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PubMed1980

The in vitro discrimination of rat immune and natural cytotoxicity by serum choice.

Natural in vitro cytotoxicity of non-immune lymphoid cells against a variety of transformed and normal iso- and allogeneic target cells has been described in a number of species (for review see Herberman, Djeu, Kay, Ortaldo, Riccardi, Bonnard, Holden, Fagnani, Santoni & Puccetti, 1979). This background cytotoxicity is a hindrance to the estimation of immune lymphocyte cytolysis (Herberman & Oldham, 1975). Other workers have demonstrated that the choice of serum in which effector (EC) or target cells (TC) are prepared or tested may greatly influence the degree of killing (Irie, Irie & Morton, 1974; Zielske & Golub, 1976; Akira & Takasugi, 1977; Ortaldo, Bonnard & Herberman, 1977). It was found that high levels of rat normal effector cell (NEC) cytotoxicity against normal rat fibroblasts observed in the presence of foetal calf serum (FCS) were markedly reduced by the inclusion of normal rat serum (NRS). This effect on NEC activity was consistently noted in eleven batches of FCS and eight batches of NRS, whereas, normal human serum (NHuS) gave variable results. Decreased TC lysis was proportional to the concentration of NRS, was independent of heat inactivation and was primarily due to an effect on the EC population. The effects of FCS and NRS were not affected by prior absorption on TC or EC nor was NEC activity related to a proliferative response of EC during the 18-48 h microcytotoxicity assay employed in these studies. Since the inclusion of NRS did not markedly diminish the levels of immune effector cell cytotoxicity we have been able consistently to demonstrate that the use of 10% NRS in long-term rat cytotoxicity assays provides a means of dissociating the measurement of immune and normal lymphoid cell cytotoxicity.

Animals↗
PubMed2005

Breaking of tolerance to native DNA in nonautoimmune mice by immunization with natural protein/DNA complexes.

A major event in the pathogenesis of systemic lupus erythematosus (SLE) is the breaking of tolerance to native DNA and the appearance of IgG anti-double-stranded (ds) DNA antibodies. The mechanisms of the losing of tolerance are not well understood. Continuous efforts have been made in the past to induce anti-native DNA IgG autoantibodies in non-autoimmune animals but the relevance of the approaches used to what happens in spontaneous disease is unclear. We succeeded in breaking tolerance to native DNA in nonautoimmune-prone BALB/c mice by immunization with natural DNA/protein complexes. These complexes included nucleosomes, crude commercial histone and nucleohistone preparations. The anti-dsDNA IgG response lasted for more than an year. IgG deposition in the kidneys of the animals was repeatedly shown. As DNA-specific B cells behave in many ways as non-autoreactive B cells, we suggest that the activity of the self-reactive B lymphocytes could be selectively inhibited in a way that mimics a physiological mechanism controlling the magnitude and duration of the IgG antibody response to foreign antigens.

Animals↗
PubMed2002

The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface antigens in naturally acquired immunity to malaria.

Plasmodium falciparum, the most virulent species of human malaria parasite, causes 1-3 million deaths per year. Because this parasite is susceptible to naturally acquired host immunity the main burden of diseases falls on young children. The mechanism of this immunity is still unclear. However, the parasite makes a considerable investment in the insertion of highly polymorphic antigens (parasite-infected-erythrocyte surface antigens, PIESA) on the infected erythrocyte surface, and these antigens are potentially important immune targets.

Animals↗
PubMed2005

Naturally acquired immunity to Plasmodium falciparum malaria in Africa.

Infection by Plasmodium falciparum parasites can lead to substantial protective immunity to malaria, and available evidence suggest that acquisition of protection against some severe malaria syndromes can be fairly rapid. Although these facts have raised hopes that the development of effective vaccines against this major cause of human misery is a realistic goal, the uncertainty regarding the antigenic targets of naturally acquired protective immunity and the immunological mechanisms involved remain major vaccine development obstacles. Nevertheless, a coherent theoretical framework of how protective immunity to P. falciparum malaria is acquired following natural exposure to the parasites is beginning to emerge, not least thanks to studies that have combined clinical and epidemiological data with basic immunological research. This framework involves IgG with specificity for clonally variant antigens on the surface of the infected erythrocytes, can explain some of the difficulties in relating particular immune responses with specificity for well-defined antigenic targets to clinical protection, and suggests a radically new approach to controlling malaria-related morbidity and mortality by immunological means.

Africa↗
PubMed2005

Naturally acquired immunity to Haemophilus influenzae type B in healthy Cuban children.

