Total Ig Levels Research Articles

B Cells from Autoimmune BXSB Mice are Hyporesponsive to Signals Provided by CD4+ T Cells

Male BXSB mice, unlike female BXSB mice, develop an early-onset, lupus-like disease characterized by high levels of anti-nuclear antibodies (Abs) and total Ig. It has recently been shown that the male BXSB mice contain an expanded population of large B cells which are hyperresponsive to stimulation by anti-CD40 mAb. The present study was undertaken to determine whether their potential for extra CD40 signaling enabled the B cells from male BXSB mice to hyper-respond to CD40L-expressing CD4+ T cells. In contrast to expectations, large B cells from male BXSB mice did not interact with CD4+ T cells in a positive manner; cultures of B cells from antigen (Ag)-primed male BXSB mice, unlike cultures of B cells from Ag-primed female mice, generated few antibody forming cells (AFC) following interaction with activated CD4+T cells. In addition, B cells from male BXSB mice, unlike B cells from female BXSB mice, failed to upregulate MHC class II molecules following interaction with activated CD4+ T cells. Subsequent experiments revealed that the inability of the B cells from the male mice to upregulate MHC class II molecules in response to T cell-mediated activation resided primarily in the population of large B cells. Large B cells from male BXSB mice were also defective in their ability to proliferate following stimulation with activated CD4+ T cells. Taken together, these findings demonstrated that similar to B cells in lupus patients, large B cells from male BXSB mice could function in a hyporesponsive manner, and that this hyporesponsiveness related to the inability of the B cells to interact in a positive manner with CD4+T cells.

CD40 stimulation promotes human secondary immunoglobulin responses in HuPBL-SCID chimeras.

Antibodies to CD40 have been demonstrated to promote B-cell growth and differentiation in vitro. In order to determine if CD40 stimulation could promote antigen-specific human immunoglobulin (Ig) production in vivo, we examined the effects of anti-human CD40 MoAb in an in vivo system where human peripheral blood lymphocytes (huPBL) were engrafted into mice with severe combined immune deficiency (SCID). The huPBL-SCID mice were then given various doses of diphtheria-tetanus toxoid (DT) vaccine and were examined for the presence of human DT-specific antibodies by ELISA. Surprisingly, treatment with anti-CD40 significantly lowered background DT responses versus untreated chimeras in unimmunized huPBL-SCID mice. However, after immunization, huPBL-SCID mice treated with anti-CD40 MoAb responded to a significantly greater extent in response to the vaccine compared with control huPBL-SCID mice, although total Ig levels were sometimes lower in anti-CD40-treated mice. The predominant Ig isotype induced after immunization was IgG. Thus, CD40 stimulation promotes human secondary IgG responses in huPBL-SCID mice. These data demonstrate that CD40 stimulation is capable of promoting antigen-specific human B-cell responses in vivo.

Influence of Microbial Stimulation on Hypergammaglobulinemia and Autoantibody Production in Pristane-Induced Lupus

Pristane induces a lupus-like syndrome characterized by autoantibody production and glomerulonephritis in nonautoimmune strains of mice. Although it has been suggested that this syndrome results from nonspecific immune activation, there is little evidence so far that B cells are activated nonspecifically by pristane or that this promotes autoimmunity. In this study, we examined whether polyclonal hypergammaglobulinemia occurs in pristane-induced lupus, and its relationship to the production of anti-DNA, nRNP/Sm, and Su autoantibodies. In conventionally housed mice, there was a marked increase in total IgM and IgG3 2 weeks after ip pristane injection, followed by increased IgG1, IgG2a, and IgG2b levels. IgM levels were higher in pristane-treated specific pathogen-free (SPF) mice than in conventionally housed mice, whereas IgG and IgA levels were reduced. Pristane induced anti-nRNP/Sm and Su autoantibodies in SPF mice, but their onset was delayed and levels were lower than those in conventionally housed mice. There was no consistent relationship between total IgG1, 2a, and 2b hypergammaglobulinemia and production of anti-nRNP/Sm and Su autoantibodies. Moreover, the total Ig levels were similar in the anti-nRNP/Sm-positive and -negative groups. In contrast, production of IgM anti-ssDNA antibodies paralleled IgM hypergammaglobulinemia in some, but not all, mice. These studies indicate that pristane-induced lupus is associated with marked hypergammaglobulinemia, the magnitude of which is influenced by the microbial environment. However, anti-nRNP/Sm and Su autoantibody production is at least partly independent of polyclonal B cell activation. The data strongly suggest that pristane-induced lupus is not exclusively the consequence of nonspecific immune stimulation. They also point to the importance of microbial stimulation in the development of hypergammaglobulinemia in this inducible lupus model.

