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PubMed2001

Intrahepatic genetic inoculation of hepatitis C virus RNA confers cross-protective immunity.

Naturally occurring hepatitis C virus (HCV) infection has long been thought to induce a weak immunity which is insufficient to protect an individual from subsequent infections and has cast doubt on the ability to develop effective vaccines. A series of intrahepatic genetic inoculations (IHGI) with type 1a HCV RNA were performed in a chimpanzee to determine whether a form of genetic immunization might stimulate protective immunity. We demonstrate that the chimpanzee not only developed protective immunity to the homologous type 1a RNA after rechallenge by IHGI but was also protected from chronic HCV infection after sequential rechallenge with 100 50% chimpanzee infectious doses of a heterologous type 1a (H77) and 1b (HC-J4) whole-virus inoculum. These results offer encouragement to pursue the development of HCV vaccines.

Amino Acid Sequence↗
PubMed1978

Natural and immune antibodies to rabbit erythrocyte antigens.

Natural agglutinins to rabbit erythrocytes were found in all human sera studied. In the newborn, the antibodies were of IgG class; in the 6-month-old infants they were mainly of IgM class. Older children and adults had both IgG and IgM antibodies. Agglutinins to rabbit erythrocytes were also found in serum from fourteen of fifteen other species studied. The trichloroacetic acid extract from rabbit erythrocyte stromata (TCA-preparation) contains at least three different antigenic determinants: one which we hitherto to have found only on rabbit erythrocytes, one which is closely related to human blood group B antigen, and one which is closely related to the I antigen. The TCA-preparation did not elicit delayed hypersensitivity skin reactions in humans in spite of high titred agglutinins in serum, but did so in immunized guinea-pigs.

Adolescent↗
PubMed1992

Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization.

Malaria transmission-blocking immunity has been studied in natural malarial infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while still in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection or following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent.

Animals↗
PubMedDate not supplied

[Neutral lipids as stimulators of natural unspecific immunity].

Neutral lipids (various monoglycerides and cholesterol derivatives) were used as stimulators of natural unspecific immunity. All the compounds studied exhibited the biological activity. Saturated monoglycerides (chimyl and batyl alcohols) and cholesterol derivatives possessed the highest activity. Unsaturated lipids with double bonds were less active.

Animals↗
PubMedDate not supplied

Tumor necrosis factor alpha and interleukin 6 productions in response to platelet-activating factor in chronic hepatitis B virus infection.

OBJECTIVE: The aim of this study was to determine tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) release in response to platelet-activating factor (PAF) induction in peripheral blood mononuclear cells (PBMCs) from chronic hepatitis B virus (HBV) carriers. METHODS: Subjects were grouped into three subgroups. The mean age was 37 +/- 10 years. Group A (n = 15), group B (n = 10) and group C (n = 9) subjects were HBV serology-negative, had natural immunity after recovery from an acute HBV infection, and were chronic HBV carriers, respectively. RESULTS: Compared with group A, PBMCs from naturally immune subjects and chronic HBV carriers produced significantly higher amounts of TNF-alpha and IL-6 in response to PAF. In chronic HBV carriers, TNF-alpha (1,633.3 +/- 793.7) and IL-6 (2,533.3 +/- 466.3) production was statistically lower than TNF-alpha (2,630.0 +/- 727.3) and IL-6 (3,870.0 +/- 728.4) obtained from naturally immune subjects to HBV. CONCLUSION: Differences of TNF-alpha levels between chronic HBV carriers and naturally immune subjects suggest that TNF-alpha may be a critical mediator of HBV clearance.

Adult↗
PubMed1982

The natural killer system in the rat: the relationship between natural and immune cell-mediated lysis of fibroblast targets.

