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PubMed1991

Development of immunity against Plasmodium falciparum malaria: clinical and parasitologic immunity cannot be separated.

A total of 1622 individuals of all ages living under conditions of continuous malarial transmission in Liberia were enrolled in a cross-sectional study of parasite rates, positive parasite densities, and body temperatures. The age-specific Plasmodium falciparum-positive parasite densities were greatest at ages 0.5-1.0 year, then slowly declined into adulthood. The age-specific mean body temperature at parasite isodensity showed a steady decline even in the oldest age group. The results do not support the hypothesis that adults have higher body temperatures at a given parasite density than do children with the same parasite density. The age-specific P. falciparum parasite density for specific isotemperatures showed that a subgroup of children in the age group 0.5-1.0 year had low temperatures (less than 36.5 degrees C) despite high parasite densities. This indicates that low body temperature should be investigated further as a possible indicator of serious malaria in young children. Parasitologic and clinical immunity develops concomitantly and cannot be separated. The findings do not support the hypothesis that a special "anti-disease" immunity exists independently of parasitologic immunity.

Adolescent↗
PubMed2003

Epigenetic control during lymphoid development and immune responses: aberrant regulation, viruses, and cancer.

Methylation of cytosines controls a number of biologic processes such as imprinting and X chromosomal inactivation. DNA hypermethylation is closely associated with transcriptional silencing, while DNA hypomethylation is associated with transcriptional activation. Hypoacetylation of histones leads to compact chromatin with reduced accessibility to the transcriptional machinery. Methyl-CpG binding proteins can recruit corepressors and histone deacetylases; thus, the interplay between these epigenetic mechanisms regulates gene activation. Methylation has been implicated as an important mechanism during immune development, controlling VDJ recombination, lineage-specific expression of cell surface antigens, and transcriptional regulation of cytokine genes during immune responses. Aberrations in epigenetic machinery, either by genetic mutations or by somatic changes such as viral infections, are associated with early alterations in chronic diseases such as immunodeficiency and cancer.

Acetylation↗
PubMed1994

Thai volunteers test HIV vaccine.

A group of 30 Thai volunteers received their final injections in a multi-national test of what doctors believe is a promising experimental AIDS vaccine. Dr. Prapan Panupark, director of the project in Thailand, said he was encouraged by initial results of the test conducted on 25 males and five females. The study of the experimental vaccine, known as the United Biomedical Inc. synthetic monovalent HIV-1 peptide, involved healthy volunteers aged from 21 to 48. Prapan told a press conference that participants received their first injections on June 6, 1994, another on July 4, 1994, and their final shot November 28, 1994. He said similar tests are taking place in Brazil and Uganda, which, like Thailand, have been hard-hit by HIV. One month after the second injection, Prapan said, blood tests revealed that out of 24 volunteers receiving the vaccine, 10 had developed immunity. "We are happy that immunity developed in 10 cases out of 24, or over 40%," he said. "We are happy because in similar tests in other countries, such as the US and Australia, only about 20% of the volunteers developed immunity." He said the volunteers will have their blood tested three more times to determine their levels of immunity. According to recently released figures, 3902 people have died of AIDS in Thailand in the past decade. Another 5215 patients are suffering from advanced AIDS in Thailand, while an estimated 600,000 people are believed to be HIV-positive.

Asia↗
PubMed1996

Sequential study of IgG antibody response in immunized rabbit and development of immunization protocol for raising monospecific antibody.