Neonatal Appendectomy Impairs Mucosal Immunity in Rabbits

We compared the effects of neonatal appendectomy in rabbits on total Ig and antigen (Ag)-specific Ig levels in the serum and gut, and on plasma cell numbers in the small intestine in response to intraperitoneal (ip) and intraduodenal (id) immunizations with ovalbumin (OVA). Animals were sacrificed after 9 weeks. Antibodies (Abs) in the duodenum were collected and quantified by enzyme-linked immunosorbent assay (ELISA) while plasma cells were quantified by double immunofluorescent staining. Appendectomy markedly reduced total intestinal IgA (P< 0.0006), IgM (P< 0.003), and IgG (P< 0.05) relative to controls, whereas total serum Ig levels were not lowered significantly. Moreover, appendectomy nearly ablated OVA-specific IgA (P< 0.007) in the gut and severely depleted OVA-specific IgG in the gut (P< 0.03) and serum (P< 0.007). The sharp decreases in total IgA and anti-OVA IgA were paralleled by decreases in total IgA+plasma cells (P< 0.0005) and OVA-reactive IgA+plasma cells (P< 0.05). These results support a major role of the rabbit appendix in seeding the intestinal lamina propria with plasma cell precursors, especially those producing IgA.

Human antibody response in human peripheral blood leukocyte/severe combined immunodeficient chimeric model is dependent on B and T cell costimulation via CD40/CD40 ligand.

We have used a human/severe combined immunodeficient (SCID) mouse chimeric model (in which human PBLs are engrafted into SCID mice) to investigate in vivo the role of the CD40/CD40 ligand (CD40L) interaction in the generation of humoral immunity by engrafted human cells. It is established in this work that the thymic dependent, multiclonal, humoral immune response of human lymphocytes to mouse erythrocyte protein Ags is inhibited significantly when CD40/CD40L ligation is prevented in vivo. Suppression of the response was observed with administration of neutralizing Abs specific for either CD40 or CD40L, or with the soluble fusion protein human CD40-Fc. Human anti-mouse erythrocyte Abs and the total human Ig levels in the sera of the SCID mice were suppressed for up to 10 wk when the neutralizing agents were administered at the time of human leukocyte engraftment, i.e., coincident with Ag stimulation, and subsequently at 2 and 4 days after Ag stimulation. These results are the first to demonstrate the ability of CD40/CD40L blocking agents to inhibit the human Ag-specific humoral immune response in vivo, and they sustain the notion that these blocking agents may be utilized clinically to eliminate immune responses associated with autoimmunity or allergy. In addition to confirming the importance of the CD40/CD40L interaction of T and B cells in vivo, it is established in this work that the mouse erythrocyte-specific humoral immune response of the lymphocytes in the human PBL/SCID mouse model is a bona fide T cell-dependent response, and that this is a viable model with which to study human lymphocyte activation in vivo. These results also suggest that the costimulatory activation of human B and T cells is not dependent on the microenvironment of the germinal centers.

Fusarium proliferatum culture material alters several production and immune performance parameters in White Leghorn chickens.