Natural killer (NK) cell cytotoxic activity is thought to operate as an early defence system before the expression of specific cytotoxic immune effectors (Leibold & Peter, 1978). Apart from this temporal relationship it is likely that other mechanisms exist to regulate these two forms of host defence and their relationship to one another. Present studies firstly substantiate evidence that normal and immune effector cells represent different cell types even though they share many functional characteristics in vitro. Normal effector cells (NEC) cytotoxic for normal dermal-derived fibroblasts in vitro were present in rats 3-36 weeks old, were tissue-dependent (with low levels in lymph nodes and thymus, unrelated to cellular suppression), were nylon wool and glass non-adherent and sensitive to 400 rad of X-irradiation in vitro. Secondly, discrimination between normal and immune cell-mediated cytotoxicity by factor(s) present in normal rat serum (Lindsay & Allardyce, 1981) allowed various aspects of their in vitro and in vivo relationship to be examined. These studies suggested that the expression of NEC cytotoxicity was temporally related to the in vivo generation of immune cytotoxic effector cells.

Animals↗
PubMed2003

Naturally occurring immune response against bacteria commonly involved in upper respiratory tract infections: analysis of the antigen-specific salivary IgA levels.

Lyophilized bacterial lysates, which actively stimulate the immune response, are widely used as vaccines or 'biological response modifiers' in subjects with recurrent bacterial respiratory infections. Since vaccines are indicated in the absence or in the presence of a weak constitutive immune response activity, a better knowledge on the 'naturally' occurring antibacterial immune response at the oropharingeal level should be helpful. A study was, therefore, designed to quantify the presence of salivary IgA directed against surface antigens bacteria frequently involved in the pathogenesis of upper respiratory tract infections: Klebsiella pneumoniae (KP), Staphylococcus aureus (SA), Streptococcus pyogenes (SPy), Morraxella catarrhalis (MC), Haemophylus influenzae (HI), and Streptococcus pnumoniae (SPn). In 34 volunteers (21 adults and 13 children), salivary fluid was collected and the presence of microorganism-specific IgA antibodies evaluated by a novel enzyme immuno-assay. In the whole population only 29 and 24% of subjects had IgA directed, respectively, to KP and SA, while the immune-response against other microbes was detectable in a small population ranging from 12 to 15% of all subjects studied. We found higher proportions of individuals with strain specific salivary IgA in the adult than in the pediatric population for all the microorganism evaluated. In addition, in children, the only strain inducing a significant production of specific IgA at oropharingeal level was KP. Interestingly, only ten out of 21 adults and two out 13 children have at least one significantly high antibody titer against one of the bacteria evaluated. Nevertheless, when a group of healthy donors was treated with a polyvalent mechanical bacterial lysate (Ismigen t.), the large majority developed a specific immune-response in the salivary fluid. These results are thus consistent with the good features of the novel enzyme-immunoassay and with a poor frequency of naturally induced specific anti-microbe antibodies in children and in adults despite the presence on recurrent respiratory infections in their clinical history.

Adult↗
PubMed2000

A quantitative approach to the determination of antigen in immune complexes.

Immune complexes are present in the circulation of healthy individuals and the formation of such complexes is part of a normal immune process. During some pathological conditions, significant amounts of immune complexes are formed and deposited in the kidney and other tissues, causing severe injury. Since the levels of immune complexes can provide valuable prognostic information, dozens of methods have been developed to detect and quantify these complexes. However, many of these methods are non-specific, not quantitative, and give false-positive results. Methods based on detecting the antigen portion of immune complexes can yield more precise information about circulating immune complexes. We have used a quantitative dot-blot assay, which permits detection of antigen even if buried, to determine the levels of antigen in circulating immune complexes. In healthy donors, significant amounts of immune complexes containing DNA and beta(2)-glycoprotein I were detected (natural immune complexes). Natural immune complexes with Lewis X antigen were also observed in the circulation of healthy persons. In experimentally induced murine systemic lupus erythematosus (SLE) and SLE patients, there was a correlation between the clinical manifestations and the levels of DNA in the circulating immune complexes. At severe SLE flares, the level of DNA in circulating immune complexes decreased, probably due to tissue deposition of immune complexes. The low levels of DNA in immune complexes circulating in SLE patients correlated with low serum concentrations of the complement component C1q. No direct correlation was found between the levels of circulating anti-dsDNA antibodies and DNA in immune complexes. Thus, quantitation of antigen levels in circulating immune complexes can be used to determine the prognosis of autoimmune diseases.

