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While exposure to radiation can be lifesaving in certain settings, it can also potentially result in long-lasting adverse effects, particularly to hematopoietic and immune cells. This study investigated hematopoietic recovery and immune function in rhesus macaques Cross-sectionally (at a single time point) 2 to 5 years after exposure to a single large dose (6.5 to 8.4 Gray) of total body radiation (TBI) derived from linear accelerator-derived photons (2 MeV, 80 cGy/minute) or Cobalt 60-derived gamma irradiation (60 cGy/min). Hematopoietic recovery was assessed through measurement of complete blood counts, lymphocyte subpopulation analysis, and thymus function assessment. Capacity to mount specific antibody responses against rabies, Streptococcus pneumoniae, and tetanus antigens was determined 2 years after TBI. Irradiated macaques showed increased white blood cells, decreased platelets, and decreased frequencies of peripheral blood T cells. Effects of prior radiation on production and export of new T cells by the thymus was dependent on age at the time of analysis, with evidence of interaction with radiation dose for CD8+ T cells. Irradiated and control animals mounted similar mean antibody responses to proteins from tetanus and rabies and to 10 of 11 serotype-specific pneumococcal polysaccharides. However, irradiated animals uniformly failed to make antibodies against polysaccharides from serotype 5 pneumococci, in contrast to the robust responses of non-irradiated controls. Trends toward decreased serum levels of anti-tetanus IgM and slower peak antibody responses to rabies were also observed. Taken together, these data show that dose-related changes in peripheral blood cells and immune responses to both novel and recall antigens can be detected 2 to 5 years after exposure to whole body radiation. Longer term follow-up data on this cohort and independent validation will be helpful to determine whether these changes persist or whether additional changes become evident with increasing time since radiation, particularly as animals begin to develop aging-related changes in immune function., Competing Interests: The authors have declared that no competing interests exist.

Ultraviolet radiation (UVr) promotes several well-known molecular changes, which may ultimately impact on health. Some of these effects are detrimental, like inflammation, carcinogenesis and immunosuppression. On the other hand, UVr also promotes vitamin D synthesis and other beneficial effects. We recently demonstrated that exposure to very low doses of UVr on four consecutive days [repetitive low UVd (rlUVd)] does not promote an inflammatory state, nor the recruitment of neutrophils or lymphocytes, as the exposure to a single high UV dose (shUVd) does. Moreover, rlUVd reinforce the epithelium by increasing antimicrobial peptides transcription and epidermal thickness. The aim of this study was to evaluate the adaptive immune response after shUVd and rlUVd, determining T-cell and B-cell responses. Finally, we challenged animals exposed to both irradiation procedures with Staphylococcus aureus to study the overall effects of both innate and adaptive immunity during a cutaneous infection. We observed, as expected, a marked suppression of T-cell and B-cell responses after exposure to an shUVd but a novel and significant increase in both specific responses after exposure to rlUVd. However, the control of the cutaneous S. aureus infection was defective in this last group, suggesting that responses against pathogens cannot be ruled out from isolated stimuli., (© 2018 John Wiley & Sons Ltd.)

Background: Ultraviolet (UV) illumination/pathogen reduction effectively inactivates white blood cells (WBCs) in whole blood. Given that cotransfused WBCs may impact recipient immune responses, we hypothesized that pathogen reduction of whole blood may alter responses to RBC antigens., Study Design and Methods: Transgenic mice expressing a model (HOD) antigen, authentic human (hGPA or KEL) antigens, or natural fluorescence (uGFP) on their RBCs were utilized as blood donors. Recipients were transfused with fresh whole blood to which riboflavin had been added or fresh whole blood treated by UV illumination/pathogen reduction treatment after the addition of riboflavin. Posttransfusion RBC recovery, survival, and alloimmunization were measured by flow cytometry., Results: UV illumination/pathogen reduction treatment did not alter RBC antigen expression, and recipients of treated syngeneic RBCs had persistently negative direct antiglobulin tests. Greater than 75% of treated and untreated syngeneic RBCs were recovered 24 hours posttransfusion in all experiments, although alterations in the long-term posttransfusion survival of treated RBCs were observed. Treated and untreated KEL RBCs induced similar recipient alloimmune responses, with all recipients making anti-KEL glycoprotein immunoglobulins (p > 0.05). Alloimmune responses to treated HOD or hGPA RBCs were no different from untreated RBCs (p > 0.05)., Conclusion: Pathogen inactivation treatment of fresh whole murine blood with riboflavin and UV illumination does not impact the rate or magnitude of RBC alloimmunization to three distinct RBC antigens. Further, UV illumination/pathogen reduction appears safe from an immunohematologic standpoint, with no immunogenic neoantigens detected on treated murine RBCs. Future studies with fresh and stored human RBCs are warranted to confirm these findings., (© 2015 AABB.)