White Leghorn Cornell K-strain chicks (3 replicates of 16 per pen) were started at Day 7 on feed amended with Fusarium proliferatum culture material containing fumonisin B1, fumonisin B2, and moniliformin at 61, 10.5, and 42.7 ppm, respectively. Observed effects on performance of treated birds included reduced feed conversion at 2 wk, and reduced body weight of males and females up to 6 wk (P < or = .05). Splenic, thymic, and liver weights, normalized for body weight, were reduced (P < or = .05) with no change in bursa of Fabricius. No significant changes were observed histologically in the spleen, bursa, kidney, heart, liver, cecal tonsils, colon, or tibia. Significant suppression in total Ig and IgG levels occurred. Macrophages from treated chicks exhibited a 34% reduction in phagocytic activity. Natural killer cell activity was not affected. These findings, which showed that Fusarium toxins alter performance and immune end points in chickens, imply that chickens exposed to mycotoxins may be more susceptible to infectious diseases.

Immunity in children with exposure to environmental lead: II. Effects on humoral immunity

Lead has been found to depress the immune system in animal studies at levels far below those responsible for overt toxicity. Literature studies in animal systems most clearly showed an effect of lead on response to a specific immunogenic stimulus. Data are sparse concerning the effects of lead on the immune system in the human population at greatest risk for exposure-children up to six years of age. This portion of the Phase I study reports concentrations of IgG, IgM, IgA, and IgE, as well as antibody titers to the specific antigenic stimuli provided by the vaccines against diphtheria, tetanus, and Rubella. The study population consisted of a group of 193 children, ages 9 months to 6 years, who participate in the WIC (Women, Infants and Children) and Lead Poisoning Prevention Programs in the urban area of Springfield-Greene County Missouri. Blood lead levels ranged from 1 to 50 μg dL(-1). Total Ig levels were determined and the data were analysed. No consistent significant differences were observed among the risk categories in the five age groups examined. A single Ig class in each of three age groups showed apparent significant differences among the various risk categories, but these differences were not correlated with blood lead. An analysis of specific antibody titers to diphtheria, tetanus, and Rubella was performed. Regression analyses of current data in Phase I of this study suggest a detrimental effect of lead on the antibody titres to diphtheria and Rubella.

BALB/c mice infected with Brucella abortus express protracted polyclonal responses of both IgG2a and IgG3 isotypes.

A polyclonal IgG2a response dependent on the secretion of endogenous IFN-gamma has been demonstrated in BALB/c mice injected with killed whole cells of Brucella abortus [1]. Here we report intense and protracted polyclonal responses of IgG2a and also of IgG3 isotypes in BALB/c mice undergoing primary infections with B. abortus attenuated vaccine strain 19 or virulent strain 2308. Ratios of total serum Ig levels between infected mice and age matched controls were greater than 38 for IgG3 and greater than 12 for IgG2a between weeks 4 and 8 post-infection. Polyclonal increases of IgM and IgG1 that were proportionally much lower (ratios < 2 and < or = 3, respectively) also occurred in infected mice during this time. It is hypothesized that both IgG3 and IgG2a polyclonal responses required IFN-gamma, which was induced by B. abortus primarily in a T cell-independent fashion during the first weeks of infection, and from T cells thereafter.

B cells are anergic in transgenic mice that express IgM anti‐DNA antibodies

B lymphocytes in individuals with systemic lupus erythematosus (SLE) secrete pathogenic autoantibodies to DNA which cause clinical nephritis. (NZB X NZW) F1 (BW) female mice also secrete pathogenic anti-DNA autoantibodies, and therefore are considered to be an animal model of SLE. The rearranged immunoglobulin (Ig) genes that encode an anti-DNA antibody from a diseased BW mouse have been cloned, and transgenic (Tg) mice have been created by microinjection of these constructs into fertilized eggs from normal mice. As we reported previously, when the construct contains the C gamma 2a heavy chain constant (CH) region, the mice spontaneously secrete anti-DNA IgG and they develop mild nephritis. This demonstrated that the Ig encoded by the transgene is pathogenic. In contrast, here we report that when the construct contains the same anti-DNA Ig variable (V) regions used previously, along with the C mu region, the autoreactive B cells are rendered tolerant. Most B cells in the Tg mice express the mu transgene product on their surface, and rearrangement of endogenous light chain genes is partially suppressed. Furthermore, most hybridomas made from Tg B cells secrete IgM anti-DNA. Despite this, the Tg mice have reduced levels of total serum Ig and they do not secrete anti-DNA IgM either spontaneously or following immunization with DNA. We conclude that most B cells in the Tg mice have been rendered anergic. Anergy is however reversible in vitro; lipopolysaccharide stimulation of Tg B cells leads to the production of a significant amount of IgM anti-DNA antibody. The studies demonstrate that in this line of Tg mice on a normal mouse genetic background potentially pathogenic B cells that express a high-affinity Ig specific for a natural autoantigen are subject to tolerance by induction of anergy.

Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp- lpr/lpr mice

MRL/Mp- lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4 + “helper” T cells, while the massively enlarged lymph nodes are composed primarily of CD3 + CD4 − CD8 − TCR α β + “double-negative” T cells. In this study we investigated the effect of treatment of MRL/lpr mice with antiCD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Igtreated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 salinetreated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4 + T cells play a central role in the disease process in this autoimmune strain.

Identification of a CD21 receptor-deficient, non-Ig-secreting peripheral B lymphocyte subset in HIV-seropositive drug abusers

We have studied 61 HIV-seropositive heroin addicts (18 asymptomatic, 20 ARC, and 23 AIDS cases), 26 HIV-seronegative heroin addicts, and 45 healthy blood donors, matching the groups each other for age and sex. We have focused on the phenotypic characteristics of B subpopulations in the peripheral blood of HIV-seropositive and -seronegative drug abusers, paying particular attention to the consistence of the “CD20+” B cell subset, which poorly expresses the CD21 membrane receptor for the C3d and Epstein-Barr virus (EBV) (referred to as “CD20 + CD21−” subset). In healthy blood donors, the ratio CD20 + CD21 − CD20 × 100 is extremely low ( x ± SEM = 8.1 ± 0.9) and rarely exceeds the value of 20. On the contrary, in HIV seropositives, the values are much more dispersed, with higher mean values ( x ± SEM = 25.8 ± 1.8 ) ranging from 50 to 60. An intermediate situation characterizes the class of HIV-seronegative heroin addicts, whose values are slightly higher and more dispersed than that of normal controls ( x ± SEM = 11.6 ± 1.3 ). The extent of the amplification of the CD20 + CD21− subset in HIV-seropositive individuals dose not apparently correlate with the progression of the disease and represents an early event in the clinical course of HIV infection. For each subject of the study group, the number of CD20 + CD21− B lymphocytes is not correlated to other early markers of HIV infection, as the T4 lymphocyte number, or total Ig levels in sera. A functional characterization of the CD20 + CD21− B cell subset indicates that, in HIV-seropositive patients, these cells are unable to produce specific and nonspecific immunoglobulins (Ig's), either spontaneously or after pokeweed mitogen stimulation. Furthermore, this cell subset is characterized by poor expression of surface Ig's. The data reported suggest that this cell subset can be regarded as situated at an early level of B cell lineage differentiation.

B cell response to T helper cell subsets. II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity.

Helper activity of several murine CD4+ T cell subsets was examined. Effector Th, derived from naive cells after 4 days of in vitro stimulation with alloantigen, when generated in the presence of IL-4, secreted high levels of IL-4, IL-5, and IL-6, and low levels of IL-2 and IFN-gamma, and induced the secretion of all Ig isotypes particularly IgM, IgG1, IgA, and IgE from resting allogeneic B cells. Effectors generated with IL-6 secreted IL-2, IL-4, IL-5, IL-6, and IFN-gamma, and induced similar levels of total Ig, 25 to 35 micrograms/ml, but with IgM, IgG3, IgG1, and IgG2a isotypes predominating. Helper activity of these Th was significantly greater than that of effectors generated with IL-2 (10-15 micrograms/ml Ig) and of 24-h-activated naive and memory cells (2-4 micrograms/ml), both of which induced mainly IgM. Unlike other isotypes, IgE was induced only by effector Th generated with IL-4. Blocking studies showed that secretion of all isotypes in response to IL-6-primed effectors was dependent on IL-2, IL-5, and IL-6. IL-4 was required for optimal IgM, IgG1, and IgA secretion, but limited secretion of IgG2a, whereas IFN-gamma was required for optimal IgG2a secretion, and limited IgM, IgG1, and IgA. In contrast, secretion of all isotypes in response to IL-4-primed effectors was dependent on IL-5, although IL-4 and IFN-gamma were also essential for IgE and IgG2a, respectively. Addition of exogenous IL-5 to B cell cultures driven by IL-6-primed effectors did not obviate the requirement for IL-2, IL-4, and IL-6, suggesting that interaction of IL-4-primed effectors with B cells was qualitatively different from that of IL-6-primed effectors, driving B cells to a stage requiring only IL-5 for differentiation. Addition of exogenous factors to IL-2-primed effector Th, particularly IL-4 in the presence of anti-IFN-gamma, resulted in levels of Ig, including IgE, comparable to those induced with other effectors. These results show that functionally distinct Th cell subsets can be generated rapidly in vitro, under the influence of distinct cytokines, which vary dramatically in their levels of help for resting B cells. The cytokines involved in responses to distinct Th cells differ depending on the quality of interaction with the B cell, and the extent of help is strongly determined by the quantity and nature of cytokines secreted by the T cells.

