66 research outputs found
Expression of Class II Major Histocompatibility Complex Antigens on Adult T Cells in Xenopus is Metamorphosis- Dependent
Class II major histocompatibility complex (MHC) antigens are expressed predominantly on B
lymphocytes and macrophages of tadpoles of the South African clawed frog, Xenopus laevis,
as is the pattern in lymphocyte populations of most mammals. However, unlike most
mammals, young postmetamorphic frogs show expression of class II MHC antigens on a
high proportion of thymocytes and most peripheral T and B lymphocytes. Using the J-strain
of Xenopus and the anticlass II monoclonal antibody, 14A2, we have studied, by indirect
immunofluorescence, whether inhibition of metamorphosis would alter the pattern of
expression of class II antigens during ontogeny. In control animals, class II antigens were
virtually absent from thymic lymphocytes and peripheral T cells of normal untreated larvae,
but could be found in increasing numbers in both populations after metamorphosis (10-12
weeks of age). In contrast, larvae, whose metamorphosis was inhibited by treatment with
sodium perchlorate, had relatively few class II+ thymic lymphocytes throughout the 6-month
period of study, and the proportion of class II+ splenic lymphocytes was approximately
equal to that of IgM+ B lymphocytes. Thus, perchlorate-treated animals retained the larval
pattern of class II epression, suggesting that emergence of class II+ T cells is dependent on
metamorphosis
Involvement of Glucocorticoids in the Reorganization of the Amphibian Immune System at Metamorphosis
In recent years, integrative animal biologists and behavioral scientists have begun to understand
the complex interactions between the immune system and the neuroendocrine system.
Amphibian metamorphosis offers a unique opportunity to study dramatic hormone-driven
changes in the immune system in a compressed time frame. In the South African clawed frog,
Xenopus laevis, the larval pattern of immunity is distinct from that of the adult, and metamorphosis
marks the transition from one pattern to the other. Climax of metamorphosis is
characterized by significant elevations in thyroid hormones, glucocorticoid hormones, and the
pituitary hormones, prolactin and growth hormone. Previously, we and others have shown that
elevated levels of unbound glucocorticoid hormones found at climax of metamorphosis are associated
with a natural decline in lymphocyte numbers, lymphocyte viability, and mitogen-induced
proliferation. Here we present evidence that the mechanism for loss of lymphocytes at
metamorphosis is glucocorticoid-induced apoptosis. Inhibition of lymphocyte function and
loss of lymphocytes in the thymus and spleen are reversible by in vitro or in vivo treatment
with the glucocorticoid receptor antagonist, RU486, whereas the mineralocorticoid receptor
antagonist, RU26752, is poorly effective. These observations support the hypothesis that loss
of larval lymphocytes and changes in lymphocyte function are due to elevated concentrations
of glucocorticoids that remove unnecessary lymphocytes to allow for development of immunological
tolerance to the new adult-specific antigens that appear as a result of metamorphosis
Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis
Metamorphosis in amphibians presents a unique problem for the developing immune
system. Because tadpoles are free-living, they need an immune system to protect against
potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific
molecules to which the tadpole immune system must become tolerant. We
hypothesized that Xenopus laevis tadpoles may avoid potentially destructive antiself
responses by largely discarding the larval immune system at metamorphosis and
acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we
examined the influx and expansion of host T-cell precursors in the donor thymus of
normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor
thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of
metamorphosis does not prevent this exchange of cells. The implanted thymuses export
T cells to the spleen. This donor-derived pool of cells declines after metamorphosis in
normally developing frogs but is retained to a greater extent if metamorphosis is
inhibited. These studies confirm previous observations of a metamorphosis-associated
wave of expansion of T cells and demonstrate that it is not dependent on the relatively
high concentrations of thyroid hormones required for metamorphosis. Although some
larval T cells persist through metamorphosis, others may be destroyed or the larval
population is significantly diluted by the expanding adult population
Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus
The major histocompatibility complex (MHC) is a cluster of genes encoding products central
to all major functions of the vertebrate immune system. Evidence for an MHC can be found
in all vertebrate groups that have been examined except the jawless fishes. Expression of
MHC class I and class II antigens early in ontogeny is critically important for development
of T lymphocytes capable of discriminating self from nonself. Because of this essential role
in T-cell development, the ontogeny of MHC expression in the South African clawed frog,
Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis.
