• 제목/요약/키워드: immune tolerance

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Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface

  • Jin Soo Joo;Dongeun Lee;Jun Young Hong
    • IMMUNE NETWORK
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    • 제24권4호
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    • pp.30.1-30.16
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    • 2024
  • Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.

Oral Tolerance: Not Simple But more Complex

  • Chung, Yeonseok;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • 제3권3호
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    • pp.169-175
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    • 2003
  • The intestinal immune system can discriminate between harmful and unharmful antigens and do not provoke productive immunity to unharmful antigen. Thus oral administration of antigen is one of classical methods for inducing antigen-specific immune tolerance in the periphery. Furthermore, oral tolerance has been investigated for the treatment of autoimmune disorders in human clinical trials. However, the detail mechanism of oral tolerance and contributing factors are not defined clearly at this time. Recent studies demonstrate unique types of immune cell that suppressing immune response, such as regulatory T cell and tolerogenic dendritic cell. This article reviews the factors involved in oral tolerance and discusses our current understanding base on the recent literatures and our works.

Antibody Diversity 원리와 Antigen Presenting Cell을 구현한 새로운 인공 면역 시스템 (A New Artificial Immune System Based on the Principle of Antibody Diversity And Antigen Presenting Cell)

  • 이상형;김은태;박민용
    • 전자공학회논문지CI
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    • 제41권4호
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    • pp.51-58
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    • 2004
  • 본 논문에서는 fault tolerant 하드웨어에서 가장 기본이 되는 온라인 하드웨어 테스트 시스템 구현을 위하여 새로운 인공면역 알고리즘을 제안한다. 인공 면역 알고리즘은 알려진 자기(self) 정보만을 이용하여 항체 즉 tolerance condition을 가장 최적으로 생성하는 알고리즘이다. 이를 위하여 본 논문에서는 생체 면역 시스템의 중요한 원리인 antibody diversity 원리를 적용한 새로운 tolerance condition 생성 알고리즘을 제안한다. 또한 생체 면역 시스템에서의 중요한 세포인 APC (Antigen Presenting Cell)를 Quine-McCluskey 방법으로 구현한 후 유전자 알고리즘을 통해 tolerance condition을 자동 생성하는 알고리즘을 구현한다. 이렇게 제안된 알고리즘은 FSM(Finite State Machine)의 가장 전형적인 예인 십진카운터에 적용한 후 컴퓨터 모의 실험을 통해 그 성능을 확인한다.

Mechanisms of immune tolerance to allergens in children

  • Kucuksezer, Umut C.;Ozdemir, Cevdet;Akdis, Mubeccel;Akdis, Cezmi A.
    • Clinical and Experimental Pediatrics
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    • 제56권12호
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    • pp.505-513
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    • 2013
  • Because the prevalence of allergic diseases has significantly increased in recent years, understanding the causes and mechanisms of these disorders is of high importance, and intense investigations are ongoing. Current knowledge pinpoints immune tolerance mechanisms as indispensable for healthy immune response to allergens in daily life. It is evident that development and maintenance of allergen-specific T cell tolerance is of vital importance for a healthy immune response to allergens. Such tolerance can be gained spontaneously by dose-dependent exposures to allergens in nature or by allergen-specific immunotherapy. Allergen-specific immunotherapy induces regulatory T cells with the capacity to secrete interleukin-10 and transforming growth factor-${\beta}$, limits activation of effector cells of allergic inflammation (such as mast cells and basophils), and switches antibody isotype from IgE to the noninflammatory type IgG4. Although allergen-specific immunotherapy is the only method of tolerance induction in allergic individuals, several factors, such as long duration of treatment, compliance problems, and life-threatening side effects, have limited widespread applicability of this immunomodulatory treatment. To overcome these limitations, current research focuses on the introduction of allergens in more efficient and safer ways. Defining the endotypes and phenotypes of allergic diseases might provide the ability to select ideal patients, and novel biomarkers might ensure new custom-tailored therapy modalities.