Estrogen induced suppression of collagen arthritis V: Physiological level of estrogen in [formula omitted] mice is therapeutic on established arthritis, suppresses anti-type II collagen T-cell dependent immunity and stimulates polyclonal B-cell activity

Immunization of castrated female DBA 1 mice with rat type II collagen (CII) induces severe polyarthritis with an onset 3–5 weeks after immunization and with 80–100% incidence. Estrogen treatment, inducing physiological 17β-estradiol (E2) levels, during a limited period before and after the immunization, or during another period before the expected onset of arthritis, delayed the arthritic onset by approximately 10 days but did not affect the incidence of severity of arthritis. Treatment with physiological doses of E2 after onset of arthritis decreased severity and duration of disease. The T-cell dependent anti-CII autoantibody response was suppressed if the E2 treatment was given immediately before and after CII immunization and was not significantly affected if E2 treatment was given after CII immunization. Neither the total anti-CII Ig levels nor the anti-CII IgG2a levels correlated with development of arthritis. We also titrated the serum levels of estrogen and recorded the vaginal smear response after injections of various doses of E2. This enabled us to work in a physiological range of estrogen levels, spanning the levels found at the end of pregnancy and those found during the normal estrous cycle. These levels were found to suppress antigen-specific T-cell functions but enhance certain B-cell activities since the delayed type hypersensitivity (DTH) reaction against CII was suppressed while the total number of splenic Ig-secreting cells increased. These findings suggest that estrogen in physiological doses is therapeutic for the development of collagen-induced arthritis and that estrogen exerts dualistic effects on the immune system by suppressing T-cell functions and stimulating certain B-cell activities. The suppressive effect on arthritis could not be explained by suppression of anti-CII autoantibody response and must therefore depend on other T-cell-mediated functions.

SPECIFIC ANTIBODY RESPONSE TO THE MYCOBACTERIAL 65 kDa STRESS PROTEIN IN ANKYLOSING SPONDYLITIS AND RHEUMATOID ARTHRITIS

Immune responses to conserved, immunogenic homologues of the mycobacterial 65 kDa stress protein (SP65) have been implicated in inflammatory arthritis. Serum anti-SP65 was measured in AS, RA and healthy controls using an indirect enzyme immunoassay with recombinant SP65. IgA anti-SP65 was elevated in 19 of 59 AS patients, but the elevation in median level was not statistically significant. Anti-SP65 of all isotypes was increased in RA, but achieved significance (P less than 0.01) for IgA only. Adjusting specific antibody results for elevations in total serum Ig levels reduced AS and RA anti-SP65 to near normal levels, suggesting that a major component of the increased anti-SP65 may be secondary to polyclonal activation.

Hemorrhage in mice induces alterations in immunoglobulin-secreting B cells.

