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Hypersensitivity Reactions: classification of the types

The purpose of the immune response is to protect against invasion by foreign organisms, but they often lead to host tissue damage.


The purpose of the immune response is to protect against invasion by foreign organisms, but they often lead to host tissue damage. An exaggerated immune response that results in tissue injury is broadly referred to as a hypersensitivity reaction.

Classification of hypersensitivity reactions

According to Gell and Comb’s classification, hypersensitivity reactions can be divided into four types (type I, II, III, and IV) depending on the mechanism of immune recognition involved and on the inflammatory mediator system recruited. Types – I II, and III reactions are dependent on the interaction of specific antibodies with the given antigen, whereas, in type IV reactions recognition is achieved by antigen receptors on T-cells.

Type I hypersensitivity (anaphylactic or immediate type) reaction




Type I hypersensitivity reaction may be defined as a rapidly developing Immunologic reaction occurring, within minutes after the combination of an antigen with antibody bound to mast cells or basophilic in individuals previously sensitized o the antigen. The reactions depend on the site of antigen exposure for example in skin – hive, upper respiratory tract – Hay fever, bronchial asthma and systemic reaction – anaphylactic syndrome

Type II hypersensitivity reaction

Type II hypersensitivity is mediated by antibodies directed towards antigens present on the surface of exogenous antigens. Three different antibody-dependent mechanisms are involved in this type of reaction.

i. Direct lysis

It is effected by complements activation, formation of membrane attack complex (C5 –9). This membrane attack complex then disrupts cell membrane integrity by drilling a hole. In a nucleated cells once and in nucleated cells many attacks of the complex are needed for cell lysis, because the latter ones have abilities to repair cell membrane injuries rapidly.
Opsoinization: By C3b, fragment of the complement to the cell surface enhances phagocytosis. Examples include red blood cells, leukocytes and platelets disorders: Transfusion reaction; haemolytic anemia; Agranuloytosis; Thrombocytopenia; Certain drug reaction

ii. Antibody dependent cell - mediated cytotoxicity /ADCC

In some cases, antibodies directed against cell surface receptors impair or dysregulated function without causing cell injury or inflammation. For example: In Myasthenia Gravis, antibodies reactive with acetylcholine receptors in the motor end plates of skeletal muscles impair neuromuscular transmission and cause muscle weakness.
The converse is noted in Graves’ disease where antibodies against the thyroid stimulating hormone receptor on thyroid epithelial cells stimulate the cells to produce more thyroid hormones.

Type III hypersensitivity / immune complex-mediated

Type III hypersensitivity reaction is induced by antigen-antibody complex that produces tissue damage as a result of their capacity to activate the complement system. The antibodies involved in this reaction are IgG, IgM or IgA.
Clinical examples of systemic immune complex diseases: Various types of glomerulonephritis, Rheumatic fever, various vasculitides, Quartan nephropathy, Systemic lupus erytomatosis and Rheumatoid arthritis

Type IV hypersensitivity (Cell-mediated) reaction




The cell-mediated type of hypersensitivity is initiated by specifically sensitized T-lymphocytes. It includes the classic delayed type hypersensitivity reactions initiated by CD4+Tcell and direct cell cytotoxicity mediated by CD8+Tcell. Typical variety of intracellular microbial agents including M. tuberculosis and so many viruses, fungi, as well as contact dermatitis and graft rejection are examples of type IV reactions.

Delayed type hypersensitivity: this is typically seen in tuberculin reaction, which is produced by the intra-cutaneous injection of tuberculin, a protein lipopolysaccharide component of the tubercle bacilli.

T-cell mediated cytotoxicity. In this variant of type IV reaction, sensitized CD8+T cells kill antigen-bearing cells. Such effector cells are called cytotoxic T lymphocytes (CTLs). CTLs are directed against cell surface of MHC type l antigens and it plays an important role in graft rejection and in resistance to viral infections. It is believed that many tumor-associated antigens are effected by CTLs.
Hypersensitivity Reactions: classification of the types Hypersensitivity Reactions: classification of the types Reviewed by gafacom on October 21, 2019 Rating: 5

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