Effect of extremely high frequency electromagnetic radiation of low intensity on parameters of humoral immunity in healthy mice

The modification of indices of the humoral immune response to thymus-dependent antigen (sheep erythrocytes) after a whole-body exposure of healthy mice to low-intensity extremely-high-frequency electromagnetic radiation was studied. Male NMRI mice were exposed in the far-field zone of horn antenna at a frequency of 42.0 GHz and energy flux density of 0.15 mW/cm2 under different regimes: once for 20 min, for 20 min daily during 5 and 20 successive days before immunization, and for 20 min daily during 5 successive days after immunization throughout the development of the humoral immune response. The intensity of the humoral immune response was estimated on day 5 after immunization by the number of antibody-forming cells of the spleen and antibody titers. Changes in cellularity of the spleen, thymus and red bone marrow were also assessed. The indices of humoral immunity and cellularity of lymphoid organs changed insignificantly after acute exposure and series of 5 exposures before and after immunization of the animals. However, after repeated exposures for 20 days before immunization, a statistically significant reduction of thymic cellularity by 17.5% (p < 0.05) and a decrease in cellularity of the spleen by 14.5% (p < 0.05) were revealed. The results show that low-intensity extremely-high-frequency electromagnetic radiation with the frequency and energy flux density used does not influence the humoral immune response intensity in healthy mice but influences immunogenesis under multiple repeated exposures.     

Persistent infection of rabbits with bovine immunodeficiency-like virus.

Chronic infection of rabbits was induced by a single intraperitoneal injection of bovine immunodeficiency-like virus (BIV)-infected cells. Ten BIV-infected animals were monitored serologically for up to 2 years. Results of serologic and virus rescue assays indicated that all animals became infected and demonstrated a rapid and sustained BIV-specific humoral response. BIV was rescued by cocultivation from spleen, lymph nodes, and peripheral blood leukocytes of infected animals. Viral DNA in immune tissues was confirmed by polymerase chain reaction amplification of BIV sequences. These data and specific immunohistochemical staining of mononuclear cells of the spleen for BIV antigen suggest that the infection is targeted to immune system cells.     

Effect of radiation-induced bystander chemosignals of mice on the humoral immune response in spleen and lymph nodes of intact recipients

The ability of post-radiation (4 Gy) bystander chemosignals (the volatile components of mouse urine) to distantly modulate the humoral immune response to the sheep red blood cells in the spleen and popliteal lymph nodes of intact recipients has been investigated. It was shown that the exposure of animals to chemosignals before antigen injection resulted in the decrease and increase of the immune response in the spleen and lymph nodes, respectively. When animals were exposed to chemosignals after the antigenic stimulus, an increased immune response was observed in both spleen and lymph nodes. The contribution of radiation-induced bystander signaling in the response of socially organized animals to the effect of ionizing irradiation is discussed.     

The adjuvant activity of synthetic N-acetylmuramyl-dipeptide: evidence of initial target cells for the adjuvant activity.

MurNAc-l-Ala-d-isoGln (N-acetylmuramyl-l-alanyl-d-isoglutamine, MDP), a synthetic compound, acts as an adjuvant on the humoral immune response and on the T cell-mediated immune response. In this report, we attempted to directly demonstrate the initial target cells of MDP for its adjuvant activity in vitro by using cell separation procedures.It was demonstrated that MDP enhanced the immune response following direct interaction with antigen-stimulated T and B lymphocytes, but nonstimulated lymphocytes, shortly after triggering by antigen, and that there was no macrophage requirement for MDP to elicite the adjuvant action in the primary anti-SRBC PFC response in vitro. It has also been demonstrated that the adjuvant activity of MDP is due to an enhancing effect which is different from the possible mitogenic activity to spleen cells and MDP replaces neither a function of macrophages, which is substituted by 2-mercaptoethanol nor a helper function of T cells.     