Infections remain the major cause of late morbidity and mortality after hemorrhage, trauma, and burns. Abnormalities in immune response appear to play a major role in the increased susceptibility to infection in this setting. In the present study, the effect of hemorrhage on the numbers of splenic B cells and isotype-specific immunoglobulin(Ig)-secreting cells in mice was investigated. No changes in the total number of splenocytes or of splenic B cells were found after hemorrhage. Decreases of greater than 40% in the total number of Ig-producing cells as well as in the numbers of B cells secreting IgM, IgA, and IgG2b were found during the period of 2 to 96 h posthemorrhage. Subsequent increases in the numbers of cells secreting IgA, IgG1, IgG2a, and IgG3 were present 96 to 144 h after hemorrhage. Total serum Ig levels fell by approximately 40% 3 days after hemorrhage, and then returned to normal within 5 days posthemorrhage. These results demonstrate that hemorrhage produces marked alteration in B-cell populations and serum Ig levels.

Characterization of immunologic and neuropathologic abnormalities in wasted mice.

Mice bearing the autosomal recessive gene "wasted" (wst/wst) have been reported to develop low or absent secretory immune responses, abnormal DNA repair mechanisms, and uncoordinated body movements. We have performed a detailed immunologic and neuropathologic investigation of the disease. Con A and LPS mitogenic responses of splenic lymphocytes as well as total serum Ig levels were equivalent in wst/wst and undiseased control littermates (wst/+ and +/+). Amounts of serum IgM, IgG2a, IgG2b, IgG3, and IgA, however, were reduced in wst/wst animals. FACS analyses of Ig+ and isotype-specific B cell populations revealed similar percentages of Ig+, mu +, gamma +, and alpha + cells in wst/wst and control mice. However, the percentage of "very bright" Ig+ cells as well as "very bright" heavy and light chain-specific B cell subpopulations was increased at least 10-fold in wst/wst B cells as compared with littermate controls. In addition, studies of Ig-specific mRNA accumulation in these animals revealed significant decreases in all isotypes except gamma 3 in spleens of wst/wst mice as compared with littermate controls. Neuropathologic studies in wst/wst mice showed prominent vacuolar degeneration of neurons within anterior horns of the spinal cord and the motor nuclei of the brain stem. No abnormalities were noted in Purkinje cells of the cerebellum nor within myelin sheaths. The abnormalities in the nervous system resembled human motor neuron disease rather than ataxia-telangiectasia as had been reported previously. The immunologic studies suggest that splenic B cells from wst/wst mice have a defect in the ability to "switch" from membrane to secreted Ig. In addition, this mutation provides a mechanism to study regulatory interactions between the immune and nervous systems.

T cell development in B cell-deficient mice. V. Stopping anti-mu treatment results in Igh-restricted expansion of the T suppressor cell repertoire concomitant with the development of normal immunoglobulin levels.

B cell-deficient (anti-mu-treated) mice have proven to be a valuable tool with which to examine the influence of Ig idiotypic determinants upon the development of the Ts repertoire. We have previously reported that ABA-specific Ts repertoires matured in normal and Ig-deficient environments differ from one another in their composition, and consequently, their functionally expressed Igh restrictions. The present report characterizes the impact of natural development of mature B cell activity upon the composition of the Ts repertoire. After stopping anti-mu treatment of C.AL-20 mice, ABA-specific Ts repertoires undergo a defined expansion shown by their acquisition of an additional Ts network that displays Igh restrictions characteristic of normal C.AL-20 mice. This Igh-1d-restricted repertoire can be readily shown within 2 wk of major increases in surface Ig spleen cells and total serum Ig levels in these mice. At the same time, the original Ts restriction specificity (Igh-1a-restricted) generated in the Ig-deficient environment of anti-mu. C.AL-20 mice, is not lost for at least 20 wk. The resulting dual Ts repertoire, characterized by expression of parallel, idiotypically restricted Ts networks, is demonstrable for at least 13 wk. These findings favor an important role for Ig determinants in determining the makeup of the T cell repertoire, and ultimately, the composition of immunologic networks as a whole.