The present study was planned to develop an immunization protocol to decide the bleeding modalities for harvesting anti IgG antibody from the immunized rabbit. A fourteen dose immunization protocol (four primary and ten boosters) of the purified human IgG spread over the one calendar year was executed. The antibody titre estimated by Reverse Single Radial Immunodiffusion displayed a six-phased pattern. The titre following the initial immunization ranged between nil to 1.02, characteristic of the primary response while the titres after 7th and 8th boosters (phase V) ranged between 0.5 to 3.87 consistent with secondary response. Phase II, III, IV had moderately elevated titres. The antibody titre amongst the six phases reached to its peak generally by the 12th day after the last dose of protocol and it took about 60 days to reach to its basal level. Administration of antigen with the higher levels of residual antibody did not produce high titre antibody and is probably ascribed to elimination of antigen through an immunecomplex mechanism. Based on the data we recommend that 15 batches. (3 per phase, phase I to phase V) with a total yield of 100 to 120 ml of serum can be procured from one immunised animal over the span of one calendar year and that should make the programme cost effective.

Animals↗
PubMed2000

Gene gun-mediated DNA immunization primes development of mucosal immunity against bovine herpesvirus 1 in cattle.

Vaccination by a mucosal route is an excellent approach to the control of mucosally acquired infections. Several reports on rodents suggest that DNA vaccines can be used to achieve mucosal immunity when applied to mucosal tissues. However, with the exception of one study with pigs and another with horses, there is no information on mucosal DNA immunization of the natural host. In this study, the potential of inducing mucosal immunity in cattle by immunization with a DNA vaccine was demonstrated. Cattle were immunized with a plasmid encoding bovine herpesvirus 1 (BHV-1) glycoprotein B, which was delivered with a gene gun either intradermally or intravulvomucosally. Intravulvomucosal DNA immunization induced strong cellular immune responses and primed humoral immune responses. This was evident after BHV-1 challenge when high levels of both immunoglobulin G (IgG) and IgA were detected. Intradermal delivery resulted in lower levels of immunity than mucosal immunization. To determine whether the differences between the immune responses induced by intravulvomucosal and intradermal immunizations might be due to the efficacy of antigen presentation, the distributions of antigen and Langerhans cells in the skin and mucosa were compared. After intravulvomucosal delivery, antigen was expressed early and throughout the mucosa, but after intradermal administration, antigen expression occurred later and superficially in the skin. Furthermore, Langerhans cells were widely distributed in the mucosal epithelium but found primarily in the basal layers of the epidermis of the skin. Collectively, these observations may account for the stronger immune response induced by mucosal administration.

Animals↗
PubMed1983

Studies of the mechanisms for the induction of in vivo tumor immunity. VII. Development of specific antitumor immunity in progressors and regressors.

The present study was aimed at comparing the development of specific antitumor immunity between hosts with progressively growing tumors and hosts with regressing tumors. The experiments were performed with a Friend virus-induced leukemia FBL-3 in syngeneic C57BL/6 mice. The specific antitumor immunity was determined by in vitro cell-mediated cytotoxicity assay and in vivo tumor neutralization test. Both the systemic immunity (demonstrated in spleen) and immunity developed at tumor site were examined. For progressors, the tumor site was in the peritoneal cavity. For regressors, it was in a subcutaneous site of both flanks. Testing by the cell-mediated cytotoxicity assay showed that immune hosts and regressors had higher levels of systemic immunity than the progressors. However, when lymphocytes isolated from tumor sites were assayed, it was found that there was no remarkable difference between lymphocytes from progressor tumors (PTL) and lymphocytes from regressor tumors (RTL). Both lymphocyte populations were similar in profile analysis; they were characterized as T cells and possessed the same antigenic specificity. Nevertheless, when in vivo tumor transplantation experiments were performed, RTL were found to give protection against FBL-3 challenge whereas PTL consistently failed to do so. On cytomorphological examination, the PTL were seen to contain large amounts of macrophages. The presence of macrophages in PTL appeared to have an inverse relationship to the in vivo protective effect. After removal of macrophages from PTL by Petri dish adherence, the nonadherent PTL were found to give in vivo protection. Furthermore, thymocytes from progressors and macrophages isolated from the progressor tumors were found to suppress the in vivo T-cell-mediated immunity. These findings demonstrated that suppressor T cells and suppressor macrophages were present in tumor-bearing hosts. These suppressor cells could interfere with the function of immune T cells at the efferent arm of the immune response.