Effect of prolactin on the level of corticosterone in the blood and synthesis of lymphocyte-activating factors by macrophages under conditions of glucocorticoid loading

The present study examines in vivo the interaction between glucocorticoids and prolactin, and immunomodulating activity of prolactin, including prolactin-induced changes in production of lymphocyte-activating factors and alteration in humoral immune response. It was shown that prolactin application increased the level of corticosterone in the rat blood. Administration of prolactin prior to hydrocortisone administration induced alteration in the level of corticosterone that depended on the dose of hydrocortisone. Application of hydrocortisone reduced humoral immune response and lymphocyte-activating factors production by peritoneal macrophages. Administration of prolactin prior to hydrocortisone administration prevents inhibitory action of glucocorticoids/on humoral immune response and lymphocyte-activating factors production by macrophages.     

Hematological, immunological and neurochemical effects of chronic amphetamine treatment in male rats

In the present study, we have analyzed the effect of chronic amphetamine sulfate (AMPH) treatment on haematological, immunological and neurochemical parameters in the male rat. AMPH increased the total peripheral leukocyte count, and altered its differential counts, decreasing lymphocytes and increasing neutrophils. Flow cytometry study showed that the decline in circulating lymphocytes was caused by the loss of a particular lymphocyte subset, B-cell, which reduced both in percentage and in absolute number by 50%. T-cell population increased by 15% but not in absolute number, however there was no difference in either CD4+ or CD8+ T lymphocyte subsets between experimental groups. Neurochemically, AMPH reduced norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus and increased dopamine (DA) content in the striatum. Chronic AMPH increased in a dose-dependent manner serum corticosterone levels, had no effect on circulating catecholamines, reduced adrenal weights, and did not affect spleen weights although reduced their cellularities. These results show that chronic AMPH have important effects on immune function, particularly on humoral immune response because it reduced the circulating B cell population by half. In addition, AMPH plays an important role in the redistribution and trafficking of leukocytes, and both effects seem to be mediated by sympathetic innervation of the lymphoid organs.     

Increased in vitro airway responsiveness in sheep following repeated exposure to antigen in vivo

We have studied the effect of repeated in vivo antigen exposure on in vitro airway responsiveness in sensitized sheep. Fourteen sheep underwent five biweekly exposures to aerosolized Ascaris suum antigen or saline. Following this exposure regimen, the animals were killed and tracheal smooth muscle and lung parenchymal strips were prepared for in vitro studies of isometric contraction in response to histamine, methacholine, prostaglandin F2 alpha, and a thromboxane A2 analogue. No alteration in tracheal smooth muscle responsiveness was observed between saline- and antigen-exposed tissue. In contrast, by use of lung parenchymal strips as an index of peripheral airway responsiveness, significant increases in responsiveness to histamine and a thromboxane A2 analogue (10(-6) and 10(-5) M) were observed in antigen-exposed tissue compared with saline controls. These results demonstrate that repeated antigen exposure in vivo selectively increase the responsiveness of peripheral lung smooth muscle to certain chemical mediators of anaphylaxis.     

野外条件下球虫感染对根田鼠免疫功能的影响

动物的免疫功能是影响动物适合度的重要因素之一。本文以根田鼠（Microtus oeconomus）为研究对象,在野外围栏条件下,通过球虫感染和混合驱虫药处理,测定根田鼠的植物血凝素反应（Phytohemagglutinin,PHA）、血清抗匙孔血蓝蛋白（Keyhole limpet haemoeyanin,KLH）的IgG 水平和血象参数,探讨寄生物感染对免疫功能的影响。结果表明,根田鼠随球虫感染率和感染强度的增加,对PHA的反应峰值降低、血清抗KLH的IgG水平、白细胞总数、淋巴细胞的百分比及血浆蛋白含量明显下降、嗜碱性粒细胞的百分比增加,嗜酸性粒细胞、嗜中性粒细胞和单核细胞的百分比未检出显著变化。由此说明,球虫感染降低了根田鼠的细胞免疫和体液免疫功能。     