Immunoglobulin levels of the winter flounder ( [formula omitted][formula omitted]) and the summer flounder ( [formula omitted][formula omitted]) injected with the microsporidan parasite [formula omitted][formula omitted

The microsporidan parasite G . stephani , has been found in the intestine of the American winter flounder Pseudopleuronectes americanus . A quantitative study of total serum immunoglobulin (Ig) levels has shown that an injection of this parasitic spore causes a decrease in serum IgM levels. The level of suppression seems to be related to the number of spores injected into the host, as well as the frequency of injections administered. As the dosage of spores injected into the winter flounder increased from 3×10 3/ml to 3×10 8/ml, the level of serum IgM's decreased proportionally. When a single IM injection of spores (3×10 6/ml) was administered, the initial decrease in serum IgM was followed by a gradual recovery of total Ig levels by day 60. Repeated injections of G . stephani on days 21 and 42 respectively, causes an even greater decrease in total IgM levels. Indomethacin (a drug that inhibits prostaglandin activity), has been shown to negate the decrease in IgM levels caused by the G . stephani spores. When injected twice weekly, the indomethacin inhibited the decrease in serum IgM caused by the spore homogenate, with IgM levels comparable to those observed in control WF. This supports previous observations, that prostaglandins are implicated in the decrease in IgM levels induced by injection of the parasite. The effects of G . stephani on serum Ig levels does not seem to be species-specific. When the spores were injected into summer flounder ( Paralichthys dentatus ) together with an erythrocyte antigen, horse red blood cells (HRBC), a decrease in total IgM levels occurred, as well as a decrease in hemagglutination titers to HRBC similar to the decrease described in winter flounder. spores were injected into summer flounder ( Paralichthys dentatus ) together with an erythrocyte antigen, horse red blood cells (HRBC), a decrease in total IgM levels occurred, as well as a decrease in hemagglutination titers to HRBC similar to the decrease described in winter flounder.

The immune response of a marine teleost, Pseudopleuronectes americanus, (winter flounder) to the protozoan parasite Glugea stephani

G. stephani is an intracellular cyst-forming microsporidan parasite that is found in the intestine of winter flounder (WF) Pseudopleuronectes americanus. No detectable humoral response was seen in parasitized fish or in fish injected with either spores or spore homogenate from this parasite. Quantification of total immunoglobulin (Ig) levels showed a decrease in Ig levels rather than enhancement, 21 days after intramuscular (IM) injections of spores (3×10 6/ml). When a second injection of spores was administered on day 21 and tested 3 weeks later, a further decrease in total serum Ig's occurred. A decrease in total IgM levels also occurred in WF that were simultaneously injected with G. stephani and the antigens, horse red blood cells (HRBC) or formalin-killed Klebsiella pneumonia (KP). The total Ig levels of fish injected with an antigen plus spores was not as low as those injected with the parasite alone. The Ig levels, as well as antibody titers to HRBC and KP were however, lower when compared to fish injected only with the HRBC or bacteria. Disrupted spore homogenate injected into winter flounder, showed a less marked decrease in Ig levels when compared with whole spores. When a single IM injection of spores was given, followed by two weekly injections of indomethacin (a drug that inhibits prostaglandin activity), no decrease in Ig levels occurred and levels were comparable to control (saline injected) fish.

The influence of age and breed on the concentrations of serum IgG, IgA and IgM in sows throughout the reproductive cycle

The influence of age and breed on the concentrations of IgG, IgA and IgM in the sera of sows throughout the reproductive cycle was investigated in 4137 sows which had had 0 – 20 gestations and representing three breeds: Swedish Landrace, German Landrace and L-12 (=Swedish Landrace × Large White). Data revealed an increase in total immunoglobulins (Ig), IgM and IgG serum levels with increasing gestation number; the latter contributed > 80% to total Ig levels. IgG was significantly increased up to the fourth gestation, whereas IgM showed a significant increase only to the third gestation. IgA showed only minor differences. Age-dependent increases in serum IgM were ascribed to the incraased probability of antigenic exposure during suckling, while failure to observe this change in serum IgA was ascribed to its role as a local Ig. Breed differences were observed to be significant for all three Ig's. It is concluded that establishment of group norms for serum Ig's should consider age and breed difference as well as stage of gestation or lactation.