Animals↗
PubMed1991

Geschwind's theory of cerebral lateralization: developing a formal, causal model.

Geschwind and Galaburda (1987) have proposed a complex and influential model of cerebral lateralization that is based on the argument that increased fetal testosterone levels modify neural development, immune development, and neural crest development. The theory can explain many aspects of cerebral lateralization and its relation to learning disorders, giftedness, and immune deficits. This article clarifies the structure of the theory by presenting it as a causal-path model. The internal coherence of the model is then evaluated by assessing the central concept of anomalous dominance, the role of timing in the articulation of the model, and the invocation of nonlinear processes. Finally, the article considers the problems implicit in testing a "grand" theoretical model and derives some principles for assessing the testability of various predictions, given the practical constraints of sample size and the problems of measurement error.

Autoimmune Diseases↗
PubMed2006

In utero pesticide exposure and childhood morbidity.

In humans, immune development begins early in embryonic life and continues throughout the early postnatal period. Although a number of pesticides have been observed to induce developmental immunotoxicity in mice, few human studies have examined the long term effects of in utero pesticide exposure on childhood morbidity. Empirical evidence suggests that the vulnerable period for toxic insults to the developing immune system extends from early gestation to adolescence in humans and animals. Using data from the Ontario Farm Family Health Study, we examined the relationship between farm couple exposures to pesticides during pregnancy and subsequent health outcomes in their offspring, including: persistent cough or bronchitis, asthma, and allergies or hayfever. No strong associations between pesticide exposures during pregnancy and persistent cough or bronchitis, or asthma were found. There was suggestive evidence that allergies and hayfever appeared to be more common in offspring, especially male offspring, exposed to certain specific pesticides during the period of pregnancy. Nevertheless, given the indirect indicators of pesticide exposure used in this study, and the scarcity of human studies on in utero exposure to pesticides and the development of allergies and other child health outcomes, these findings serve primarily to generate hypotheses for future research.

Adult↗
PubMed2005

Genistein enhancement of respiratory allergen trimellitic anhydride-induced IgE production by adult B6C3F1 mice following in utero and postnatal exposure.

The objective of the present study was to determine if exposure to the phytoestrogen genistein (GEN) during immune development had any effects on the production of IgE by adult mice following dermal treatment with trimellitic anhydride (TMA), a respiratory allergen. B6C3F1 mice were exposed to GEN either by feeding at 500 ppm or by gavage (20 mg/kg) for varied periods from gestation day (GD) 14 to postnatal day (PND) 84. In utero exposure to GEN by feeding increased the production of IgE at PND 84 in male mice but not in female mice. In male mice, continuous exposure to GEN postnatally diminished the in utero exposure-induced enhancement in serum total IgE production. However, continuous exposure to GEN from GD 14 to PND 84 was required to increase serum total IgE production in female mice. In utero exposure to GEN by gavage increased the production of IgE at PND 84 in female mice but not in male mice when the mice were maintained on the NIH-07 rodent diet in which a medium level of phytoestrogens was present. The enhancement in IgE production after GEN exposure in females but not in males was associated with decreases in the percentages of CD4(+)CD25(+) T suppressor cells, and increases in the natural killer (NK) cell activity, the basal splenocyte proliferation, the expression of CD86 by B cells, and the production of IL-2 and IL-4. Overall, the results demonstrated that GEN differentially modulated the developing immune system in male and female mice, and that more IgE was produced upon exposure to TMA in the adult.

Allergens↗
PubMedDate not supplied

MHC dosage effects on primary immune organ development in the chicken.