Literally, all living forms are either directly or indirectly dependent upon sun for energy. Radiation from sun is differentiated into several components of a spectrum based on the wavelength. Ultraviolet (UV) radiation may be one of the infamous radiations emitted by the sun. Ozone depletion is another critical factor by which UV induced ill-effects are intensified. Though there are numerous studies on effects of UV radiation on terrestrial organisms, its effect on freshwater and aquaculture ecosystems has been largely neglected. Here, we report that enhanced UV irradiation may suppress the primary and secondary antibody responses to a soluble protein antigen in fish. Fishes exposed for longer periods (80min) were particularly very sensitive to infection, as shown by our sensitivity index., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Both leukoreduction and ultraviolet (UV) light treatment of blood products have been shown to reduce the incidence of HLA antibody development in recipients, but the impact of these treatments on the magnitude and persistence of the antibody response is less clear., Study Design and Methods: Longitudinal samples from 319 subjects taken from four different study cohorts were evaluated for HLA antibodies to determine the effects of leukoreduction and UV treatment on HLA antibody generation and persistence., Results: Subjects receiving leukoreduced or UV-treated blood products were less likely to generate Class I HLA antibodies, and those receiving leukoreduced blood were also less likely to generate Class II HLA antibodies. Among those receiving nonleukoreduced blood, 55% developed Class I HLA antibodies and 51% developed Class II HLA antibodies compared with 28% (Class I) and 15% (Class II) for those receiving leukoreduced blood and 36% (Class I) and 54% (Class II) for those receiving UV-treated blood. Among alloimmunized subjects, leukoreduction resulted in a significant twofold reduction in the magnitude of Class I HLA antibodies, and UV treatment resulted in a significant threefold reduction in the magnitude of Class II HLA antibodies. Both treatments resulted in shorter persistence of Class I HLA antibodies., Conclusions: These data demonstrate that leukoreduction and UV treatment of blood products results not only in a reduction in the incidence of HLA antibody production, but also in lower and more transient HLA antibody levels among sensitized transfusion recipients., (© 2013 American Association of Blood Banks.)

Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.

Exposure to ultraviolet radiation (UVR) suppresses immunity by complex pathways, initiated by chromophores located in the skin and ending with the generation of specific subsets of T and B regulatory cells. The primary and memory (recall) immune response to a wide variety of antigens, including microorganisms, can be reduced by UVR, leading to the possibility that the efficacy of vaccination could be similarly reduced. A limited number of animal models of vaccination demonstrate that this may indeed be the case. The situation in human subjects has not been rigorously assessed but there are indications from a variety of sources that UVR adversely affects the immune responses to several vaccines. These studies are reviewed and the implications for vaccine administration discussed. As vaccination represents a major public health measure world-wide for the control of an increasing number of common infections, it is important to maximise its efficacy; therefore further evaluation of UVR in the context of vaccination is required and warranted., (This journal is © The Royal Society of Chemistry and Owner Societies 2011)

Background: Busulfan treatment as a chemotherapeutic agent has been considered an alternative approach in xenograft model because it offers a simple, convenient, effective, and less toxic conditioning regimen., Objective and Methods: To investigate busulfan effects on the reconstitution of human immune cells and the generation of immune response to foreign antigens, we generated humanized NOD/SCID/IL-2Rγ(null) (NSG) mice conditioned either busulfan or total body irradiation (TBI) with hCD34(+) CB cells., Results: Busulfan resulted in a high survival rate and effective reconstitution of human immune cells including B, T, macrophage, and dendritic cells in humanized NSG mice, compared to that of TBI. Moreover, the humanized NSG mice conditioned busulfan showed effective B cell development and thereby the high production of human antibody against immunized antigen., Conclusion: Humanized mice conditioned by busulfan provide a powerful and versatile tool for studying the entire process of human B-lymphocyte development and for producing specific human antibodies.

The most prevalent cancer diagnosed in the world is sunlight-induced skin cancer. In addition to being a complete carcinogen, UV radiation, the causative agent of skin cancer, induces immune suppression. Because UV-induced immune suppression is a well-recognized risk factor for skin cancer induction, it is crucial to understand the mechanisms underlying UV-induced immune suppression. Mast cells, which have recently emerged as immune regulatory cells, are particularly important in UV-induced immune suppression. UV exposure does not induce immune suppression in mast cell-deficient mice. We report that UV irradiation blocks germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell function, in part by altering the expression of transcription factors BCL-6 and BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab secretion was observed in UV-irradiated mast cell-deficient (Kit(W-sh/W-sh)) mice. When mast cell-deficient mice were reconstituted with wild type mast cells, immune suppression was restored. Reconstituting the mast cell-deficient mice with bone marrow-derived mast cells from IL-10-deficient mice failed to restore the ability of UV radiation to suppress GC formation. Our findings demonstrate a function for mast cells, suppression of Tfh cell production, GC formation, and Ab production in vivo.

During embryogenesis, the development of tissues, organs and systems, including the immune system, is particularly susceptible to the effects of noxious agents. We examined the effects of prenatal (in utero) exposure to WiFi signals on pregnancy outcome and the immune B-cell compartment, including antibody production. Sixteen mated (plug-positive) female mice were assigned to each of the following groups: cage control, sham-exposed and microwave-exposed (WiFi signals at 2.45 GHz, whole body, SAR 4 W/kg, 2 h/day, 14 consecutive days starting 5 days after mating). No effects due to exposure to WiFi signals during pregnancy on mating success, number of newborns/mother and body weight at birth were found. Newborn mice were left to grow until 5 or 26 weeks of age, when immunological analyses were performed. No differences due to exposure were found in spleen cell number, B-cell frequency or antibody serum levels. When challenged in vitro with LPS, B cells from all groups produced comparable amounts of IgM and IgG, and proliferated at a similar level. All these findings were consistently observed in the female and male offspring at both juvenile (5 weeks) and adult (26 weeks) ages. Stress-associated effects as well as age- and/or sex-related differences were observed for several parameters. In conclusion, our results do not show any effect on pregnancy outcome or any early or late effects on B-cell differentiation and function due to prenatal exposure to WiFi signals.

In the early period after exposure to the radiation in the lethal dose (10 Gy) mice secreted with urine the volatile components, that attract for intact individuals. In the late period appear components with aversive property. In the terminal period after exposure to superlethal dose (70 Gy) dominate the secretions with aversive property. The exposure of intact recipients with the volatile secretions attractive or aversive in equal degree depression result in suppression their ability to the humoral immune response.

