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IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation.

The IL-15 receptor alpha subunit (IL-15Ralpha) mediates high-affinity binding of IL-15, a pleiotropic cytokine implicated in the development of innate immune cells. We have generated IL-15Ralpha null (IL-15Ralpha-/-) mice to understand the role of IL-15Ralpha in immune development and function. IL-15Ralpha-/- mice are markedly lymphopenic despite grossly normal T and B lymphocyte development. This lymphopenia is due to decreased proliferation and decreased homing of IL-15Ralpha-/- lymphocytes to peripheral lymph nodes. These mice are also deficient in natural killer cells, natural killer T cells, CD8+ T lymphocytes, and TCRgammadelta intraepithelial lymphocytes. In addition, memory phenotype CD8+ T cells are selectively reduced in number. Thus, IL-15Ralpha has pleiotropic roles in immune development and function, including the positive maintenance of lymphocyte homeostasis.

Animals↗

Development of immunity in natural Plasmodium falciparum malaria: antibodies to the falciparum sporozoite vaccine 1 antigen (R32tet32).

Antibodies that reacted with a candidate sporozoite vaccine antigen (R32tet32) were found in 20 of 21 patients treated for acute infection with Plasmodium falciparum and monitored longitudinally over 67 days. R32tet32 contains 32 tandem copies of a tetrapeptide sequence that constitutes the immunodominant epitope of the circumsporozoite surface protein. The magnitude of the antibody response varied considerably among individuals and appeared to be independent of the number of previous clinical infections. Recrudescence of infection or infection with Plasmodium vivax had no demonstrable effect on antibody levels, although reinfection with P. falciparum produced a rapid rise in antibody titer. Antibody levels were observed to decline rapidly after treatment of clinical infection with mefloquine. The apparent antibody half-life was 27 days, which is comparable to the half-life of circulating immunoglobulin G in humans. The data suggest that antisporozoite antibody production ceased on about day 4 after treatment of acute infection. A similar pattern of response was observed for antibodies against the erythrocytic forms of the parasite. The cessation of antibody synthesis was interpreted as being due to immunosuppression induced by the presence of intraerythrocytic parasites and may explain in part why protective immunity is poorly developed in natural malaria infections.

Acute Disease↗

Response to early measles-mumps-rubella vaccination in infants with chronic renal failure and/or receiving peritoneal dialysis.

Achieving immunity to childhood viral infections before renal transplantation is crucial. However, children with chronic renal failure (CRF) may respond poorly to vaccination, making it difficult to achieve immunity before transplantation, particularly if they will require transplantation at a young age. To address this problem, we developed a protocol of early measles-mumps-rubella (MMR) vaccination in infants with CRF. Nine infants received MMR vaccine at a mean age of 11.6 +/- 2.5 months. When vaccinated, 6 of the children (67%) were on peritoneal dialysis, and 3 (33%) had CRF [glomerular filtration rate (GFR) < 30 mL/min/1.73 m2]. Eight patients were later transplanted at a mean age of 16.8 +/- 4.8 months. Titers were measured before transplantation in all patients. Response to vaccination was excellent, with 89% developing immunity to measles, 88% developing immunity to mumps, 100% developing immunity to rubella, and 88% developing immunity to all three components of the vaccine. These response rates were equivalent to, or slightly better than, those previously reported by Schulman for older children (19 +/- 6 months) on dialysis: 80% for measles, 50% for mumps, 100% for rubella, and 30% for all three components. We conclude that early MMR vaccination induces immunity in most infants with CRF, even those on peritoneal dialysis. Response rates are similar to those previously reported in older children. This approach may help to facilitate transplantation in young infants by achieving immunity earlier than traditional vaccination schedules.

Adolescent↗

Development of immunity to ocular chlamydial infection.

The development of "natural immunity" to homologous and heterologous ocular challenge with Chlamydia trachomatis was examined in cynomolgus monkeys given primary or secondary inoculations of C. trachomatis serovars B, C, and E. Overall, serovar E gave more severe disease than the other serovars. The amount of disease induced by the 2 serovar B strains examined, TW-5 and HAR-36, varied. In general, animals showed resistance to homologous secondary challenge, which was better characterized by a reduction in the recovery of culturable organisms than by a reduction in clinical disease. However, following initial heterologous challenge, neither resistance nor aggravation of disease was seen. These observations suggest that a trachoma vaccine will have to contain the serovar-specific antigenic determinants for multiple chlamydial serovars.

