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PubMed2002

Early development of immune system in pigs.

Prenatal and early postnatal immune system development has been studied in minipigs. First leukocytes were observed in the yolk sac and fetal liver (FL) on the 17th day of gestation, the majority of them being SWC3(+). The colonization of the thymus (TH) with leukocytes was observed 21 days later. Two waves of fetal TH colonization with pro-T cells were deduced from the frequency of thymocyte subsets. Thymic B cells and immunoglobulin-secreting cells (Ig-SC) were studied by flow cytometry and ELISPOT, respectively. When the total numbers of fetal Ig-SC were compared, the TH was identified as the main source of natural antibodies and the only site of IgA and IgG synthesis. In germ-free animals, the TH also represented the major site of IgG and IgA production and the number of Ig-SC was not influenced by colonization with microflora. FL and bone marrow were identified as primary B lymphopoietic sites. The phenotype of B precursors was characterized and pre-B II cells were shown to be the dominant mononuclear fraction between DG50 and DG105. In the periphery, relative proportions of lymphocyte subsets were determined. Studies in gnotobiotic piglets have revealed that the appearance of CD4(+)CD8(+) T cells and CD2(-) B cells is absolutely dependent on the contact of immune system with live viruses and bacteria, respectively.

Animals↗
PubMed2005

Normal immune system development in mice lacking the Deltex-1 RING finger domain.

The Notch signaling pathway controls several cell fate decisions during lymphocyte development, from T-cell lineage commitment to the peripheral differentiation of B and T lymphocytes. Deltex-1 is a RING finger ubiquitin ligase which is conserved from Drosophila to humans and has been proposed to be a regulator of Notch signaling. Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment. Deltex-1 was also found to be highly expressed in germinal-center B cells. To investigate the physiological function of Deltex-1, we generated a mouse strain lacking the Deltex-1 RING finger domain, which is essential for its ubiquitin ligase activity. Deltex-1(Delta/Delta) mice were viable and fertile. A detailed histological analysis did not reveal any defects in major organs. T- and B-cell development was normal, as were humoral responses against T-dependent and T-independent antigens. These data indicate that the Deltex-1 ubiquitin ligase activity is dispensable for mouse development and immune function. Possible compensatory mechanisms, in particular those from a fourth Deltex gene identified during the course of this study, are also discussed.

Amino Acid Sequence↗
PubMed2003

Species comparison of anatomical and functional immune system development.

The components of the immune system have not been traditionally emphasized as potential target organs in standard developmental and reproductive toxicity (DART) protocols. A number of workshops have been organized in recent years to examine scientific questions that underlie developmental immunotoxicity tests, and the interpretation of results as they relate to human risk assessment. A key question that must be addressed is to determine the most appropriate species and strains to model the developing human immune system. The objective of this review is to compare the anatomical and functional development of the immune system in several species important to either preclinical studies for drug development or safety assessments for chemicals, with what is known in humans. The development of the immune system in humans will be compared to what is known in mice, rats, dogs and nonhuman primates.

Age Distribution↗
PubMed1999

Measles vaccines, new developments and immunization strategies.

The development of an attenuated measles virus vaccine gave us a tool to combat a disease which has ravaged the child population throughout the centuries. Three decades later the vaccine has shown its qualities and its problems. Using this vaccine the WHO have decided on a measles eradication policy. This article discusses some of the issues which are being addressed and possible solutions.

Animals↗
PubMed1995

Development of immunity to malaria may not be an entirely active process.

It has never been explained why it takes so long for humans to develop immunity to malaria, although factors such as antigenic variation, antigenic polymorphism, and poor immunological responses to critical antigens are thought to be important. Models of malaria, particularly in rodents, have not been helpful. The course of malaria infection differs considerably between humans and rodents. Mice rapidly develop immunity whereas for most humans it takes several years of exposure for this to occur. Mice typically exhibit high parasitaemias whereas humans typically do not. A significant difference in the immune response of humans and mice to malaria parasites might, in part, explain these differences. Most humans have a preexisting population of activated malaria parasite-specific T cells (cross-reactive T cells) which we have referred to as 'natural' T cells, but such cells have not been observed in mice. These cells, many of which secrete interferon-gamma, might control parasitaemia early in the infection, but a by-product of their further activation by malaria parasites might be disease symptoms. Development of immunity has been thought of as an active process--acquisition of specific antibody and effector T cell responses. However, it might in part reflect induction of tolerance of this preexisting population of disease-inducing T cells as a result of chronic parasitaemia. The initial presence of these Th1-like cells may also impede the development of a Th2-like response necessary for the production of protective antibodies. Persistent cross-reactive stimulation may significantly impede this process.

Animals↗
PubMed2005

Ikaros integrates endocrine and immune system development.

