Classical Allergy

The classical allergy response is the immediate hypersensitivity response. The pathway to the immediate hypersensitivity response starts with the allergen, which is recognized by a specialized group of white blood cells called antigen-presenting cells (APCs), which include macrophages, dendritic cells, and Langerhans cells. These APCs absorb, repackage, and, then, present the antigen to T-lymphocytes. T-lymphocytes, in turn, secrete proteins, called cytokines, such as interleukin-4, which, in conjunction with second signals such as the physical contact of T-lymphocyte with B-lymphocytes, stimulate B-lymphocytes to create IgE specific to the allergen.

This IgE is secreted into the blood and binds to mast cells. The IgE, in fact, remains on the surface of these mast cells and, when an individual is re-exposed to the antigen, binds to the allergen and triggers degranulation and the release, from mast cells, of the mediators of the immediate hypersensitivity response, such as histamine. Histamine and other mediators of the immediate hypersensitivity response which are released by mast cells lead to a wide variety of local and systemic changes, which results in such typical clinical findings as nasal congestion, sneezing, hives, swelling, and wheezing.

Other Types of Allergy

The different types of allergy are described by the Gell and Combs classification system. Note that the classical allergy response is, under this classification system, Type Ia.

Type I Mast Cell Mediated

  • IgE-Dependent (anaphylactic)
    IgE-Independent (anaphylactoid)

Type II Antibody Mediated (Non-IgE)

  • Opsonization (antibody coating)(cytotoxicity by phagocytic cells)
  • Complement lysis (cytotoxicity by complement)
  • ADCC (antibody-dependent cellular cytotoxicity) (cytotoxicity by NK cells)
  • Stimulating (such as in Grave’s disease)
  • Blocking (such as in some forms of diabetes)

Type III Immune Complex (Serum Sickness)

Type IV Cell Mediated

  • CD4+ T cell (delayed hypersensitivity, such as in poison ivy exposure)
  • CD8+ T-cell
  • NK (natural killer) cell


As described above, hypersensitivity (in all its forms) involves a heightened, and usually inappropriate, response to an antigen. The antigen is usually a complex macromolecule, such as a protein, phospholipid, polysaccharide or nucleic acid that may be floating freely in the circulation or may be part of a greater structure, such as a bacterial cell wall.

Another type of antigen is the hapten. Haptens are actually substances that are too small to be recognized by themselves, but, when complexed to larger molecules, they are able to stimulate a response. Therefore, haptens are non-immunogenic themselves, but become immunogenic when combined with carriers. Carriers may be artificial or may come from the host, such as human albumin.

Once antibody production is initiated, the hapten is capable of reaction with antibody even when the hapten is not complexed to a carrier, but precipitation or agglutination reactions will not occur. This is because the hapten has a single antigenic determinant site and is not capable of forming the cross-links with more than one antibody molecule that are necessary for precipitation or agglutination. Examples of haptens are chemicals, such as DNP, m-aminobenzene sulfonate, and catechols (from poison ivy).

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