Animals↗

[Investigations of the development of immunity in the course of experimental murine toxocariasis].

Mice were infected with Toxocara canis by an oral administration of embryonated eggs of the parasite, then they were killed between 1st and 8th week after infection to obtain sera and splenic lymphocytes. The lymphocytes were kept in culture medium for 3 to 6 days with either concanavalin A or excretory-secretory antigen of T. canis and assayed for proliferative responses. The obtained sera were examined for the presence of specific IgG and IgM antibodies. It was found that cell-mediated immunity was depressed for 3 weeks after infection and the first signs of the developing immunity were detected only at the 4th week of infection. Subsequently, the blastogenic responses increased reaching a level significantly higher when compared with those of the control cultures at 8th week of infection. Specific toxocaral IgG and IgM antibodies were first detected in the samples collected at the 4th week.

Animals↗

Polyspecific malaria antibodies present at the time of infection inhibit the development of immunity to malaria but antibodies specific for the malaria merozoite surface protein, MSP1, facilitate immunity.

Serum taken from mice immune to malaria as a result of infection and drug cure, or from mice immunized with a recombinant form of the merozoite surface protein, MSP1, can provide passive protection of recipient mice against the lethal parasite, Plasmodium yoelii YM. However, recipients of MSP1-immune serum go on to develop long-term immunity, whereas recipients of serum from mice naturally immune to malaria rapidly lose their resistance to infection. We demonstrate that 'infection/cure' serum suppresses the development of both antibody and cell-mediated parasite-specific responses in recipients, whereas these develop in recipients of MSP1-specific antibodies. These data have profound implications for our understanding of the development of malaria immunity in babies who passively acquire antibodies from their mothers.

Animals↗

The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity.

The development of secondary lymphoid organs is a complex process dependent on a coordinated interaction of cells of hematopoietic and non-hematopoietic origin. In this context, chemokines and cytokines belonging to the tumor necrosis factor (TNF)/lymphotoxin (LT) family are critical signaling molecules during the initial steps of lymph node and Peyer's patch organogenesis. Homeostatic chemokines, such as CXCL13, CCL21, and CCL19, as well as their corresponding receptors, CXCR5 and CCR7, have now been shown to closely cooperate in the development of lymphoid organs and the maintenance of lymphoid tissue microarchitecture. We summarize recent data on the function of CXCR5 and CCR7 and their intricate connection to the TNF/LT system in order to refine the current model of lymphoid organ development.

Animals↗

[Effect of daily immunization and antirabies gamma-globulin on the development of immune T-killers in inbred mice infected with the street rabies virus].

Daily administration of vaccine as well as combined use of antirabies gamma-globulin and vaccine were shown not to induce the production of immune T-killers possessing protective properties in adoptive transfer in mice pre-infected with street rabies virus in contrast to a single administration of a shock dose of antigen. Immune splenocytes protected 31-43% of mice infected with street rabies virus in a dose of 2-4 im LD50 and did not protect the animals infected with a dose of 12 im-LD50. After combined administration of immune splenocytes and an interferon inducer (double-stranded RNA) the additive protective effect was observed.

Animals↗

Development of immunity to lungworm in vaccinated calves treated with an ivermectin sustained release bolus or an oxfendazole pulse release bolus at turnout.

