The immune system plays a crucial role in maintaining health and protecting the human body against microbial invasions. Hypersensitivity reactions are exaggerated immune and inflammatory responses that result in adverse outcomes. There are four traditional classifications for hypersensitivity reactions, and these include Type I, Type II, Type III, and Type IV reactions.
Type I hypersensitivity reaction
is a rapid immunologic reaction occurring in a previously sensitized individual, occurs within minutes and is mediated by IgE antibody, which results in allergy, anaphylaxis and atopic disease.
When an individual first encounters an antigen, their immune system may produce large amounts of IgE antibodies against this specific substance. These IgE molecules attach themselves to mast cells and basophils. The individual is now ‘sensitised’ to the antigen. When this antigen is encountered again, it will cause cross-linking of the bound IgE and degranulation of mast cells and basophils, releasing potent vasoactive molecules such as histamine and Serotonin that act on vessels and smooth muscle and pro-inflammatory cytokines that recruit inflammatory cells. Examples are: bronchial asthma, allergic rhinitis, anaphylaxis reactions.
Type II hypersensitivity reaction
is also known as Antibody-mediated. Antibodies that react with antigens present on cell surfaces or in the extracellular matrix cause disease by destroying these cells, triggering inflammation, or interfering with normal functions. The antibodies may be specific for normal cell or tissue antigens (endogenous autoantibodies) or for exogenous antigens, such as chemical or microbial proteins that bind to a cell surface or tissue matrix.
Depending on the mechanism of tissue injury and outcome, there are 3 main types of Type II Hypersensitivity reaction
1. Antibody Dependent Cytotoxicity
2. Complement and Fc receptor Mediated Inflammation and Tissue Destruction
3. Antibody-Mediated Cellular Dysfunction
Type III (Immune complex mediated) hypersensitivity reaction
Antigen-antibody complexes produce tissue damage mainly by causing inflammatory reaction at the sites of deposition. Tissue damage results when antigen combines with antibody in the circulation, forming immune complexes that typically deposit in vessel walls. The complexes may also be formed at sites where antigen has been previously “planted” (called in situ immune complexes).
The antigens that form immune complexes may be exogenous, such as a foreign protein that is injected or produced by an infectious microbe, or endogenous, if the individual produces antibody against self antigen (autoantibodies). Immune complex–mediated diseases tend be systemic, often preferentially involve the kidney (Glomerulonephritis), Joints (Arthritis), and Small blood vessels (Vasculitis),
Morphologically, immune complex disease manifests as fibrinoid necrosis, characterized by necrosis of the vessel wall, intense neutrophilic infiltration and immune complex deposition. Examples are systemic Lupus Erythematosus (SLE), poststreptococcal glomerulonephritis.
Type IV (T cell–mediated) delayed hypersensitivity reactions
Type IV hypersensitivity is also known as delayed hypersensitivity, as the reaction typically occurs 24 to 72 hours after antigen exposure. Unlike types I to III, it is T cell-mediated. It is involved in the process of the tuberculin skin test (Mantoux). When an individual first encounters an antigen, it can be processed by antigen-presenting cells and lead to sensitisation of T helper cells.
On subsequent exposure to this antigen, these T helper cells will become activated and this leads to an inflammatory response involving several immune cells such as macrophages, though there will be a delay of 24 to 72 hours as cells are recruited to the site of antigen exposure. This can cause local tissue inflammation and damage with sustained activation, macrophages often undergo a morphologic transformation into epithelioid cells, which are large epithelium-like cells with abundant cytoplasm. Morphologically, the hallmark of delayed hypersensitivity reaction is typified by a granuloma, which is a microscopic aggregation of epithelioid cells, usually surrounded by a collar of lymphocytes.