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PubMed2001

AIDS possibly caused by HIV and latent malaria coinfection.

The presented hypothesis suggests that chronic latent malaria infection prepares the niche where the otherwise feeble HIV coinfection can thrive and cause AIDS. It is suggested that the roots of the HIV outbreak and AIDS pandemic lay in the urbanization processes in Africa that resulted in the eradication of the Anopheles vector from previously endemic areas, which changed the immunological status of the inhabitants there as they lost their natural immunity to malaria. Since malarial parasites may persist in the lymphatic network for a lifetime and reduce T cell proliferation while adhering to immature dendritic cells, the loss of this natural immunity made the African population, which was chronically affected with scanty parasitemia, vulnerable to opportunistic infections, HIV among them. The specific transmission modes of latent malaria infection elucidate why AIDS flares up in Africa and spreads there evenly in the population, while in the West it expands rather slowly and is restricted mainly to homosexuals and blood recipients.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The immune response in immunized and naturally infected rainbow trout (Salmo gairdneri) to Diplostomum spathaceum as detected by enzyme-linked immunosorbent assay (ELISA).

The enzyme-linked immunosorbent assay (ELISA) procedure was modified and adapted for detection of circulating antibodies in rainbow trout (Salmo gairdneri) against metacercariae of the digenean trematode Diplostomum spathaceum, the causative agent for diplostomiasis. Rainbow trout (Salmo gairdneri) were injected with sonicated metacercariae representing 10, 40, and 100 metacercariae per fish. Three weeks after immunization the average titers for trout injected with 10, 40, and 100 metacercariae were 874, 841, and 525, and by six weeks the titers had fallen to 299, 349, and 203, respectively. Nine weeks after initial immunization, two remaining fish initially immunized with 100 metacercariae per fish were injected with a booster of 50 sonicated metacercariae per fish. Four weeks later the average titer was 1204. Serum samples from naturally infected wild fish tested for the presence of circulating antibodies against Diplostomum spathaceum showed 25 of 27 with positive titers.

Animals↗
PubMed1998

Activation and suppression of natural cellular immune functions by Pneumocystis carinii.

The regulatory role of soluble cytokines in innate cellular immune responses induced by Pneumocystis carinii was assessed in vitro in direct comparison to induction by Listeria monocytogenes. This report shows that P. carinii organisms, as well as L. monocytogenes, stimulated in whole spleen cell cultures of SCID mice the release of IFN-gamma, TNF-alpha/beta, IL-10, IL-12, and iNO. This response was independent of functional T cells. Both macrophages (M phi) and natural killer (NK) cells were necessary for either microorganism to induce release of these cytokines. Cocultures of purified M phi--including alveolar M phi--and purified NK cells indicated that no other cell population was necessarily involved. Microbial induction of NK cell-derived IFN-gamma has been reported to be mediated by the combined effects of TNF-alpha and IL-12 released by M phi upon adequate microbial stimulation. Interestingly, only L. monocytogenes, but not P. carinii organisms could directly induce detectable amounts of TNF-alpha/beta, IL-12, or iNO in purified M phi cultures. In dose-response experiments, release of IFN-gamma, TNF-alpha/beta, and iNO was reduced at high relative concentrations of either microorganism. This high-dose suppression was at least partially controlled by M phi-produced IL-10. Our data show that, P. carinii potently induces activating and inhibitory innate cellular immune response mechanisms and indicate that the initial step of macrophage-mediated NK cell activation might also involve other pathways than those described to date.

Animals↗
PubMed1991

Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity.

In recent studies of 'low natural killer (NK) cell syndrome', low NK activity was measured in individuals who were symptomatic, and therefore a causal relationship between low NK activity and infectious or other disease manifestations could not be concluded. However, preliminary work by members of our collaborative team (S.L. and R.H.) provided some indications for chronic low NK activity preceding and predicting subsequent infectious morbidity. This present study was designed to address this causal question in a larger sample, using a longitudinal design. Subjects were 106 healthy normal volunteers from the community. They were examined medically and psychosocially at baseline, and were then followed over a 6-month interval, with serial monthly assessments over the study period. The results supported our hypothesis that individuals who were currently healthy, but who exhibited a pattern of natural immunity characterized by persistently low NK cytotoxicity would be at risk for development of infectious sequelae over a 6-month follow-up period. The results also showed that younger age and the perception of more severe 'hassles' or stressors also predicted more infectious morbidity during the 6-month study period. Chronological age appeared to have both a direct, as well as indirect (via NK activity) association with illness outcome. Contrary to our expectation, the report of environmental stressors was directly associated with illness outcome, but not indirectly associated with outcome via natural immunity.