The ivermectin sustained release bolus (IVSRB), when used at turnout as recommended, will provide season-long control of parasitic bronchitis, thus obviating the need for use of a lungworm vaccine. However, some concerns have been expressed that calves treated with an IVSRB will receive so little exposure to Dictyocaulus viviparus that it will compromise their immunity in subsequent grazing seasons, which would be of particular importance in dairy herds. Although there is evidence that IVSRB-treated calves can develop immunity to D. viviparus when exposed to pasture infection, it was considered worthwhile to evaluate the compatibility of the IVSRB and lungworm vaccination to allow veterinary surgeons the option of using these products concurrently when they have particular concerns about the long term immune status of replacement dairy heifers. Thirty-two dairy replacement heifers were vaccinated with two doses of lungworm vaccine and, at turnout, half the calves received an IVSRB and the remainder an oxfendazole pulse release bolus (OPRB). At the end of the grazing season four replicate bolus treated pairs and four parasite-naive calves were challenged with 1000 D. viviparus infective larvae. At slaughter there was a 95% and 93% reduction in D. viviparus burdens in the IVSRB and OPRB treated calves respectively, compared with the unvaccinated, untreated controls. These results indicate that where it is considered necessary to use lungworm vaccination in addition to an IVSRB or an OPRB, the compatibility of these products with lungworm vaccine will allow development of a protective level of immunity to D. viviparus.

Animals↗

Development of immunity to incoming radiolabelled larvae in lambs continuously infected with Ostertagia circumcincta.

Infective larvae of Ostertagia circumcincta were radiolabelled with 75selenium by a method which did not affect their viability. Three groups of five-month-old lambs were infected daily with 1000 unlabelled infective larvae for four, eight and 12 weeks, respectively. After each period one of these groups and a group of worm-free controls were challenged with three consecutive daily doses of 1000 radiolabelled third stage larvae. The lambs were killed 13 days after the first dose of challenge larvae and their worm burdens examined. The first indication of immunity was retardation of developing worms observed at four weeks. Resistance to the establishment of incoming worms developed between four and eight weeks and a brief period of population turnover probably took place at this time. Simultaneously a greater inhibition of worm development occurred resulting in an increase in the number of parasites recovered as early fourth stage larvae. By 12 weeks the animals were almost completely immune to incoming worms. The development of resistance to incoming worms correlated with a rise in serum antibody titre and an increase in the number of intraepithelial globule leucocytes in the gastric mucosa.

Animals↗

Immunizations in developing countries.

The WHO Expanded Programme on immunization has greatly improved the prevention of 6 major diseases of infants in developing countries, but a number of other immunizations are left aside. They concern diseases which are either specific to tropical countries or common to both developed and developing countries. Preventive immunization programmes against these diseases are often non-existent and countries rely on "fire-fighting" immunization campaigns whenever an outbreak occurs. This deficiency is the result of logistic difficulties, most of which could be overcome. Recent progress in research will bring improved classical vaccines and new vaccines which are eagerly awaited. However, logistic problems in developing countries will have to be solved to make the best use of multiple antigens which will soon be at hand.

Developing Countries↗

Observations on a herd of beef cattle maintained in a tsetse area. II. Assessment of the development of immunity in association with trypanocidal drug treatment.

Three groups of Boran cattle were maintained under different trypanocidal drug regimes for 29 months in an area of "medium" tsetse challenge. The development of immunity to trypanosmiasis in the cattle was assessed on the basis of changes in trypanocidal drug requirement, development of parasitaemia, ability to maintain normal blood values, growth and response to challenge after the withdrawal of the drugs. Observations were also made on serum antibody content by immunofluorescence and on serum immunoglobulin levels. Cattle treated with Berenil on the development of clinical disease developed a partial immunity to trypanosomiasis after two years. Cattle treated as a group with Berenil on the development of patent parasitaemia in any one animal of the group did not develop immunity. Cattle treated as a group with Samorin using the same criterion for treatment developed a degree of immunity to the disease. It was concluded that group treatment with Samorin was the most suitable of the three regimes examined for the maintenance of beef cattle is a tsetse infested area.

Animals↗

Control of development and immunity by rel transcription factors in Drosophila.

The Drosophila Rel/NF-kappaB transcription factors - Dorsal, Dif, and Relish - control several biological processes, including embryonic pattern formation, muscle development, immunity, and hematopoiesis. Molecular-genetic analysis of 12 mutations that cause embryonic dorsal/ventral patterning defects has defined the steps that control the formation of this axis. Regulated activation of the Toll receptor leads to the establishment of a gradient of nuclear Dorsal protein, which in turn governs the subdivision of the axis and specification of ventral, lateral and dorsal fates. Phenotypic analysis of dorsal-ventral embryonic mutants and the characterization of the two other fly Rel proteins, Dif and Relish, have shown that the intracellular portion of the Toll to Cactus pathway also controls the innate immune response in Drosophila. Innate immunity and hematopoiesis are regulated by analogous Rel/NF-kappaB-family pathways in mammals. The elucidation of the complex regulation and diverse functions of Drosophila Rel proteins underscores the relevance of basic studies in Drosophila.