Background: This study was designed to investigate the immune effect of intrathymic inoculation and whole body irradiation on the production of monkey anti-pig xenoantibodies in a pig-to-monkey model., Method: Donor (Meishan pig) and recipient (Rhesus monkey) animals were divided randomly into three groups: 1) the control group (group A), 2) the whole body irradiation (WBI) group (group B), and 3) the irradiation and intrathymic inoculation group (group C). The change in the percentage of antibody-positive (IgM and IgG) cells after pretreatment and xenografting were detected by flow cytometry., Results: After WBI, the level of natural IgM antibody decreased significantly (p<0.01), but the level of natural IgG antibody did not change (p>0.05). After xenografting, the levels of elicited xenoreactive IgM and IgG antibodies (EXA) in group C rose slower than in groups A and B (p<0.01)., Conclusions: Irradiation and intrathymic inoculation dampened the production of elicited xenoreactive IgM and IgG antibodies in a pig-to-monkey model.

A total of 260 one-day-old Arbor Acres male broilers were exposed to red light (RL), green light (GL), blue light (BL), and white light (WL), respectively, by using a light-emitting diode system for 7 wk. There were 5 replicate pens for each light treatment and 13 birds per pen. The effects of monochromatic light on the immune response were studied. The results indicated that proliferation of peripheral blood T lymphocytes in the GL group was significantly increased (by 80.8 and 54.8%) compared with those in the RL and BL groups, respectively, at 21 d of age (P < 0.05). At 49 d of age, however, the proliferation response was significantly increased in the BL group compared with the RL group (26.9%, P< 0.05). Moreover, the GL group showed a significant elevation in the serum anti-Newcastle disease virus level as compared with that of the RL group at 28 d of age (32.9%, P < 0.05). In contrast, no significant difference in serum anti-Newcastle disease virus level was observed among the BL, RL, and WL groups at this age (P > 0.05). By 49 d of age, the antibody titer was higher in the BL group than in the RL group (62.8%, P < 0.05). However, no significant difference in antibody titer was seen among the BL, GL, and WL groups at this age. Interestingly, the BL group showed a 44.0% reduction in the level of serum interleukin-1beta as compared with that in the RL group at 49 d of age (P < 0.05). These results suggest that GL and BL enhance the immune response better than RL, and that BL may play a role in alleviating the stress response in broilers.

The influence of volatile urine chemosignals of irradiated (4 Gy) mice on the primary humoral immune response to sheep red blood cells in intact recipients was investigated. It was demonstrated that the direction of immunomodulatory effect is dependent upon the time at which the postradiation chemosignals was initially applied. The antibody response to antigen was markedly suppressed in mice that were exposed before antigen injection. When chemosignals applied immediately following inoculation of antigen the antibody response was unaffected. The immune response was increased when chemosignals was loadeded for 1-10 days after immunization. The possible mechanisms of immunomodulation are considered.

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations.

It is well documented that UV radiation present in sunlight suppresses immune responses, especially T(h)1-driven cellular immune responses, resulting in the exacerbation of skin cancer and infectious diseases. However, the effects of UV irradiation on humoral immune responses remain less clearly defined. In addition, the majority of studies documenting immunosuppressive effects of UV irradiation has been demonstrated in animals exposed to UV radiation before immunization. In the present study, therefore, we examined the effects of UV irradiation on humoral immune responses in mice that had been immunized before UV irradiation. Both T(h)1- and T(h)2-associated Ig responses were significantly suppressed by UV irradiation given 7 days after immunization in an antigen-specific manner. Adoptive transfer experiments revealed that CD4(+) T cells from UV-irradiated mice are responsible for the UV-induced suppression of antibody responses. These CD4(+) regulatory T cells suppressed proliferation of conventional CD4(+) T cells in vivo and in vitro and contained IL-10-producing cells that did not express Foxp3. Mice depleted of CD25(+) cells also exhibited reduced antibody responses by UV irradiation. Finally, we showed that CD4(+) T cells from UV-irradiated mice treated with anti-IL-10 mAb failed to suppress antibody responses upon transfer. These results indicate that UV irradiation after immunization suppresses T(h)1- and T(h)2-mediated humoral immunity via the generation of Tr1-like regulatory T cells, in the process of which IL-10 appears to be important. Possible detrimental effects of UV irradiation after vaccination are also discussed.

Despite the unequivocal role of B lymphocytes as effecter cells in humoral immunity, studies have reported that B cells are tolerogenic. The impact of B cell-mediated tolerance and its underlying mechanisms are incompletely understood. Using primary B cells as APCs and allogeneic CD4 T cells as responder cells in mixed leukocyte reactions, we find that B cells preferentially expand FoxP3(+) over FoxP3(-) CD4 T cells in the absence of exogenous cytokines. The preferential expansion of Foxp3(+) T cells is further enhanced by a partial blockade of class II MHC-TCR interaction but diminished by stimulatory anti-CD28 Ab or at high B to T cell ratios. Gamma irradiation of B cells selectively abrogates their ability to expand isolated CD25(+) but not CD25(-) CD4 T cells; exogenous IL-2 supplement can partially restore this function. B cell-expanded CD25(+) T cells express high levels of FoxP3 and are highly inhibitory in an Ag-specific manner.

Human papillomaviruses (HPV) infect skin or mucosal epithelia causing warts and dysplasia. Infections with certain high-risk HPV types in the anogenital tract can lead to malignant transformation. Cervical cancer is the second most common malignant disease in young women responsible for 275000 deaths annually worldwide. More than 50% of sexually active people acquire HPV infections over their lifetime. Around 80% of infections remain subclinical and are cleared by the immune system. Recently prophylactic vaccines against the two most common high-risk types HPV16 and 18, and additionally low-risk types HPV6 and 11, respectively, have become available. We present an overview concerning recent knowledge on natural and vaccine-induced immunity against HPV infections.

