treg ( t ) cells can be broadly classified as cytotoxic cd8 + t cells , which can directly kill an antigen - expressing cell or cytokine - secreting cd4 + t cells . the cd4 + t - cell ( t helper ) response can elicit both immune stimulatory or immune inhibitory effects . t helper type 1 ( th1 ) lymphocytes ( lym ) secrete interleukin ( il)-2 , interferon ( inf)- , and lymphotoxin - a and stimulate type 1 immunity , which is characterized by intense phagocytic activity . but , th2 cells secrete il-4 , il-5 , il-9 , il-10 , and il-13 and stimulate type 2 immunity , which is characterized by high antibody titers . type 1 and type 2 immunity are not strictly synonymous with cell - mediated and humoral immunity , because th1 cells also stimulate moderate levels of antibody production , whereas th2 cells actively suppress phagocytosis . specific cd4 + t - helper cell phenotypes are crucial for the expansion and persistence of tissue - destructive cd8 + t cells . natural killer ( nk ) cells are a subset that plays a central role in the innate immune response to tumors and infections . nk cells are an important component of the innate immune responses they are able to lyse tumor cells or virally infected cells without prior antigen sensitization . cytotoxic t cells destroy virally infected cells and tumor cells , and are also implicated in transplant rejection . these cells are also known as cd8 + t cells since they express the cd8 glycoprotein at their surface . these cells recognize their targets by binding to antigen associated with major histocompatibility complex ( mhc ) class i , which is present on the surface of nearly every cell of the body . through il-10 , adenosine and other molecules secreted by regulatory t cells , the cd8 + cells can be inactivated to an anergic state , which prevent autoimmune diseases such as experimental autoimmune encephalomyelitis . there are a few areas in the world that have high natural background radiation . among these areas , this high dose radiation is mainly from radium-226 and its progenies coming from hot springs eventually spreading in the environment . the effective dose received by the inhabitants of ramsar , especially in talesh mahalleh , is even many times greater than the dose limit for radiation workers ( 260 msv / y versus 20 msv / y).[810 ] according to international commission on radiological protection recommendation , the maximum effective dose to public at large should be < 1 msv / y . many studies about radiation doses and health indices of inhabitants of ramsar are conducted . in the study of their health status and frequency of cancer by monfared et al . , they have reported that although the radiation doses received by these individuals is many times greater than residents of normal background radiation areas ( nbras ) and the cytogenetic studies showed that there is higher chromosomal aberration in the lym of the residents of high background radiation area ( hbra ) of ramsar , the frequency of cancer in these people , was not higher than other people living in nbras of ramsar.[1214 ] according to immune surveillance theory , one of the important roles of immune system is to identify and to kill tumor cells . lysosomal - associated membrane protein-1 ( lamp-1 or cd107a ) has been described as a marker of cd8 + t cell degranulation following stimulation and recently , galit alter et al . , described cd107a as marker of nk cell functional activity using multi - parameter flowcytometry . cd107a is significantly upregulated on the surface of nk cells following stimulation with mhc devoid targets . additionally , cd107a expression correlates with both cytokine - secretion and nk cell - mediated lysis of target cells . in this study , we have counted activated cd8 + t cells and nk cells and our hypothesis was that hbra residents exhibit a similar immunological change observed in acutely and heavily exposed people . the higher number of activated cells in hbra residents could indicate that high level of radiation dose received by these individuals could induce tumor cells and activated nk and cd8 + cells , eradicate these tumors . thus it can be as evidence for the relationship between activation of immune system and cancer prevention , and immunological implication in radiation carcinogenesis . thirty healthy residents of hbra and 30 healthy residents of nbra were selected randomly and a questionnaire were filled by interview . the age and sex was matched and pregnant women , recently operated , and individuals suffering from an illness or taking medications were excluded from the study . the people who were living for at least 10 years in this area considered as study population . radiation dose rates of their homes were measured by calibrated dosimeter ( gratez a , germany ) . to estimate the annual effective dose that is the total dose resulting from exposures of ionizing radiation over a year ( sv / y ) , the dose rate ( nsv / h ) was multiplied by occupancy factor . the occupancy factor was the proportion of exposure time multiplied by 4380 ( 365 days  24 h ) . , sari , iran ) in k3edta tubes and the cell count was performed automatic hematology analyzer ( sysmex kx-21 , japan ) . twenty microliter of each sample was stained with 10 l of cd107a - pe ( exbio , czech republic ) and 10 l cd45-pe ( partec , germany ) monoclonal antibody for 15 min in dark . then we added buffer 1 and 2 according to catalog for detection of all cd45 + cells ( partec , germany ) . this method is simplified volumetric flowcytometry that allows feasible and accurate determination of cd45 + cells that do nt need to lyse and washing buff er . afterward , the samples were shaken and stimulated cd107a + cells were counted by flowcytometer ( partec pas , germany ) . this study was approved by the accredited ethics committee of babol university of medical sciences , babol , iran . the results of hbra and nbra inhabitants were compared by independent sample t test and p < 0.05 assumed significant . the radiation dose rate at hbra was significantly more than nbra [ table 1 ] . annual effective doses of hbra group were between 4511 and 57000 and its mean was 9770 sv / y . on the other hand nbra group received 570 - 3020 sv / y and the mean of their effective dose was 1207 sv / y . radiation dose rate of habitats of individuals ( nsv / h ) , their ages ( year ) and the habitance duration of them ( years ) , difference between doses is significant the difference in counts of white blood cells ( wbc ) , content of the mixture ( mxd ) , neutrophils and lym between two groups was not significant [ table 2 ] . white blood cells , mixture , neutrophils , lymphocytes counts ( per l ) in two regions . none of the differences are statistically significant the difference between mxd , neutrophils and lym percentages of two groups was not significant [ table 3 ] . none of the differences are statistically significant the number of cd107a + cells in nbra group was higher in comparison with hbra inhabitants [ figure 1 ] . the number of cd107a+ cells per l ( p < 0.005 ) there are a lot of studies that have evaluated the radiation effects on the immune system of animals . studies showed that following a single dose of 100 and 200 mgy , increase in cytotoxic activity of nk cells is observable 24 until 72 h later.