Animals↗

Dynamics of swine mange: a critical review of the literature.

This paper summarizes the literature on swine mange, incorporating relevant literature on human scabies and on acarine associations with other mammals. Discussed are how mite populations affect immune development, how immune hypersensitivity affects host behavior and performance, and how immune hypersensitivity determines whether or not crusted lesions develop. Several key gaps in our understanding of swine mange are identified. The temporal pattern of immunity has not been studied beyond the 20th week of infestation. Desensitization as occurs in other host-parasite systems has not been documented. It is unclear if components of immune hypersensitivity regulate mite populations. Location of mites on the body and movement of mites among hosts have not been studied. And finally, improved methods for judging the severity of mange are needed to understand the biological and economic effects of mange on the swine industry.

Animals↗

Role of oestrogen receptors alpha and beta in immune organ development and in oestrogen-mediated effects on thymus.

Oestrogens affect the development and regulation of the immune system. To determine the role of oestrogen receptors alpha (ER-alpha) and beta (ER-beta) on the development of the immune system, male ER-alpha (ERKO) and ER-beta (BERKO) mice, as well as alphabeta-double knockout (DERKO) mice, were studied. Deletion of ER-alpha led to hypoplasia of both thymus and spleen. Interestingly, a higher frequency of immature double CD4+ CD8+ thymocytes was found in ER-alpha(-) mice compared with ER-alpha(+) mice. Female oophorectomized BERKO mice given oestradiol (E2) displayed a similar degree of thymic atrophy compared with the wild-type strain but showed only limited involution of thymus cortex and no alteration of thymic CD4/CD8 phenotype expression. Our data demonstrate that expression of ER-alpha, but not ER-beta, is mandatory in males for development of full-size thymus and spleen, whereas expression of ER-beta is required for E2-mediated thymic cortex atrophy and thymocyte phenotype shift in females. A potential background for the above findings may be down-regulated activity in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in males lacking ER-alpha and suppressed sensitivity of females lacking ER-beta to E2-mediated suppression of IGF-1.

Animals↗

Effect of passive immunity on the development of a protective immune response against bovine viral diarrhea virus in calves.

OBJECTIVE: To determine whether passively acquired antibodies prevent development of a protective immune response to live virus in calves. ANIMALS: 18 calves. PROCEDURES: Calves were caught immediately after birth and tested free of bovine viral diarrhea virus (BVDV) and serum antibodies against BVDV. Within 48 hours, 12 calves were fed colostrum that contained antibodies against BVDV and 6 calves received BVDV antibody free milk replacer. Three milk replacer fed and 6 colostrum fed calves were exposed to virulent BVDV2-1373 at 2 to 5 weeks of life when passively acquired serum antibody titers were high. After serum antibody titers against BVDV had decayed to undetectable concentrations (at 7 to 9 months of age), the 3 remaining milk replacer fed calves, 6 colostrum fed calves previously exposed to BVDV2-1373, and 6 colostrum fed calves that had not been exposed to the virus were inoculated with BVDV2-1373. RESULTS: Passively acquired antibodies prevented clinical disease in inoculated colostrum fed calves at 2 to 5 weeks of life. Serum antibody titers did not increase in these calves following virus inoculation, and serum antibody titers decayed at the same rate as in noninoculated colostrum fed calves. Inoculated colostrum fed calves were still protected from clinical disease after serum antibody titers had decayed to nondetectable concentrations. Same age colostrum fed calves that had not been previously exposed to the virus were not protected. CONCLUSIONS AND CLINICAL RELEVANCE: A protective immune response was mounted in calves with passive immunity, but was not reflected by serum antibodies titers. This finding has implications for evaluating vaccine efficacy and immune status.

Animals↗