Immune development in vertebrates is thought to be influenced by many factors including genotype. We used the Trisomic avian model to probe for influences of the major histocompatibility complex (MHC) on the development of the primary immune organs. Chickens were produced having two, three, and four copies of the MHC-encoding microchromosome. Studies of growth, immune organ development and structure, and lymphocyte populations were performed at three post-hatching time points. Chickens with three and four MHC copies (trisomic and tetrasomic) exhibited reduced overall growth and had smaller bursae and thymuses compared to disomic controls. However, the fold reductions in immune organ weights were much greater than for body weights. Histological analysis of the immune organs revealed dramatic alterations in follicular composition in tetrasomic bursae compared to disomic controls. No obvious alterations were observed in thymic and splenic histology of tetrasomics. Studies of organ lymphocyte numbers revealed a sharp reduction in bursal and thymic lymphocyte counts of trisomic and tetrasomic chickens. Based on these results, it appears that MHC dosage modulates, in a targeted fashion, the cellularity of the primary immune organs through an extended period in differentiation of B and T lymphocytes.

Animals↗
PubMedDate not supplied

Safety monitoring in vaccine development and immunization.

The development of vaccines has been one of the most important achievement in preventive medicine. As the incidence of vaccine-preventable diseases is reduced by immunization, general public becomes increasingly concerned about the safety associated with vaccine. Vaccine safety is extensively evaluated through animal safety studies, clinical trials, during manufacturing processes, and postlicensure surveillance. Safety monitoring in postlicensure surveillance has relied on passive reporting system and epidemiological studies, including Vaccine Adverse Event Reporting System (VARES), Vaccine Safety Datalink (VSD) Project and others. Approximately 10,000 reports per year are submitted to VAERS. About 15% of these describe serious events and 85% of reports are classified as not-serious events. The system analyzed frequently reported adverse reactions, rare events, intussusception after rotavirus vaccine, cases of sudden infant death syndrome (SIDS), and safety of various vaccines. The evidence for a causal relationship with vaccines can be classified into five categories: no evidence, evidence was inadequate to accept or reject, evidence favors rejection, evidence favors a causal relationship, and evidence established. Future challenges involve improving survey and monitoring system of adverse events after immunization, enhancing vaccine safety research and vaccine risk communication, and possibility of increased reactogenicity in new and combined vaccines.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

The development of immunity to Eimeria species in broilers given anticoccidial drugs.

The acquisition of immunity to Eimeria species was studied in broilers reared in floor-pens on new and used litter, and given different anticoccidial drug programmes. Programmes included a single drug (synthetic compound or ionophore) given in the starter and grower feed, or 'shuttle' programmes comprising a synthetic drug followed by an ionophore (or vice versa) given in the starter and grower feeds, respectively. None of the drug programmes prevented parasite multiplication, since oocysts were found in the intestines of birds and in the litter. Birds were challenged at weekly intervals with a mixture of species (E. acervulina, E. maxima and E. tenella) in order to establish whether protective immunity had developed. Birds reared on used litter that received no medication acquired immunity by 5 weeks, whereas birds reared on new litter were not fully protected against a challenge inoculum until 7 weeks of age. Apart from birds given an ionophore followed by a synthetic drug, medicated birds developed immunity by 7 weeks, irrespective of the type of drug programme, or whether they had been reared on new or used litter. Birds reared in commercial houses (where one and seven previous flocks had been raised) and given a synthetic drug followed by ionophores, also developed immunity to Eimeria species. Immunity was acquired more rapidly to E. maxima than E. acervulina or E. tenella.

Journal Article↗
PubMed2002

Maternal modulation of neonatal immune system development.

Changes in programming of neonatal immune development were effected through maternal immune modulation (Leishmania major inoculation). In progeny of these dams, immune profiles in both blood and spleen were changed throughout the neonatal period and were pronounced after weaning. White blood cell (WBC) and lymphocyte counts in blood of 45-day-old progeny were two-fold less than control animals. In blood, proportions of B cells were greater, while T helpers, Tc/s and NK cells were less than in controls. In contrast, proportions of splenic B and NK cells were greater than controls. But, proportions of all T and Tc/s cells on d20 and 45 were lower than controls. In blood, absolute numbers of all T, Th naïve and Th memory cells were lower than in controls. In contrast, in the spleen, numbers of NK, T and Th naive and memory cells were up to 200% greater than in control pups. Cytokine responses of splenic lymphocytes stimulated through CD3 ligation revealed no difference in IL-4 production. In contrast, IL-2 and IFNgamma were lower on d45 and 5, respectively, in the experimental compared to control mice. These data support the hypothesis that maternal immune events during gestation can modulate the pattern of immune development in offspring.