Adult↗
PubMed2000

Role of natural and immune IgM antibodies in immune responses.

IgM antibodies constitute the major component of the natural antibodies and is also the first class of antibodies produced during a primary antibody response. The IgM-type antibodies differ from other classes of antibodies in that they are predominantly produced by B1 cells, in the absence of apparent stimulation by specific antigens. In addition, IgM antibodies are mostly encoded by germline V gene segments and have low affinities but broad specificites to both foreign and self structures. New developments regarding the function of both immune IgM antibodies and natural IgM antibodies will be examined here.

Antibody Formation↗
PubMed1998

Immunization status and sociodemographic characteristics: the mediating role of beliefs, attitudes, and perceived control.

OBJECTIVES: This study examined how immunization-related beliefs, attitudes, and perceived control mediate up-to-date immunization among various sociodemographic groups. METHODS: Statewide estimates of immunization rates among children up to the age of 2 years were obtained via a multistage cluster sample. In-person interviews were conducted with 4832 parents. Information about immunization was obtained from official records or from health care providers. RESULTS: Differences in immunization among sociodemographic groups were mediated by beliefs about objective barriers to immunization, protection, medical contraindication, safety concerns, distrust, and natural immunity. Protection beliefs contributed to positive attitudes toward immunization; beliefs in natural immunity and safety concerns contributed to negative attitudes. Beliefs about objective barriers, distrust, safety concerns, and medical contraindications influenced perceived control over immunization. Positive attitudes and a strong sense of control contributed to higher immunization rates. CONCLUSION: These findings provide a basis for efficient educational campaigns by specifying which beliefs should be bolstered (because they facilitate proper immunization) and which should be targeted for change (because they hinder proper immunization) in various sociodemographic groups.

Adult↗
PubMed1991

Immunization with subunit human immunodeficiency virus vaccine generates stronger T helper cell immunity than natural infection.

Healthy, human immunodeficiency virus seronegative (HIV-) volunteers were multiply immunized with a recombinant gp160 (rgp160) candidate acquired immunodeficiency syndrome (AIDS) vaccine. Peripheral blood lymphocytes from volunteers immunized with 40 micrograms or with 80 micrograms (two volunteers per group) of rgp160, as well as from control donors, were tested for T helper (Th) cell function either prior to immunization, 8 to 12 months after the third immunization, or 2 to 5 months after the fourth immunization. The Th cell functional tests included antigen-induced in vitro interleukin 2 (IL 2) production and proliferation in response to influenza A virus (FLU) and to four synthetic peptides of HIV gp120 and gp160, previously demonstrated to be recognized by T cells from HIV naturally infected patients. Our results demonstrate the following: (a) immunization of HIV- individuals with rgp160 results in IL 2 production and T cell proliferation in response to HIV determinants; (b) boosting with rgp160 enhances Th function; (c) HIV-specific Th function is up to 100-fold greater in the multiply immunized volunteers than that observed in asymptomatic, HIV-infected individuals; and (d) multiple immunization with rgp160 does not impair Th function to a non-HIV antigen such as influenza A virus. These results indicate that immunization of uninfected individuals with an HIV subunit vaccine results in much stronger Th cell immunity than does natural infection and suggests that vaccination against HIV may be possible.

Gene Products, env↗
PubMed2006

The role of the NKG2D receptor for tumor immunity.

Natural killer (NK) cells have originally been identified based on their capacity to kill transformed cells in a seemingly non-specific fashion. Over the last 15 years, knowledge on receptor ligand systems used by NK cells to specifically detect transformed cells has been accumulating rapidly. One of these receptor ligand systems, the NKG2D pathway, has received particular attention, and now serves as a paradigm for how the immune system is able to gather information about the health status of autologous host cells. In addition to its significance on NK cells, NKG2D, as well as other NK cell receptors, play significant roles on T cells. This review aims at summarizing recent insights into the regulation of NKG2D function, the control over NKG2D ligand expression and the role of NKG2D in tumor immunity. Finally, we will discuss first attempts to exploit NKG2D function to improve immunity to tumors.