We therefore examined the possible role of thyroid hormones (TH) in the induction
of class I. By flow cytometry, a small amount of class I expression was detectable on
splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the
amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis
is associated with increased intensity of class I expression. Neither inhibition nor acceleration
of metamorphosis altered the timing of onset of class I expression. However, inhibition
of metamorphosis prevented the increase in class I expression characteristic of adult
cell populations. Because expression was not accelerated in TH-treated frogs or delayed in
metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that
induce expression, although they seem to be required for the upregulation of class I expression
occurring at metamorphosis. Differences in the pattern of expression in different subpopulations
of cells suggest a complex pattern of regulation of expression of class I antigens
during ontogeny
Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus
The major histocompatibility complex (MHC) is a cluster of genes encoding products central
to all major functions of the vertebrate immune system. Evidence for an MHC can be found
in all vertebrate groups that have been examined except the jawless fishes. Expression of
MHC class I and class II antigens early in ontogeny is critically important for development
of T lymphocytes capable of discriminating self from nonself. Because of this essential role
in T-cell development, the ontogeny of MHC expression in the South African clawed frog,
Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis.
We therefore examined the possible role of thyroid hormones (TH) in the induction
of class I. By flow cytometry, a small amount of class I expression was detectable on
splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the
amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis
is associated with increased intensity of class I expression. Neither inhibition nor acceleration
of metamorphosis altered the timing of onset of class I expression. However, inhibition
of metamorphosis prevented the increase in class I expression characteristic of adult
cell populations. Because expression was not accelerated in TH-treated frogs or delayed in
metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that
induce expression, although they seem to be required for the upregulation of class I expression
occurring at metamorphosis. Differences in the pattern of expression in different subpopulations
of cells suggest a complex pattern of regulation of expression of class I antigens
during ontogeny
Amphibian Immune Defenses against Chytridiomycosis: Impacts of Changing Environments
Eco-immunology is the field of study that attempts to understand the functions of the immune system in the context of the host's environment. Amphibians are currently suffering devastating declines and extinctions in nearly all parts of the world due to the emerging infectious disease chytridiomycosis caused by the chytrid fungus, Batrachochytrium dendrobatidis. Because chytridiomycosis is a skin infection and remains confined to the skin, immune defenses of the skin are critical for survival. Skin defenses include secreted antimicrobial peptides and immunoglobulins as well as antifungal metabolites produced by symbiotic skin bacteria. Low temperatures, toxic chemicals, and stress inhibit the immune system and may impair natural defenses against B. dendrobatidis. Tadpoles' mouth parts can be infected by B. dendrobatidis. Damage to the mouth parts can impair growth, and the affected tadpoles maintain the pathogen in the environment even when adults have dispersed. Newly metamorphosing frogs appear to be especially vulnerable to infection and to the lethal effects of this pathogen because the immune system undergoes a dramatic reorganization at metamorphosis, and postmetamorphic defenses are not yet mature. Here we review our current understanding of amphibian immune defenses against B. dendrobatidis and the ability of the pathogen to resist those defenses. We also briefly review what is known about the impacts of temperature, environmental chemicals, and stress on the host-pathogen interactions and suggest future directions for researc
Life history linked to immune investment in developing amphibians
The broad diversity of amphibian developmental strategies has been shaped, in part, by pathogen pressure, yet trade-offs between the rate of larval development and immune investment remain poorly understood. The expression of antimicrobial peptides (AMPs) in skin secretions is a crucial defense against emerging amphibian pathogens and can also indirectly affect host defense by influencing the composition of skin microbiota. We examined the constitutive or induced expression of AMPs in 17 species at multiple life-history stages. We found that AMP defenses in tadpoles of species with short larval periods (fast pace of life) were reduced in comparison with species that overwinter as tadpoles and grow to a large size. A complete set of defensive peptides emerged soon after metamorphosis. These findings support the hypothesis that species with a slow pace of life invest energy in AMP production to resist potential pathogens encountered during the long larval period, whereas species with a fast pace of life trade this investment in defense for more rapid growth and development
