Type Ihypersensitivity is an inappropriate immune response to harmless foreignantigen to which the individual is previously sensitized. This allergicreaction is usually IgE-mediated, which induces mast cells and basophils activation1. It occurs within minutes of exposure to the antigen (also termedimmediate hypersensitivity), may be local as well as systemic. Severity rangesfrom irritating (hay fever) to fatal (systemic anaphylaxis).
Anallergic reaction occurs in 2 sequences:1) primaryexposure of sensitization2) subsequentexposurePrimary exposure of sensitizationAn allergenis inhaled and acquired by an antigen-presenting cell (APC), such as dendriticcell or B cells. Dendritic cell migrates to the lymph nodes and present it to aCD4 T cell. Naïve T cell gets activated and differentiates into TH2 cell 2.In theother hand, B cell was bound to an allergen. It processes the antigen anddisplays class II MHC-peptide complexes on the surface. B cell binds to the TH2cell through TCR-MHC interaction and by CD40-CD40L interaction 2, 3.
The TH2cell releases cytokines such as IL-4, IL-5 and IL-13 upon subsequent exposure withthe antigen. IL-4 stimulates the differentiation of TH2 cells and classswitching of B cell to IgE-producing plasma cell. IL-5 develops and activateseosinophils, which release toxic substances that can damage host cells. IL-13enhances IgE production and stimulates epithelial cells to secrete mucus. Secreted IgE bindsto the high affinity receptor (Fc?RI) of mast cells and basophils. This end thesensitization phase. Figure 1 showed the key steps in T- and B-cell collaboration to produce antibodies during sensitization.
Subsequent exposureA subsequentre-exposure to the same allergen triggers the cross linking of IgE antibodies,which result in mast cells degranulation and release of pro-inflammatorymediators that give the clinical effect seen in an allergic reaction 4,5.Type I hypersensitivityreactions can be classified into early and late phase reactions.Early phase reactions occur withinminutes of the second exposure and may subside within 60 minutes.
Some of thepreformed mediators contained in the mast cells granules are histamine, enzymeslike chymase, tryptase and eosinophilic chemotactic factors.o Histaminecauses smooth muscle contraction of the airways making it more difficult tobreath. It also causes vasodilation and increased vascular permeability. Thus,local blood flow increased and leakage of fluid through vessels causing edemaand swelling 4, 5.o Enzymescause tissue damage and lead to generation of kinins and complements leading tofurther inflammation 4.
o Eosinophilicchemotactic factors recruits eosinophils to the affected site and areimplicated in later phase reactions.Late phase reactions occur 2-24hours later without additional allergen exposure. They may last for severaldays and are due to infiltration of eosinophils, neutrophils, monocytes, CD4 Tcells as well as sustained epithelial tissue inflammation. Newly synthesizedmediators include arachidonic acid derivatives (leukotrienes, prostaglandins)and cytokines will be released.o LeukotrieneC4 and D4 are several thousand times more potent than histamine in causingsmooth muscle constriction and vascular permeability.
Leukotriene B4 is aneutrophil chemotaxis 4, 5.o ProstaglandinD2 produced mainly in mast cells cause bronchoconstrictive and vasodilatingeffect. It also increased mucus secretion 5.o Cytokinesinclude IL-1 and TNF-? are pro-inflammatory cytokines that promotes leukocytesinflux 4, 5. References1) Stephen J Galli, M. T.
(2012). IgE and mast cells in allergicdisease. Nature Medicine, 693-704.2) Alberts B, J. A. (2002).
Molecular Biology of the Cell.4th edition. T Cells and MHC Proteins. New York: Garland Sciences.3) Agrawal, R. G.
(2013). Clinical View on the Importance ofDendritic Cells in Asthma. Expert Review of Clinical Immunology,899-919.4) Janeway CA Jr, T. P. (2001).
Immunobiology: The ImmuneSystem in Health and Disease. 5th edition. Effector mechanisms in allergicreactions. New York: Garland Science.5) Oettgen, O. T.
(2011). Beyond immediate hypersensitivity:evolving roles for IgE antibodies in immune homeostasis and allergic diseases. ImmunologicalReviews, 128-143.