The inseminating bull and plasma pregnancy-associated glycoprotein (PAG) levels were related to peripheral leukocyte counts during the late pregnancy/early postpartum period in high-producing dairy cows

It has been established that the immunologic and endocrine status of the peripartum dairy cow determines the animal's subsequent productive and reproductive performance. Thus, at parturition reduced immune functions of peripheral blood polymorphonuclear cells (PMN) has been observed after a peak in pregnancy-associated glycoproteins (PAGs), and, more recently, the inseminating bull was linked to plasma levels of bovine PAGs in pregnant Holstein-Friesian dairy cows. The present study sought to determine whether changes in leukocyte counts during the peripartum period, indicative of the animal's immune status, could be related to the inseminating bull and to PAG levels. Ninety-six clinically healthy, single pregnant cows in a commercial dairy herd were selected. Four samples were collected before parturition (on gestation Days 220-226, 234-240, 248-254, and 262-268) and two samples after parturition (on Days 14-21, and 28-34 postpartum) to analyze total and differential blood cell counts. Based on GLM analysis procedures of variance for repeated measures, the inseminating bull was found to affect counts of total leukocytes and lymphocytes (P < 0.001; between-subject effects) throughout the peripartum period. In addition, cows with high plasma PAG levels (> 900 ng/ml) on Day 262-268 of gestation had higher numbers of total leukocytes and neutrophils throughout the peripartum (P < 0.001; between-subject effects). Young animals (≤ 1 lactation) had higher total leukocyte and lymphocyte counts than older cows (2 or more lactations) throughout the study period. These results reveal a clear relationship between the inseminating bull or plasma PAG levels and peripheral leukocyte counts during the peripartum period in dairy cows.     

Effect of unilateral nephrectomy in mice on the level of the humoral immune response to T-independent antigen

The influence of unilateral nephrectomy on the degree of humoral immune response to T-independent (polyvinylpyrrolidone, PVP) and T-dependent (sheep red blood cells, SRBC) antigens was studied. The increase in the number in antibody-forming cells (AFC) and nonspecific immunoglobulin-forming cells (nIFC) was investigated by means of the adaptive transfer model. The lethally irradiated recipients were injected with the antigen and also the spleen cells of operated and intact donors. PVP did not induce significant alterations of antibody genesis in mice receiving spleen cells of unilaterally nephrectomized animals comparing with recipients of intact spleen cells. At the same time, the kidney operation induced the increase in the number of AFC and nIFC when the SRBC were used. Hence the activation of humoral immune response induced by kidney operation was related not to the direct activation of B-lymphocytes but to T-cells. The possible causes of this activation were analyzed. Spleen cells of operated animals enhance both specific and antigen-dependent nonspecific immune response.     

Immunomodulatory effects of anaesthetic sevoflurane in septic mouse model

Sepsis is one among the dangerous medical threat that is very much related to body’s immune system having no proper treatment for this condition. About19 million cases of sepsis have been recorded and out of which 5 million cases die every year. Sevoflurane other than controlling the depth of anaesthesia, it does have a vital role in immunomodulations. The study is focused on investigating the immunomodulatory effects of sevoflurane in the septic mouse model induced by CLP. Mortality rate, organ damage, inflammatory mediators, bacterial load, coagulopathy, hepto and renal functional changes, serum lactate, blood glucose, neutrophil sequestration and finally histopathological examination were investigated. The results were interesting that exposure to sevoflurane improves the polymicrobial abdominal sepsis outcome. Mice exposed to sevoflurane after CLP significantly improved outcomes of polymicrobial abdominal sepsis and reduced mortality by improving overall 7-day survival (83.3%) compared to mice without sevoflurane (no treatment group 16.6%) additionally decreasing the surrogate marker levels in the experimental sepsis animal model conducted. Our study suggests that the selection of certain anaesthetic drugs could be critical in the management of septic patients because their immunomodulatory effects could be large enough to affect sepsis pathophysiology.     

