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