In the human body, every day billions of apoptotic cells are produced. Removal of these cells is necessary, to prevent the release of intracellular toxic constituents, and occurs very effectively via phagocytosis by (semi)-professional phagocytes. This elimination process occurs rapidly and without inflammation. In systemic lupus erythematosus (SLE) a disturbed elimination of apoptotic cells has been implicated in the induction and reactivation of the disease. Accumulation of apoptotic cells may result in autoantibody formation. A delayed, pro-inflammatory clearance is also thought to play a crucial role in the development of inflammatory lesions once the disease has manifested. One of the hallmarks of patients with SLE is the development of cutaneous lesions upon exposure to sunlight. In this review, we will focus on apoptotic cells, their elimination, and the consequences of a disturbed elimination of apoptotic cells on the development of UVB induced inflammatory skin lesions.

(1-->3)-beta-D-Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. However, it is still unknown how they mediate their effects. The aim of this study was to evaluate both intraperitoneal and oral application of seaweed-derived (1-->3)-beta-D-glucan Phycarine. Phycarine showed significant stimulation of phagocytosis by peripheral blood cells. In addition, the efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was potentiated by Phycarine administration. Phycarine also strongly shortened the recovery of leucopenia caused either by chemotherapy or irradiation. Besides the role in stimulation of cellular immunity, we also found a significant increase of antibody formation. Using a suckling rat model for evaluation of the absorption and tissues distribution of enterally administered (125)I-Phycarine, we found that the majority of Phycarine was detected in the stomach and duodenum 5 min after the administration. This amount sharply decreased during first 30 min. A significant amount of Phycarine entered proximal intestine in a shortly after the gavage. Its transit through proximal intestine was decreasing with time and simultaneously increasing in the ileum. Systemic blood levels were very low (less than 0.5%). Taken together, these observations suggest that Phycarine is similarly effective both after i.p. and oral application, has very strong stimulating effects on three types of experimentally induced leucopenia and stimulates both humoral and cellular branch of immune reactions. The majority of Phycarine can be detected throughout the gastrointestinal tract, supporting the feasibility of enteral administration of Phycarine in the treatment of gastrointestinal diseases.

The appearance of lines CBA and C57Bl/6 in the urine of mice irradiation volatile excretions with immunosupression property was associated with the violation at mice of ability to immunogenesis. It was established, that immunosupression activity of excretions irradiated mice CBA and C57Bl/6 did not depend on genotip of mice. However, by irradiated mice C57Bl/6 immunosupression components, depressing antibody formation at intact mice, appeared earlier, than at CBA. Immunosypression, limited postradiation volatile secretion in view of depression humoral immune response at intact mice kept for not a long time and mostly expressed on the course 2-3 days after exposition with postradiation secretion.

A single dose of 6 Gy irradiation significantly reduced the total WBC count while in herbal formulation (AC II) treated groups it was found to be significantly increased. Similarly bone marrow cellularity and alpha-esterase positive cells, which were lowered by radiation, were partly restored in AC II treated groups. The data indicate that AC II can overcome the immunosuppression produced by irradiation.

We examined the effects of in vivo exposure to a GSM-modulated 900 MHz RF field on B-cell peripheral differentiation and antibody production in mice. Our results show that exposure to a whole-body average specific absorption rate (SAR) of 2 W/kg, 2 h/day for 4 consecutive weeks does not affect the frequencies of differentiating transitional 1 (T1) and T2 B cells or those of mature follicular B and marginal zone B cells in the spleen. IgM and IgG serum levels are also not significantly different among exposed, sham-exposed and control mice. B cells from these mice, challenged in vitro with LPS, produce comparable amounts of IgM and IgG. Moreover, exposure of immunized mice to RF fields does not change the antigen-specific antibody serum level. Interestingly, not only the production of antigen-specific IgM but also that of IgG (which requires T-B-cell interaction) is not affected by RF-field exposure. This indicates that the exposure does not alter an ongoing in vivo antigen-specific immune response. In conclusion, our results do not indicate any effects of GSM-modulated RF radiation on the B-cell peripheral compartment and antibody production and thus provide no support for health-threatening effects.

The single exposition of 3- and 4-week mice in a dose 0.1 Gy resulted in depressing primary T-dependent humoral immune response. Unlike juvenile ones at adult 16-week animals the stimulation antibody-formation took place. As a result of the administration of immunomodulating drugs, thymogene and nucleinate of a sodium in irradiation mice of 3-week age was an augmentation of the number of antibody-producing cells relatively in 2 and 4 times. At the same time at irradiated in dose 0.1 Gy of adult mice thymogene abrogated the stimulating effect of radiation. It is suggested that the probable cause of the immunosuppressing effect of a small dose of radiation can be an inactivation of a radiosensitive subpopulation of helper cells or selective stimulation of the functional activity of neonatal suppressor cells.

