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At least 235 records · Page 13Linked to original sources

PubMed2003

Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response.

The expression of antimicrobial peptides and proteins is an important innate immune defense mechanism that has recently been shown to be essential for cutaneous defense against invasive bacterial disease. Newborns have an immature cellular immune defense system that leads to increased susceptibility to infections. Here we show that skin from embryonic and newborn mice, as well as human newborn foreskin, express antimicrobial peptides of the cathelicidin and beta-defensin gene families. Immunohistochemistry and in situ hybridization demonstrated abundant cathelicidin protein and mRNA is present in normal skin during the perinatal period. Quantitative real-time PCR showed mouse cathelicidin expression (CRAMP) is 10- to 100-fold greater in the perinatal period than adult. Murine beta-defensins-1 and -4 and human beta-defensin-2 were also present in newborn skin. Combined, human cathelicidin (LL-37/hCAP/18) and beta-defensin-2 demonstrated synergistic antimicrobial activity and efficiently killed group B Streptococcus, an important neonatal pathogen. Antimicrobial peptides may therefore provide a compensatory innate defense mechanism during development of cellular immune response mechanisms in the newborn period.

Adaptation, Physiological↗

PubMed1978

Gamma-irradiated scrub typhus immunogens: development and duration of immunity.

The development and duration of immunity to lethal scrub typhus infection was studied in BALB/c mice vaccinated with gamma-irradiated Rickettsia tsutsugamushi, strain Karp. One intraperitoneal injection containing approximately 10(8) 50% mouse lethal doses (MLD(50)) of irradiated organisms elicited an immune response protective against challenge with 10(5) MLD(50) of viable Karp. The same mass of immunogen given in three injections at 5-day intervals increased homologous (Karp strain) protection 25-fold and heterologous (Kato strain) protection 60-fold. Further temporal expansion of the immunization regimen did not increase protection. Subcutaneous vaccination provided significant, but lower, levels of protection than were achieved by intraperitoneal immunization, but the levels of cell-transferable immunity elicited by the two routes were approximately the same. Immunologically specific protection after intraperitoneal vaccination developed rapidly enough to provide resistance against simultaneous challenge with 200 MLD(50) of Karp. Homologous immunity was protective against a 10(6)-MLD(50) challenge 7 days after completion of the three-injection regimen, remained at that level for 3 months, dropped to 10(4) MLD(50) by 9 months, and was effective against a 50-MLD(50) Karp challenge at 12 months. Protection against heterologous challenge was first observed on day 17 and peaked on day 38, when the mice resisted a 10(5)-MLD(50) Kato challenge. Thereafter, heterologous protection waned rapidly and was not significant at 6 months.

Animals↗

PubMed1968

The development of acquired immunity to tapeworms and progress towards active immunization, with special reference to Echinococcus spp.

An assessment is made of the present state of knowledge on acquired immune responses developed by the intermediate and definitive hosts to tapeworm infections. From this evaluation, some gaps in knowledge and some of the problems associated with the development of practical immunization techniques are described. The principal conclusion reached is that absolute resistance to the larval stage can be acquired and resistance to a number of cestode species can be artificially induced in a number of hosts. Thus, research directed towards isolation and characterization of the functional antigens may lead to the development of vaccines for use in public health programmes, such as for the control of echinococcosis, as well as for improving the present status of meat hygiene in regions where cysticercosis, for example, exists.

Animals↗

PubMed1996

Enumeration and characterization of memory cells in the TH compartment.

There is a great deal of interest in understanding how helper T cells differentiate in vivo and exert their regulatory role on a developing, immune response. Essential to development of protective immunity is the development of memory T cells. To study memory T cells in vivo we first need the means to identify and characterize these cells as they develop in their complex microenvironments. We have developed a method which allows us to directly purify both primary and memory helper T cells from the draining lymph nodes of mice as they respond to pigeon cytochrome c in vivo. Junctional sequences from these populations and from individual T cells show a strong selection for CDR3 length and residues characteristic of antigen binding. Overall these studies support a model of progressive clonal maturation with the memory T cell repertoire being more homogeneous than that of the primary response. There is some suggestion that affinity maturation may take place after repeated immunization, but on a more modest scale than that seen for antibodies. Finally we present the use of two new technologies that promise to greatly expand the analysis of immune responses in vivo. The use of flow cytometry with simultaneous detection of five and six fluorescence parameters helps to reliably resolve rare subsets of antigen-specific cells in order to understand the progression of their differentiation in vivo. Lastly, we have developed peptide/MHC tetramers as a new class of staining reagent that has wide applicability in the study of T cell responses in vivo.