Ikaros transcription factors are essential regulators of lymphopoiesis and the development of the immune system. We now show that Ikaros is expressed in hormone-producing pituitary corticomelanotroph cells, where it binds the proopiomelanocortin promoter and regulates endogenous gene expression. Loss of Ikaros in vivo results in contraction of the pituitary corticomelanotroph population, reduced circulating adrenocorticotrophic hormone levels, and adrenal glucocorticoid insufficiency. While hemopoietic reconstitution failed to correct this hormonal deficit, the phenotype of reduced body weight and diminished survival was rescued by systemic glucocorticoid-hormone administration. Given the established immunomodulatory properties of glucocorticoid hormones, these findings reveal a novel role for Ikaros in orchestrating immune-endocrine development and function.

Adrenocorticotropic Hormone↗
PubMed2004

CD40/CD154 interactions at the interface of tolerance and immunity.

Development of the acquired immune response is dependent on the signaling of CD40 by its ligand, CD154. These molecules govern both the magnitude and quality of humoral- and cell-mediated immunity. A litany of studies have conclusively documented that blockade of this ligand-receptor pair can prevent, and also intervene in, the progression of antibody- and cell-mediated autoimmune diseases, and can instill long-lived allogeneic and xenogeneic graft tolerance. Many effector mechanisms of inflammation are abolished as a result of CD154 blockade, but we are now beginning to understand that CD154 blockade may, in some instances, engender long-lived, antigen-specific tolerance. In the context of transplantation tolerance, we present a hypothesis that alpha CD154 blockade is most effective at inducing long-lived allospecific tolerance if anergy and regulation can be elicited prior to the onslaught of inflammation that is induced by grafting (preemptive tolerance). This facet of alpha CD154-induced tolerance appears to co-opt the normal processes of peripheral tolerance induced by immature DCs and can be exploited to induce long-lived antigen-specific tolerance. The underlying science and the prospects for inducing long-lived antigen-specific tolerance in a model of allograft tolerance through CD154 blockade are presented and discussed.

Animals↗
PubMedDate not supplied

[Mucosal immune response development: breastfeeding and environmental influence].

A review of the current knowledge of mucosal immune response development indicates that migration of immunocytes to mucosal surfaces is an early event during fetal life. The morphologic development of gut-associated lymphoid tissues (lymphoid follicles, Peyer's patches and tonsils) occurs from 11-20 weeks' gestation upwards. But they are active only after birth, when usually antigenic challenge takes place. The complete development of secretory immunity is a postnatal achievement. In infancy, some environmental factors such as feeding and oral antigenic challenge seems to modulate immune response development. Breastfeeding, by means of antiinfectious, antiinflammatory and immunomodulating properties, besides completing infant secretory immunity, also stimulates immunological maturation on mucosal surfaces.

English Abstract↗
PubMed2003

Effect of anti-cytomegalovirus therapy on the incidence of immune recovery uveitis in AIDS patients with healed cytomegalovirus retinitis.

PURPOSE: To determine the association between anticytomegalovirus (CMV) maintenance therapy after immune recovery and immune recovery uveitis in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). DESIGN: Observational cohort study. METHODS: Data were obtained on AIDS patients with CMV retinitis followed up at the AIDS Ocular Research Unit of University of California San Diego from November 1995 to October 1999. Immune recovery was defined as CD4 count greater than 50 cells/microl for more than 3 months. Patients with immune recovery uveitis presented with vitritis, cystoid macular edema, or epiretinal membrane. Statistical analyses were conducted to determine the risk of continued use of anti-CMV therapy after immune recovery and the relationship of developing immune recovery uveitis with the type of anti-CMV therapy. RESULTS: Forty-three patients (64 eyes) had healed CMV retinitis and had achieved immune recovery. Thirty-one patients (48 eyes) received anti-CMV therapy after immune recovery, and 20 patients (29 eyes) developed immune recovery uveitis. Per-eye analyses revealed a 3.8-fold increase in the odds of developing immune recovery uveitis with anti-CMV therapy compared with no treatment (P =.02). If treated with cidofovir the odds were 3.3 greater than if treated with an alternative regimen (P =.04), 4.1 greater if treated intravenously (P =.01), and 5.2 greater than if not treated (P =.004). If not treated with cidofovir, a nonsignificant increase in the risk (2.4) of immune recovery uveitis was found (P =.15). Neither the potency nor the use of implants for noncidofovir treatment was related to the risk of recovery uveitis (P >.62). CONCLUSIONS: The use of cidofovir is a primary risk factor in the subsequent development of immune recovery uveitis. Ongoing treatment of healed CMV retinitis after immune recovery does not appear to protect against the development of immune recovery uveitis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Establishment of Ascaris suum in the pig: development of immunity following a single primary infection.