Conservation risk of Batrachochytrium salamandrivorans to endemic lungless salamanders
The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal ), is a significant conservation threat to salamander biodiversity in Europe, although its potential to affect North American species is poorly understood. We tested the susceptibility of two genera (Eurycea and Pseudotriton ) and three populations of lungless salamanders (Plethodontidae ) to Bsal . All species became infected with Bsal and two (Pseudotriton ruber and Eurycea wilderae ) developed chytridiomycosis. We also documented that susceptibility of E. wilderae differed among populations. Regardless of susceptibility, all species reduced feeding when exposed to Bsal at the highest zoospore dose, and P. ruber and one population of E. wilderae used cover objects less. Our results indicate that Bsal invasion in eastern North America could have significant negative impacts on endemic lungless salamander populations. Future conservation efforts should include surveillance for Bsal in the wild and in captivity, and championing legislation that requires and subsidizes pathogenâfree trade of amphibians
Conservation risk of Batrachochytrium salamandrivorans to endemic lungless salamanders
The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal), is a significant conservation threat to salamander biodiversity in Europe, although its potential to affect North American species is poorly understood. We tested the susceptibility of two genera (Eurycea and Pseudotriton) and three populations of lungless salamanders (Plethodontidae) to Bsal. All species became infected with Bsal and two (Pseudotriton ruber and Eurycea wilderae) developed chytridiomycosis. We also documented that susceptibility of E. wilderae differed among populations. Regardless of susceptibility, all species reduced feeding when exposed to Bsal at the highest zoospore dose, and P. ruber and one population of E. wilderae used cover objects less. Our results indicate that Bsal invasion in eastern North America could have significant negative impacts on endemic lungless salamander populations. Future conservation efforts should include surveillance for Bsal in the wild and in captivity, and championing legislation that requires and subsidizes pathogen-free trade of amphibians
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Larval exposure to predator cues alters immune function and response to a fungal pathogen in post-metamorphic wood frogs
For the past several decades, amphibian populations have been decreasing
around the globe at an unprecedented rate. Batrachochytrium dendrobatidis (Bd), the fungal
pathogen that causes chytridiomycosis in amphibians, is contributing to amphibian declines.
Natural and anthropogenic environmental factors are hypothesized to contribute to these
declines by reducing the immunocompetence of amphibian hosts, making them more
susceptible to infection. Antimicrobial peptides (AMPs) produced in the granular glands of a
frogâs skin are thought to be a key defense against Bd infection. These peptides may be a
critical immune defense during metamorphosis because many acquired immune functions are
suppressed during this time. To test if stressors alter AMP production and survival of frogs
exposed to Bd, we exposed wood frog (Lithobates sylvaticus) tadpoles to the presence or
absence of dragonfly predator cues crossed with a single exposure to three nominal
concentrations of the insecticide malathion (0, 10, or 100 parts per billion [ppb]). We then
exposed a subset of post-metamorphic frogs to the presence or absence of Bd zoospores and
measured frog survival. Although predator cues and malathion had no effect on survival or
size at metamorphosis, predator cues increased the time to metamorphosis by 1.5 days and
caused a trend of a 20% decrease in hydrophobic skin peptides. Despite this decrease in
peptides determined shortly after metamorphosis, previous exposure to predator cues
increased survival in both Bd-exposed and unexposed frogs several weeks after metamorphosis.
These results suggest that exposing tadpoles to predator cues confers fitness benefits later
in life.Keywords: immunosuppression,
AchE inhibitor,
chytridiomycosis,
disease ecology,
brevinin,
emerging infectious disease,
Batrachochytrium dendrobatidis,
temporin,
Lithobates sylvaticus,
indirect effect
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