바이러스 감염에 대한 면역반응

황응수,박정규,차창용 대한면역학회 2004 Immune Network Vol.4 No.2

Viruses are obligate intracellular parasites which cause infection by invading and replicating within cells. The immune system has mechanisms which can attack the virus in extracellular and intracellular phase of life cycle, and which involve both non-specific and specific effectors. The survival of viruses depends on the survival of their hosts, and therefore the immune system and viruses have evolved together. Immune responses to viral infection may be variable depending on the site of infection, the mechanism of cell-to-cell spread of virus, physiology of the host, host genetic variation, and environmental condition. Viral infection of cells directly stimulates the production of interferons and they induce antiviral state in the surrounding cells. Complement system is also involved in the elimination of viruses and establishes the first line of defence with other non-specific immunity. During the course of viral infection, antibody is most effective at an early stage, especially before the virus enters its target cells. The virus- specific cytotoxic T lymphocytes are the principal effector cells in clearing established viral infections. But many viruses have resistant mechanism to host immune responses in every step of viral infection to cells. Some viruses have immune evasion mechanism and establish latency or persistency indefinitely. Furthermore antibodies to some viruses can enhance the disease by the second infection. Immune responses to viral infection are very different from those to bacterial infection. (Immune Network 2004;4(2):73-80) 바이러스는 세포 내 절대 기생체로서 세포에 침투하여 복제하여 증식한다. 면역계는 바이러스가 세포 밖에 존재하는 시기와 세포 내에 있는 시기 모두 공격을 할 수 있으며, 비특이적으로나 특이적인 반응을 보인다. 바이러스의 궁극적인 생존은 숙주의 생존 여부에 달려 있으므로 숙주의 면역체계와 바이러스는 상호 진화하여 왔다. 바이러스 감염에 대한 면역반응은 감염부위, 세포 간 바이러스의 전파기전, 숙주의 생리학적 상태, 유전적 소인과 환경요인에 따라 매우 다양하게 나타난다. 바이러스 감염은 인터페론의 생산을 유도해서 항바이러스 상태를 유발하고, 보체의 작용 등 선천면역에 의해 일차적으로 방어된다. 항체는 감염 초기 단계에 바이러스가 표적세포에 침투하기 전에는 매우 효과적으로 항바이러스 기능을 발휘한다. 확립된 바이러스 감염을 제거하고 완결시키는 데는 세포독성 T 림프구가 결정적인 역할을 한다. 그러나 바이러스는 이와 같은 단계별 숙주의 방어기전에 대항하는 기전을 갖고 있어서 바이러스에 따라서는 평생 숙주의 몸에서 잠복 또는 지속 감염을 이루게 된다. 한편 면역반응이 형성된 경우에 재감염이 되면 오히려 증상을 악화시키는 경우도 있는 등 바이러스 감염에 대한 면역반응의 특성은 다른 세균 등의 면역반응과 상당히 다른 점이 있다.

Concanavalin A가 細胞性免疫反應과 體液性免疫反應에 미치는 影響 : 마우스의 T依存性 體液免疫反應에 대한 Con A의 抑制作用 Suppression of a thymus Dependent Humoral Response by Con A in Mice

張友鉉,金翼詳,李明洙,崔明植 大韓免疫學會 1981 大韓免疫學會誌 Vol.3 No.1

Mice treated with Con A 1 or 2 days prior to primary immunization with SRBC exhibited a significai.F suppression of direct PFC response. This immunosuppressive effect could be reversed by using higher doses of antigen designad to by pass T-cell function. Normal syngeneic recipient mice transferred with Con A-activated spleen cells showed a suppression of primary direct PFC response on day 6. Recipients transferred with Con A-activated thymocytes showed no effect on direct PFC responses. It is suggested that Con A induced immunosuppression of thymus-dependent humoral immune response in mice is at least partly due to the activation of a subpopulation of thymus derived cells, of which tissue source is not thymus but spleen, and that the effect is short-lived and the suppressive effect of HIR is marked in late stage.

Dye-Ligand Affinity Chromatography를 이용한 Staphylococcus aureus의 장독소 B 분리

박선미,정민호,이상화,서수영,송진미,김화숙,이성태,임영진 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.4

Staphylococcal enterotoxins, which cause staphylococcal food poisoning, have been purified by several methods. These procedures have usually included various combinations of ion-exchange chromatogram and gel filtration; such procedures can be time-consuming and may also result in low recoveries of enterotoxins. Although high recoveries of staphylococcal enterotoxins have been reported with chromatofocusing, this technique is expensive and cannot easily be adapted for large-scale purification. In this study we applied a simple, single-step procedure for the purification of Staphylococcal enterotoxin B (SEB) from culture supernatant fluids, namely, dye ligand affinity chromatography in which dye is coupled to an agarose support matrix. Dye ligand affinity chromatography has been used to purify a wide range of enzymes and some blood proteins. We used ten kinds of dye ligand affinity columns. The results showed that SEB had the binding ability to Red A, Reactive Green 19, Reactive Green 5, Reactive Brown 10 and Cibacron Blue 3GA-Agarose. We had the highest resolution by using the Reactive Green 19 dye affinity column. The purified SEB produced a single band when subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) and western blot using anti-SEB. We could also confirm that the purified SEB produced superantigenic effect. Therefore, it could be concluded that SEB was produced purely in single step process by dye-ligand affinity chromatography. Such a method will form the basis of a high-yielding, rapid means of purifying the staphylococcal enterotoxins that can easily be adapted to large-scale production.

Regulation of Immune Response by Arachidonic Acid Metabolites

Chung, Hun-Taeg,Ahn, Byoung-Sun,Kim, Uh-Hyun,Ahn, Deuk-Soo 大韓免疫學會 1987 大韓免疫學會誌 Vol.9 No.1

아라키돈산 대사물질은 면역-염증반응에 관여하는 모든 세포들에 의하여 생성되는 것으로 알려진 왔었지만 최근 세포분리법이 발달하여 한 종류의 세포가 순수히 분리되면서 대식세포로부터는 프로스타 그란딘이나 류코트리엔둥이 만들어지나 림파구로부터는 Cyclooxygenase나 lipoxygenase산물이 만들어 지지 않는다고 밝혀졌다. 이러한 실험적 결과는 면역조절에 중요한 면역세포간의 상호작용에 대하여 새로운 가설을 가능케 하는 바 저자들은 아라키돈산 대사물질이 면역반응에 미치는 여러 실험결과를 토대로 프로스타그란딘이나 류코트리엔의 정상적인 면역반응의 조절작용 및 병적상태 하에서의 역할에 관여하는 작용기전을 논하였다. This paper reviews work on the regulation of humoral and cellular immune responses by arachidonic acid metabalites. There are many reports which demonstrate prostaglandins E, and E2 as local feedback inhibitors of T-and B-cells functions in vitro and in vivo. The immunoregulatory effects of leukotrienes are complicated and more studies are needed. Several disease states are discussed where abnormal in crease of prostaglandins or leukotrienes have a role in the altered immune responsiveness. We propose arachidonic acid metabolites derived from immuno-inflammatory cell as mediators of the homeostatic regulation of immune cell function by a mechanism of controlling lymphocyte recirculation and the mechanism's breakdown contributes to the pathogenesis of diseases in which immunological alteration plays a part.

