indices in mice against a background of varied fat and carbohydrate correlations in the diet].

In mice of the SWR, C3HA, CBA/j and non-inbred lines kept on diets with different combinations of carbohydrates and fats some characteristics of the natural immunity (phagocytic activity of leucocytes, bactericidal and lysozyme activity of the blood serum) were studied. It is shown that the proportions of the fatty and carbohydrate components in the diet is of a definite significance for the defensive forces of the organism.

Animals↗
PubMed2000

Training and natural immunity: effects of diets rich in fat or carbohydrate.

The purpose of the study was to investigate whether a carbohydrate-rich versus fat-rich diet influenced the effect of training on the immune system. Ten untrained young men ingested a carbohydrate-rich diet [65 energy percent (E%) carbohydrate] and ten subjects a fat-rich diet (62E% fat) while endurance training was performed 3-4 times a week for 7 weeks. Maximal oxygen uptake increased by 11% in both groups. Blood samples for immune monitoring were collected before and at the end of the study. Blood samples were also collected, in parallel, from 20 age-matched subjects, and data from these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated with interleukin (IL)-2 or interferon (IFN)-alpha, did not change. Furthermore, training did not influence the percentages of CD3+, CD4+, CD8+, CD19+ or CD14+ cells. However, when the two diet groups were compared, it was found that the NK-cell activity had increased in the group on the carbohydrate-rich diet [from 16 (3)% to 27 (2)%] and decreased in the group on the fat-rich diet [from 26 (2)% to 20 (4)%] in response to training. The effect of training on unstimulated NK-cell activity was significantly different between the groups (P = 0.007). These data indicate that diet manipulation during training may influence natural immunity, and suggest that ingestion of a fat-rich diet during training is detrimental to the immune system compared to the effect of a carbohydrate-rich diet.

Adult↗
PubMed1982

Immunomodulation of the lymphoresponsive phases of carcinogenesis: mechanisms of natural immunity.

Biphasic modulation of the frequency of 3-methylcholanthrene-induced tumors in relation to increasing immunocompetence of tumor-bearing mice is indicative of lymphoresponsive stimulatory and inhibitory phases of carcinogenesis; components and mechanisms contributing to the paradoxical ability of the native or natural immune system to stimulate as well as to inhibit the development of cancer were identified with the use of an in vitro model of carcinogenesis. Normal NIH/N Syrian golden hamster spleen leukocytes caused a biphasic modulation of UV-irradiated hamster cell morphologic transformation that was dependent on the leukocyte-to-target cell (L:TC) ratio. Whereas low (less than 50:1) and high (greater than 200:1) L:TC ratios inhibited the transformation frequency, intermediate ratios were less inhibitory and seemingly immunostimulatory. Inhibition alone occurred with antigen- or mitogen-activated leukocytes or with macrophages. An anticarcinogenic lymphocyte hormone, lymphotoxin, eliminated the leukocyte-mediated stimulatory phase; galactose, a lymphotoxin inhibitor, blocked the leukocyte-mediated inhibitory phases. Thus immunoinhibition was mediated through lymphotoxin, and the apparent immunostimulation possibly resulted from immune cell regulation of lymphotoxin activity during the early stages of carcinogenesis.

Animals↗
PubMed1986

Natural immunity to grafts of FLD-3 erythroleukemia cells by irradiated mice.

Mice were irradiated and infused with BALB/c Friend virus-induced FLD-3 erythroleukemia cells. Growth of the cells was estimated by measuring splenic incorporation of 5-iodo-2'-deoxyuridine-125I 5 days after cell transfer. BALB/cJ and C3H mice were 'poor responders' in that FLD-3 cells grew well in their spleens, while mice of other strains were 'good responders', resisting the growth of FLD-3 cells. No H-2 or Fv genetic locus was associated with resistance. Athymic nude mice and mice depleted of marrow tissue by 89Sr or estradiol resisted FLD-3 cells, indicating that the effectors were thymus- and marrow-independent. Silica, carrageenan and Propionibacterium acnes organisms all altered resistance, suggesting a function of macrophages. Neither interferon nor anti-interferon serum treatment altered resistance. Anti-asialo GM1 serum inhibited resistance to FLD-3 cells in vivo and inhibited natural cytotoxic (NC) activity against FLD-3 cells in vitro. NC (FLD-3) activity was greatly decreased in spleens 3 days after irradiation, in contrast with NK (YAC-1) and NC(WEHI-164.1) activities. Moreover, a 3-day delay in infusion of FLD-3 cells 'synergized' with silica in weakening genetic resistance in vivo. Thus, natural immunity to FLD-3 cells in vivo differs from that of genetic resistance to normal bone marrow cell allografts, and the lysis of FLD-3 cells in vitro seems to be mediated by cells which do not easily fit into the definition of natural killer (NK) or natural cytotoxic (NC) cells.

Animals↗
PubMed1991

[Natural immunity to Haemophilus influenzae type b. ELISA study of the distribution of IgG, IgG1 and IgG2 in France and Africa].

A Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate vaccine will be released for use in infants in developing and industrialized countries in the near future. This prompted a comparative study of the natural immunity of mothers and passive immunity of their newborns in France and Africa. An ELISA method capable of discriminating immunoglobulin classes and subclasses was used. Monoclonal antibodies were used to determine titers of IgG1 and IgG2 antibodies. Because capsular polyribose ribitol phosphate does not bind readily to polystyrene, the plate was coated with streptavidine which bound to biotin linked to the antigen. Antibody titers were found to be identical in French and African study groups. Both IgG1 and IgG2 antibodies were found, often with higher titers for the latter. Both subclasses were found in cord blood of French and African children.

Adult↗
PubMed1996

Voluntary chronic exercise augments in vivo natural immunity in rats.

The effect of chronic voluntary exercise on the immune response was studied in spontaneously hypertensive rats. Exercise consisted of voluntary running in wheels for 5 wk, and the mean running distance was 4.2 km/24 h. 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 compared with sedentary controls (P < 0.001). The total number of mononuclear cells in the spleen was significantly decreased in runners compared with controls. Analysis of splenic lymphocyte phenotypes revealed a significantly increased fraction of OX52+/CD5- natural killer cells in runners compared with sedentary controls. In contrast to changes in natural immunity, immunoglobulins G and M levels in serum, the antibody response to antigen in vivo, and the proliferation of splenic T cells in vitro were unchanged. Our data suggest that chronic voluntary exercise augments natural cytotoxicity mechanisms in vivo, whereas splenic T-cell proliferation and the antibody-mediated immune response remain unchanged.

Animals↗
PubMed1996

Natural immune reactivity-associated therapeutic response in patients with metastatic renal cell carcinoma receiving tumor-infiltrating lymphocytes and interleukin-2-based therapy.

Combination therapy with systemically administered interleukin-2 (IL-2) and tumor infiltrating lymphocytes (TIL) demonstrates significant clinical activity in some patients with metastatic renal cell carcinoma (RCC). The objective of this study was to identify predictors of therapeutic response in patients with IL-2- and TIL-based immunotherapy. We characterized and compared immunologic properties of tumors, TILs, peripheral blood lymphocytes (PBLs) and sera of responding (R, n = 8) with nonresponding patients (NR, n = 9). Before undergoing nephrectomy, responding patients exhibited a higher percentage of circulating natural killer (NK) cells (CD56+ CD3-) (43 +/- 20%) as compared with nonresponders (18 +/- 16%) (p < 0.01). After nephrectomy, the CD56+ CD3-/CD56- CD3+ ratio in responding patients (pre: 2.60 +/- 2.24; post: 0.28 +/- 0.19; p < 0.05) significantly decreased and was similar to that of patients not responding to therapy (0.42 +/- 0.36). Sera from patients responding to immunotherapy, obtained before and after completion of therapy, contained natural killer (NK)-enhancing factor(s) that significantly enhanced the proliferation (3.2 x 10(3) +/- 25%/ 3.6 x 10(3) +/- 13% counts/min) and cytotoxicity [17.6 +/- 4.0/18.0 +/- 1.9 lytic units (LU)] of fresh PBLs as compared with normal serum (1.8 x 10(3) +/- 8% counts/min; 13.4 +/- 2.5 LU) or sera from nonresponders (1.6 x 10(3) +/- 25%/1.5 x 10(3) +/- 20% counts/min; 8.3 +/- 5.9/6.8 +/- 4.8 LU). In contrast to noncultured tumor suspension, IL-2 cultivation induced TIL growth, cytotoxicity, and multicytokine synthesis, and a complete clearance of tumor cells. No significant differences were observed between responders and nonresponders in the in vitro characteristics of tumor/TIL, which include the degree of intratumoral lymphocytic infiltrate, TIL expansion, specific lysis of autologous tumor, phenotype, expansion time, quantity of TIL infused, cytokine release, and degree of tumor aggressiveness. We conclude that clinical response to TIL and IL-2-based immunotherapy is associated with patients' baseline natural immune status. The percentage of circulating NK cells and the presence of serum NK-cell-enhancing factors may serve as potential predictors of response in patients with advanced RCC. The in vitro study of RCC-TIL suggests that activated TIL may provide a synergistic effect to that of administered IL-2 on activation of cellular immune response in situ, rendering a tumor eradication, while the clinical outcome is largely dependent on the pretreatment immune status of patient.

Adult↗
PubMed1997

Impaired mast cell-dependent natural immunity in complement C3-deficient mice.