자가 면역 (Autoimmunity)

  • 김중곤
    • Clinical and Experimental Pediatrics
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    • 제50권12호
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    • pp.1165-1172
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    • 2007
  • Self/non-self discrimination and unresponsiveness to self is the fundamental properties of the immune system. Self-tolerance is a state in which the individual is incapable of developing an immune response to an individual's own antigens and it underlies the ability to remain tolerant of individual's own tissue components. Several mechanisms have been postulated to explain the tolerant state. They can be broadly classified into two groups: central tolerance and peripheral tolerance. Several mechanisms exist, some of which are shared between T cells and B cells. In central tolerance, the recognition of self-antigen by lymphocytes in bone marrow or thymus during development is required, resulting in receptor editing (revision), clonal deletion, anergy or generation of regulatory T cells. Not all self-reactive B or T cells are centrally purged from the repertoire. Additional mechanisms of peripheral tolerance are required, such as anergy, suppression, deletion or clonal ignorance. Tolerance is antigen specific. Generating and maintaining the self-tolerance for T cells and B cells are complex. Failure of self-tolerance results in immune responses against self-antigens. Such reactions are called autoimmunity and may give rise to autoimmune diseases. Development of autoimmune disease is affected by properties of the genes of the individual and the environment, both infectious and non-infectious. The host's genes affect its susceptibility to autoimmunity and the environmental factors promote the activation of self-reactive lymphocytes, developing the autoimmunity. The changes in participating antigens (epitope spreading), cells, cytokines or other inflammatory mediators contribute to the progress from initial activation to a chronic state of autoimmune diseases.

A New Artificial Immune Approach to Hardware Test Based on the Principle of Antibody Diversity

  • Lee, Sanghyung;Kim, Euntai;Park, Mignon
    • International Journal of Fuzzy Logic and Intelligent Systems
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    • 제3권1호
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    • pp.23-26
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    • 2003
  • This paper proposes a new artificial immune approach to hardware test. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

하드웨어 테스트를 위한 새로운 인공 면역 시스템 (A New Artificial Immune Approach to Hardware Test Based on The Principle of Antibody Diversity)

  • 이상형;김은태;박민용
    • 대한전자공학회:학술대회논문집
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    • 대한전자공학회 2003년도 하계종합학술대회 논문집 V
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    • pp.2673-2676
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    • 2003
  • This Paper proposes a new artificial immune approach to hardware test. A Novel Algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

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Oral Tolerance Increased the Proportion of CD8+ T Cells in Mouse Intestinal Lamina Propria

  • Cho, Kyung-Ah;Cha, Je-Eun;Woo, So-Youn
    • IMMUNE NETWORK
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    • 제8권2호
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    • pp.46-52
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    • 2008
  • Background: Oral tolerance is defined by the inhibition of immune responsiveness to a protein previously exposed via the oral route. Protein antigens exposed via the oral route can be absorbed through the mucosal surfaces of the gastrointestinal tract and can make physical contact with immune cells residing in the intestinal lamina propria (LP). However, the mechanisms of oral tolerance and immune regulation in the intestines currently remain to be clearly elucidated. Methods: In order to determine the effect of oral protein antigen intake (ovalbumin, OVA) on the intestinal LP, we assessed the expression profile of the T cell receptor and the co-receptors on the cells from the intestines of the tolerant and immune mouse groups. Results: We determined that the proportion of OVA-specific B cells and ${\gamma}{\delta}$ T cells had decreased, but the CD8${\alpha}{\beta}$ and D8${\alpha}{\alpha}$ T cells were increased in the LP from the tolerant group. The proportion of CD8+ T cells in the spleen did not evidence any significant differences between treatment groups. Conclusion: These results indicate that CD8+ T cells in the intestinal LP may perform a regulatory role following antigen challenge via the oral route.

Induction of Oral Tolerance to Japanese Cedar Pollen

  • Kim, Joung-Hoon;Mun, Yeun-Ja;Ahn, Seong-Hun;Park, Joung-Suk;Woo, Won-Hong
    • Archives of Pharmacal Research
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    • 제24권6호
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    • pp.557-563
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    • 2001
  • Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10 mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total Igl level and anti-JCP IgGl level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

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Dendritic Cell-based Immunotherapy for Rheumatoid Arthritis: from Bench to Bedside

  • Md. Selim Ahmed;Yong-Soo Bae
    • IMMUNE NETWORK
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    • 제16권1호
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    • pp.44-51
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    • 2016
  • Dendritic cells (DCs) are professional antigen presenting cells, and play an important role in the induction of antigen-specific adaptive immunity. However, some DC populations are involved in immune regulation and immune tolerance. These DC populations are believed to take part in the control of immune exaggeration and immune disorder, and maintain immune homeostasis in the body. Tolerogenic DCs (tolDCs) can be generated in vitro by genetic or pharmacological modification or by controlling the maturation stages of cytokine-derived DCs. These tolDCs have been investigated for the treatment of rheumatoid arthritis (RA) in experimental animal models. In the last decade, several in vitro and in vivo approaches have been translated into clinical trials. As of 2015, three tolDC trials for RA are on the list of ClinicalTrial.gov (www.clinicaltrials.gov). Other trials for RA are in progress and will be listed soon. In this review, we discuss the evolution of tolDC-based immunotherapy for RA and its limitations and future prospects.