Adolescent↗
PubMed1998

Some aspects of humoral and cellular immunity in naturally occuring feline infectious peritonitis.

Haematology, antibody titers and serum protein electrophoresis from 48 cats (34 effusive and 14 noneffusive forms) affected with feline infectious peritonitis (FIP) were studied and compared with those of 20 healthy cats. In the effusive form, antibody titers and protein electrophoresis in the effusions were analyzed. The distribution of the immune cells and of the virus in FIP lesions were also investigated immunohistochemically with the avidin-biotin complex (ABC) method, using antibodies against the FIP virus (FIPV), myelomonocytic (MAC387) and lymphoid (CD3, CD4 and CD8 for T-cells and IgM and IgG for B-cells) antigens. Seropositive animals (antibody titer>1:100) were present among both the FIP infected cats (73%) and the healthy cats (70%). Cats with effusive FIP had neutrophilic leukocytosis (P>0.05), lymphopenia (P<0.01) and eosinopenia (P<0.001). In both effusive and noneffusive forms decreased albumin/globulin ratio (P<0.001) with hypoalbuminemia (P<0.001), hyperglobulinemia (P<0.001) and increased alpha2- (P<0.05), beta- (P<0.05) and gamma-globulins (P<0.001) were found. Hypergammaglobulinemia was not related to the antibody titers, suggesting the presence of other proteins with gamma-motility (e.g. complement fractions). The electrophoretic pattern of the effusions was always similar to that of the corresponding serum. Antibody titers higher than those of the corresponding serum were often detected in the effusions. Immunohistochemical findings were not related to the antibody titers, but they were related to the histological aspect of the lesions. In cellular foci of FIP lesions many virus-infected macrophages and few lymphocytes, mainly CD4+, were found. Extracellular viral and myelomonocytic antigens were also detectable in the foci with intercellular necrosis. Only few FIPV-infected cells were present at the periphery of the larger necrotic foci: in these lesions MAC387+ cells were mainly neutrophils, with many MAC387 macrophages, probably due to their activated state; a small number of lymphocytes, with an increasing percentage of CD8+ cells was present. Lymphocytes were more abundant when cellular foci and FIP-infected macrophages were centered around neoformed vessels. IgM and IgG exposing B-cells were always few and scattered. In conclusion the simultaneous analysis of body fluids and of the cellular composition of the lesions showed a complex immune status, on which type III and type IV hypersensitivity could coexist.

Animals↗
PubMed1999

Lassa fever: implications of T-cell immunity for vaccine development.

Lassa fever is a re-emerging viral hemorrhagic fever, which causes significant human morbidity in endemic regions of West Africa. Attempts to vaccinate against this virus in animal models including non-human primates have revealed that eliciting a strong cellular immune response protects from clinical disease, but not infection, in the absence of measurable neutralizing antibodies. As there is renewed interest in developing a vaccine against Lassa fever for use in humans, several questions should be addressed in view of the scarce knowledge of the mechanisms of natural immunity against this disease. MHC-dependency of a vaccine relying mainly on the induction of T-cell immunity and its ability to cross-protect against different Lassa virus strains will be important issues. Furthermore, the question whether the vaccine can prevent human-to-human transmission of the virus should be discussed and the possibility that vaccination could predispose to immunopathology should be excluded. We are addressing some of the above mentioned problems concerning natural immunity through field studies in the Republic of Guinea, West Africa, and are presently studying the CD4 cell responses of Lassa antibody positive subjects on the basis of T-cell proliferation assays using recombinant Lassa virus proteins.

Animals↗
PubMed2001

Human immunodeficiency virus-1 specific and natural cellular immunity in HIV seronegative subjects with multiple sexual exposures to virus.

