The plasticity and dynamism in the immune responses to both self and environmental stimulation promote the maintenance and adaptation of a system that tends to harmoniously survive and evolve. Fluctuating antigenic fo...The plasticity and dynamism in the immune responses to both self and environmental stimulation promote the maintenance and adaptation of a system that tends to harmoniously survive and evolve. Fluctuating antigenic forces coexist within the immune system and oscillate between order and chaos to the equilibrium. Thus, when mounting a response to internal or environmental antigens, the main host responses can be divided into two immunological categories. The first, a well-adapted mechanism of complex multi-cellular organisms classically known as tolerance, promotes persistent immunological responses. In the second, opposite way, the modulation of inflammatory immune responses occurs, which we call “intolerance”. Tolerance and intolerance can be mediated by humoral molecules, such as inflammatory compounds, complement, and antibodies, and by different cell types, such as sentinel cells, antigen-presenting cells, and cells that orchestrate the immune response. Tolerogenesis is important in vertebrates because it predisposes species to adapt to self and environmental negative-selective forces. This process depends, in large part, on antigenic co-stimulation (AgCS), which operates as a multi-integrated network formed by all immune and non-immune cells of the body that establishes tolerant immunoregulatory interactions from cells to cells and from cells to the environment. Antigenic distribution, quantity, nature, route of administration, and antigenic convergence on co-stimulatory pathways, and concurrent infections, and the presence of microorganisms (commensals and pathogens) in more than one site are important factors for activating AgCS. To conclude, the AgCS route is a natural immune response generated by heterogeneous APC profile with centralized regulation that promote the counterbalance between intolerant e tolerant status, which can have several applications in the medical and biological fields.展开更多
Normal pregnancy is a contradictory and complicated physiological process.Although the fetus carries the human leukocyte antigen(HLA)inherited from the paternal line,it does not cause maternal immune rejection.As the ...Normal pregnancy is a contradictory and complicated physiological process.Although the fetus carries the human leukocyte antigen(HLA)inherited from the paternal line,it does not cause maternal immune rejection.As the only exception to immunological principles,maternal-fetal immune tolerance has been a reproductive immunology focus.In early pregnancy,fetal extravillous trophoblast cells(EVTs)invade decidual tissues and come into direct contact with maternal decidual immune cells(DICs)and decidual stromal cells(DSCs)to establish a sophisticated maternal-fetal crosstalk.This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk.Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion,pre-eclampsia,and premature birth.展开更多
Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability pos...Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival.Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory interventions.Immunological tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression strategies.Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks.Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities.Biomaterials,stem cell therapies,and precision immunomodulation represent promising avenues in this pursuit.Ultimately,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical practice.Through concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.展开更多
The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the...The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.展开更多
Objective: To investigate the significance of FTY 720 in combination with donor spleen cells in allogeneic tolerance induction. Methods: Different doses of FTY720 (1 mg· kg 1d1 or 10 mg· kg －1d －1 ) and di...Objective: To investigate the significance of FTY 720 in combination with donor spleen cells in allogeneic tolerance induction. Methods: Different doses of FTY720 (1 mg· kg 1d1 or 10 mg· kg －1d －1 ) and different number of donor spleen cells (5 ×107ｏr 5×108 ) were preoperatively administrated into rat cardiac allograft recipients. Resuits: It showed that FTY 720 had a synergistic effect with donor spleen cells on prolonging allograft survival as compared with FTY 720 alone. The number of donor spleen cells and FTY 720 doses are important factors influencing allograft curvival . Conclusion: It is suggested that allogeneic tolerance induction is related to the ways and frequency of antigen presentation by donor APC to recipient T cells.展开更多
文摘The plasticity and dynamism in the immune responses to both self and environmental stimulation promote the maintenance and adaptation of a system that tends to harmoniously survive and evolve. Fluctuating antigenic forces coexist within the immune system and oscillate between order and chaos to the equilibrium. Thus, when mounting a response to internal or environmental antigens, the main host responses can be divided into two immunological categories. The first, a well-adapted mechanism of complex multi-cellular organisms classically known as tolerance, promotes persistent immunological responses. In the second, opposite way, the modulation of inflammatory immune responses occurs, which we call “intolerance”. Tolerance and intolerance can be mediated by humoral molecules, such as inflammatory compounds, complement, and antibodies, and by different cell types, such as sentinel cells, antigen-presenting cells, and cells that orchestrate the immune response. Tolerogenesis is important in vertebrates because it predisposes species to adapt to self and environmental negative-selective forces. This process depends, in large part, on antigenic co-stimulation (AgCS), which operates as a multi-integrated network formed by all immune and non-immune cells of the body that establishes tolerant immunoregulatory interactions from cells to cells and from cells to the environment. Antigenic distribution, quantity, nature, route of administration, and antigenic convergence on co-stimulatory pathways, and concurrent infections, and the presence of microorganisms (commensals and pathogens) in more than one site are important factors for activating AgCS. To conclude, the AgCS route is a natural immune response generated by heterogeneous APC profile with centralized regulation that promote the counterbalance between intolerant e tolerant status, which can have several applications in the medical and biological fields.
基金supported by the Key R&D Projects of Shaanxi Province(No.2021SF-005)the Youth Independent Innovation Project of Tangdu Hospital(No.2023BTDQN020)
文摘Normal pregnancy is a contradictory and complicated physiological process.Although the fetus carries the human leukocyte antigen(HLA)inherited from the paternal line,it does not cause maternal immune rejection.As the only exception to immunological principles,maternal-fetal immune tolerance has been a reproductive immunology focus.In early pregnancy,fetal extravillous trophoblast cells(EVTs)invade decidual tissues and come into direct contact with maternal decidual immune cells(DICs)and decidual stromal cells(DSCs)to establish a sophisticated maternal-fetal crosstalk.This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk.Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion,pre-eclampsia,and premature birth.
文摘Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival.Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory interventions.Immunological tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression strategies.Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks.Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities.Biomaterials,stem cell therapies,and precision immunomodulation represent promising avenues in this pursuit.Ultimately,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical practice.Through concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.
基金Supported by Sao Paulo Research Foundation-FAPESP,Nos.2012/23347-3,2014/14147-6,2012/02270-2 and CNPq
文摘The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.
文摘Objective: To investigate the significance of FTY 720 in combination with donor spleen cells in allogeneic tolerance induction. Methods: Different doses of FTY720 (1 mg· kg 1d1 or 10 mg· kg －1d －1 ) and different number of donor spleen cells (5 ×107ｏr 5×108 ) were preoperatively administrated into rat cardiac allograft recipients. Resuits: It showed that FTY 720 had a synergistic effect with donor spleen cells on prolonging allograft survival as compared with FTY 720 alone. The number of donor spleen cells and FTY 720 doses are important factors influencing allograft curvival . Conclusion: It is suggested that allogeneic tolerance induction is related to the ways and frequency of antigen presentation by donor APC to recipient T cells.
