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.
Autoantigens ; Autoimmune Diseases ; Autoimmunity* ; B-Lymphocytes ; Bone Marrow ; Central Tolerance ; Clonal Deletion ; Cytokines ; Discrimination (Psychology) ; Immune System ; Lymphocytes ; Peripheral Tolerance ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Thymus Gland

How is the balance between immune response and immune tolerance dynamically kept in the complicated immune system of human body? To answer this question, many scientists have proposed various models since 1950's. A brief introduction to these models is given in this mini-review, which might reflect the historical process in the development of immunology in the past half century.
Animals ; Clonal Anergy ; Clone Cells ; Humans ; Immune Tolerance ; Immunity ; Models, Immunological

The development of immunosuppressant treatments has enabled remarkable progress in the tissue and organ transplantation field by helping to prevent acute graft rejection. However, complications related to transplantation, such as infection by bacteria and viruses, and the occurrence of cancers resulting from prolonged immune suppression are major obstacles to overcome. Therefore, transplantation immunology research efforts should focus on the induction of donor-specific immune tolerance which preserves patient immune competence which promotes infection and cancer surveillance. Additionally, lifelong administration of immunosuppressants should be forgone in preference to short term therapies. In the 1990s, Dr. Shimon Sakaguchi identified the CD4+CD25+ regulatory T cells which develop in the thymus, and demonstrated that these cells play crucial roles in the maintenance of immune self tolerance. Studies which followed proved that these regulatory T cells are important to the control of autoimmune disease and prevention of graft rejection. Regulatory T cells have also been found to induce immune tolerance in rodent models. In this review, we discuss several considerations for the use of regulatory T cell therapy in the clinical transplantation field.
Autoimmune Diseases ; Bacteria ; Graft Rejection ; Humans ; Immune Tolerance ; Immunosuppressive Agents ; Mental Competency ; Organ Transplantation ; Rodentia ; Self Tolerance ; T-Lymphocytes, Regulatory ; Thymus Gland ; Tissue Therapy ; Transplantation Immunology ; Transplants

Dendritic cells (DC) play an important roles in the maintenance of central immune tolerance and peripheral immune tolerance. DC can be involved in formation of autoimmune tolerance by many mechanisms and demonstrate strong plasticity, so that DC become hot issue in the research of transplantation tolerance recently. In this article the DC typing and its role, the indirect pathway of DC-inducing immune tolerance, the F1t3L and apoptotic cell role, the modified DC by genetic engineering and the immune inhibitors were summarized.
Dendritic Cells ; immunology ; Humans ; Immune Tolerance ; Transplantation Tolerance ; immunology

Hepatitis, Autoimmune ; Humans ; Immune Tolerance ; Liver Transplantation

The immune system is continuously exposed to great amounts of different antigens from both food and intestinal microbes. Immune tolerance to these antigens is very important for intestinal and systemic immune homeostasis. Oral tolerance is a specific type of peripheral tolerance induced by exposure to antigen via the oral route. Investigations on the role of intestinal immune system in preventing hypersensitivity reactions to innocuous dietary and microbial antigens have been intensively performed during the last 2 decades. In this review article, we discuss how food allergens are recognized by the intestinal immune system and draw attention to the role of regulatory T (Treg) and B (Breg) cells in the establishment of oral tolerance and tolerogenic features of intestinal dendritic cells. We also emphasize the potential role of tonsils in oral tolerance induction because of their anatomical location, cellular composition, and possible usage to develop novel ways of specific immunotherapy for the treatment of allergic diseases.
Allergens ; Dendritic Cells ; Food Hypersensitivity ; Homeostasis ; Hypersensitivity ; Immune System ; Immune Tolerance ; Immunotherapy ; Palatine Tonsil ; Peripheral Tolerance

No abstract available.
Immune Tolerance*

Veto activity was defined as the capacity of specifically downregulating cytotoxic T-precursor cell (CTL-p) directed against antigens of the veto cells themselves but not against third-party antigens. Many studies have shown that the most potent veto cells are CD8(+) cytotoxic T lymphocytes (CD8(+)CTLs). Effectively, CD8(+)CTLs of donor origin can facilitate engraftment of donor's stem cells by eliminating host-alloreactive T lymphocytes. In this article, effect mechanisms, depletion of GVH ex vivo, application in vivo, synergistic enhancement with rapamycin and regulatory T cells, and anti-tumor effect in the hematopoietic stem cell transplantation are summarized.
Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; T-Lymphocytes, Cytotoxic

The development of immunosuprressants has had a significant influence on inhibition of acute allograft rejection. However, long-term graft survival has not been achieved by immunosuppressants, probably because of their nonspecific suppression of T cell activity and nonimmune side effects. The ideal way to overcome the limitations of current immunosuppressants is to induce allograft-specific immune tolerance. Transplant immunologists are exerting their efforts in achieving transplantation tolerance using four different approaches; costimulatory blockade, mixed hematopoietic chimerism, T cell depletion, and regulation by regulatory T cells. It is expected that transplantation tolerance will soon be established as a standard immunosuppressive regimen with little side effects in preventing and reversing allograft rejection.
Allografts ; Chimerism ; Graft Survival ; Immune Tolerance ; Immunosuppressive Agents ; T-Lymphocytes, Regulatory ; Transplantation Tolerance*

The development of immunosuprressants has had a significant contribution to inhibition of acute allograft rejection. However, long-term graft survival has not been realized by immunosuppressants, probably because of their nonspecific suppression of T cell activity and nonimmune side effects. The ideal way to overcome the limitations of current immunosuppressants is to induce allograft-specific immune tolerance. Transplant immunologists are exerting their efforts in achieving transplantation tolerance using three different approaches; mixed hematopoietic chimerism, costimulatory blockade, and regulation by regulatory T cells. It is expected that transplantation tolerance will soon be established as a standard immunosuppressive regimen with little side effects in preventing and reversing allograft rejection.
Allografts* ; Chimerism ; Graft Survival ; Immune Tolerance* ; Immunosuppressive Agents ; T-Lymphocytes, Regulatory ; Transplantation Tolerance