The reaction of blood lymphocytes on adaptive irradiation in vitro (0.05 Gy) and challenge irradiation (1.0 Gy) 5 h after has been studied among 320 children 3-16 years old by micronuclei test with cytochalasin B cytokinetic block. The adaptive response or the hypersensitivity phenomenon (HS) has been determined by the calculation of the number of binucleated cells with micronuclei (MN) in 1000-2000 binucleated cells. For each individual by the chi2 criteria significant differences between the frequencies of damaged cells by irradiation in challenge dose and by combined action of adaptive and challenge doses have been detected. On the base of the results obtained the connection between AR or HS and the somatic diseases of different type and the disturbancies in systems of humoral and cell immunity has been studied. It was shown that in the row of allergic diseases and tuberculous infection among the significant part of the children (approximately 50%) the HS phenomenon was registered. The connection between the HS phenomenon and inflammatory processes (without allergic components), the logopedic disturbancies wasn't observed. It was shown in the group of HS children the deviation in the cell immunity system is registered. Significant deviations in HS group in the system of the humoral immunity is observed. So by the HS phenomenon significant number of the children have the somatic diseases and the deviation in the systems of cell and humoral immunity.

Background: It has been reported that subgroups of T-lymphocytes are affected at different levels and different cell groups of immune system give different responses in individuals exposed to long-term ionizing radiation. The aim of this study was to investigate the effect of occupational exposure to low levels of ionizing radiation in selected indices of cellular and humoral immunity in radiology workers., Methods: Level of subgroups of peripheral blood lymphocytes, complements (C(3), C(4)), and total immunoglobulins (IgG, IgA, IgM) were analyzed in 50 radiology workers occupationally exposed to low levels of ionizing radiation and 35 age-matched healthy controls., Results: CD4(+) T lymphocyte (T-helper) levels were determined as significantly low in radiology workers exposed to ionizing radiation compared with controls (p <0.05). There were no statistically significant differences in groups in terms of other subgroups of lymphocytes (p >0.05). In addition, levels of serum total IgG, IgA, IgM, C(3,) and C(4) were determined as significantly lower in workers exposed to ionizing radiation compared with controls (p <0.001). Total IgA and IgM levels in radiology workers who were smokers were determined as significantly lower compared with non-smoking radiology workers (p >0.05)., Conclusions: Levels of CD4(+) T lymphocytes and humoral immune response (total immunoglobulins and complements) were determined as weaker in workers exposed to low levels of ionizing radiation compared with controls, indicating the importance of taking appropriate measures to protect radiology workers from exposure to ionizing radiation and for these workers to avoid smoking. Further studies are needed for determining the appropriateness of periodic check-ups of immune functions and the most efficient and cost-effective ways of monitoring immune functions in radiology workers for detecting early changes in the immune system.

Ultrasound irradiation and hyperosmotic treatments were compared as facilitators of antigen (BSA) penetration through the skin by bath vaccination and as enhancers of the antibody response in goldfish. The kinetics of BSA penetration and accumulation into the skin, and via it to the blood, and the consequent specific stimulation of the humoral immune response, were studied. The main findings are: (1). ultrasonic treatment is more effective than hyperosmotic treatment in enhancing both antigen transport through the skin and antibody production; (2). the requirements for high antigen concentrations, which are needed for simple bath immersion, could be reduced five times in presonicated fish; and (3). anesthesia, which significantly reduced gill uptake following hyperosmotic treatment, had no effect on skin uptake. The importance of these finding for mass vaccination of adult fish and larvae is discussed.

Ultraviolet (UV) light is known to induce skin cancers by causing DNA gene mutations and inducing immunosuppression. Taking advantage of these immunosuppressive capacities, UV light has been used, with different modalities, as an immunosuppressive therapy in a variety of diseases including allograft rejection and graft-versus-host disease. Phototherapy includes UVB irradiation, UVA irradiation, oral psoralen (+)UVA irradiation (PUVA), photodynamic therapy, and extracorporeal photopheresis, which consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and incubated with 8-methoxypsoralen. According to numerous experimental models and human data, there is increasing evidence that UVB irradiation and extracorporeal photopheresis can induce regulatory T cells and anticlonotypic activity. These therapies induce apoptosis of activated T cells or of extracorporally treated mononuclear cells, and up-regulate the expression of costimulary molecules and adhesion molecules on antigen presenting cells. UVB- or UVA-induced apoptotic cells could secrete immune suppressive cytokines (interleukin (IL)-4, IL-10). The processing and presentation of apoptotic T cell antigens from clones of pathogenic T cells by activated antigen presenting cells might explain the induction of systemic anticlonotypic activity by photopheresis. This induction of cell-mediated suppressive activity opens up future prospects with the aim of expanding regulatory T cells and/or anticlonotypic activity, especially by photopheresis in organ and cell transplantation.

Changes in day length affect several measures of immunity in seasonally breeding mammals. In Siberian hamsters (Phodopus sungorus), short day lengths suppress specific secondary antibody responses to the keyhole limpet hemocyanin (KLH) antigen and enhance cutaneous delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). These experiments tested whether day length affects secondary antibody and DTH responses by altering immune function solely during the interval after the initial exposure to each antigen, solely during the interval after the second exposure, or during both stages of the respective immune responses. Adult male Siberian hamsters were exposed to either a long (16 h light/day; LD) or a short (8 h light/day; SD) photoperiod for 7.5 wk before receiving an initial exposure to each antigen (KLH injection, cutaneous DNFB treatment; separate groups of animals for each antigen). A subset of LD hamsters was transferred to the SD photo-period, and a subset of SD hamsters was transferred to the LD photoperiod. Other hamsters remained in LD or SD. Eight weeks later, all hamsters were challenged with a second subcutaneous injection of KLH or a second application of DNFB to the ear, and immune responses were measured. Exposure to SD during the primary antibody response did not affect secondary IgG responses, but SD exposure during the secondary response significantly suppressed IgG production independent of day length during the initial KLH treatment. In contrast, exposure to SD during the DNFB challenge enhanced the ensuing DTH response, but this enhancement depended on the photoperiod prevailing during the initial exposure. Exposure to SD during the sensitization stage did not enhance DTH in hamsters subsequently exposed to LD. The data suggest that short photoperiods have enduring effects on immune responsiveness and on the establishment and retention of immunological memory.

