Objective: Due to the special anatomical structure and pathophysiological mechanism of the central nervous system (CNS), there is a big difference between the repair of brain injury and other systems of the body. More and more evidence shows that targetedly reducing the autoimmune response of brain tissue without affecting the immune function in other parts of the body will be the best optimized treatment for brain injury. Data Sources: This review was based on data in articles published in PubMed up to June 5, 2017, with the following keywords: "immune tolerance", "traumatic brain injury", and "central nervous system". Study Selection: Original articles and critical reviews on immune tolerance and brain damage were selected for this review. References of the retrieved articles were also screened to search for potentially relevant papers. Results: The CNS is isolated from the immune system through the blood-brain barrier. After brain injury, brain antigens are released into the systemic circulation to induce damaging immune responses. Immune tolerance can effectively reduce the brain edema and neurological inflammatory response after brain injury, which is beneficial to the recovery of neurological function. The clinical application prospect and theoretical research value of the treatment of immune tolerance on traumatic brain injury (TBI) is worth attention. Conclusions The establishment of immune tolerance mechanism has a high clinical value in the treatment of TBI. It opens up new opportunities for the treatment of brain damage.
Brain ; immunology ; Brain Injuries, Traumatic ; immunology ; therapy ; Central Nervous System ; Humans ; Immune Tolerance ; Immunotherapy

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

Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.
Autoantigens ; Blood Vessels ; Central Tolerance* ; Clonal Deletion ; Dendritic Cells* ; Epithelial Cells ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Thymocytes ; Thymus Gland

AIMTo investigate the effects of intragastric administration of thenorphine (Then) on behavioral sensitization to morphine (Mor) in mice.

METHODSLocomotor activity was detected after intragastric administration of thenorphine or co-administration of thenorphine with Mor in mice. Mice were induced to be behaviorally sensitive to Mor, and were given the combination of Mor and thenorphine to observe the effects of thenorphine on the development, transfer and expression of Mor-induced behavioral sensitization.

RESULTSA single intragastric administration of thenorphine (1.25 - 5.0 mg x kg(-1)) dose-dependently inhibited the locomotor activity in mice (P < 0.01) and the effects of thenorphine on locomotor activity developed tolerance after repeated administration. Co-administration of thenorphine effectively inhibited Mor-induced hyperactivity (P < 0.05) and the development, transfer, expression of Mor-induced behavioral sensitization in mice (P < 0.05 or P < 0.01).

CONCLUSIONThenorphine was shown to suppress the central nervous system and may be effective against the abuse and addiction to opioids.

Animals ; Behavior, Animal ; drug effects ; Buprenorphine ; analogs & derivatives ; pharmacology ; Central Nervous System Depressants ; pharmacology ; Dose-Response Relationship, Drug ; Drug Tolerance ; Female ; Male ; Mice ; Morphine ; antagonists & inhibitors ; Motor Activity ; drug effects ; Random Allocation