Animals↗
PubMed1998

Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria.

The feasibility of a malaria vaccine is supported by the fact that children in endemic areas develop naturally acquired immunity to disease. Development of disease immunity is characterized by a decrease in the frequency and severity of disease episodes over several years despite almost continuous infection, suggesting that immunity may develop through the acquisition of a repertoire of specific, protective antibodies directed against polymorphic target antigens. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of target antigens, because these proteins are inserted into the red cell surface and are prominently exposed and because they are highly polymorphic and undergo clonal antigenic variation, a mechanism of immune evasion maintained by a large family of var genes. In a large prospective study of Kenyan children, we have used the fact that anti-PfEMP1 antibodies agglutinate infected erythrocytes in a variant-specific manner, to show that the PfEMP1 variants expressed during episodes of clinical malaria were less likely to be recognized by the corresponding child's own preexisting antibody response than by that of children of the same age from the same community. In contrast, a heterologous parasite isolate was just as likely to be recognized. The apparent selective pressure exerted by established anti-PfEMP1 antibodies on infecting parasites supports the idea that such responses provide variant-specific protection against disease.

Age Factors↗
PubMed1986

The IgG detected in the C1q solid-phase immune-complex assay is not always of immune-complex nature.

The properties of the solid-phase C1q immune-complex assay as well as the nature of the IgG detected by this assay in patients' sera were investigated. Aggregated IgG was used as a model for immune complexes. Aggregated IgG bound to solid-phase C1q was detected by 125I-anti-IgG. Fluid-phase C1q (either in normal human serum or purified) neither inhibited the binding of aggregated IgG to solid-phase C1q nor dissociated bound aggregated IgG from the solid-phase C1q. Therefore, we concluded that the solid-phase C1q has a higher affinity for aggregated IgG than the fluid-phase C1q, probably because of the polymerization of the solid-phase C1q. To get more insight into the nature of the IgG detected by the C1q solid-phase assay in patients' sera, we investigated whether C4 and/or C3 were present on it. With the use of 125I-anti-C4 and 125I-anti-C3 instead of 125I-anti-IgG, C4 and C3, respectively, were easily detected on the aggregated IgG that had bound to the solid-phase C1q. The lower limit of detection of these assays was 30 micrograms aggregated IgG/ml of normal human serum. Sera of patients suffering from rheumatoid arthritis and systemic lupus erythematosus were tested with these assays and, despite positive results with 125I-anti-IgG, no positive results were obtained with either 125I-anti-C4 or 125I-anti-C3. So, on the IgG detected by the C1q solid-phase assay in patients' sera, neither C4 nor C3 are present. Furthermore, in five of the six sera tested, this IgG sedimented as monomeric IgG. Therefore, it seems unjustified to refer to this IgG as circulating immune complexes.

Antigen-Antibody Complex↗
PubMed1977

The mechanism of group differences in the character of the vaccinal process in immunization against natural smallpox.

The effect of antigenic polymorphism of the ABO-system blood groups on the character of the vaccinal process after immunization against natural smallpox was investigated. The increased susceptibility of persons possessing A antigen to the harmful effect of smallpox vaccine virus is due to hereditary rather than to acquired factors. The leukocytes of peripheral blood of these persons showed a poorer binding capacity with respect to the smallpoxvaccine virus; they also exhibited a high rate of chromosomal aberration after vaccination, resulting to some extent from increased proliferative ability of the cells.

ABO Blood-Group System↗
PubMed1994

Rate of antigen entry into the circulation in experimental versus naturally occurring immune complex glomerulonephritis.