Development of immunity after a single primary infection of Ascaris suum in pigs was investigated with regard to the worm population dynamics of a superimposed A. suum infection, host immune response and gross liver pathological changes. Group A was given a primary infection of 60,000 infective A. suum eggs and group B was left uninfected. Four weeks later both groups A and B were inoculated with 1,000 A. suum eggs, and subgroups were slaughtered 7, 14 and 21 days post challenge infection (p.c.i.). An uninfected control group C was slaughtered on day 21 p.c.i. The challenge worm recovery in group A was reduced compared to group B by 12%, 50% and 75% on day 7, 14 and 21 days p.c.i., respectively. In both groups was the expulsion of worms initiated between day 14 and 21 p.c.i. However, in group A the worms were recovered more posteriorly in the small intestine and 21 days p.c.i. the mean worm length was significantly shorter than in group B (p = 0.01). The results above were associated with significantly higher (p < 0.05) antibody response and higher eosinophil counts in group A compared to group B. The present results suggest that the larval growth and survival of a challenge infection are decreased, probably due to higher antibody and eosinophil attack during the migratory phase.

Analysis of Variance↗
PubMed2005

The development of mucosal immunity.

The development of the intestinal immune system is a complex sequence of events that begins in utero under various genetic influences, but continues after birth, being modified by factors such as bacteria, hormones and feeds. This review discusses what is known about the ontogeny of each aspect of the mucosal immune system so as to provide a better understanding of how aberrations in the system might lead to systemic disease.

Animals↗
PubMed1995

Androgen-sensitive period of humoral immune reactivity development in male mice.

The influence of androgens on the humoral immune reactivity development was investigated in male CBA mice. Positive correlation was found to exist between the plasma androgen level and the primary immune response throughout the pubertal period. The androgen-sensitive period of the humoral immune reactivity development coincided with the early stages of sexual maturation (from the 18th to the 30th day of life). In mice orchidectomized on the 18th day of life (18 ORx) the immune response followed the pattern of that in intact males up to 3 months of age but did not reach its peak at 4 months of age. On the contrary, in mice orchidectomized on the 30th day of life (30 ORx) the immune response was maximal at 2 months of age and remained high thereafter. Ten-day treatment of 18 ORx mice with daily injections of testosterone propionate at a dose of 0.1 or 1 mg/kg b.w. was ineffective in making their immune reactivity pattern similar to that in 30 ORx mice, while daily injections of 5 alpha-dihydrotestosterone (DHT, 1 mg/kg b.w.) was effective. The results suggest that the stimulating influence of testes on the humoral immune reactivity development in maturing mice is effected via DHT.

Androgens↗
PubMed2002

The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease.

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system and there is accumulating evidence indicating that an intimate interaction between gut microbiota and host defence mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate antiinflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.

Food Hypersensitivity↗
PubMed2003

Immunotoxicological consequences of perinatal chemical exposures: a plea for inclusion of immune parameters in reproduction studies.

The developing immune system may be especially vulnerable to the toxic effects of immunotoxicants. TCDD, a notorious immunotoxicant, has been shown to produce such effects in rodents as well as in man, and may be considered a prototype developmental immunotoxicant. A number of other chemicals have been identified that have been shown to affect the developing immune system. Yet, so far there are no immune parameters included in current OECD guidelines for developmental or reproductive toxicity testing. It is recommended that such tests are amended so that also the developing immune system is considered as a potential target of toxicity during developmental stages.

Animals↗
PubMed1980

The immune system development and function.

The immune system in its four components T cells, B cells, complement and phagocytes is vital for the defense of the organism against foreign substances or antigens. Elimination of an antigen involves the interaction of the four complements of the immune system with antigen and with each other. The final common pathway is the breakdown of the antigen by the intracellular machinery of the phagocytic cell. The maintenance of the self depends on the integrity of the immune system. Whenever this integrity is breached (by aging, congenital immune deficiency, cytotoxic drugs, irradiation, infiltrative disease...) the organism becomes prone to uncontrolled invasion by antigens (viruses, bacteria, fungi, neoplasms) and its survival is threatened.

Complement System Proteins↗
PubMed1993

The role of T lymphocytes in pulmonary microbial defense mechanisms.

Understanding how lung immunity develops against pulmonary pathogens should lead to more rational approaches in vaccine design and to the use of recombinant cytokines in lung disease. T lymphocytes are central to the development of effective immune responses; therefore, understanding how lung immunity develops will require a study of how and where T cells respond to respiratory antigens. Our laboratory has helped define the phenotype and function of lung dendritic cells, which likely play an essential role in stimulating naive T cells to respond to antigens. We found that both interstitial and alveolar macrophages can regulate the function of these cells, the former to enhance activity, the latter to suppress. In addition, we developed a murine pulmonary infection model using the fungus, Cryptococcus neoformans, in which T-cell-mediated immunity is essential for effective host clearance of the organism. The role of T cells in this model is to recruit and activate effector cells to resolve the lung infection; both CD4 and CD8 T-cell subsets are required for optimal effector cell recruitment. These studies are summarized as examples of current approaches to understanding pulmonary immunity.

Animals↗