Amino Acid Sequence↗

PubMed1976

Ronidazole in low concentrations in drinking water for treatment and development of immunity to swine dysentery.

The addition of ronidazole to the drinking water at the concentration of 0.003% was effective for the treatment of experimentally induced swine dysentery in swine. Ronidazole at concentrations of 0.0015% and 0.00075% aided in the treatment of swine dysentery and the development of immunity to the disease. In experiment I, in which swine were given concentrations of 0.003, 0.0015, and 0.00075%, there were more survivors, fewer days of hemorrhagic diarrhea, greater feed and water consumption and body weight gain, and more favorable feed efficiency in the medicated swine than in the nonmedicated swine. With the 0.003% concentration, there were no deaths, and the diarrhea receded during or after treatment with the 0.0015% and 0.00075% concentrations, the incidence of nonhemorrhagic diarrhea was greater in medicated than in nonmedicated swine, and the diarrhea did not subside during treatment. In experimetn II, there were more survivors in the groups of swine medicated with the 0.0015% concentration than in the nonmedicated groups of swine. All surviving nonmedicated swine in experiment I were immune to reexposure 3 months after initial exposure. More swine given to the 0.0015% and 0.00075% concentrations in the same experiment were immune to reexposure 3 months after initial exposure than were the swine given the 0.003% concentration. In experiment II, neither the swine previously medicated with the 0.0015% concentration nor the nonmedicated swine were immune to reexposure 5 weeks after initial expsoure. Large spirochetes were observed in fecal smears from all exposed swine which developed either hemorrhagic or nonhemorrhagic diarrhea.

Administration, Oral↗

PubMed2004

Immunotoxicological consequences of perinatal chemical exposures.

The developing immune system may be especially vulnerable to the toxic effects of immunotoxicants. A number of chemicals has been identified that affect the developing immune system. Yet, so far there are no immune parameters included in current guidelines for developmental or reproductive toxicity testing. It is recommended that such guidelines are updated so that also the developing immune system is evaluated as a potential target of toxicity during developmental stages.

Animals↗

PubMed2001

The strategy of immunologic control of HIV-1 with structured treatment interruptions (STIs).

Structured treatment interruptions (STIs) have evolved as an experimental approach of interrupting highly active antiretroviral therapy (HAART) similar to cycles of cancer chemotherapy in order to develop immune control of HIV-1. There are multiple, ongoing clinical trials examining interruptions in antiviral therapy with and without immune-based therapies. If successful in developing immune control, STIs may be clinically useful but require large scale clinical trials to prove their utility and safety.

AIDS Vaccines↗

PubMed2003

Dietary supplementation with Echinacea and development of immunity to challenge infection with coccidia.

An experiment was conducted to examine the effects of dietary supplementation with 0.1% and 0.5% ground root preparations of Echinacea purpurea (EP; common name: purple cone flower) on the development of immunity following live vaccination and subsequent challenge with multiple coccidia species in an experimental model using a commercial live vaccine preparation. Effects of immunization and EP supplementation on weight gains before challenge, and weight gains, lesion scores and plasma levels of carotenoids and NO2-+NO3- following challenge were determined. In this experiment, combined live vaccination and feed supplementation with 0.1% or 0.5% EP during the first 2 weeks of life provided significant weight gain advantage compared to live vaccination alone. This advantage persisted through 2 weeks of EP withdrawal and subsequent challenge infection. EP supplementation also significantly lowered total lesion scores but did not significantly modify the effects of vaccination and challenge on plasma carotenoids or NO2-+NO3-.

Animals↗

PubMed1993

New perspectives in vaccine development: mucosal immunity to infections.