The complement system is widely regarded as essential for normal inflammation, not least because of its ability to activate mast cells. However, recent studies have called into question the importance of complement in several examples of mast cell-dependent inflammatory responses. To investigate the role of complement in mast cell-dependent natural immunity, we examined the responses of complement-deficient mice to caecal ligation and puncture, a model of acute septic peritonitis that is dependent on mast cells and tumour necrosis factor-alpha (TNF-alpha). We found that C4- or C3-deficient mice were much more sensitive to caecal ligation and puncture than wild-type (WT) controls (100% versus 20% in 24-h mortality, respectively). C3-deficient mice also exhibited reductions in peritoneal mast cell degranulation, production of TNF-alpha, neutrophil infiltration and clearance of bacteria. Treating the C3-deficient mice with purified C3 protein enhanced activation of peritoneal mast cells, TNF-alpha production, neutrophil recruitment, opsonophagocytosis of bacteria and resistance to caecal ligation and puncture, confirming that the defects were complement-dependent. These results provide formal evidence that complement activation is essential for the full expression of innate immunity in this mast cell-dependent model of bacterial infection.

Animals↗
PubMed1993

The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production.

The immunological basis for atopy is currently ascribed to an inherent bias in the CD4+ T cell response to nonreplicating antigens presented at mucosal surfaces, resulting in dominance of the T helper 2 (Th2) interleukin 4 (IL-4)-producing phenotype, which favors IgE production. In contrast, the "normal" response to such antigens involves a predominance of interferon gamma (IFN-gamma)-producing Th1 clones. This difference has been suggested to be the result of active selection in atopics for Th2 (and hence against Th1) clones at the time of initial antigen presentation. In the study below, we demonstrate that the natural immune response to inhaled protein antigens, particularly in animals expressing the low immunoglobulin E (IgE) responder phenotype, includes a major histocompatibility complex (MHC) class I-restricted CD8+ T cell component, the appearance of which is associated with active suppression of IgE antibody production. Thus, continued exposure of rats to aerosolized ovalbumin (OVA) antigen elicits a transient IgE response, that is terminated by the onset of a state of apparent "tolerance" to further challenge, and this tolerant state is transferable to naive animals with CD8+ T cells. Kinetic studies on in vitro T cell reactivity in these aerosol-exposed rats demonstrated biphasic CD4+ Th2 responses which terminated, together with IgE antibody production, and coincident with the appearance of MHC class I-restricted OVA-specific IFN-gamma-producing CD8+ T cells. However, the latter were not autonomous in vitro and required a source of exogenous IL-2 for initial activation, which in CD(8+)-enriched splenocyte cultures could be provided by small numbers of contaminating OVA-specific CD4+ T cells. This represents the first formal evidence for the induction of an MHC class I-restricted T cell response to natural mucosal exposure to an inert protein antigen, and is consistent with a growing literature demonstrating sensitization of MHC class I-restricted CD8+ T cells by deliberate immunization with soluble proteins. We suggest that crossregulation of MHC class II-restricted CD4+ T cells via cytokine signals generated in parallel CD8+ T cell responses represents a covert and potentially important selection pressure that can shape the nature of host responses to nonreplicating antigens presented at mucosal surfaces.

Aerosols↗
PubMed1990

[The status of natural immunity in children with acute lymphoblastic leukemia evaluated by long-term monitoring of complement-dependent bacteriocidal antibodies against B. anthracis and its relation to prognosis].

The authors investigated the function of the time factor as regards changes of bacteriocidity levels of serum against B. anthracis. Due to the fact that anthrax has not occurred in this country for several decades, we can speak of an investigation of natural immunity in the wider sense of the word. In the course of 15 years the authors collected repeatedly blood specimens from 53 children with ALL before, during and after treatment. Active sera were examined by quantitative titration by means of microbes labelled with 51Cr. The results of the investigation revealed that mean values of bacteriocidity calculated from all specimens and for each child separately are higher in the groups of children with a favourable course of the disease, as compared with children with an adverse course of the disease. It was also found that in a high percentage (78%) patients with long-term remission of leukaemia have a rising trend of bacteriocidity and the majority of children with a relapse of the disease (69%) had a bacteriocidity of serum with a declining trend (p = 0.01). The prognostic value of the test is unequivocally apparent from the results of the "life table" analysis. Children with an event free survival as well as the number of surviving children was significantly higher in the group with a rising trend of bacteriocidity than in patients with a declining trend of bacteriocidity (p = 0.008 and p = 0.02).

Adolescent↗
PubMed1981

Age-related increases in mitogenic responses and natural immunity to a syngeneic fibrosarcoma in rats.

An increase in natural (innate) immunity with age (through 65 weeks) of NBR rats to a syngeneic methylcholanthrene-induced fibrosarcoma (MCA) is described. This increase is characterized by the appearance of spontaneous tumor regressor animals and an increase in the incidence of tumor non-takes by rats 45 weeks of age and older when compared to younger animals. Age-related changes were observed in the in vitro proliferative responses of normal unfractionated and nylon wool fractionated spleen cells to Con A, PHA and irradiated MCA tumor cells. Certain of these different proliferative responses either increased and/or decreases independently at different ages. Relative to normal spleen cell proliferative responses, tumor progressors have decreased proliferative responses and tumor regressors display increased proliferative responses. The significance of this in light of current aging research is discussed.

Aging↗