The immunological effects of visible and infrared light from laser and non-laser sources have remained insufficiently studied, which has restricted the use of light in the treatment of diseases associated with immune system disorders. The present randomised, placebo-controlled double-blind trial was designed to study changes in the humoral immunity of a large group of volunteers after exposure of a small body area to polychromatic visible and infrared polarized (VIP) and non-polarized (VInP) light (400-3400 nm, 95% polarization, 40 mW cm(-2), 12 J cm(-2) and 400-3400 nm, no polarization, 38 mW cm(-2), 11.2 J cm(-2), respectively). Serum immunoglobulins (Ig) M, A, and G were determined turbidimetrically, and the immune complexes (ICs) by precipitation with 5% polyethylene glycol and subsequent spectrophotometric analysis. A single VIP irradiation induced an average rise in serum IgM levels of 13% (p < 0.05). By the end of the 10 day course, it has exceeded the baseline level by 26%, with an increase in IgA levels of 17 and 12% (p < 0.04) one week after the last session. In subjects with a high IC content, it decreased rapidly to the normal level. A single exposure of volunteers to VInP light rapidly produced changes similar to those observed on VIP irradiation, but with an increase in IgM 2.3 to 3 times lower, independent of the initial levels. On the other hand, VInP light exposure decreased the IC content more than VIP light.

Ramsar, a northern coastal city of Iran, overlooking the Caspian Sea, has some high level natural radiation areas (HLNRAs) as well as over 50 hot springs with low and high radium contents used as spas by the public and vacationers. The average whole body dose received by population in these areas is about 5 times higher than the normal background radiation level. Studies on the long-term effects of high level natural radioactivity on some immunological and cytogenetical parameters, in the Ramsar inhabitants are summarized in this paper. Our results showed a significant increase of CD69 expression on TCD4+ stimulated cells (P < 0.004) and a significant increase of total serum IgE (P < 0.05), and also higher incidence of stable and unstable chromosomal aberrations in the HLNRA group compared to the control group with normal background radiation (P < 0.05).Other humoral immune parameters, did not show significant differences between the two groups.

Laser iridotherapy was carried out simultaneously with irradiation of immuno-competent zones on the integument of the human body in patients with stomach and duodenal ulcers. As a result of such treatment, it was discovered that laser therapy has immunomodulating action leading to the reduction of the ulcer cicatrisation period.

Biological activity of low molecular DNA isolated from salmon milt was studied. When administered subcutaneously to mice with with acute experimental radiation disease in a course dose of 10 mg/kg, it showed a therapeutic effect, stimulated hemopoiesis, increased the survival rate and the average life span of the animals. Moreover, its marked effect on the humoral immunity was observed.

The aim of our investigation was to study the influence of low-intensity laser therapy at the immunologic parameters and Helicobacter pylori (HP) microbial contamination in patients with exacerbation of peptic and duodenal ulcer. 100 patients aged 18-65 were examined and divided into 2 groups. The experimental group (75 patients) underwent a complex drug and laser therapy of various therapeutic techniques. The control group (25 patients) underwent only drug therapy. The results of this study show the immunocorrective effect of different methods of low-intensity laser therapy in the exacerbation period and more essential decrease of HP microbial contamination in the experimental group.

Background: WBCs in blood components are a major factor contributing to immune responses such as GVHD and alloimmunization that follow transfusion. Irradiation of blood components has been used to regulate the contribution of donor WBCs to these immune responses. A systematic comparison of how the exposure of lymphoid cells to gamma-irradiation, UVB light, or psoralen + UVA light (PUVA) effects immune response was conducted to better define the best type of irradiation to be used in different clinical settings., Study Design and Methods: Murine spleen cells were irradiated with varying doses and tested for their in vitro ability to be activated, to proliferate in response to mitogen or allogeneic stimulator cells, or to serve as stimulator cells. Irradiated donor cells were also tested for in vivo generation of GVHD, induction of alloantibody production, induction of restricted cytolytic T lymphocytes, and persistence of irradiated cells., Results: In general, increasing amounts of irradiation resulted in increased inhibition of in vitro and in vivo responses, although the doses required for inhibition differed from assay to assay. In contrast, irradiation of donor cells did not always result in inhibition of recipient alloantibody responses but was dependent on the donor-recipient combination that was studied., Conclusion: Control of the in vivo outcomes of transfusing allogeneic cells is regulated by the type and dose of irradiation used and by the genotype of the donor and/or recipient.

To obtain insight into the mechanism(s) of posttransplantation humoral immunodeficiency, we evaluated factors affecting serum antibody levels against polio, tetanus, Haemophilus influenzae, and Streptococcus pneumoniae in 87 patients. Patients with hematologic malignancies were randomized to receive marrow versus blood stem cells, which contain approximately 10 times more lymphocytes than marrow. Blood stem cell recipients did not have higher antibody levels than marrow recipients. Recipient pretransplantation antibody levels were correlated with the posttransplantation levels, especially in the first 6 months after transplantation when the correlation coefficients typically exceeded 0.6. Donor pretransplantation antibody levels had less of a correlation with posttransplantation levels in the recipient. Patient or donor age, total body irradiation, and graft-versus-host disease or its treatment appeared to have no effect. In conclusion, antibody levels in the first year after transplantation are affected primarily by pretransplantation antibody levels in the recipient and, to a lesser degree, in the donor. These findings suggest that immunization of the recipient and the donor before transplantation may be more effective in improving antibody immunity after transplantation than manipulating graft-versus-host disease, changing conditioning, or increasing the number of lymphocytes in the graft.