Suppression of humoral antibody synthesis on exposure to hyperbaric oxygenation

The influence of hyperbaric oxygenation (HBO) on the immune response in mice, immunized intraperitoneally with sheep red blood cells, was studied. HBO was shown to reduce hemagglutinin and hemolysin titres in peripheral blood as well as to decrease the amount of antibody-forming cells in the spleen. The most pronounced immunodepressant HBO effect is seen when hyperbaric oxygenation is carried out under toxic conditions before immunization of the animals with low antigen doses. Relationship is shown between the immunodepressant HBO effect and reduced leucocyte and lymphocyte counts in peripheral blood of the animals.     

Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen.

The immune response to a thymus-dependent antigen was depressed in vivo and in vitro in spleen cells from mice injected with LPS i.p. a few days before challenge with the antigen. Spleen cells from LPS-injected mice could, however, respond with increase DNA synthesis after activation with polyclonal B and T cell activators in vitro. The LPS-activated spleen cells could actively suppress normal cells in their response to the antigen sheep red blood cells. The suppressor cells contained in the LPS-activated spleens were most likely B lymphocytes, and the possible mechanism for their inhibitory function is discussed.     

Immunosuppressive activity of antibody directed against endogenous C-type virus interferes with early events of the immune response.

We have analyzed the effects of an antiserum prepared against BALB/c endogenous xenotropic C-type virus on the humoral immune response of mice. Both in vivo and in vitro, this serum suppresses the response to sheep red blood cells, an effect that can be absorbed out by purified BALB/c xenotropic C-type virus or Friend leukemia virus, but not by Rous sarcoma virus. The serum produces its maximum effect when administered together with or before the antigen, but not 24 hr later. This suggests that it acts on an early event of the immune response. Evidence is presented to show that the critical viral antigen is expressed before the spleen cells are experimentally stimulated by antigen. The same immunosuppressive effect was observed in a variety of mouse strains, including the high-leukemia incidence AKR strain and virus-free 129/J mice, indicating that it is independent of the expression of endogenous virus. The finding that a viral antigen is involved in the transition from a resting to a dividing lymphocyte is discussed with respect to viral involvement in leukemia.     

Development of antihuman IgG antibodies and hematologic deficits but not clinical abnormalities in C57BL/6 mice after repeated administration of human intravenous immunoglobulin

Intravenous immunoglobulin (IvIg) preparations consist of purified human immunoglobulins collected from large numbers of healthy persons and are used to treat autoimmune, immunodeficiency, and inflammatory disorders. Studying the effects of IvIg effects in experimental animal models might clarify its mechanisms of action in these disorders, but whether 'serum sickness' or other abnormalities occur after repeated IvIg administration to immunocompetent animals is unknown. In the current study, male C57BL/6 mice (8 to 10 wk old; n = 27) received IvIg (1 g/kg IP) weekly for 6 wk. They were observed for clinical abnormalities, and body weight, temperature, renal function, hematologic parameters, and serum antihuman IgG antibodies were measured before and during treatment. Postmortem evaluations were performed on kidney, spleen, liver, and heart. No clinical or histologic abnormalities were noted despite a transient increase in BUN. Mean antibody levels to human IgG on days 21 and 43 after IvIg administration were increased by 23-fold compared with pretreatment levels. 88% and 89% of the mice were antibody responders on those days. Unexpectedly, hemoglobin, hematocrit, and RBC, WBC, lymphocyte, and platelet counts decreased after IvIg administration. These findings suggest that although it does not produce serum sickness, repeated IvIg administration to immunocompetent mice induces a strong humoral immune response and hematologic deficits of unknown etiology. These factors could cause the effects of IvIg preparations in mouse models of human disease to differ from their effects in the human disorders.     

