IMMUNOLOGY: Tolerance & Hypersensitivity
¹Kwakye Sylvester, ²Obiri Darko Stella, ³Sackey Lyanne
Tolerance
Immune tolerance also referred to as immunological tolerance or immunotolerance, is an active state of unresponsiveness to specific antigens in an effort to prevent the destructive over-reactivity of the immune system. It prevents an immune response to antigens produced by the body itself or recognized from a prior encounter.
Immune tolerance mechanisms are separated into two categories: ¹central tolerance and ²peripheral tolerance. These mechanisms occur at different stages of the lymphocyte lifecycle, and a deficiency in either category can result in serious consequences to the body.
Central Tolerance
Central tolerance mechanisms occur during lymphocyte development, either in the thymus for T cells or in the bone marrow for B cells. Through this process, immune cells with T cell receptors (TCRs) or B cell receptors (BCRs) that can recognize and bind to self-antigens are eliminated or, for some T cells, are differentiated into Regulatory T-cells (Tregs). By preventing the maturation of autoreactive lymphocytes, central tolerance helps the immune system discriminate between self-antigens and foreign materials.
Elimination of self-reactive lymphocytes can occur by one of several immune tolerance mechanisms:
Deletion - Cell death is induced in autoreactive immune cells
Anergy - Autoreactive immune cells are given signals that cause their antigen stimulation to cease, leaving them functionally incapable of differentiating into effector cells
Ignorance - Autoreactive immune cells that either do not encounter their self-antigen or bind to their self-antigen so weakly that they are “ignorant” of their own reaction and do not differentiate into effector cells
Peripheral Tolerance
Peripheral tolerance mechanisms occur after mature lymphocytes are released into the lymph nodes or other tissues. These mechanisms are intended to prevent autoreactive immune cells that have survived the mechanisms of central tolerance from damaging the periphery. One mechanism of peripheral tolerance is via Regulatory T-cells (Tregs), which can induce suppression or anergy of escaped cells with self-antigen receptors. This process prevents the immune system from overreacting to self-antigens or non-harmful materials.
Hypersensitivity reactions
A hypersensitivity reaction is an extreme immune response that the body has to an antigen. There are four different types of hypersensitivity reactions.
Each type of hypersensitivity reaction is an extreme immune response to an antigen. Each type of reaction differs based on the type of antigen the body identifies, what type of immune response the body generates, and how quickly the body produces the response.
Type 1 hypersensitivity reaction
Type 1 hypersensitivity causes an immediate response and occurs after a person has exposure to an antigen. With this type of reaction, the body responds to an antigen by producing IgE.
There are different components that can trigger type 1 hypersensitivity responses, including antigens that come from food products(eg; such as nuts, shellfish, and soy), animal sources( eg; cats, rats, or bee stings), environmental sources(eg; mold, latex, and dust), allergic conditions(such as allergic rhinitis, allergic asthma, and conjunctivitis).
There are two stages to type 1 hypersensitivity: ᵃthe sensitization stage and ᵇthe effect stage.
During the ᵃsensitization stage, the person encounters the antigen but does not experience any symptoms.
During the ᵇeffect stage, the person has exposure to the antigen again. As the body now recognizes the antigen, it is able to produce a response that results in the symptoms that people typically experience with an allergic reaction.
Type 2 hypersensitivity reaction
Type 2 hypersensitivity, also known as antibody-mediated cytotoxic hypersensitivity, is caused by immunoglobulin G (IgG) and IgM directed against antigens on cells or extracellular materials. The reaction leads to cytotoxic processes involving antibodies. Interference with the normal cellular operation generating either stimulatory or inhibitory dysfunction is another mechanism that occurs. The inciting antigen can be intrinsic or part of the host cell. Extrinsic antigens such as blood products or medications can provoke a similar reaction.
Type 2 hypersensitivity causes cytotoxic reactions, meaning that healthy cells die as they respond to the antigens. This can cause long-term damage to cells and tissues, resulting in conditions such as: ⁽ᶦ⁾the blood disorder immune thrombocytopenia if there are not enough platelets, ⁽ᶦᶦ⁾autoimmune hemolytic anaemia if the red blood cells burst, ⁽ᶦᶦᶦ⁾autoimmune neutropenia if the body destroys neutrophils, ⁽ᶦᵛ⁾autoimmune conditions such as Graves’ disease
Common causes of type 2 hypersensitivity reactions include drugs such as: penicillins, thiazides, cephalosporins, methyldopa.
Type 3 hypersensitivity reaction
In type 3 hypersensitivity, antigens and antibodies form complexes in the skin, blood vessels, joints, and kidney tissues. These complexes cause a series of reactions that lead to tissue damage.
Causes of a type 3 hypersensitivity reaction can include: ⁽ᶦ⁾drugs that contain proteins from different organisms(eg; antivenins), ⁽ᶦᶦ⁾the drug infliximab, which people use to manage autoimmune conditions, ⁽ᶦᶦᶦ⁾animal sources(eg; insect stings or tick bites).
Type 3 hypersensitivity reactions can lead to: serum sickness, Lupus, rheumatoid arthritis, small-vessel vasculitis, Henoch-Schönlein purpura
Type 4 hypersensitivity reaction
Unlike the other types, type 4 hypersensitivity reactions are cell-mediated. It is mediated by antigen-activated(sensitized) T lymphocytes. It is composed of delayed hypersensitivity mediated by CD4+ T cells and direct cell cytotoxicity mediated by CD8+ T cells. This type also differs from the other three in that it causes a delayed reaction.
Type 4 hypersensitivity is placed in three(3)as follows: ⁽ᶦ⁾contact dermatitis, ⁽ᶦᶦ⁾tuberculin-type hypersensitivity, ⁽ᶦᶦᶦ⁾granulomatous-type hypersensitivity.
Some common causes of type 4 hypersensitivity reactions include exposure to poison ivy, certain metals, and drugs such as antibiotics or anticonvulsants.
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