We have evaluated the prevalence of antibody to immunogenicity of Haemophilus influenzae type b (Hib) in a group of 4 to 5 years old healthy children, who were too old to be included in the first vaccinated cohort when Hib vaccination begun in Cuba in 1999. Serum capsular polysaccharide specific IgG antibody concentrations were measured in 974 healthy children, between February and May 2002. The prevalence of Hib nasopharyngeal carriage was also estimated. The majority of children (99.7%) had more than 1 microg/ml of antibody. The preliminary report of the nasopharyngeal cultures was positive for H. influenzae in 16 children, but in only one was confirmed as Hib after serotyping (0.1% Hib nasopharyngeal carrier). These results provide evidence that in Cuba the natural active immunity to Hib can be acquired at an early age.

Antibodies, Bacterial↗
PubMed1994

Recommendations for Prevention of Hepatitis A Based on a Cost-Effectiveness Analysis.

Hepatitis A viral infection poses a substantial risk for travelers from low-endemic countries visiting high-endemic destinations. In this study, the general indications for the optimal prevention of hepatitis A are derived using a cost-effectiveness analysis based on the risk exposure determined by frequency and duration of travel as well as natural immunity. Three possible hepatitis A prevention strategies are compared to no prophylaxis: active immunization; an initial screening for HAV followed by active immunization of susceptible travelers; and passive immunization with immune globulins. Using a number of baseline assumptions, a scenario for travel from low- to high-endemic countries and an average travel duration and frequency rate, threshold values were obtained comparing active versus passive immunization. The study shows that, for travelers not expected to journey more than twice in a 10-year period, passive immunization is the most cost-effective prophylaxis for travel from both very-low or low-to-high endemic areas. For more frequent travel, vaccination is more cost effective, as well as for journeys of 6-months' duration or longer. As well, pretravel screening before vaccination was shown to be worthwhile, except when the probability of natural immunity is low. As the results indicate, the cost effectiveness of a strategy is related to several considerations: the prices of vaccine and screening tests, travel destinations and endemic conditions, frequency and duration of travel, and natural immunity. A decision-tree-based simulation model is helpful in determining the strategy to employ.

Journal Article↗
PubMed2005

Maximizing statistical power in group-randomized vaccine trials.

Statistical power in group-randomized vaccine trials is complex: group randomization may increase power by capturing more transmission effects but may decrease power as more individuals are affected by a common source of variance. The former effect dominates when most infections arise from within the group and the latter when most arise outside. This process is complicated further when individuals possess partial natural immunity. Vaccine trials typically compare infection frequency (as measured by agent or antibody detection) in vaccinated vs. unvaccinated groups. To assess the relative contributions to statistical power by direct agent detection vs. serological detection of recent infection, we constructed stochastic compartmental models using differential equations describing all possible discrete states of the group. We contrasted models where natural immunity was absent, altered only the susceptible state, or altered both the susceptible and infected states. We observed the effects of endemic infection levels, the fraction of infection arising from outside the group, infectiousness vs. susceptibility vaccine effects and waning rates. There was significant enhancement of statistical power when serological testing separated infected and susceptible classes into subsets by natural immunity status.

Haemophilus Infections↗
PubMed1987

Systemic and intestinal immunities after natural typhoid infection.

A 2-year study of systemic and intestinal immunity to Salmonella typhi was performed in 14 patients who were suffering from typhoid fever in an attempt to extrapolate the mechanism of immune responses in this disease. The methods employed were the leukocyte migration inhibition agarose test for the measurement of systemic cell-mediated immunity. The systemic immunoglobulin G (IgG) and IgM that were specific to S. typhi and anti-O and anti-H agglutinins were measured by indirect enzyme-linked immunosorbent assay (ELISA) and the Widal test, respectively. The immunobead ELISA was used to measure total secretory IgA (SIgA), and indirect ELISA was used to measure SIgA that was specific to S. typhi in the intestinal lavage fluid. The results revealed that the patients developed various types of immune response to S. typhi that had various magnitudes and durations. After the onset of illness, the cell-mediated immunity persisted for 16 weeks; IgG, IgM, and anti-O and anti-H agglutinin persisted for 2 years, 16 weeks, 16 weeks, and 36 weeks, respectively. SIgA can persist in the gut for about 48 weeks. Thus, the immunities as a whole can barely persist beyond 1 year after the onset of illness, unless there are persistent booster stimulations by S. typhi bacilli that exist in the environment, and then the immunities may be lifelong.

Adolescent↗
PubMed2007

Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians.

Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (chi (2) = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3'-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.

Adolescent↗
PubMed1988

Reactivities of 4 murine coronavirus antigens with immunized or naturally infected rat sera by enzyme linked immunosorbent assay.

