Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen[1][2] and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.
Immune tolerance is important for normal physiology and homeostasis. Central tolerance is crucial for enabling the immune system to differentiate between self and non-self antigens, thereby preventing autoimmunity. Peripheral tolerance plays a significant role in preventing excessive immune reactions to environmental agents, including allergens and gut microbiota. Deficiencies in either central or peripheral tolerance mechanisms can lead to autoimmune diseases, with conditions such as systemic lupus erythematosus,[3] rheumatoid arthritis, type 1 diabetes,[4] autoimmune polyendocrine syndrome type 1 (APS-1),[5] and immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX)[6] as examples. Furthermore, disruptions in immune tolerance are implicated in the development of asthma, atopy,[7] and inflammatory bowel disease.[4]
In the context of pregnancy, immune tolerance is vital for the gestation of genetically distinct offspring, as it moderates the alloimmune response sufficiently to prevent miscarriage.
However, immune tolerance is not without its drawbacks. It can permit the successful infection of a host by pathogenic microbes that manage to evade immune elimination.[8] Additionally, the induction of peripheral tolerance within the local microenvironment is a strategy employed by many cancers to avoid detection and destruction by the host's immune system.[9]
^Medawar P (December 12, 1960). "Nobel Lecture: Immunological Tolerance". The Nobel Prize. Retrieved 24 July 2020.
^Murphy K (2012). "Chapter 15: Autoimmunity and Transplantation". Janeway's Immunobiology (8th ed.). Garland Science. pp. 611–668. ISBN 978-0-8153-4243-4.
^Choi J, Kim ST, Craft J (December 2012). "The pathogenesis of systemic lupus erythematosus-an update". Current Opinion in Immunology. 24 (6): 651–657. doi:10.1016/j.coi.2012.10.004. PMC 3508331. PMID 23131610.
^ abRound JL, O'Connell RM, Mazmanian SK (May 2010). "Coordination of tolerogenic immune responses by the commensal microbiota". Journal of Autoimmunity. 34 (3): J220–J225. doi:10.1016/j.jaut.2009.11.007. PMC 3155383. PMID 19963349.
^Perniola R (2012). "Expression of the autoimmune regulator gene and its relevance to the mechanisms of central and peripheral tolerance". Clinical & Developmental Immunology. 2012: 207403. doi:10.1155/2012/207403. PMC 3485510. PMID 23125865.
^Verbsky JW, Chatila TA (December 2013). "Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders: an evolving web of heritable autoimmune diseases". Current Opinion in Pediatrics. 25 (6): 708–714. doi:10.1097/mop.0000000000000029. PMC 4047515. PMID 24240290.
^Maazi H, Lam J, Lombardi V, Akbari O (June 2013). "Role of plasmacytoid dendritic cell subsets in allergic asthma". Allergy. 68 (6): 695–701. doi:10.1111/all.12166. PMC 3693732. PMID 23662841.
^Curotto de Lafaille MA, Lafaille JJ (May 2009). "Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?". Immunity. 30 (5): 626–635. doi:10.1016/j.immuni.2009.05.002. PMID 19464985.
^Becker JC, Andersen MH, Schrama D, Thor Straten P (July 2013). "Immune-suppressive properties of the tumor microenvironment". Cancer Immunology, Immunotherapy. 62 (7): 1137–1148. doi:10.1007/s00262-013-1434-6. PMC 11029603. PMID 23666510. S2CID 20996186.
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disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies...
rendered non-reactive to self Immunetolerance in pregnancy or gestational/maternal immunetolerance Low frustration tolerance, a concept in Rational Emotive...
healthy individuals, immunetolerance prevents the immune system from attacking the body's own cells. When this process fails, the immune system may produce...
immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T...
from immune privileged regions have been found to interact with T cells in an unusual way: inducing tolerance of normally rejected stimuli. Immune privilege...
autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides. Lymphocyte maturation (and central tolerance) occurs in primary...
autoaggressive immune responses in the immune system. Tolerance can also be differentiated into "central" and "peripheral" tolerance, on whether or not...
The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of...
absence of them) between the immune system and components related to the reproductive system, such as maternal immunetolerance towards the fetus, or immunological...
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induce tolerance through immunotherapy) on Treg function and epigenetic changes. This research led to novel findings on markers of immunetolerance in clinical...
can lead to common complaints, such as palpitations, decreased exercise tolerance, and dizziness. Uterine enlargement beyond 20 weeks' size can compress...
writer, whose works on graft rejection and the discovery of acquired immunetolerance have been fundamental to the medical practice of tissue and organ transplants...
role in central tolerance. Clonal deletion can help protect individuals against autoimmunity, which is when an organism produces and immune response on its...
as well, being intimately involved in wound healing, angiogenesis, immunetolerance, defense against pathogens, and vascular permeability in brain tumors...
differentiating to Treg cells and preventing a fetal immune response to maternal antigens. This expanded immunetolerance persists in both mother and offspring after...
T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells...
allergies by strengthening the immune system. In particular, a lack of such exposure is thought to lead to poor immunetolerance. The time period for exposure...
their T-cell receptor, or TCR. Immunetolerance is maintained by central and peripheral tolerance. During central tolerance, T-cells are selected in the...
to immunology. He won a Nobel Prize in 1960 for predicting acquired immunetolerance and he developed the theory of clonal selection. Burnet received his...
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from...
MHC class II and for his seminal studies in the fields of transplant immunetolerance and xenotransplantation. David Sachs graduated summa cum laude in organic...
Patients then come to clinical attention when this tumor immune response breaks immunetolerance and begins to attack the normal tissue expressing that...
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