In this review, we focus on six key areas currently receiving attention in the mucosal immune system. These six areas are of considerable importance for development of vaccines. They are (a) the necessity to understand the unique features of the mucosal immune system; (b) the possibility that the common mucosal immune system may contain distinct compartments; (c) differences in antigen uptake and in types of antigen-presenting cells in mucosal inductive and effector sites; (d) more careful consideration of mucosal memory in vaccine development; (e) recent studies, which show that oral vaccines induce T-helper (Th)-cell subsets that regulate mucosal IgA responses; and (f) the mechanisms whereby mucosal S-IgA and T cells provide mucosal immune protection. An example of the above suffices to illustrate why the selected areas are of importance in vaccine development. Oral immunization preferentially induces type 2 Th (Th2) cell responses that directly correlate with antigen-specific IgA responses in mucosal effector sites. It is likely that activated, antigen-specific Th2 cells that are induced in Peyer's patches are continuously supplied to mucosal effector sites for regulation of IgA responses. These Th2 cells are producing cytokines such as interleukin (IL)-5 and IL-6 and these cytokines may direct antigen-specific surface IgA-positive B cells to become IgA-producing plasma cells. Nevertheless, additional studies will be required to establish that IgA responses to T-cell-dependent antigens depend on Th2 cell-derived help. What are the implications of these studies for current oral vaccines, including novel antigen delivery systems? The most obvious would be that vaccines should be optimized for induction of Th2-cell responses in IgA inductive sites such as the gut-associated lymphoreticular tissues. It is now clear that induction of Th2-type responses in both mucosal inductive and mucosal effector sites are essential for oral vaccines to induce S-IgA responses. However, antigens delivered by live vectors such as Salmonella typhimurium in the murine system and S. typhi in humans must consider T-cell responses induced against a live vector in addition to the inserted recombinant antigen. In this regard, it has been shown that these microorganisms induce cell-mediated immunity responses that largely result from Th1-type cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Chronic ethanol consumption before retrovirus infection is a cofactor in the development of immune dysfunction during murine AIDS.

Chronic ethanol (EtOH) consumption has been presumed to be a cofactor in the development of acquired immune deficiency syndrome (AIDS). AIDS is identified as a major public health priority in the United States, with heavy economic and social impact. In the present study, we tested this hypothesis that EtOH users are more predisposed to immunosuppression because of retrovirus infection in murine AIDS. Adult female C57BL/6 mice were fed 4.5% (v/v) in liquid diet and control diets for 10 weeks. Then all mice were infected with LP-BM5 retrovirus, causing murine AIDS, and were fed control liquid diets without EtOH. Interleukin (IL)-2 production produced by concanavalin A (Con A)-stimulated splenocytes was suppressed during murine AIDS. It was further inhibited in EtOH-fed mice compared with controls at 6 weeks postinfection, whereas decreased level of interferon-gamma during murine AIDS was not further affected in EtOH-fed mice. The levels of IL-5, IL-6, and IL-10 secreted by Con A-induced splenocytes, elevated during murine AIDS, were significantly further enhanced in EtOH-fed mice compared with controls at 6 weeks postinfection, whereas retrovirus-induced elevated release of IL-6 and tumor necrosis factor-alpha, produced by lipopolysaccharide (LPS)-stimulated splenocytes, were further increased in EtOH-fed mice compared with controls at 6 and 9 weeks postinfection, respectively. Con A- and LPS-induced splenocyte proliferation, inhibited by retrovirus infection, was significantly further suppressed in EtOH-fed mice compared with controls. These results suggest that dietary EtOH consumption before retrovirus infection aggravated progression of immune dysfunction, because it modified production of immunological regulatory cytokines and immune functions.

Alcoholism↗

PubMed1987

Prolonging survival in vascularized bone allograft transplantation: developing specific immune unresponsiveness.

