HYPERSENTIVITY: Mechanism of Type-I Hypersensitivity

 Immunity was originally considered a protective process helping the body to overcome infectious agents and their toxins. However, immune response may sometimes be harmful to the host. Sensitized individual respond to subsequent antigenic stimuli in an inappropriate or exaggerated manner leading to tissue damage, disease or even death. The term 'hypersensitivity' thus refers to the injurious consequences in the sensitized host following contact with specific antigen. The initial contact with antigens called sensitizing dose sensitizes appropriate B or T cells and the subsequent dose of same antigen called shocking dose produces abnormal reactions.

 Therefore, hypersensitivity is an abnormal immune response which produces damage either histopathological or physiological in the host.

Types of Hypersensitivity
 Hypersensitivity as classified by Gell and Coomb are of 4 types:
•Type I: Anphylatic or IgE mediated hypersensitivity
•Type II: Antibody mediated cytoxicity
•Type III: Immune complex mediated hypersensitivity
•Type IV: Cell mediated hypersensitivity

Types of Hypersensitivity

 •Immediate: Type I, II and III are immediate type of hypersensitivity since the symptoms are manifest within minutes or hours after a sensitized recipient encounters antigen.

      •Delayed: Type IV is delayed type of hypersensitivity because of the delay of symptoms until days after exposure.

Type I Hypersensitivity
        Also called as IgE mediated or Reagin mediated or anaphylatic immediate type of hypersensitivity.

   Antigens that induce Type I hypersensitivity include pollen, fungal spores, insect venom, animal danders, mites, helminthic infections, etc.

Mechanism of Type I hypersensitivity

Exposure to antigen activates B cells to form IgE secreting plasma cells.


      The secreted IgE molecules bind to IgE specific Fc receptors on the mast cells  and blood basophiles. 

      Thus, Fab fragments of IgE remains exposed. 

     Upon re-exposure to the same antigen, antigen gets attached to the free Fab fragments of IgE bound on mast cells.

      This results in the cross linking of IgE molecules. 

The cross linking triggers the biochemical signals which stimulates the phospholipid metabolism that opens channels in the cell membrane, thus leading to calcium influx.

As a result, an energy dependent disorganisation of intracellular granules occurs with the eventual release of granules contents in the extracellular fluid. 



The granule contents are the vasoactive amines such as histamins, heparin, Eosinohpile chemotactic factors for anaphylaxis (ECFA), Neutrophil chemotactic factor (NCFA), etc. 



These causes smooth muscle contraction, increased vascular permeability and vasodilation. 

The phospholipid metabolism makes the arachidonic acid available which generates prostaglandins and leukotrienes. 

Prostaglandins cause vascular dilation and leukotrienes cause smooth muscle contractions. 

The mast cells also secrete cytokines such as TNF, IL-4 and IL-5 which promotes the recruitment of eosinophiles to the site of their release and cause inflammation. 

Eosinophiles and neutrophiles release protease which causes the neighbouring tissue damage.

Typical manisfestation include systemic anaphylaxis and localized anaphylaxis such as hay fever, asthama, hives, food allergies, eczema, etc.



References
1. Kuby immunology
Author: Judith A OwenJenni PuntSharon A StranfordPatricia P JonesJanis Kuby

Publisher: New York: W.H. Freeman, ©2013.
Edition: 7th edition



No comments: