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PubMed2004

IL-5 links adaptive and natural immunity in reducing atherosclerotic disease.

Oxidized LDL induces changes in several facets of the immune system, although the relationships between these facets and their contributions to atherogenesis have yet to be fully elucidated. A report in this issue of the JCI provides a novel demonstration of the adaptive immune system influencing the production of natural antibodies. The results demonstrate that injection of malondialdehyde-modified LDL promotes a Th2 response that in turn increases the titers of the natural antibody T15/EO6, which recognizes the oxidized phospholipid POVPC. Atherosclerotic lesion size in LDL receptor-deficient mice is reduced as a consequence of the increase in natural antibody titers, and IL-5 is identified as the link between the adaptive and natural immune systems.

Animals↗
PubMed2006

Possible role of natural immune response against altered fibroblasts in the development of post-operative adhesions.

PROBLEM: Post-operative adhesion tissue fibroblasts (ATF) differ from normal peritoneal fibroblasts (NPF). Natural immune response participates in the elimination of altered cells. In this study, we investigated NPF and ATF expression patterns of immune response-related markers, and lymphokine-activated killer (LAK) cell-mediated fibroblast elimination in vitro. METHOD OF STUDY: Primary cell cultures of both NPF and ATF obtained from the same four patients were used in the experiments. The expression of CD54, CD40 and CD120b, and allogeneic LAK cell-mediated ATF and NPF elimination were studied by flow cytometry. RESULTS: Average expression of CD54 in ATF was greater by 12.3-fold compared with NPF (P = 0.021), with ratios of 2.4 and 1.9-fold for CD40 (P < 0.001) and CD120b (P = 0.013), respectively. Average LAK cell-mediated fibroblast killing was 1.8 +/- 0.8-fold greater in ATF over NPF (P = 0.008). Furthermore, LAK cell-mediated fibroblast elimination correlated significantly with the increased CD40, CD54 and CD120b expression (R > 0.956; P < 0.05 for each). CONCLUSIONS: These results demonstrate that ATF are more susceptible to lymphocyte-mediated elimination than NPF and the development of adhesions despite this could be explained by either impaired or overwhelmed autologous natural immune response against reactive fibroblasts.

CD40 Antigens↗
PubMedDate not supplied

[Natural immunity factors as indices of body reaction to heliogeophysical effects].

The data treatment of immunological examinations of 2300 donors with the aid of the Distribution and Factor Analysis programs revealed a distinct relationship between natural immunity parameters and the heliophysical activity. The main heliophysical complex included solar flare intensity, radiofrequency radiation and surface area of sunspots. Among the natural immunity parameters humoral factors of nonspecific protection showed the greatest variations.

Antibody Formation↗
PubMed1982

[Humoral factors of natural immunity in patients with neurologic manifestations of lumbar osteochondrosis].

Natural immunity parameters (the complement, beta-lysine, lysozyme) were examined in 179 patients with the non-radicular and radicular stages of lumbar osteochondrosis with regard to the disease stage, the patients' age and sex, the efficacy of treatment, and the latter's late results. It was found that the degree of the shifts of the parameters examined depended primarily on the disease stage and the efficacy of the treatment, and to lesser extent on the patients' age and sex. The parameters examined may serve to a certain measure as a objective criterion of the body's general physiological state, and can be used for predicting the disease outcome.

Complement System Proteins↗
PubMed2000

The significance of intensity and duration of exercise on natural immunity in rats.

PURPOSE: The purpose of this study was to examine a) the relationship between running distance (km x d(-1)) and b) the duration of exercise training in weeks on the effects on natural immune function in spontaneously hypertensive rats (SHR). METHODS: Exercise consisted of voluntary running in wheels for 5 or 11 wk. In vivo cytotoxicity was measured as clearance of injected 51Cr-labeled YAC-1 lymphoma cells from the lungs. RESULTS: Increased in vivo cytotoxicity was seen after 5 wk of exercise (P < 0.001) but not after voluntary exercise for 11 wk. If the wheels were locked 3 d x wk(-1) during the last 6 wk of running, thus restricting the exercise to 4 d x wk(-1), the exercise-induced immunoenhancement seen after 5 wk of exercise was maintained also after 11 wk of exercise. When compared with the sedentary controls after 5 wk of exercise, all runners regardless of running distance exhibited significantly higher in vivo clearance of tumor cells from the lungs, and no overall significant correlation was seen between running distance and retained radioactivity. However, the lowest activity runners (< 4 km x d(-1)) exhibited significantly lower in vivo clearance of tumor cells from the lungs when compared with animals running more than 4 km x d(-1). CONCLUSION: We conclude that the duration of exercise training, and to some extent the running distance, has significant effects on the training-induced increase in natural immune function in rats. Furthermore, we conclude that a resting or recovery period during long-term exercise training is important to maintain the immunoenhancing effects in response to exercise.

Animals↗
PubMed1976

[Rubella vaccination with "Cendehill" and "RA 27/3". Reinfection of vaccinated and naturally immune persons compared with the infection rate of susceptible persons within a 3-resp. 5-year observation period (author's transl)].

Many investigators in Europe and the USA have usually found high rates of serum conversion after vaccination with the rubella vaccines Cendehill and RA 27/3, but the resistance of vaccinated individuals against superinfection without disease induced by wild virus strains under experimental or natural conditions seems to be very low; e.g. up to 80% of the vaccinees reacted with increasing titers of hemagglutination inhibiting antibodies after super-infection with a wild virus in a special epidemiological situation. In our two studies performed under natural conditions of infection including an observation period of three years resp. five years after vaccination a more favourable picture evolved, perhaps reflecting a different epidemiological situation, a different susceptibility or a less virulence of wild virus in our region: Three years after vaccination of 14 years old girls with Cendehill and RA 27/3 in a double blind trial a significant increase in the titers of hemagglutination inhibiting antibodies was observed after vaccination with Cendehill by the subcutaneous route in only 1,16% (1/86) and in 1,18% (1/85) after vaccination with RA 27/3 by the same route. In the same observation period the infection rate in a control group not protected by natural immunity or by vaccination was 54,72% (87/159) and in a second control group, protected by natural immunity 1,82% (3/165)...

Adolescent↗
PubMed2003

Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity.

Animals↗
PubMed1997

Natural immunity against human immunodeficiency viruses: prospects for AIDS vaccines.

We have hypothesized and have presented evidence that there may be another form of immunity, other than humoral and cellular immunities, which operates against retroviruses. In order to distinguish it from the traditional immune responses, we have named this form of immunity "molecular immunity". The major goal of this hypothesis is to better define the "messenger molecules" that are critical in forming the molecular immunity against retroviruses, and to further determine the activation pathways of this relatively unexplored form of immunity. We have provided evidence that this natural immunity against retroviruses and specifically against HIV-1, can be activated and optimized, and have made some interesting observations. We believe that resistance to HIV-1 and to other retroviruses can be induced by various means, including low dose exposure, infection with replication defective viruses and exposure to non-pathogenic but genetically related viruses.

AIDS Vaccines↗
PubMed1999

Isolation of measles virus from a naturally-immune, asymptomatically re-infected individual.

BACKGROUND: The changing epidemiology of measles with mild measles cases increasingly being recognised in previously-vaccinated individuals, suggests that more asymptomatic or subclinical cases might be occurring. Although this has been clearly documented in previously-vaccinated individuals, the frequency of these asymptomatic infections in individuals previously naturally-infected with measles is not known. Also, it is not known whether these asymptomatic or mildly-infected individuals who do not display the full range of clinical signs of measles are capable of transmitting the virus to other susceptible persons. OBJECTIVES: To demonstrate the isolation of measles virus (MV) from previously, naturally-immune individuals asymptomatically infected with measles while in close contact with acutely infected family members and to document the secondary immune responses (SIR) associated with asymptomatic measles infection. STUDY DESIGN: Throat swab and urine specimens from five acute measles cases and their family contacts, taken within 5 days of onset of rash in each acute case, were used to isolate MV by tissue culture. Positive tissue culture results were confirmed by indirect immunofluorescence (IF) staining. Measles specific antibodies (IgG and IgM), IgG urea avidity and measles-neutralising antibodies were measured in the one family (index family) where an asymptomatic measles infection of a contact was demonstrated. RESULTS: The acutely infected patient in the index family (T1/96) had a measles-neutralising antibody titre of < 1:10, measles IgG urea avidity of 24% and MV was isolated and confirmed by IF from urine and throat swab specimens. T1/96 represents acute measles infection after primary vaccine failure because he had a clear history of being vaccinated against measles as a child. MV was also successfully isolated from throat swab and urine specimens from the other four acute cases and from the urine but not the throat swab of an asymptomatically infected family contact in the index family (mother, T2/96). T2/96 had a history of natural measles infection as a child approximately 50 years ago. In addition to detectable MV in urine this contact also had a SIR with a rise in measles specific neutralising antibody titre. No virus was isolated from the other contact in the index family (father, T3/96) or from the contacts of the other four acute cases examined. CONCLUSIONS: This is the first report of a confirmed asymptomatic MV infection, by MV isolation and IF testing and a concurrent SIR, in a previously naturally-immune contact of an acute case. The importance of these findings to the epidemiology and control of MV as well as the diagnostic value of MV urine isolation and IF confirmation for mild or asymptomatic cases must be examined further.

Adult↗
PubMed1997

Immunomodulatory effects of Viscum album agglutinin-I on natural immunity.

In 24 h cultured human peripheral blood mononuclear cells, treated with various (1 microgram/ml to 1 ng/ml) concentrations of Viscum album agglutinin-I, quantitative assessment of DNA breaks labelled with terminal deoxynucleotidyl transferase revealed a dose-dependent Viscum album agglutinin-I-induced apoptosis above a lectin concentration of 10 ng/ml. After 24 h incubation of peripheral blood mononuclear cells with non-cytotoxic concentrations of Viscum album agglutinin-I (10 and 1 ng/ml), messenger (m)RNA expression and secretion of a panel of cytokines were evaluated by reverse polymerase chain reaction and by enzyme-linked immunosorbent assay (ELISA), respectively. The lectin induced expression of interleukin-1 alpha, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, interferon-gamma, granulocyte-monocyte colony stimulating factor and interleukin-10 genes, but no expression of interleukin-2 or interferon-gamma production could be detected. In addition, cellular components of the natural immune system (such as monocytes and granulocytes) bound Viscum album agglutinin-I molecules to a higher degree than lymphocytes. To establish the modulatory potency of Viscum album agglutinin-I on the natural immunity of human subjects, four randomized, double-blind crossover trials were performed on healthy volunteers. In contrast to the significant lectin-induced increases in number and activity of natural killer cells observed in animal models, in the first and second trial human healthy individuals showed no significant differences between their natural killer responses following an injection of lectin-enriched preparation or saline. Due to considerable intrinsic fluctuation of these parameters, a third and fourth double-blind trial with freshly isolated Viscum album agglutinin-I was performed using a more rapidly detectable parameter, the priming of granulocytes. Here, significant lectin-induced increases were found.

Agglutinins↗
PubMed2004

Immunological modulation by lidocaine-epinephrine and prilocaine-felypressin on the functions related to natural immunity in neutrophils and macrophages.

There is accumulating evidence that local anesthetics have immunological properties in addition to their direct anesthetic activity. Because local anesthetics are often used together with blood vessel contraction drugs, such as epinephrine and felypressin in the clinical setting, we have examined possible abilities of both local anesthetic alone including lidocaine, mepivacaine, procaine, prilocaine and tetracaine, and local anesthetics with blood vessel contraction drugs including lidocaine with epinephrine and prilocaine with felypressin on the functions related to natural immunity in neutrophils and macrophages. In contrast, lidocaine, mepivacaine, procaine, prilocaine and tetracaine all inhibited adhesion, chemotaxis, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils and macrophages. Lidocaine with epinephrine and prilocaine with felypressin were effective in significantly inhibiting adhesion, chemotaxis, phagocytosis, and the production of hydrogen peroxide by neutrophils and macrophages. Interestingly, lidocaine with epinephrine potentiated the production of superoxide anion, whereas prilocaine with felypressine inhibited the production, irrespective of cells. In addition, epinephrine potentiated the production of superoxide anion, whereas epinephrine inhibited the production of hydrogen peroxide as well as lidocaine with epinephrine. This potentiation by epinephrine was not prevented by adrenergic antagonists. Furthermore, superoxide dismutase potentiated the production of hydrogen peroxide, which was in part prevented by epinephrine. These results suggest that local anesthetics may inhibit the functions related to natural immunity in neutrophils and macrophages. In addition, lidocaine with epinephrine evidently differs from prilocaine with felypressine regarding the molecular mechanisms underlying the modulation of superoxide anion production by neutrophils and macrophages.

Anesthetics, Local↗
PubMed1995

Defective natural immunity: an early manifestation of human immunodeficiency virus infection.

Cytotoxicity mediated by natural killer (NK) and lymphokine-activated killer (LAK) cells may be of significance in host defense against viral infections. This study included 347 patients infected with human immunodeficiency syndrome virus (HIV) type 1 and 110 controls. The NK cell activity, either unstimulated or stimulated with interferon-alpha (IFN-alpha) or interleukin-2 (IL-2), and the LAK cell activity were suppressed in patients, but the NK/LAK cell activity did not differ between patients with AIDS and patients without AIDS. However, the IFN-alpha-stimulated NK cell activity and LAK cell activity were reduced in patients with symptoms of HIV disease (CDCIV) when compared with asymptomatic patients (CDCII+III). When the data were analyzed by multiple linear regression, the percentage of CD4+ cells had a positive effect on these two parameters in patients without AIDS, whereas the percentage of CD4+ cells had no significant effect on unstimulated and IL-2-stimulated NK cell activity in these patients. In controls and AIDS patients, the percentage of CD4+ cells had no effect on NK/LAK cell activity in multiple linear models. The total number of CD16+ cells was low in patients compared to controls, whereas the percentages of CD16+, CD56+, and CD16+CD56+ were either normal or elevated. Therefore, the decrease in NK cell subpopulations did not contribute to the observed depression in NK/LAK cell activity in vitro. It is concluded that natural immunity is suppressed in HIV-seropositive patients primarily because of a qualitative defect of the NK/LAK cells. This qualitative defect includes a reduced responsiveness to IFN-alpha, which is progressive until the onset of symptoms, and possibly related to the loss of CD4+ cells.

Adult↗
PubMed1975

Autogenous immunity to endogenous RNA tumor virus: reactivity of natural immune sera to antigenic determinants of several biologically distinct murine leukemia viruses.

Sera from normal (C57BL/6XC3H/Anf)F1(B6C3F1) mice reacted with several biologically distinct murine leukemia virus(es) (MuLV) by radioimmune precipitation assays with the use of purified tritiated leucine-labeled virus. The reactivities of this natural antibody to viral envelope antigens of two laboratory strains (Rauscher and Moloney) and two endogenous mouse C-type viruses (AKR and BALB:virus-2) were further analyzed and compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Similar patterns of antibody reactivities to AKR MuLV and the two member viruses of the Friend-Moloney-Rauscher group were found. Three major antigenic determinants of the virus envelope, gp71, gp43, and p15, were recognized by and precipitated natural antibody. In all viruses examined, normal B6C3F1 sera precipitated comparable amounts of gp71 and gp43. However, compared with the other viruses, the amount of p15 (relative to the glycoproteins) precipitating from BALB:virus-2 was significantly lower. This appears to be due to a lesser amount of p15 on the xenotropic virus. While heterologous antisera to purified gp71 and p15 of MuLV reacted to a certain degree with rhabdomyosarcoma virus 114 and rat leukemia virus, natural mouse antibody did not. These results suggest that MuLV have common antigenic determinants recognized by natural antibody, and that the reactivities of natural antibody in an autogenous immune response are restrictive in contrast to immune antibody produced in a heterologous host.

Animals↗
PubMed1994

Comparison of two immunization schedules with recombinant hepatitis B vaccine and natural immunity acquired by hepatitis B infection in dialysis patients.

In a prospective study over a 2-year period we compared two practical dosage schedules to vaccinate dialysis patients against hepatitis B virus (HBV) infection using a yeast-derived recombinant hepatitis B vaccine (Engerix-B). In addition, the natural history of this acquired immunity was compared with that developed through HBV infection in dialysis patients and healthy subjects. Patients on dialysis treatment (haemo or peritoneal) who were tested to be negative for hepatitis B surface antigen (HBsAg), anti-HBs and anti-HB core were allocated at random to receive HB vaccine according to one of the two schedules. The two groups receiving the vaccine were matched for age, sex, mean duration on dialysis and the form of dialysis treatment received. The group of patients who received a four-dose schedule (at 0, 1, 2 and 6 months) of 40 micrograms of HB vaccine each time (group 2) achieved a seroconversion rate of 79% 1 month after the last dose (at month 7) compared with a seroconversion rate of 55% in those who received three doses (at 0, 1 and 6 months) of 40 micrograms each (group 1). Healthy controls who received half the amount of vaccine on a three-dose schedule (group 3) attained 100% seroconversion (p < 0.05). When retested at 24 months, 30% of seroconverters in group 1 had lost their protective immunity, compared with only 6% in group 2 and 15% in group 3. The magnitude of antibody response (total and anti-(a)-specific) was assessed in the vaccinees at 24 months and compared with that of two other control groups, dialysis patients (group 4) and healthy volunteers (group 5), who had acquired immunity from HBV infection. In general, the total and anti-(a)-specific HBs titres in the dialysis patients (groups 1, 2 and 4) were lower than in their corresponding healthy controls (groups 3 and 5), irrespective of whether the protective immunity was acquired by vaccination or HBV infection. However, the anti-HBs titres in dialysis patients who received four doses were significantly higher than in those who received only three doses (p < 0.05), which indicated a better protective immunity in favour of the former regime. The magnitude of antibody response in the vaccinees of groups 2 and 3 compared well with their respective controls, groups 4 and 5, who had acquired their immunity through HBV infection. This implied that the yeast-derived vaccine was sufficiently immunogenic and provided lasting protection in patients and healthy subjects vaccinated by an appropriate dosage schedule.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer.

