effective dose of the public varies substantially depending on where they live , occupation , personal habits , diet , building type , and house utilization patterns . the effective dose of humans from natural sources is about 2.4 msv y while for all artificial sources is 0.8 msv y. a few geographical hotspots receive high natural background radiation . the average and maximum annual effective doses of the inhabitants of ramsar are 10.2 and 260 msv , respectively . the radiation effective doses of ramsar inhabitants are mainly due to ra-226 and its decay products . in addition , the concentrations of natural radionuclides in food and drinking water of the residents are higher than the world average , and are correlated with the high concentration of these radionuclides in soil and water . studies of inhabitants of high background radiation areas ( hbras ) are very useful in predicting disease risks from chronic radiation exposures in nuclear and medical workers and in other exposed populations . in the last 10 years , there has been a significant increase in studies about the function of the immune system due in part to the importance of immune function in the maintenance of a disease - free homeostasis . t cells can home into antigen - expressing tumor even in deep tissue beds and can continue to proliferate in response to immunogenic proteins expressed in cancer until eradication of the tumor cells . the immune system has been reported to suppress the development and progression of neoplastic lesions by not well understood mechanisms . nevertheless , tumors may suppress the immune system , especially by the formation of exosomes . uptake of the exosomes by immune cells may suppress of the number and activity of natural killer ( nk ) cells and also suppressing the activity of t cells . t lymphocytes can be broadly classified as cytotoxic cd8 + and cd4 + t cells . the cd4 + t - cell response can elicit both immune stimulatory or immune inhibitory effects . specific cd4 + t - helper ( th ) cell phenotypes are crucial for the expansion and persistence of tissue - destructive cd8 + t cells . they are able to lyse tumor cells or virally infected cells without prior antigen sensitization . cytotoxic t cells ( ctls ) , also known as cd8 + t cells , recognize their targets by binding to antigen associated with 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 prevents autoimmune diseases such as experimental autoimmune encephalomyelitis . in this study , the effective radiation dose received by inhabitants of hbras of ramsar was estimated by external radiation measurements , occupancy factor , and period of residence of individuals , and then , the changes on cd4 + , cd8 + , nk cells , leukocytes , red blood cells , platelets ( plt ) , and their percentages were investigated . the purpose of the study was to investigate the association between exposure time and changes in immune cells . fifty residents of hbras , whose ages were between 25 and 35 years and who were fully healthy , were selected randomly . a questionnaire was filled by interview and people with smoking , pregnancy , medications , surgery , cancer , and immune - related diseases were excluded . the mean age of participants was 30.2  3.72 and their maximum and minimum was 25 and 35 , respectively . two cubic centimeters of fresh peripheral blood were taken in sterile conditions and cell counts were performed using an automatic hematology analyzer ( sysmex kx-21 , japan ) . twenty microliters of each blood sample were stained for 15 min at room temperature in dark with 20 l cd4/cd45 antihuman monoclonal antibody ( partec , germany ) , and 400 l of buffer 1 and then 400 l of buffer 2 were added to each sample and were analyzed with a flowcytometer ( partec pas , germany ) . according to the cd8 easy count kit ( partec , germany ) instruction , 20 l of each sample were stained for 15 min at room temperature in dark with 10 l cd8 antihuman monoclonal antibody ( partec , germany ) . in addition , 400 l of buffer 1 and then 400 l of buffer 2 were added to each sample and the samples were analyzed with a flowcytometer ( partec pas , germany ) . twenty microliters of each blood sample were stained with 10 l of cd107a - pe ( exbio , czech republic ) and 10 l cd45-pe ( partec , germany ) monoclonal antibody , and the other 20 l of blood samples were stained with 10 l cd56-pe ( exbio , czech republic ) and 10 l cd45-pe ( partec , germany ) for 15 minutes in the dark conditions . the samples were shacked , and the numbers of in vivo stimulated cd107a+ cells and cd56 + cells were counted using a calibrated flowcytometer ( partec pas , germany ) . this study was approved by the accredited ethics committee of babol university of medical sciences , babol , iran . , we used log transformation of cell counts and cumulative doses since their distributions are skewed and have long tails . two cubic centimeters of fresh peripheral blood were taken in sterile conditions and cell counts were performed using an automatic hematology analyzer ( sysmex kx-21 , japan ) . twenty microliters of each blood sample were stained for 15 min at room temperature in dark with 20 l cd4/cd45 antihuman monoclonal antibody ( partec , germany ) , and 400 l of buffer 1 and then 400 l of buffer 2 were added to each sample and were analyzed with a flowcytometer ( partec pas , germany ) . according to the cd8 easy count kit ( partec , germany ) instruction , 20 l of each sample were stained for 15 min at room temperature in dark with 10 l cd8 antihuman monoclonal antibody ( partec , germany ) . in addition , 400 l of buffer 1 and then 400 l of buffer 2 were added to each sample and the samples were analyzed with a flowcytometer ( partec pas , germany ) . twenty microliters of each blood sample were stained with 10 l of cd107a - pe ( exbio , czech republic ) and 10 l cd45-pe ( partec , germany ) monoclonal antibody , and the other 20 l of blood samples were stained with 10 l cd56-pe ( exbio , czech republic ) and 10 l cd45-pe ( partec , germany ) for 15 minutes in the dark conditions . the samples were shacked , and the numbers of in vivo stimulated cd107a+ cells and cd56 + cells were counted using a calibrated flowcytometer ( partec pas , germany ) . this study was approved by the accredited ethics committee of babol university of medical sciences , babol , iran . , we used log transformation of cell counts and cumulative doses since their distributions are skewed and have long tails . the mean exposure duration was 22.28  8.71 and its minimum was 10 and its maximum was 35 years in studied