Animals↗
PubMed1999

Anticoccidial drugs and their effects upon the development of immunity to Eimeria infections in poultry.

The long-held view that anticoccidial drugs, to a greater or lesser extent, interfere with the development of immunity to Eimeria species may no longer be correct because few drugs, if any, are capable of preventing some degree of parasite multiplication. Acquisition of immunity is, therefore, a real possibility, providing sufficient parasites are present in the environment. Immunity is an important consideration during the rearing of replacement layers, broiler breeders, turkeys, and gamebirds, but little research has been carried out on the effects of drugs on immunity development in these categories of stock. In recent years, there has been a change in the perception of the significance of immunity in broilers, and some broiler producers have taken this into consideration when designing drug programs for use in the field. Studies in floor pens and the field indicate that broilers given various drug programs can develop immunity when exposed to natural infections but that this process takes time: solid immunity not developing until birds are 6 to 7 weeks of age. This suggests that drugs should not be withdrawn from the feed prematurely since birds may not have had time to develop adequate immunity.

Journal Article↗
PubMed2000

Progress in development of immunization registries--United States, 1999.

Community-based and state-based immunization registries are confidential, population-based, computerized information systems that contain data about children's vaccinations and represent an important tool to increase and sustain high vaccination coverage. Immunization registries consolidate vaccination records for children from multiple providers, provide a vaccination needs assessment for each child, generate reminder and recall vaccination notices, produce an official vaccination record, and provide practice-specific and community-based vaccination coverage assessments. One of the Healthy People 2010 national objectives is to increase to 95% the proportion of children aged <6 years who are enrolled in a fully operational population-based immunization registry. To assess the status of immunization registry development, CDC analyzed data from the 1999 Immunization Registry Annual Report (IRAR) of 64 jurisdictions (grantees) that receive federal immunization funds under section 317d of the Public Health Service Act. Findings from this analysis indicate that substantial progress has been made in the United States in developing and implementing community-based and state-based immunization registries.

Child, Preschool↗
PubMed2001

Progress in development of immunization registries--United States, 2000.

Immunization registries are confidential, population-based, computerized information systems that attempt to collect vaccination data about all children within a geographic area. Registries are an important tool to increase and sustain high vaccination coverage by consolidating vaccination records of children from multiple providers, generating reminder and recall vaccination notices for each child, and providing official vaccination forms and vaccination coverage assessments. One of the national health objectives for 2010 is to increase to 95% the proportion of children aged <6 years who participate in fully operational population-based immunization registries (objective 14.26). To assess the status of immunization registry development, CDC analyzed self-reported data from 62 immunization grantees on the basis of data from the 2000 Immunization Registry Annual Report (IRAR). This report summarizes the results of this analysis, which indicate that approximately half of the grantees are operating population-based immunization registries that target their entire catchment areas; however, approximately 75% of children aged <6 years still need to be included in an immunization registry to reach the national health objective.

Child↗
PubMed1976

Development of immunity against antigens of the A and B blood groups during postembryogenesis in chickens.

51Cr-labelled erythrocytes were injected into young chicks, F1 hybrids of the inbred chicken lines, from hatching to 2 months of age. The onset of immunity was measured by means of elimination of labelled red blood cells. It was found that with the B-locus difference between donors and recipients the immune response developed from 4 days of age to the end of the first week, whereas with the A-locus difference it developed during the second week of life. The onset of immunity is delayed in inbred chickens compared to outbred chickens, because we have used one alloantigen difference.

ABO Blood-Group System↗