Photorefractoriness (PR) in the turkey breeder hen is characterized by a lack of responsiveness to photoperiods that previously induced or maintained egg production. The consequence of PR is spontaneous regression of ovarian function and cessation of lay. Photosensitivity (PS) may be regained by giving at least 8 wk of short photoperiod (8L:16D) (light restriction). Following the transition from PR to PS, the birds may be photostimulated with long photoperiods, which allows for the recrudescence of ovarian function and normal egg production. Although the return of reproductive viability is the parameter for determining the successful recycle of ovarian function, there are no known reports of the physiological costs of this transition on immune function in the turkey breeder hen. We conducted an experiment to determine the immune responsiveness at various stages of recycle in the turkey breeder hen. Fifty photorefractory birds were selected and distributed equally among five treatment groups (time points). All birds were given an 8-wk period of light restriction (8L:16D) followed by a 12-wk period of photostimulation (16L:8D). The cellular (cutaneous basophil hypersensitivity CBH) and humoral (antibody titer) immune responses were determined in each treatment group (sequential time points): prelight restriction, 2-wk light restriction, 7-wk light restriction, 2-wk photostimulation, and 12-wk photostimulation. After 2-wk light restriction, there was a reduction in the cellular (64.1%) and humoral (59.5%) immune responses from that of the PR hens at the start. After 7-wk light restriction, the humoral responses increased (33.5%) as compared to the 2-wk light restriction time point Upon photostimulation, both the cellular (23.3%) and humoral (52.4%) immune responses were reduced at 2 wk of photostimulation as compared to the prior 7-wk light restriction time point. Finally, there was a rise in cellular (45.7%) and humoral (72.3%) immune responses after 12 wk of photostimulation as compared to the prior 2-wk photostimulation time point. We concluded that recycling of PR turkey hens was associated with altered cellular and humoral immune responses characterized by initial decline then recovery in both the light restriction and the postphotostimulation periods.

An evaluation was done of immunological parameters in the post accident period in 41 examined person. Of these, 26 subjects had chronic maxillary sinusitis, 15 were healthy persons (control group). In patients with chronic maxillary sinusitis, the state of the T-system of immunity has been shown to be characterised by a drop in the total count of T-lymphocytes, T-helpers, T-suppresors. Parameters for humoral immunity are characterised by elevation of the peripheral blood levels of B-lymphocytes, prominent disimmunoglobulinaemia--significant reduction of class G immunoglobulins and macroglobulins. The T-cells-helpers ratio is significantly reduced both in group I and group II. Reduction has been ascertained in the ratio of those T-cells-suppressors blocking antibody formation by B-lymphocytes. In patients after the Chernobyl accident, there was noted a significant decline in the functional activity of macrophages.

Hemolysis may occur after organ transplantation. In most cases, hemolysis is drug-related, such as to cyclosporin, etc. However, it is important to consider graft-versus-host antibody formation as one of the causes of hemolysis. We evaluated the effect of local graft irradiation as a method of preventing hemolysis arising from ABO antibody formation after ABO-mismatched renal transplantations. The participants in this study were 44 patients who had undergone ABO-mismatched renal transplantation. Of these patients, 23 were subjected to postoperative local irradiation, and 21 were not. We examined the characteristics of anti-blood-type antibodies, and we also compared the frequency of the development of antibody formation and hemolysis development between the groups. The development rates of anti-ABO-antibody formation and hemolysis were significantly higher in the patients without local irradiation (15/21, 71%; 6/21, 29%) than in those with local irradiation (1/23, 4%; 0/23, 0%). The elevated antibodies mainly belonged to the IgG class, not the IgM class. The hemolysis- and antibody formation observed in the patients originally without postoperative local irradiation was dramatically improved by graft irradiation. Local graft irradiation after ABO-mismatched renal transplantations may be needed to prevent the formation of anti-ABO antibodies and to impede the development of hemolysis.

Ultraviolet light exposure can impair immune responses that are not restricted to the exposed skin but is also found at other sites, i.e. systemic immunosuppression. Therefore, we investigated the UV-induced modulating effects on vaccination against hepatitis B in a mouse model. Two different mouse strains, BALB/c and C57B1/ 6, were vaccinated intramuscularly against hepatitis B. Mice were exposed to different doses of ultraviolet B (UVB) for five consecutive days on shaved back skin before the vaccination. Vaccination against hepatitis B induced cellular (delayed-type hypersensitivity [DTH] and lymphocyte stimulation test) as well as humoral immune responses in both mouse strains. The DTH responses in C57BB1/6 mice were statistically significantly higher compared with BALB/c mice. UVB exposure induced a dose-dependent suppression of cellular immunity in both strains of mice. C57B1/6 mice seemed to be more susceptible to this suppression. Anti-hepatitis B surface antibodies (total-Ig) were only marginally suppressed after UVB exposure. IgG2a and interferon-gamma levels, both indicators for Th1 immune response, were suppressed in both mouse strains after UVB exposure. In summary, UVB exposure induced a dose-dependent suppression of both cellular and humoral immune responses after hepatitis B vaccination, although the suppressive effects on humoral immunity were limited to IgG2a production. Susceptibility to UVB-induced immunomodulation depended on the strain of mice and their predilection for developing different T cell responses.