위암세포에 의한 종양침윤 림프구의 면역반응 억제기전에 관한 연구

박정규,송규상,서광선,최정목,배진선,장일성,윤완희,노승무,조은경,백태현 大韓免疫學會 1995 大韓免疫學會誌 Vol.17 No.3

Tumor-infiltrating lymphocytes ('1°ILs) interact most closely with tumor cells and thus are more likely to reflect tumor host interactions accurately. But it is unknown whether such T cells are nonspecific inflammatory cells or a subset of specific host immune responses. In this study, there was no clear correlation between the infiltration of T lymphocytes in stomach cancer and the overexpression of c-ErbB-2 or increasing class I MHC expression on tumor cells. A positive correlation was seen between the presence of TILs in the tumor and tumors with diploidy by flow cytometric DNA analysis. The proliferative responses of Ills stimulated with IL-2, anti-CD3 mAb, or both were examined. When compared to normal mucosal-associated lymphoid tissue lymphocytes, the proliferative response of TILs to high dose IL-2 was minimal. A similarly poor response to anti-CD3 mAb plus IL-2 was also observed. The freshly isolated TILs exhibit reduced ability to proliferate in response to IL-2, anti-CD3 mAb or both. The microenvironment of the tumor suppresses the proliferative capacity of the TILs. The mechanism of this suppression remains unknown. It could be mediated by suppressor cells, by soluble substances within the tumor, or both. To examine this question, supernatants of stomach cancer cells (SNSNU-1) were tested for the presence of immunosuppressive factors. Human peripheral blood T-cells and tumor-draining lymph node lymphocytes (TDLNL) were incubated for 3 days with SNSNU-1 and then assessed for proliferative responses to PMA, anti-CD28 mAb, or both and for the inducibility to express IFN- r or IL-4 mRNA to PMA. Peripheral blood T-cells pretreated with SNSNU-1 were unable to proliferate in response to PMA, anti-CD28 mAb or both. SNSNU-1 also produces inhibitory activities of TDLNL proliferative response to PMA or anti-CD28 mAb and PMA (49%, 52%, respectively). In contrast, culture supernatants obtained from HEp-2, K562 or Daudi showed normal proliferative responsiveness of peripheral blood T-cells and TDLNL by PMA, anti-CD28 mAb or both.

알콜에 의한 면역반응 변조

박영민,오양호 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

Ethanol(EtOH) has an immunomodulatory, largely suppressive, influence upon the immune system. The present study was undertaken to investigate the effects of EtOH feeding on immune response potential by analyzing various parameters of immunocompetency in mice. Experimental groups of mice were fed ad libitum both pellet and 20% EtOH solution in their drinking water for 60 days. Control mice were fed a similar diet and water. Concanavalin A(Con A)-induced proliferation of splenocytes, and the expression of interleukin(IL) 2 receptor and changes of T cell subsets of thymocytes were analyzed by microculture technique and flow cytometry, respectively. Nitric oxide(NO) has been identified recently as a multifunctional mediator in biological response. NO has been known to be produced by most cells and influence on most cells of the body. The released NO could be toxic to immune and inflammatory cells as well as microorganisms and tumor cells. Thus, NO might be regarded as both immune effector and regulatory molecules. In this study, the authors intended to observe the effects of EtOH on the release of NO and the expression of inducible nitric oxide synthase(iNOS) mRNA of peritoneal macrophages. We have also assessed the ability of animals to respond to a sublethal dose of Cryptococcus neoformans to determine whether EtOH alters host defense mechanisms. It was found that mice fed with EtOH solution showed a significant suppression in Con A-activated proliferation of splenocytes and the number of the CD4+CD8- cell subsets. Interestingly, EtOH feeding did not induce the changes of IL 2 receptor expression in mice. The feeding of EtOH before C. neoformans infection enhanced significantly the recovery of C. neoformans from brain and spleen of the infected mice as compared to that of control mice. NO production and iNOS mRNA expression were decreased in EtOH-fed mice. In summary, our study findings show that EtOH ingestion in experimental animals results in demonstrable changes in T cell function and NO production as measured by in vivo and in vitro assays of immunocompetence. These changes obviously may increase the susceptibility of mice to fungal infection. It is still unclear how EtOH affects host defense mechanisms but this model will provide a useful system to define these mechanisms.

중력가속스트레스가 마우스의 면역반응에 미치는 영향 : I. 흉선에 있어서 여러가지 면역학적 매개요소의 변화 I. Changes of Various Immunological Parameters in Thymus

박영민 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

The present study was undertaken to investigate the effect of gravitational stress on immune response potential by analyzing various parameters of immune respose in mice. Experimental groups of mice were subjected to a gravitational stress of +7Gz for 30sec/time/ day for 4 or 7 days. Concanavalin A(Con A)-induced proliferation of thymocytes, and expression of interleukin 2(IL-2) receptor and T cell subsets of thymocytes were analyzed by microculture technique and flow cytometry(FCM), respectively. And also DNA fragmentation was analyzed by FCM and by agarose gel electrophoresis. Gravitational stress induced the thymic hypoplasia. It was also found that stress-exposed mice showed the significant enhancement in Con A -induced proliferation of thymocytes but suppression of IL-2 receptor expression in resting and Con A-activated thymocytes. Exposure to the stress clearly changed the T cell subsets of thymus, i.e., the relative number of CD4+ CD8-, CD4-CD8+ and CD4- CD8- cells was increased, but the relative number of CD4+ CDS+ cells was de-creased profoundly. DNA fragmentation of thymocytes was not detected in stress-exposed and in vivo hydrocortisone-treated mice. The present study strongly suggests that gravitational stress can act as a potent stressor. And also these results would seem to indicate that gravitational stress may enhance blastogenic activity but decreases IL-2 receptor expression of thymocytes, and may changes the relative number of T cell subsets of thymocytes in mice. However, our experimental model using gravitational stress didn't show the apoptotic phenomenon.