individuals . cd4 + and cd8 + percentages , cd4/cd8 ratio , cd4 + , cd8 + , nk and cd107a+ cell counts , and complete blood cell counts of inhabitants of hbra are shown in tables 1 and 2 , respectively . cd4 + and cd8 + percentages , cd4/cd8 ratio , cd4 + , cd8 + , nk , and cd107a+cell counts of inhabitants of high background radiation area the complete blood counts results the regressions between exposure duration and cd4% ( p = 0.045 ) , also with cd107a+ counts ( p = 0.048 ) , cd8% are shown in figure 1 . the cd4 + cells percentage increases , but the count of cd107a+ cells decreases with duration of living in hbra of ramsar there is not significant regression between exposure duration and the other studied parameters including log cd4 , log cd8 , log nk , log lym , log neut , log wbc , log mxd counts and cd4/cd8 ratio , cd8% , lym% , neut% , and mxd% . these results showed that living in hbras may induce some changes in the immune system gradually . cd4 + or t - helper ( th ) cell phenotypes are crucial for the expansion and persistence of tissue - destructive cd8 + t cells . cd107a+ cells that are the marker of cd8 and nk cell activity decrease gradually in the individuals living in hbras lacoste - collin et al . studied the biological effects of 10 cgy year gamma rays on the life span of 560 4-week - old sjl / j female mice and on various parameters of the cell - mediated immune response and they reported that life span was slightly prolonged there . in lymph nodes and spleen , lower percentages of cd4 + and cd8 + t cells were observed in irradiated mice before 32 weeks . however , the percentages of cd49 + nk cells were increased in the spleens of irradiated mice at 28 weeks and at 32 weeks , while nk cell activity remained unchanged in exposed mice . focused on the immunostimulatory effects of low dose radiation at in vivo models and its clinical efficacy . they focused effects that supporting the use of low dose radiation regimens as an anticancer treatment . matsubara et al . have emphasized on the existence of a lag time between the time of low dose irradiation in vivo and the appearance of radioresistance . they showed that low - dose irradiation induces thymocyte apoptosis with a peak at 6 h postirradiation , but returned to background levels after 24 h. at the same time , no morphological alteration of splenocytes and no early modification of the intensity of t - cell - dependent immune responses have been seen . shankar et al . reported that alteration in the immune response following the low dose irradiation depends on antigen , type of response as well as the strain of mice used . furthermore , the alterations in the expression of pro - apoptosis gene p53 and activation - induced apoptosis in the effector or regulatory cells seem to contribute to the end result . 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 igg , igm and ige , and depressed nk cell activity . attar et al . showed that the total serum antioxidant level in the exposed inhabitants of hbras of ramsar was significantly lower than control and they also had higher lymphocyte - induced il-4 and il-10 production , and lower il-2 and ifn - g production . 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 . evaluated hormone levels associated with immune responses of inhabitants in hlnras of ramsar was seen and their study demonstrated a decreased level of dhea and increased level of cortisol in the elderly hlnra group , which might be possibly associated with higher cumulative doses . there was a higher incidence of hypothyroidism in the hlnra group , mostly in the elder group . a significant increase of cd69 expression on cd4 + t lymphocytes was found in the young hlnra group . low levels of dhea in the elder group were correlated to their increased ige levels . the comparison of cd4 + and cd8 + cell counts , their percentages , and the cd4+/cd8 + ratio in 2011 by borzoueisileh et al . showed that the increase in cd4+% and cd8+% in the hbra group and other measurements were not significantly different between hbra and ordinary background radiation area ( obra ) residents of ramsar . our results showed that the percentage of cd4 + cells increases but the count of cd107a+ cells decreases with duration of living in hbra of ramsar . other measured parameters , cd8 + , nk cells , leukocytes ( wbc ) and content of the mixture ( mxd ) , neutrophil , lymphocyte counts , and percentages did not show significant regression by exposure time . we concluded that alterations have seen in the immune systems of hbra inhabitants , but the study of other t - cell subsets including th1 ( t helper ) , th2 , th17 , and regulatory t cells to determine other aspects of the immune involvement could be important . 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 , are important .
purpose : the effective dose received by humans from natural sources is about 2.4 msv y-1 , but this is 10.2 msv y-1 for inhabitants of ramsar , a city in northern iran . 
 carcinogenesis is one of the most studied effects of radiation , especially in high doses . 
 nonetheless carcinogenesis of low doses is uncertain . 
 a recent epidemiological study in high background radiation areas of ramsar showed that the cancer incidence in this era is lower than neighbors . 
 the reason of this different behavior is under study yet . 
 nk cells , helper , and cytotoxic t cells are most important components of the tumor immune surveillance . 
 the counts and activities of these cells and also leukocytes , lymphocyte , neutrophil cells , and other important parameters were studied in the residents of ramsar with different duration of exposure to chronic low dose radiation.materials and methods : fifty residents of high background radiation areas , who were between 25 and 35 years and fully healthy , were selected randomly and their consent was obtained . 
 then , 2 cc fresh peripheral bloods were taken in sterile conditions . 
 complete blood cell counts were performed by an automatic hematology analyzer and cd4 + , cd8 + , nk , and cd107a+ cell counts were determined by monoclonal antibodies and flowcytometry . 
 cd4 + and cd8 + percentages and the cd4/cd8 ratio were determined and the data were analyzed using spss 16.results:the percentages of cd4 + cells increase , but the counts of cd107a+ cells decline in higher exposure durations . 
 the other parameters did not have significant regression with exposure duration.conclusions:these confirm that living in high background radiation areas may induce changes in the immune system gradually and address more investigations .