Hypersensitivity Reactions

Hypersensitivity reactions are immune responses that are excessive or have undesirable effects like disease or damage to the body. They are categorized as type I, II, III, or IV based on the immune response and its effect.

Type I hypersensitivity reactions, also called immediate hypersensitivity reactions or IgE-mediated reactions, occur in response to normally harmless triggers, like pollen, bee stings, or medications.

Type I hypersensitivity reactions occur in two steps which involve a primary exposure, called sensitization, and a subsequent exposure, when the inflammatory reaction occurs.

First, the immune system is exposed to an antigen, or allergen.

Next, antigen-presenting cells, called APCs, present the allergen to T cells which then become helper T-cells, or Th2 cells. The Th2 cells then release large amounts of cytokines that signal B cells to proliferate and turn into plasma cells that start producing IgE antibodies, which bind to mast cells, sensitizing them.

Then, during subsequent exposure, the antigen forms crosslinks on the IgE antibodies on the mast cell membrane, causing mast cell degranulation and release of proinflammatory mediators like histamine, resulting in an acute inflammatory reaction.

Because this is an immediate hypersensitivity reaction, clinical manifestations typically occur within 15 to 30 minutes of subsequent exposure to the antigen.

Manifestations can include rhinitis, characterized by sneezing and nasal congestion; hives, along with rash, redness, and itching; angioedema, where swelling occurs in the deep layers of skin; bronchospasm, which is a tightening of the bronchial smooth muscle; and even systemic reactions like anaphylaxis, characterized by difficulty breathing, hypotension, and death if left untreated.

Next, type II hypersensitivity reactions, also called tissue-specific or cytotoxic reactions, are mediated by IgG or IgM antibodies against target antigens on a specific tissue or cell.

Examples of type II hypersensitivity reactions include complement-mediated lysis; antibody-dependent cell-mediated cytotoxicity, or ADCC; and antireceptor antibodies, also called antibody-mediated cellular dysfunction.

Each mechanism begins with antibodies binding to tissue-specific antigens, which are expressed on certain cell surfaces.

First, with complement-mediated lysis, antibody-antigen binding activates a complement cascade that ultimately forms membrane attack complexes, or MACs, which then bind to the target cell and induce cell lysis.

A common type of complement-mediated lysis is an ABO transfusion reaction. For example, if a patient with type A blood is given a transfusion from a donor with type B blood, the patient’s immune system, which has anti-B antibodies, will attack the donor blood, leading to red blood cell hemolysis.

Next, ADCC happens when antibodies bind to antigens on target cells. This attracts immune cells like natural killer cells, which release toxic substances onto the target cell causing cell lysis.