The probability of HIV infection by sexual contact, although it varies greatly, appears to be lower than that of infection by other routes of exposure. The aim of this study was to evaluate immunological determinants involved in protection against HIV infection in subjects with multiple and repeated sexual exposures to the virus. Twenty-two subjects were studied for CD8+ cell anti-HIV suppression activity and serum neutralizing activity against the HIV strain of their own partners, beta-chemokine production, and natural killer cell activity. CD8+ cell anti-HIV activity and neutralizing activity of sera were found in 13 (76%) and 12 (70.5%) out of 17 HIV-1 negative subjects, respectively. Six individuals had a relevant immune response against HIV: three subjects with a high CD8+ cell antiviral suppression activity and three individuals with sera neutralizing activity titer >1:10. These last three subjects had the highest beta-chemokine levels, a very prolonged period of multiple sexual intercourse (>6 years) and a seropositive partner with a high viral load. A partial reduction of neutralizing activity titer was observed when pre-incubating the sera with anti-beta-chemokine neutralizing antibodies. A spontaneous natural killer cell activity was suppressed in the majority of HIV-1 negative subjects with sexual exposure in comparison with normal individuals. The protection from sexual HIV transmission appears to be the result of a network of different humoral and cellular factors.

Adult↗
PubMedDate not supplied

Mongoose rabies.

Mongooses are indigenous to Africa and Asia and have been introduced elsewhere. In Cuba, Puerto Rico, Grenada, and South Africa they are the major reservoir and vector of rabies. Elsewhere, sporadic cases of mongoose rabies are reported, but dog rabies can mask their importance. Population density probably determines the importance of the mongoose as a reservoir of rabies. In Grenada during a 4-year period, nearly 30% (and in some areas greater than 50%) of mongooses were found to have rabies serum neutralizing antibodies. The annual proportions of mongooses that were serum antibody-positive and virus-positive, respectively, were inversely related. Natural immunity in mongooses probably lasts for life. In contrast with foxes, in mongooses immunity is an important factor in the epizootiology of rabies. Inoculation of mongooses with Evelyn-Rokitnicki-Abelseth (ERA) vaccine induced a good immunologic response and augurs well for the success of vaccination in the field. The effects of wildlife vaccination on animal populations with high levels of natural immunity need to be investigated before costly campaigns are started.

Animals↗
PubMed1995

Human schistosomiasis: potential consequences of vaccination.

The potential outcomes of a Phase II schistosomiasis vaccine trial are explored using mathematical models which assume some natural immunity and a vaccine providing partial protection for a limited time. Analyses suggest that vaccination may have only a limited impact on life-long cumulative worm burdens and may lead to increased susceptibility and higher worm burdens at some ages, a "rebound" effect which results reduced opportunity to acquire natural immunity. There is a trade-off between the degree and duration of vaccine-induced protection; long-lived vaccines may be preferable to vaccines giving greater protection but for a shorter time.

Adolescent↗
PubMed1984

Class specificity of naturally acquired and vaccine-induced antibody to type III group B streptococcal capsular polysaccharide: determination with a radioimmunoprecipitin assay.

A radioimmunoprecipitin test was developed to determine the immunoglobulin class distribution of naturally acquired and vaccine-induced antibody to the native capsular polysaccharide of type III group B streptococci (III-GBS). In sera from adults and pregnant women with naturally acquired antibody, the mean percentage of antigen bound by immunoglobulin G (IgG) was 74.9 and 78.6, respectively, whereas antigen bound by IgM comprised less than 10% of the total. In contrast, early-convalescent-phase sera (mean, 16.3 days) from neonates responding to III-GBS infection with an increase in specific antibody had significantly more IgM (mean, 36%; P less than 0.001, unpaired t test). However, in late convalescence, the immunoglobulin class distribution in sera from these neonates was similar to that of naturally immune adults. Four weeks after immunization with III-GBS polysaccharide vaccine, sera from adults with low (less than 2 micrograms/ml) preimmunization antibody levels in their sera and from those with moderate (mean, 5.5 micrograms/ml) preimmunization levels contained specific antibody predominantly of the IgG class. Although the percentage of IgG-specific antibody was greater in sera from naturally immune adults than in that from vaccinees with a presumed primary immune response, the major portion of antigen bound by sera at 4 weeks postimmunization (62.5%) was associated with IgG. These observations support the opinion that immunization of pregnant women with III-GBS capsular polysaccharide could be efficacious for the prevention of invasive neonatal III-GBS disease.

