IMMUNOLOGICAL TOLERANCE
DEFINITION
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in a given organism. It is induced by prior exposure to that specific antigen
MAJOR TYPES
Natural or "self" tolerance
This is the failure (a good thing) to attack the body's own proteins and other antigens. If the immune system should respond to "self", an autoimmune disease may result.
Induced tolerance.
deliberately manipulating the immune system to protect us from unpleasant, even dangerous, allergic reactions to such things as food
deliberately manipulating the immune system to enable transplanted organs (e.g., kidney, heart, liver) to survive in their new host; that is, to avoid graft rejection.
Preventing the immune system from mounting an inflammatory attack against the vast numbers of harmless (even beneficial) bacteria living in the intestine.
T-CELL TOLERANCE
Central Tolerance
T cells develop in the thymus. As they mature, recombination of gene segments creates the two chains that make up the T-cell receptor for antigen (TCR). Although the receptors on a single T cell are all alike, there is a virtually unlimited repertoire of receptor specificities created in the population of T cells within the thymus.
epitopes recognised by receptors
a small molecule, usually a peptide of 6–8 amino acids derived from body proteins
a histocompatibility molecule
class II for CD4+ T cells
class I for CD8+ T cells
T cells whose receptors bind these epitopes so tightly that they could attack the cell displaying them are deleted by apoptosis. The T cells that survive this negative selection leave the thymus and migrate throughout the immune system (lymph nodes, spleen, etc.).
proteins aiding in the process
the precursor to insulin
thyroglobulin (precursor of the thyroxine secreted by the thyroid gland)
casein (protein in the milk secreted by the mammary glands)
a protein secreted by the salivary glands
Peripheral Tolerance
The T cells that leave the thymus are relatively — but not completely — safe.
receptors (TCRs) that can respond to self antigens
that are present in such high concentration that they can bind to "weak" receptor
that they may not have encountered in the thymus.
Negative Selection in the Peripheral Immune System
Lack of Costimulation
Failure to Encounter Self Antigens
Receipt of Death Signals
Control by Regulatory T Cells
B-CELL TOLERANCE
The problem of B-cell tolerance is not so acute because B cells cannot respond to most antigens unless they receive help from T helper cells.
Central Tolerance
Any cells that produce a receptor for antigen (BCR) that would bind self components too tightly undergo a process of receptor editing. They dip again into their pool of gene segments that encode the light and heavy chains of their BCRand try to make a new BCR that is not a threat. If they fail, they commit suicide (apoptosis).
Peripheral Tolerance
B cells with a potential for attacking self can be kept in check by the absence of the T-helper cells they need; that is, T-cell tolerance is probably the most important (but not the only) mechanism for maintaining B-cell tolerance
AUTO IMMUNE DISORDERS
Type 1 diabetes mellitus
multiple sclerosis (MS)
systemic lupus erythematosus (SLE)
some forms of hyperthyroidism
Causes
mutant genes
immune hemolytic anemia
immune thrombocytopenia
Infections
rheumatic heart disease.
TOLERANCE IN COMMENSAL BACTERIA
Stimulating the development of regulatory T cells (Treg) which provide protection against any inflammatory response that effector T cells might mount against the bacteria.
Enlisting the aid of a subset of innate lymphoid cells designated ILC3. ILC3 cells engulf bacterial antigens and process these into peptides nestled in the MHC class II molecules on their surface
ALLERGY TREATMENTS
the active ingredient in poison ivy that triggers this cell-mediated immune response
allergens that trigger IgE-mediated allergic responses
ragweed, grass, and tree pollens;
insect stings;
food allergens, e.g., peanuts and other nuts
TOLERANCE IN PHYSIOLOGY AND MEDICINE
Allograft tolerance
Fetal development
The microbiome
Oral tolerance and hypersensitivity
The tumor microenvironment
SANDHYA A 191822016