Four murine coronavirus antigens, sialodacryoadenitis virus (SDAV) strain TG, Parker's rat coronavirus (PCV) strain 8190, mouse hepatitis virus (MHV) strains S and NuU, were examined for their reactivities to hyperimmunized and naturally infected rat sera by ELISA. With the immunized sera, SDAV and PCV antigens reacted best with respective homologous sera. MHV antigens reacted with all antisera, anti-SDAV, anti-PCV, and anti-MHV-S at approximately the same level, and MHV-S showed a slightly higher reactivity than MHV-NuU. The reactivities of the sera from various colonies to these antigens were in the order--from high to low--of SDAV, MHV-S, MHV-NuU, and PCV. None of sera negative for SDAV antigen reacted positively to the other antigens. Within the sera positive for SDAV, the positivities were in the order of MHV-S, MHV-NuU, and PCV. These results suggested that, although homologous antigens are best to detect SDAV or PCV infection by ELISA, MHV antigen can be used if highly cross-reactive viral strain is selected.

Animals↗
PubMed1993

Antibody response to meningococcal polysaccharides A and C in patients with complement defects.

Patients with defects of terminal complement components are particularly exposed to the risk of developing neisserial infections and seem to respond poorly to meningococcal capsular polysaccharide (PS) C via natural immunization. The sole meningococcal PSC is, on the other hand, an excellent immunogen in normal people. Considering the great importance of vaccine prophylaxis for the prevention of meningococcal infections in patients with complement defects, it is crucial to study the antibody response to the sole meningococcal PS in these patients. We therefore analysed the levels of anti-PSA and PSC antibodies in the members of four families including patients with homozygous and heterozygous defects of C7, C8 or factor H, before and after vaccination with the sole PSA + C. Surprisingly, we found the highest levels of antibodies before vaccination in homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapability to respond to sole meningococcal PS. In conclusion, this study demonstrates (1) the capacity to respond to meningococcal PS via natural immunization by patients with total complement defects, and (2) the low responsiveness to meningococcal PS via vaccine immunization by the same patients. We propose that vaccination should be given to patients lacking specific antibodies and their serological response should be assessed. In addition this study confirms previous observations on a likely lower immunogenic power of meningococcal serogroup C via natural immunization compared with the better immunogenicity of the sole PSC.

Adolescent↗
PubMed1997

[Immune response of rubella vaccine in the populations with different age groups].

The natural immunity status in different age groups was investigated. The positive rate of HI antibody under the age of 4 was less than 25%. The natural immunity level increased gradually with age and the positive rate of the antibody reached 80% among the group aged 13-25. Rate of seroconversion was 100% in any age group one month after immunization, and GMT rose from 13.33 to 243.16. It was suggested that immunogenicity of domestic attenuated live rubella vaccine BRD II was satisfactory. For the population with positive-antibody before immunization, the total GMT rose from 189.59 to 259.00 after vaccination and the difference between immunization before and after was highly significant. According to the above result, we suggested that the vaccination strategy for rubella among young children and women of child-bearing age should be implemented.

Adolescent↗
PubMed1981

Strain specificity of serum antibody to the haemagglutinin of influenza A (H3N2) viruses in children following immunization or natural infection.

The specificity of serum anti-HA antibody from children immunized or infected with A/Victoria/75 (H3N2 or A/Texas/77 (H3N2) virus was examined using the single radial haemolysis test together with adsorption of antibody with three antigenic variants A/Hong Kong/68 (H3N2), A/Port Chalmers/73 (H3N2) and A/Victoria/75 (H3N2). The majority of young children reacted to vaccination or infection by producing strain-specific (SS) antibody to the homologous virus. A small proportion of children's sera contained cross-reacting (CR) antibodies capable of reacting with the haemagglutinins of all antigenic variants of the sub-type including A/HK/1/68. In contrast, most adults reacted immunologically to either vaccination or infection by producing CR antibody, reacting with all variants of the antigenic subtype including the prototype virus A/HK/1/68 (H3N2).

Adolescent↗
PubMed1996

Immunity induced by vaccination with Rhipicephalus appendiculatus salivary gland antigens does not augment protective immunity acquired naturally by exposing rabbits to adult ticks.