[1821 ] fuggetta et al . inf- ( 200 iu / ml ) was able to completely reverse this inhibitory radiation induced effect , but was not able to modify the number of cd16 + and cd56 + cells that died by apoptosis after irradiation . concerning in vivo radiation exposure , no changes in nk cell activity were found in 1341 atomic bombing survivors residing in hiroshima . evaluated the immune status in children with goiter living in highly contaminated area of gomel . they found increased serum levels of immunoglobulin g ( igg ) , igm and ige and depressed nk cell activity . although ifn- and il-2 enhanced the cytotoxicity of these nk cells , the response to ifn- was still below control values . attar et al . have studied the immune responses to infection and inflammation of the exposed residents of ramsar . their results showed that the total serum antioxidant level in the exposed people was significantly lower than control and the exposed individuals also had higher lym - induced il-4 and il-10 production , and lower il-2 and ifn- production . in addition , neutrophil nitroblue tetrazolium , phagocytosis , and locomotion were higher in the exposed group . the authors conclude that the immune system of individuals exposed to high dose ionizing radiation has adapted to its environment by shifting from a type 1 to a type 2 response to promote anti - inflammation . this may be because inflammatory type 1 responses generate more free radicals than type 2 responses , in addition to the free radicals generated as a result of high environmental radiation . thus , the serum total antioxidant level in the exposed residents was lower than the unexposed group . zakeri and kariminia have evaluated hormone levels associated with immune responses of inhabitants in hbras of ramsar and their study demonstrated a decreased level of dehydroepiandrosterone ( dhea ) and increased level of cortisol in the elderly hbra group which might be possibly associated with higher cumulative doses . there was a higher incidence of hypothyroidism in the hbra group , mostly in elder group . a significant increase of cd69 expression on cd4 + t lym was found in the young hbra group . low levels of dhea in the elder group were correlated to their increased ige levels . but the absolute counts of cd4 + and cd8 + and cd4+/cd8 + ratio was not significantly different between hbra and nbra residents of ramsar . mechanisms for putative tumor suppression or other mechanisms defending against tumor induction and development include the dna repair , apoptosis , terminal differentiation , phenotypic suppression and radioprotectors should be considered . altogether , these mechanisms will reduce the probability that a specifically damaged target cell will progress to frank malignancy . we recommend the measurements of the proportions or counts of the other t - cell subsets including t helper 1 ( th1 ) , th2 , th17 and regulatory t cells to determine other aspects of the immune involvement . the ratios of th1/th2 and th17/tregs that could reflect altered states of immune responses against foreign antigens or tumor antigens and the proportions or counts of peripheral leucocytes including monocytes and polymorph nuclear leucocytes , which also modify or even suppress antitumor immunity also , are important . our results showed that although the effective radiation doses received by inhabitants of hbra of ramsar were significantly higher than normal , the count of cd107a + cells is lower than nbra inhabitants . this maybe as the result of higher radiosensitivity of active cells and shows that these cells are present and immune surveillance are active there . other measured parameters , wbc and mxd , neutrophil , lym counts and percentages were not significantly different between two groups .
the effective radiation dose of human from natural sources is about 2.4 msv / y and the dose limit for radiation workers is 20 msv / y . 
 ramsar , a city in iran , has been the subject of concern in the last forty years for a high level of radiation measured in some spots as high as 260 msv / y . 
 carcinogenesis is one of the most studied effects of radiation especially in high doses . 
 recent studies showed that the high level of natural radiation received by inhabitants of this area , paradoxically do nt have significant health effect . 
 natural killer ( nk ) cells and cytotoxic t cells are the most important cells in tumor immune surveillance and cd107a is a widely expressed intracellular protein located in the lysosomal / endosomal membrane . 
 cd107a transiently located on the cell membrane can be used as a marker of cd8 + t cell degranulation following stimulation . 
 it is also expressed , to a lower extent , on activated nk cells . in this study , 60 healthy people were selected randomly and their consent obtained and confounding factors such as sex , age , life - styles was matched then the count of activated nk and cd8 + cells was compared in high and normal background radiation areas inhabitants of ramsar . after filling the questionnaire and measurement of background radiation , blood samples of 30 healthy people from each region were analyzed immediately by means of flowcytometry . the leukocytes and their subsets were not significantly different between two groups and the count of active cells was higher in control group . 
 the result shows that the changes in immune system occur due to radiation and maybe it is as a result of higher radiosensitivity of activated cells .