Vascularized bone allografts (VBAs) could be useful adjuncts to the clinical reconstructive surgeon's arsenal. These grafts are known experimentally to be subject to host rejection. One way to control the rejection problem would be to develop specific immune unresponsiveness via host conditioning. Using a proven reliable model in inbred rats for studying heterotopic VBA transplantation, recipient animals were conditioned preoperatively with third-party unrelated blood, donor-specific blood (DSB) alone and with cyclosporine, and ultraviolet irradiated donor-specific blood. The combination of DSB plus cyclosporine delayed rejection of grafts across a strong histocompatibility barrier for three to four weeks. However, rejection was delayed across a weak histocompatibility barrier for five to six weeks using this same host pretreatment. The implications are that specific immunosuppression, although possible, is difficult to achieve in VBA transplantation, and that such techniques will rely on tissue-matching to minimize the genetic disparity between graft and host.

Animals↗

PubMed1982

Pathways to inflammation induced by immune complexes: development of the Arthus reaction.

The changes associated with inflammation induced by immune complexes (reversed passive Arthus reaction induced with egg albumin-anti-egg albumin) were quantitated and the kinetics of the various vascular phenomena were ascertained. Hyperemia, increase in vascular permeability, platelet accumulation, and polymorphonuclear (PMN) leukocyte accumulation occurred relatively early after induction of the inflammatory lesions, and peaked in 2-4 h. Hemorrhage peaked in 6-h-old lesions. Morphological studies confirmed that almost all infiltrating cells were PMN leukocytes and immunofluorescent tracer studies showed immune complexes in vessel walls as early as 15 min after i.v. injection of the fluoresceinated antigen and the intradermal injection of antibody. By 8 h the progression of the lesions had subsided and by 24 h there were signs of resolution. A pathway for the development of the inflammatory lesions induced with immune complexes is proposed.

Animals↗

PubMed2000

Dietary polyunsaturated fatty acids alter lymphocyte subset proportion and proliferation, serum immunoglobulin G concentration, and immune tissue development in chicks.

The effects of fat source on immune response of the offspring of the Single Comb White Leghorn laying hens were investigated. The laying hens were fed for 6 wk with a wheat-soybean meal basal diet with added sunflower oil (SO), animal oil (AO), linseed oil (LO), or menhaden fish oil (FO) at 5% (wt/wt). Upon hatching, the chicks (30/group) were given the same types of diets for 8 wk. The dietary SO, AO, and LO provided different n-6 to n-3 polyunsaturated fatty acids (PUFA) ratios. The FO and LO had ratios of n-6 to n-3 PUFA that were close but had different components of n-3 PUFA. The results demonstrated that the chicks fed LO or FO had significantly lower (P < 0.05) splenocyte proliferative response to ConA than the chicks fed SO or AO at either 4 wk or 8 wk of age, with a stronger (P < 0.05) suppressive effect produced by LO at 4 wk. A significantly lower (P < 0.05) splenocyte response to PWM was produced by the chicks fed AO, LO, and FO compared with the chicks fed SO at 8 wk. The thymus lymphocyte proliferation in response to ConA at 4 wk was lower (P < 0.05) in the chicks fed AO, LO, and FO than in the chicks fed SO. Both LO and FO elevated (P < 0.05) the proportion of IgM+ lymphocytes in spleen, but only FO increased (P < 0.05) the serum IgG concentration. The LO elevated (P < 0.05) the percentage of CD8+ T-lymphocytes but not the ratio of CD4+ to CD8+ cells (P > 0.05) in spleen. Growths of thymus, spleen, and bursa were impacted significantly (P < 0.05) by the amount of dietary PUFA, the ratio of n-6 to n-3 fatty acids, and n-3 PUFA components.

Animals↗

PubMed2006

Perinatal immunotoxicity: why adult exposure assessment fails to predict risk.