Deficient natural killer (NK) cell activity may contribute to the development of distant metastases in the head and neck cancer patient. A total of 246 previously untreated patients expressed deficient NK activity against K562 target cells when compared to 110 age-matched healthy controls (70 +/- 48 lytic units (LU) versus 95 +/- 52 LU) (P less than 0.001). Some 164 consecutive patients have undergone definitive therapy subsequent to NK cell assessment and have been followed for a minimum of 12 months (median = 16 months), and 23 have developed recurrent disease in distant sites. The risk of subsequently (1) developing distant metastases, (2) developing regional metastases, and (3) dying of progressive cancer was inversely related to pretreatment NK LU values (P less than 0.02, less than 0.02, less than 0.005, respectively, by the Cox proportional hazards model). NK cell function within the peripheral blood of the patient with head and neck cancer could be related to the percentage of Leu 11+ NK cell subsets (P less than 0.01 by linear regression analysis) as determined by both single-parameter and multiparameter flow cytometric assessment. Contrastingly, no relationship could be identified between NK function with the percentage of circulating Leu 7+ cell subsets. In vitro measured NK cell function identifies a population at increased risk for developing distant metastases, thus supporting the role of natural immunity as defense mechanism against blood-borne disease.

Adult↗
PubMed1980

Quantitative studies of natural immunity to solid tumours in rats. The nature of the killer cell depends on the type of assay.

Cell fractionation techniques were used to identify the cells in rat spleen responsible for natural killing of a syngeneic sarcoma cell in short-term (6 h and 18 h) and long-term (72 h) cytotoxicity assays. Cytotoxicity was quantified precisely using a method previously derived from consideration of natural cytotoxicity as an enzyme-substrate reaction, and by analysing results in terms of lytic units. Killing in all three assays displayed 'single-hit' kinetics implying that a single effector cell was sufficient to lyse a single target cell. The fractionation studies, using glass adherence, carbonyl iron, nylon wool, EA and EAC monolayers and congenitally athymic rats, revealed two populations of cytotoxic cells. In the 6 h assay most of the activity was due to cells with similar characteristics to the NK cells previously defined using leukaemic targets, but in the 18 h and 72 h assays macrophages played an important rôle. The activity exerted by the macrophages was cell lysis and not cytostasis. No evidence that the macrophages acted by releasing factors which stimulated NK cells could be found.

Animals↗
PubMed1986

Natural immunity to measles, rubella and mumps among Spanish children in the pre-vaccination era.

Prior to the start of mass vaccination campaigns against measles, rubella and mumps, a prevalence study of natural immunity to these diseases was undertaken in a sample of 1700 unvaccinated Spanish children. They were representative of the 3-7 year-old population in terms of age, regional distribution and urban or rural environment. Measles infection prevalence was significantly higher than that for rubella and mumps from 3 (48.3%, 14.2%, 25.5%, respectively) through 7 years of age, (64%, 40.9%, 39%). As a function of age, naturally-acquired immunity increased according to parabolic progressions. In the 3-5 year-old group, rural environment, low socioeconomic status, no school attendance and lack of brothers were associated with statistically lower levels of measles, rubella, or mumps infection. In the 6-7 year-old group, only 12% of the children showed antibodies against the three diseases and 18.7% exhibited triple susceptibility.

Age Factors↗
PubMed1992

The natural immune barrier to xenotransplantation.

As the shortage of available organs for transplantation becomes critical, many investigators have turned to the possibility of using animals as a source of donor organs. Although there have been several attempts to use organs from closely related species for transplantation into human, there is relatively little experience in the use of nonprimate animals as clinical donor animals. The major problem in transplants between widely disparate species is hyperacute rejection, a rapid and violent rejection reaction that leads to the destruction of the graft within minutes or hours. Hyperacute rejection appears to be triggered by components of natural immunity, most notably natural antibodies and complement. Recent data suggest that hyperacute rejection may not represent an insurmountable barrier to discordant xenotransplantation. There have recently been several examples of survival of grafts in recipients in the face of antigraft antibodies and an intact complement system referred to as accommodation. Once hyperacute rejection can be averted, it becomes necessary to consider elicited cellular responses. There are a number of issues to be considered in the clinically relevant model of porcine to primate xenografts. These include the size of the responding T-cell repertoire and the extent to which the cell adhesion molecules and cytokines of the donor will be able to stimulate recipient immune responses. Finally, the interactions between T cells and the cells forming the inner layer of blood vessels may have profound effects on the outcome of the graft.

Animals↗