Definition of Immunological Tolerance

Immunological tolerance is a state of specific immunologic nonreactivity to a specific antigen to which an individual has been previously exposed. Immune tolerance stops the immune system from responding to self-antigens.

Mechanisms of Tolerance

The proposed mechanisms of tolerance are clonal deletion, clonal anergy, and suppression.

• Clonal deletion: Clones of B and T cells that detect self-antigens are eliminated selectively during embryonic development; hence, they are unavailable to respond to subsequent antigen exposure. This process is called clonal deletion.
• Clonal anergy: Clonal anergy is a condition where clones of B and T cells that detect self-antigens are present but cannot be activated.
• Suppression: This technique of suppression preserves clones of B and T cells expressing receptors that identify self-antigens. Nonetheless, active suppression may impede the expression of immunological responses following antigen identification.

Types of Immune Tolerance

There are two types of immunological tolerance: natural and acquired.

1. Natural tolerance

• Natural tolerance is the absence of a response to self-antigens.
• It develops throughout embryonic development, and every antigen that contacts the immune system during embryonic development is regarded as self-antigen.
• There would be no immunological response to the selfantigen.
• Burnet and Fenner (1949) similarly hypothesised that foreign antigens supplied during foetal development would not elicit an immunological response.

2. Acquired tolerance

• The development of acquired tolerance occurs when a potential immunogen produces a state of desensitisation to itself.
• Antigen must be delivered repeatedly or continuously to maintain acquired tolerance.
• This is likely required due to the constant creation of new B and T cells that must be made tolerant.
• Several factors affect the induction of immunological tolerance. These include (a) the host’s species and immunological competency and (b) the physical nature, dosage, and method of delivery of antigens.

a. Species and immune competence of the host

• The level of immunological development of the host determines tolerance.
• Because embryos and newborn animals are immunologically young, they are more sensitive to tolerance induction.
• It is easier to inculcate tolerance in rabbits and mice than in guinea pigs and chickens.

b. Physical nature, dose, and route of administration of antigens

• Antigens and haptens that are soluble can generate greater immunological tolerance than aggregated antigens. To illustrate, heat-aggregated human gamma globulin is more tolerogenic than deaggregated mouse gamma globulin.
• It may be owing to increased phagocytosis of aggregated proteins than soluble antigens by macrophages, where they can be delivered to antibody-forming cells, hence stimulating antibody formation. Tolerance induction is also dosage dependant.
• A simple molecule induces tolerance more rapidly than a complex compound, for instance. Repeated low and high doses of antigen induce B-cell tolerance, whereas a moderate amount of the same antigen may be immunogenic.
• The administrative route is also significant. Certain haptens administered intravenously or orally induce tolerance in guinea pigs, whereas intradermal treatment induces immunity.
• T cells acquire tolerance more quickly than B cells and also maintain tolerance for a longer duration than B cells. Tolerance can be overcome either naturally or through the injection of cross-reacting antigens.
• In rabbits, immunisation with cross-reacting human serum albumin can eliminate tolerance to bovine serum albumin.
• By administering immunosuppressive medicines, tolerance can be increased. For instance, tolerance is increased among patients who have had organ transplantation.

References

• Waldmann, H. (2014). Immunological Tolerance. Reference Module in Biomedical Sciences. doi:10.1016/b978-0-12-801238-3.00116-1