Recent research has pointed to the developing immune system as a remarkably sensitive toxicologic target for environmental chemicals and drugs. In fact, the perinatal period before and just after birth is replete with dynamic immune changes, many of which do not occur in adults. These include not only the basic maturation and distribution of immune cell types and selection against autoreactive lymphocytes but also changes designed specifically to protect the pregnancy against immune-mediated miscarriage. The newborn is then faced with critical immune maturational adjustments to achieve an immune balance necessary to combat myriad childhood and later-life diseases. All these processes set the fetus and neonate completely apart from the adult regarding immunotoxicologic risk. Yet for decades, safety evaluation has relied almost exclusively upon exposure of the adult immune system to predict perinatal immune risk. Recent workshops and forums have suggested a benefit in employing alternative exposures that include exposure throughout early life stages. However, issues remain concerning when and where such applications might be required. In this review we discuss the reasons why immunotoxic assessment is important for current childhood diseases and why adult exposure assessment cannot predict the effect of xenobiotics on the developing immune system. It also provides examples of developmental immunotoxicants where age-based risk appears to differ. Finally, it stresses the need to replace adult exposure assessment for immune evaluation with protocols that can protect the developing immune system.

Adult↗

PubMed1976

Immunologic response and factors affecting its assessment.

The potential harmful effects of toxic compounds on the developing immune system are discussed. This discussion is illustrated by results of studies of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the developing immune system of Fischer rats. While this compound and several others have been shown to have immunosuppressive effects, the available data do not support routine evaluation of the consequence of chemical exposure to the developing immune system.

Animals↗

PubMed1991

Evidence that cyclosporine treatment during pregnancy predisposes offspring to develop autoantibodies.

Cyclosporine was administered (11 mg/kg/day) to pregnant mice to study the effects of passively transferred CsA on the developing immune system. Placental transfer of CsA was shown by the detection of fetal-tissue levels ranging from 400 to 1500 ng CsA/g tissue. Treatment clearly altered the developing immune system. Thymuses from the day-18 embryos exposed to CsA were partially depleted of CD4+CD8- single positive cells. Eleven of 50 offspring born to CsA-treated mothers developed significant levels of IgG autoantibodies to gastric antigens. In addition, two animals that received CsA in utero developed an extensive mononuclear cell infiltrate in the gastric mucosa resembling autoimmune gastritis. These results raise the possibility that the administration of CsA during pregnancy may result in potential long-term effects on the developing immune system. Offspring of such pregnancies may suffer an increased incidence or severity of autoimmune diseases.

Animals↗

PubMed1988

Production of monovalent anti-Bothrops asper antivenom: development of immune response in horses and neutralizing ability.

A monovalent antivenom was produced by immunizing two horses with venom of the pit viper Bothrops asper (Ophidia: Viperidae). Although development of the immune response against four toxic and enzymatic activities of the venom was similar in both horses during the first two thirds of the immunization schedule, antibody response in one of the horses reached much higher levels in the last part of the immunization. Immunoelectrophoretic analysis indicates that there were precipitating antibodies in the sera of these horses during all the stages of immunization. However, immunoprecipitation did not correlate with the ability of sera to neutralize toxic activities of B. asper venom. Monovalent antivenom was more effective than the commercially available polyvalent antivenom in the neutralization of Bothrops asper venom. On the other hand, despite the fact that it neutralizes lethal and hemorrhagic activities of the venoms of Lachesia muta and Crotalus durissus durissus, it was less effective than polyvalent antivenom in these neutralizations. Moreover, it does not neutralize defibrinating activity induced by these two venoms, whereas it neutralizes this effect in the case of B. asper venom. It is proposed that monovalent antivenom may be highly effective in the case of envenomations induced by Bothrops asper venom; its use in treating accidents by L. muta and C. durissus would be indicated only if polyvalent antivenom is not available. Results also demonstrate that it is important to monitor antibody response individually in horses being immunized for antivenom production, due to the conspicuous variability in the response of different animals.

Animals↗

PubMedDate not supplied

Measles immunity and immunization in developing countries of Africa: a review.

Although an effective vaccine against measles has been available for several years, the disease is still prevelant in Africa. The disease is characterized by its occurrence in younger age groups and high morbidity and mortality. The African child is born with a high transplacentally acquired measles antibody level. However, the antibody declines rapidly, so that it is virtually absent after the age of 6 months. The measles vaccine with which the African child is immunized is of reduced potency because of poor storage and transportation facilities and the adverse effect of tropical climate on the vaccine. The pattern of measles immunity in Africa is different from that in developed countries. Measles immunization schedule in Africa, as in any other part of the world, must be based on sound epidemiological and serological data.

Africa↗