A study was conducted using rabbits to ascertain the effects of immunity induced with salivary gland antigens (SGA) on naturally acquired host resistance, which was confirmed by exposing groups of rabbits to adult Rhipicephalus appendiculatus (Neumann) ticks. A reciprocal experiment was conducted to establish the effect of naturally acquired resistance on vaccination with SGA. After the acquisition of resistance by either method of vaccination, rabbits were then challenged with the 3 life stages of the tick. Results of the experiment demonstrated 3 phenomena: infestation of rabbits with 60 adult ticks leads to high protection in terms of reduction in the engorged weight against adult ticks, larvae, and nymphs (88.6, 31.5, and 55.9%, respectively); vaccination alone provides 53.9, 29.7, and 35.7% reduction in adult, larval, and nymphal ticks, respectively; and vaccination of rabbits already exposed to adult tick infestation appeared to have no additive immunological benefit above that already provided by adult ticks. Sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analyses revealed that antibodies with high avidity to SGA were directed to a 39-kDa polypeptide. This polypeptide was not revealed by sera from rabbits that were first infested with adult ticks. Sera from rabbits that were first vaccinated with SGA consistently reacted with the 39-kDa polypeptide. Sera from rabbits that were infested recognized strongly a 42-kDa polypeptide among 5 polypeptides in the SGA. Results of the experiment show that resistance resulting from adult tick infestation is not augmented by immunity caused by vaccination with SGA.

Animals↗
PubMed1978

Cell-mediated immunity during natural measles infection.

Natural measles causes prolonged depression of cell-mediated immunity yet little is known as to how the infection influences lymphocyte function. Therefore, we studied the properties and function of lymphocytes during and after measles. The number and proportion of circulating thymus-derived lymphocytes was low during the acute stage of measles, and at this time 37% of these cells showed positive immunofluorescent staining for measles virus after stimulation with phytohemagglutinin. 7% of B cells were shown to contain virus but their numbers did not alter during the infection. Acute-phase lymphocytes, when stimulated, yielded infective virus and half were killed on incubation with autologous serum and complement. In acute measles the increase in [(3)H]-thymidine uptake of lymphocytes when stimulated with an optimal dose of PHA was normal in media with 10% fetal calf serum and low in media containing 10% autologous serum: the mean values were 56.8+/-34.1 and 23.7+/-25.9 cpm x 10(3) per 10(6) lymphocytes, respectively. Stimulation of acute-phase lymphocytes by Candida antigen was also low in media containing autologous serum averaging 1.2 x 10(3) cpm per 10(6) lymphocytes. On recovery 4-6 wk later this rose significantly to 18.9+/-19.8. The mean migration index of leukocytes to heat-killed candida cells in acute measles was 0.84+/-SD 0.08, and this fell significantly to 0.75+/-SD 0.08 4 wk later. Thus, depletion of T cells, an inhibitor of lymphocyte proliferation in the serum and a possible defect in antigen processing, interacts to depress cell-mediated immunity in measles.

Antigens, Fungal↗
PubMed1991

Effects of alcohol on natural resistance to Ancylostoma caninum in mice.

Experiments were performed to study the effect of alcohol on natural immunity of Swiss albino mice during Ancylostoma caninum infection. Natural resistance is lowered in alcoholic mice; 40% alcohol by mouth produced significant effect after 20 daily injections. The effect of the drug on natural immunity depended upon the concentration and the period of consumption. Animals retained maximum number of larvae during alcohol treatment.

Alcoholism↗
PubMed2005

Naturally-acquired immunity to Neisseria meningitidis group A.

Group A meningococcal disease is epidemic in Sudan, less common in Uganda, a country bordering the "meningitis belt," and rare in North America. The basis of naturally-acquired group A immunity is unknown but in North America protection has been attributed to a high prevalence of serum anticapsular antibodies elicited by cross-reacting bacteria. We measured group A anticapsular antibody concentrations and bactericidal titers in sera from 236 adults (47 from the Sudan obtained at the height of a group A epidemic, 57 from Uganda, and 132 from North America). Anticapsular antibody concentrations were higher in Sudanese sera than in North American or Ugandan sera (geometric mean of 31.5 versus 5.4 and 5.3 microg/ml, respectively, P < 0.0001). Bactericidal titers of > or =1:4 (presumed to be a protective titer when measured with human complement) were detected in 66% of Sudanese sera as compared with 27 and 23%, respectively, of North American and Ugandan sera (P < 0.0001). Bactericidal activity was inhibited by group A polysaccharide in 58% of the Sudanese bactericidal sera as compared to 17 and 6% of North America and Ugandan bactericidal sera (P < 0.0005). Approximately 50% of non-bactericidal Sudanese sera had high IgA anticapsular antibody concentrations, which were rare in bactericidal Sudanese sera. Thus, serum anticapsular antibodies and bactericidal activity are prevalent in Sudanese exposed to a group A epidemic. Cross-reacting group A anticapsular antibodies are prevalent in North American and Ugandan sera, but bactericidal activity is infrequent and when present is largely directed at non-capsular antigens.

Adolescent↗