In situ activation of syngeneic tumour-specific cytotoxic T lymphocytes: Intra-pinna immunization followed by restimulation in the peritoneal cavity

Summary Tumour-specific cytotoxic T lymphocytes (CTL) are usually obtained after immunization in vivo and restimulation of immune cells in vitro. We here describe the generation of syngeneic tumour-specific CTL within no more than 9 days by priming and restimulation in vivo. This is achieved only if the correct sites are used both for primary immunization (ear pinna) and for restimulation (peritoneal cavity). The kinetics of immune T cell induction and of the secondary response in vivo will be reported. While a secondary CTL response could be generated in the peritoneal cavity, this was not possible in the spleen, no matter which routes of antigen restimulation were used. Upon transfer of immune spleen cells into the peritoneal cavity but not into the spleen, a secondary response could be generated upon in situ restimulation, indicating the importance of the correct microenvironment for this type of response. The peritoneal effector cells were true T cells and recognized a tumour-associated antigen in association with the K^d major histocompatibility (MHC class I) antigen. Finally the activated tumour-specific peritoneal exudate cells were able to transfer protective immunity without exogenous interleukin-2 into normal syngeneic mice.     

Interrelations of cellular and humoral immune response and different doses of sheep erythrocytes in mice]

In experiments on CBA and C57BL/6 mice the generation of antibody-forming cells respectively either in the popliteal lymph nodes or spleen as well as a rate of delayed type hypersensitivity response (DTHR) on the background of subcutaneous (into foot) or intraperitoneal injection of different doses of sheep erythrocytes (from 10(4) to 10(8)) have been studied. In so doing two types of immune response can be isolated on the dependence upon the sensitivity threshold to antigen of DTHR and humoral immunity. Thus in C57BL/6 mice the antigen threshold for DTHR is of one time (in intraperitoneal immunization) or of a two times (in subcutaneous) lower order than for antibody response. In CBA line mice under subcutaneous immunization there can be seen quite an opposite picture while intraperitoneal immunization causes exact correlation of antigen threshold for cellular and humoral immune response.     

Effect of highly purified thymus factor on the cellular and humoral indices of immunity in thymectomized mice]

Effect of homogeneous polypeptide thymus factor of mol weight about 5000 (thymarin-III) on cellular and humoral immune responses of thymectomized adult CBA mice was studied. Thymectomy proved to greatly decrease the number of T-cells in the spleen. Accordingly, the capability of these mice to produce both IgM and IgG antibody-forming cells in response to the thymus-dependent antigen (sheep red blood cells) was significantly depressed. Subcutaneous injections of thymarin-III (1 microgram per g of body weight) for 7 days completely restored the T-cell spleen population and normalized the animals' immune response.     

Tissue zinc dynamics during the immune reaction in mice

Owing to the importance of zinc for the functioning of the immune system, the role of endogenous Zn, located both in lymphoid and nonlymphoid organs, was investigated during the standard humoral and cellular types of immune response. For this purpose, the dynamics of hepatic, thymic, splenic, and renal Zn content was determined in mice sensitized with (a) sheep red blood cells and (b) semiallogeneic lymphocytes during the local host vs graft reaction (HVGR). The data obtained by ion-coupled plasma spectrometry revealed that the humoral type of immunity is characterized by a significant increase of Zn concentration in the liver and in the thymus. Simultaneously, linear regression analysis showed that the generation of plaque-forming cells in the individual mouse was highly positively correlated with Zn concentration in the liver (r = 0.897), and spleen (r = 0.833), and negatively with Zn concentration in the thymus (r = -0.624). Similar relationships between the intensity of local immune reaction and tissue Zn levels were found in local HVGR at the fifth day in the liver and spleen (r = 0.861 andr = 0.695, respectively), at the seventh day in the thymus (r = -0.797), and at the tenth day in the liver (r = -0.859). The data emphasize the necessity of Zn for the development of normal immune response and point to the existence of a Zndependent hepato-thymic axis during the humoral and cellular types of immune reactivity.