This study tested the hypothesis that the rate of antigen entry into the circulation in systemic lupus erythematosus (SLE), a naturally occurring immune complex glomerulonephritis (IC-GN), is slow compared with that of traditional experimental models of IC-GN, in which the antigen is delivered rapidly as a daily iv bolus. This hypothesis was tested by comparing rates of decline of the third component of complement (C3) and of circulating neutrophils (PMN) in SLE patients with active disease with those of cynomolgus monkeys (CYN) undergoing induction of experimental IC-GN by means of a daily bolus infusion of antigen. It has previously been shown that, as antigen enters the circulation and forms circulating IC, C3 levels and circulating PMN decline acutely. Thus, acute changes in these parameters can be surrogates for the rate of antigen entry into the circulation. In the CYN undergoing induction of IC-GN (N = 11), infusion of the antigen (bovine gamma-globulin) over 10 min resulted in acute declines in C3 levels (25 +/- 6.6%; P = 0.0018 and PMN counts (59 +/- 9%; P < 0.0002). In addition, the CYN experienced the onset of acute respiratory distress and hypotension. By contrast, in patients with active SLE (N = 9), C3 and white blood cell counts measured at 24-h intervals did not change significantly, and episodes of acute hypotension or respiratory distress were not observed. In the CYN, the onset of visible vasculitic lesions in the omentum were also documented within minutes of the infusion of bovine gamma-globulin. The rapidity of onset of these vascular lesions suggests that the tempo at which lesions develop in experimental models of IC disease is faster than that of naturally occurring IC diseases. It was concluded that, in naturally occurring IC diseases, antigen probably enters the circulation slowly over prolonged periods of time, rather than as large boluses over short periods of time, as in traditional experimental models of IC-GN. Thus, models of IC-GN involving a daily bolus infusion of antigen may not be clinically relevant, particularly when IC clearing mechanisms are tested, because the efficiency of these mechanisms may be markedly influenced by the rate at which IC form in the circulation.

Animals↗
PubMed1979

Relationships among differentiated T-cell subpopulations. IV. Preferential induction of delayed footpad reaction to xenografts and its radioresistant nature.

Immune response in mice to xenogeneic cells was characterized by positive delayed footpad reaction and negative macrophage migration inhibition. Mice immunized with allogeneic cells exhibited negative delayed footpad reaction and positive macrophage migration inhibition. Cytotoxic T lymphocytes were detected only in mice immunized with allogeneic tumour cells. Delayed footpad reaction against xenogeneic cells was radioresistant and the immune lymphocytes responsible for such a reaction were presumed to have some relation to xenograft rejection.

Animals↗
PubMed2006

Loss of maternally-derived human herpesvirus-7 immunity and natural infection in Argentinian infants.

BACKGROUND: Human herpes virus-7 (HHV-7) infection is widespread throughout the world. No data are available in Argentina about loss of maternally-derived HHV-7 immunity and natural infection. OBJECTIVES: The objective of this study was to characterize the time when children lose maternal antibodies and become susceptible to natural infection. METHODS: Sera from 39 pregnant women and 207 infants between 2 and 29 months of age were tested. Determination of IgG antibodies was made by indirect immunofluorescence. RESULTS: The seropositive ratio fell in the 2-4 month group (15% seropositive) and increased between 5 months (47% seropositive) and 23 months (67%). Geometric mean titers (GMT) of the infants aged 2-4 months (GMT = 60) were statistically different (p < 0.0001, Student's t-test) to those from the group of pregnant women (GMT = 83) and those from the other infant groups (p < 0.001, least significant difference (LSD) test). The GMT of the groups between 5 and 23 months did not show significant differences whereas those of infants between 24 and 29 months (GMT = 179, 79% seropositive) were different from all the groups studied (p < 0.0001, LSD test). CONCLUSIONS: This study shows a significant association between the loss of passive HHV-7 antibody and age. HHV-7 enters the susceptible population at 5 months, leading to the high prevalence of antibodies between 24 and 29 months of age. This study also shows that natural infection by HHV-7 in children during their first years of life follows the infection pattern found in developing countries.

Adult↗