암세포에 반응하는 면역 세포에 미치는 Ascorbate의 영향 : Ascorbate의 항암 효과 기작 Mechanism of Anticancer Effects

강영준,정가진 大韓免疫學會 1993 大韓免疫學會誌 Vol.15 No.-

Ascorbate is well-known as the anticancer molecule and has been studied as the anticancer drug, but its action mechanism is not well understood. We examined the anticancer effects and mechanism of ascorbate on EL-4 lymphoma-implanted mice. Intraperitoneal administration of ascorbate expanded the survival of EL-4-bearing mice compared with control group(p<0.05). In vitro treatment of ascorbate did not affect the physiology of tumor cells, but in vivo treatment of ascorbate did on the immune function. Injection of ascorbate into EL-4-implanted mice enhanced the cell-mediated cytotoxicity of NK ceIls(p<0.05), without any significant effect on CTL activity. However, in vitro treatment of ascorbate did not enhance the cytotoxic activity of enriched NK cells. So, it is thought that anticancer effect of ascorbate due to the enhancement of ascorbate may be mediated by the nthar mPrhanicmc

질내투여 인정장(人精漿)의 인정자(人精子) 및 면양적혈구에 대한 면역반응 억제작용

이헌구,김용탁,하대유 大韓免疫學會 1987 大韓免疫學會誌 Vol.9 No.1

A number of evidence has been accumulated to show that human seminal plasma (HSP) can suppress the immune responeses in vitro and in vivo. Several immunosuppressive factors have been identified from HSP and it has been proposed that these factors play a critical role in preventing sensitization of females to spermantigens after insemination. The purpose of the present study is to answer the q question whether HSI' is able to suppress in vivo immune responses induced by some antigens such as human sperms and sheep red blood cells(SRBC) which are introduced into the vagina of females. In this study the author used an experimental model in which mice were immunized intravaginally with human sperms and SRBC, and delayed-type hypersensitivity reacion (DTH) to these antigens was eva- luated by footpad swelling reaction. Repeated simultaneous intravaginal administrations of HSP with human sperms or SRBC significantly suppressed the DTH but failed to suppress the antibody formation to these antigens. However, intravaginal administration of a high molecular weigt fraction(G― 200 F, greater than 200 KD) which was partially purified by ammonium sulfate precipitation, DEAE- cellulose and Sephadex G -200 chromatography from HSP resulted in a significant suppression of DTH as well as antibody formation to SRBC. Furthermore, when various concentrations of G―200 F were ad-ministered intraperitoneally, a dose-dependent suppression of both DTH and antibody formation to SR BC was observed. These results provide the evidence that in vivo immunosuppressive activity of HSP is mediated by a high molecular weight fraction of greater than 200 KD and strongly support the concept that HSP can prevent sensitization of females to sperm antigens after insemination.

인체 각질형성세포의 Interleukin-6 생산에 미치는 UVB, UVA 및 PUVA의 영향

고우석,김규한,정진호,윤상호,윤재일,은희철 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

Huma Keratinocytes are capable of producing a wide variety of cytokines and growth factors that may act as mediator in an immune response and play an important role in proliferation and repair. Production of epidermal cytokines may be induced by bacterial products, by other proinflammatory cytokines, or by physical alteration including ultraviolet radiation. In the present study, we investigated the effect of UVA and PUVA on the production of IL-6 by cultured human keratinocyte. Human keratinocytes derived from normal foreskin were treated with various dose of UVB, UVA and PUVA. With the irradiated keratinocytes or culture supernatant we measured the expression of IL-6 mRNA and the production of IL-6. The result of - the present study was that the UVB increased the production of IL-6 but UVA and PUVA didn't increase the production of IL-6 by human keratinocyte.