Adult↗
PubMed1988

Immunity to whole varicella-zoster virus antigen and glycoproteins I and p170: relation to the immunizing regimen of live attenuated varicella vaccine.

Humoral and cellular immune responses to whole varicella-zoster virus (VZV) antigen and the VZV proteins glycoprotein I (gpI) and nonglycosylated protein p170 were evaluated in healthy children and adults given lyophilized live-attenuated varicella vaccine. Children received one dose of vaccine containing 950 pfu, whereas adults received two doses of 2500 pfu. After one year, the antibody titers of adult vaccinees to whole VZV and to gpI were significantly higher than those of children. Antibody titers to whole VZV, gpI, and p170 were lower among both vaccine populations than titers in naturally immune individuals, but vaccinees who seroconverted initially retained detectable VZV antibodies. Using T lymphocyte proliferation to measure cellular immunity, we found the mean (+/- SE) transformation index to whole VZV antigen to be 4.1 +/- 0.96 in children tested at one year, a mean significantly lower than the mean of 12.7 +/- 3.39 in adults and 13.0 +/- 1.67 in naturally immune subjects. These observations suggest that the vaccine dose affects vaccine-induced immunity to VZV.

Adolescent↗
PubMed1987

Abnormalities of cellular immunity and natural killer cells in Gaucher's disease.

Gaucher's disease (GD) which is a congenital defect characterized by the accumulation of glucocerebroside in cells of the reticulo endothelial system, is associated with malignancies of the lymphoid system such as multiple myeloma, chronic lymphatic leukemia, as well as acute leukemia of childhood. We report the immunological profile of the T-cell system in GD patients and in GD carriers. We found a variable response to lectins stimulation (PHA, Con A, PWM in various concentrations) which supports the hypothesis that a persistent antigenic stimulation in GD affects all components of the immune system of those patients. A highly significant decrease in the number of NK cells was also found, which might be a predisposing factor to the increase in malignant B and other lymphoid cell proliferations described in patients with GD.

B-Lymphocytes↗
PubMed1994

Exercise and the immune system. Natural killer cells, interleukins and related responses.

The main methods for the evaluation of natural killer (NK, CD16+ CD56+) cells, interleukins and related subsets of lymphocytes are briefly described. Moderate endurance exercise causes either no change or an increase in lymphocyte and NK cell counts, total T cell (CD3+) count, the ratio of T helper (CD3+ CD4+) to T suppressor (CD3+ CD8+) cells, mitogen-induced lymphocyte proliferation, serum immunoglobulin levels and in vitro immunoglobulin production. Plasma levels of interleukin-1 increase but interleukin-2 (IL-2) levels generally fall. Decreases in plasma IL-2 levels reflect increased expression of beta (CD122) receptors for IL-2, and thus increased binding of IL-2, changes in cell distribution or a lesser production of IL-2 by peripheral blood mononuclear cells. Exercise to exhaustion induces adverse changes in many of these indices of immune function, particularly if the physical activity is accompanied by psychological or environmental stress. Moderate, appropriately graded training reduces the adverse reactions initially associated with a given bout of exhausting exercise, and cross-sectional comparisons show an increased expression of beta IL-2 receptors on the peripheral blood mononuclear cells of trained individuals. However, excessive training, nutrient deficiency and/or muscle damage has adverse consequences for both the production of interleukins and the response of the immune system to these cytokines.

Exercise↗
PubMed2000

Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control.

The authors provide an analysis of data from a two-year (1996-1998), multicenter (ten US cities), double-blinded, placebo-controlled influenza vaccine trial in children. The vaccine was the trivalent cold-adapted influenza vaccine. Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza (VE(S)) while taking inter-center variability in the risk of infection into account. Our overall estimate of VE(S) against influenza is 0.92 (95% confidence interval (CI) 0.89-0.94). In addition, for the second year, although the vaccine contained antigen for A/Wuhan-like (H3N2), the estimated VE(S) for epidemic variant A/Sydney-like (H3N2) was 0.89 (95% CI 0.81-0.94). Thus, the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen. With regard to natural immunity, an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 (95% CI 0.21-0.98). When comparing year 1 to year 2, there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups. This is consistent with the theory that natural immunity provides overall community protection to children. The authors argue that mass vaccination of 70% of the children with the cold-adapted influenza vaccine could provide substantial protection to the community at large.

Child, Preschool↗