Advances in methodologies for evaluating cell-mediated immune responses / 生物工程学报

Cell-mediated immune response is an important part of machinery in maintaining the body's homeostasis. After the innate immune system selectively activates the adaptive immune system, the cell-mediated immunity exerts its killing and clearance functions. Therefore, evaluating the level of cell-mediated immune response is crucial in the diagnosis and treatment of cancer, monitoring the immune status after organ transplantation, diagnosing and preventing viral diseases, and evaluating the effectiveness of vaccines and other areas. From the initial overall assessment of the immune effects in vivo to the precise detection of the number and function of multiple immune cells, the evaluation methods of cell-mediated immune response have greatly advanced. However, cell-mediated immune response involves multiple levels in the body, and it's difficult to choose the numerous detection methods available. The article systematically compares the evaluation methods of cell-mediated immune response at four different levels: the organism, the tissue and organ, the immune cells and the immune molecules, with the aim to facilitate the applications of related technologies.

Inmunidad celular en la patogénesis de la cardiopatía chagásica crónica / Cell-mediated immunity in the pathogenesis of chronic Chagas cardiomyopathy

Resumen La cardiopatía chagásica crónica se presenta en un 30% de las personas infectadas con Trypanosoma cruzi. Aunque el parásito puede ser controlado por la respuesta inmune después de la fase aguda, su detección se hace difícil en la fase crónica a pesar de la persistencia de éste en los tejidos de los individuos infectados. Dado que solo un porcentaje de estos individuos crónicamente infectados desarrolla el daño tisular, se sugiere la existencia de factores asociados que predicen la aparición de la sintomatología crónica: a) la genética del hospedero (moléculas del HLA), cuyo papel aún no se ha dilucidado, b) factores dependientes del parásito cómo la variabilidad de los genotipos (TcI a TcVI), su asociación con tropismo y daño tisular; y c) otros factores como la cantidad del inóculo, la reexposición constante a vectores infectados, las diferentes vías de infección y el estado inmunológico del hospedero. Varias teorías han sido implicadas en el compromiso cardiaco, como la persistencia del T. cruzi en los tejidos, la autoinmunidad inducida y el daño tisular producido por la respuesta inmune. En esta revisión se pretende emitir una hipótesis respecto a la disfunción celular inmune producida por la persistencia parasitaria en los tejidos y su papel en la patogénesis de la enfermedad. Se consideran aspectos como el pronóstico de los pacientes con cardiopatía chagásica llevados a trasplante de corazón por falla cardiaca avanzada comparado con otras causas de falla que conducen a trasplante y la posible organización de los infiltrados inflamatorios en el tejido cardiaco, el cual podría funcionar como un tejido linfoide terciario.

Abstract Chronic Chagas cardiomyopathy is present in 30% of people infected with Trypanosoma cruzi. Even though the parasite can be controlled by immune response after the acute phase, its detection is hard in the chronic phase despite its persistence in the tissues of infected individuals. Since only a fraction of these chronically infected individuals develop tissue damage, the existence of associated predictive factors for appearance of chronic symptoms is suggested: a) host's genetics (HLA molecules) whose role has not yet been clarified; b) parasitedependent factors such as genotype variability (TcI to TcVI), their association with tropism and tissue damage; and c) other factors like the amount of inoculum, the constant reexposure to infected vectors, the different infection routes and the host's immune status. Several theories have been put forward with regard to cardiac compromise, such as T. cruzi persistence in tissues, induce autoimmunity and tissue damage caused by immune response. This review intends to propose a hypothesis on cellular immune dysfunction produced by parasite persistence in tissues and their role in the pathogenesis of the disease. Aspects such as prognosis of patients with Chagas cardiomyopathy who undergo heart transplant due to advanced heart failure are taken into consideration and compared to other failure causes that lead to transplants, and also the possibly organisation of inflammatory infiltrates in heart tissue, which could function as a tertiary lymphoid tissue.

Comparison of Cell-Mediated Immune Response after Laparoscopic vs Open Gastrectomy in Gastric Cancer

Purpose: We compared the changes in the perioperative peripheral lymphocyte subsets and the acute inflammatory reactants (CRP and SAA) to compare the immune responses between a Laparoscopy-assisted distal gastrectomy (LADG) and a conventional open distal gastrectomy (CODG). METHODS: 23 patients, who underwent an operation for early gastric cancer, between Nov. 2003 and Feb. 2004, were enrolled in this study. The total WBC, lymphocytes, peripheral lymphocyte subsets and acute inflammatory reactants (CRP and SAA) were evaluated on the preoperative day, and 2, and 24 hrs and on the 4th postoperative day in 20 of the 23 cases. RESULTS: There were no significant differences in the preoperative total WBC, lymphocyte, peripheral lymphocyte subsets, CRP and SAA between the two groups (P 0.05). The postoperative CRP and SAA levels; however, gradually increased compared to the preoperative levels, and were significantly lower in the LADG than the CODG group (CRP: P=0.03 and SAA: P=0.01). Conclusion: No difference was detected in the immune-cell numbers in the gastric cancers between the LADG and CODG groups. The LADG was found to influence the acute inflammatory reaction less than the CODG.