It is well established that ultraviolet radiation has immunomodulatory effects which may be involved in skin cancer. Recent studies have shown that UVA radiation (320-400 nm) as well as UVB (290-320 nm) is immunosuppressive. This means that sunscreens which mainly absorb UVB (protection against erythema) may be less effective in preventing UVR-induced immunosuppression than broad-spectrum products. We have studied the effects of UVA exposure on the human delayed-type hypersensitivity response (DTH) and compared the efficacy of sunscreens having different levels of UVA protection under both solar-simulated radiation (SSR) chronic exposures or acute exposure and outdoor real-life solar exposure conditions. DTH was assessed using recall antigens. Our studies clearly demonstrate the role of UVA in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire UV spectrum. These data suggest that sun protection factor may not be sufficient to predict the ability of sunscreens for protection from UV-induced immune suppression. Determining the level of UVA protection is particularly necessary, because UVA seems to have a relatively low contribution to erythema but is highly involved in immunosuppression.

Exposure to ultraviolet radiation can modulate immune responses in animal and humans. Remarkably, the ultraviolet-induced immunosuppression is not restricted to the exposed skin but is also found at other body sites, i.e., systemic immunosuppression. Effects of ultraviolet radiation on infections cannot be determined by experimentation on humans, but the effects of ultraviolet on vaccination may serve as a model. Moreover, it is important in its own right to assess whether ultraviolet radiation affects vaccination responses. In this study the effect of ultraviolet B exposure on the development of immune responses after hepatitis B vaccination in human volunteers was investigated. To this end, 191 human volunteers were vaccinated against hepatitis B with the Engerix-B vaccine. Ninety-seven of them were prior to the first vaccination exposed to ultraviolet B on 5 consecutive days with one personal minimal erythema dose per day. At several time-points before and after the ultraviolet B exposure regimen and the vaccination, blood samples were taken. Parameters for specific as well as nonspecific cellular and humoral immunity were analyzed. It was demonstrated that ultraviolet B exposure prior to hepatitis B vaccination did not alter the cellular (lymphocyte stimulation test) nor the humoral (antibody titers) immune response against hepatitis B surface antigen significantly. In contrast, contact hypersensitivity to diphenylcyclopropenone was significantly suppressed after ultraviolet B exposure, as was natural killer cell activity. These latter results confirm earlier findings and demonstrate immunosuppressive effectiveness of the ultraviolet regimen. In summary, although natural killer cell activity and contact hypersensitivity responses were suppressed, the ultraviolet B radiation protocol did not alter the humoral nor the cellular immune responses against hepatitis B surface antigen after vaccination.

The ultraviolet radiation present in sunlight is the primary cause of nonmelanoma skin cancer and has been implicated in the development of cutaneous malignant melanoma. In addition, ultraviolet is immune suppressive and the suppression induced by ultraviolet radiation has been identified as a risk factor for skin cancer induction. Ultraviolet also suppresses the immune response to infectious agents. In most experimental models, ultraviolet is applied to immunologically naive animals prior to immunization. Of equal concern, however, is the ability of sunlight to suppress established immune reactions, such as the recall reaction in humans, which protects against microbial infections. Here we demonstrate that solar-simulated ultraviolet radiation, applied after immunization, suppresses immunologic memory and the elicitation of delayed-type hypersensitivity. Further, we found that wavelengths in the ultraviolet A region of the solar spectrum were critical for inducing immune suppression. Ultraviolet A (320-400 nm) radiation was as effective as solar-simulated ultraviolet A + B (290-400 nm) in suppressing the elicitation of an established immune response. Irradiation with ultraviolet AI (340-400 nm) had no effect. Supporting a critical role for ultraviolet A in ultraviolet-induced immune suppression was the observation that applying a sunscreen that contained an ultraviolet B only filter had no protective effect, whereas, a sunscreen containing both ultraviolet A and ultraviolet B filters totally blocked ultraviolet-induced immune suppression. These data suggest that sunlight may depress the protective effect of prior vaccination. In addition, the observation that ultraviolet A is immunosuppressive indicates the need for ultraviolet A protection when designing sun protection strategies.

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.

Thirty-one previously untreated patients with follicular low-grade B-cell non-Hodgkin's lymphoma expressing the CD20 antigen were treated with iodine-131 tositumomab therapy between 1996 and 1998. The therapy led to a temporary depletion of peripheral blood B-lymphocytes. Recovery of B-cells occurred in most cases by 3 to 6 months and in all patients by 12 months posttherapy. A temporary decline in T-cell subpopulations, but no reduction in serum immunoglobulin levels, could be observed. ELISA techniques were used to detect specific antibodies against rubella, mumps, varicella zoster, measles, and tetanus. Almost all patients remained seropositive against the different antigens during the 1- to 2-year follow-up. No significant reduction in antibody concentrations to tetanus or measles could be detected. The data show that acquired humoral immunity against common antigens appears to be preserved despite a temporary loss of B-lymphocytes., (Copyright 2001 Academic Press.)

Purpose: To investigate whether continuous, very low-dose gamma-irradiation (10 cGy/year) modifies immune parameters in mice., Material and Methods: C57BL/6 female mice, 4 weeks old, were irradiated for 24 months and compared with control mice living in the same room. B- and T-cell subsets were evaluated by flow cytometry before and after stimulation with lectins; subclasses of immunoglobulins were determined by ELISA 2, 4, 6, 8, 12, 18 and 24 months after the beginning of the irradiation., Results: No difference was found in the percentage of CD4(+) and CD8(+) cells in the thymus and the spleen, or in the reactivity of T-cells to lectins. While the number of B-cells in the spleen remained unchanged, a significant decrease of IgG1, IgG2b and IgG2a was observed after respectively 12, 18 and 24 months of irradiation., Conclusion: The parameters of cellular immunity studied were not affected by this chronic low-dose of irradiation, but this dose rate is probably too low to induce the hormetic effect previously described. Further investigations are necessary to assess whether the decline of immunoglobulin secretion is indicative of a lower rate of infectious diseases or a defect in B-cell function.