The Effects of High-dose Vitamin C Administration on the Cell-mediated Immune Response in Mice

BACKGROUND: Vitamin C is an essential nutrient, taken as a daily supplement by many people. Recently, high-dose vitamin C is considered as a therapeutic regimen in some clinical situations. Until now, few studies have been done with the effects of high-dose vitamin C on the immune response. METHODS: In this experiment, the effects of high-dose vitamin C on cell-mediated immune response in immunologically competent mice were evaluated. After intraperitoneal injection of 2.5, 5, or 10 mg/day of vitamin C for 10 days, delayed type hypersensitivity (DTH) was provoked against DNFB in the pinnae as a model for cell-mediated immune response. Severity of DTH reaction was evaluated as the thickness of pinnae, and the vitamin C levels were measured in the serum, liver, kidney, lung, pinnae, and splenocytes. RESULTS: After challenge, the thickness increased at its peak on the 2(nd) day in all groups. On the first day, the pinnae were thicker in the injected groups than in the control. On the contrary, the increment of the pinnae thickness was attenuated and the number of cells infiltrated in the site of DTH decreased proportionately to the amount of vitamin C administered from the second day on. With vitamin C exogenously given, the serum level peaked at 30 min after injection, and returned abruptly to its basal level without accumulation. However, it accumulated in the liver, kidney, and especially in the pinnae inflamed and splenopcytes, proportionately to the amount administered. CONCLUSION: Based on these results, it is suggested that, in one hand, exogenously administered high-dose vitamin C accumulated in the splenocytes and presumably changed the function of them resulting in the augmented cell-mediated immune response, as was revealed in the first day of DTH reaction. On the other hand, it seems likely that the vitamin C also showed anti-inflammatory effects.

Soluble IL-2R, IFN-gamma and Neopterin as Immunologic Markers in Patients with Tuberculosis / 결핵

BACKGROUND: The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-gamma with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-gamma and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. METHOD: The serum sIL-2R, IFN-gamma and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-gamma and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. RESULTS: 1) The serum sIL-2R and IFN-gamma levels were elevated in patients with tuberculosis when compared to those of healthy subjects (0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis(2967+/-2132.8 pg/ml) than in healthy controls(4949+/-1242.1 pg/ml)(p0.05), 41 52.8 pg/ml to 22+/-23.9 pg/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from 3158+/-2272.6 pg/ml to 3737+/-2307.5 pg/ml(0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. CONCLUSION: On the basis of this study, sIL-2R, IFN-gamma and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

A Study of Altered Cell-Mediated Immunity in Peritoneal Fluid of Patients with Endometriosis / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to investigate the relationship between the levels of IL-6 and tumor necrosis factor-alpha in the peritoneal fluid(PF) of women with and without endometriosis and infertile women. Design: Prospective and case-control study. Setting: University hospital. Patients: Twenty-nine women with laparotomy or laparoscopic findings of minimal to severe endometriosis, and twenty-eight women with no visual evidence of pelvic endometriosis and with benign gynecologic disease. Main Outcome Measures: PF IL-6 and tumor necrosis factor-alpha levels were determined using commercial ELISA. IL-6 and tumor necrosis factor-alpha concentrations were compared among women with and without endometriosis, and with infertile and fertile women, and then also compared according the revised American Fertility Society classification. RESULTS: IL-6 and tumor necrosis factor-alpha concentrations were higher than in the PF of women with endometriosis than in matched normal controls. Cyclic variations in IL-6 concentrations were seen in PF from patients with endometriosis: the concentrations in the secretory phase were significantly higher than those in the proliferative phase. IL-6 concentrations were higher than in the PF among of infertile women than in fertile women. A significant correlation between PF IL-6 and tumor necrosis factor-alpha concentrations and endometriosis stage III and IV was noted. CONCLUSIONS: Increased PF levels of IL-6 and tumor necrosis factor-alpha in patients with endometriosis may be relate to endometriosis-associated infertility and to the pathogenesis of endometriosis suggesting that partially contribute to the disturbed immune regulation observed in patients with endometriosis.