Chemistry of Asthma and Allergy

The allergy and asthma are very serious immunologic disorders. Everyone of us has been blessed with immune system to fight infections and respond to vaccines for acquiring active immunity. Allergens too are immunogenic but elicit hypersensitive response which could cause a local or systemic reaction like asthma. It has been learnt through animal experiments that the animals sensitized (immunized) with egg albumin react very dramatically on subsequent challenge with egg albumin. In my experience the animals have shown the symptoms of generalized anaphylaxis, respiratory distress and 50% of them died probably due to asphyxia as an intense constriction of bronchioles and bronchi was observed due to the contraction of smooth muscles. Similar reactions also occur in human subjects due a variety of conditions/causes. An injection of penicillin or an insect bite may trigger anaphylaxis in sensitive individuals. Only a timely intravenous injection of adrenaline may help in countering the smooth muscle contraction.

Mediators of Anaphylaxis or Allergic Reaction:

It was resolved by Sir Henry Dale that histamine mimics the systemic changes of anaphylaxis. Experimental studies in guinea-pigs had demonstrated that serum from sensitized animals could passively sensitize normal animals of the same species. Sir Henry Dale had demonstrated that the uterus of sensitized guinea-pig released histamine and contracted on exposure to antigen. The cells that release the mediators of anaphylaxis are the mast cells (in tissues) and basophils (in blood). The mast cells in sensitive subjects are coated by hemocytotropic antibodies of IgE class (reagins) and on interaction with the specific allergen or antigen stimulate the mast cell degranulation and release of mediators of anaphylaxis. In addition to histamine, 5-hydroxytryptamine (serotonin) is also released in some species. The contraction of smooth muscles is associated with the explosive degranulation of mast cells. Other mediators released are: slow reacting substance of anaphylaxis (SRS-A; capable of inducing prolonged contraction of certain smooth muscles), platelet activating factor (PAF), heparin and chemotactic factor for both the neutrophils and eosinophils (types of white blood cells).

Anti-anaphylaxis substances produced by Eosinophils:

The mediators of anaphylaxis released by mast cells are countered by certain substances produced by eosinophils like: histamine produced by mast cells is neutralized by histaminase, eosinophil chemotactic factor (ECF-A) is countered by aryl sulfatase and SRS-A is neutralized by phospholipase produced by eosinophils in an effort of the body to control the reaction. Systemic allergic reaction as well as percutaneous anaphylaxis leads to changes in cyclic nucleotide levels. A fall in cyclic AMP (c-AMP) and a rise in cyclic GMP (c-GMP) level, favors degranulation of mast cells, whereas high concentration of c-AMP stabilize the mast cell granules. All the anti-allergic drugs either neutralize histamine or activate c-AMP to stabilize mast cells or bind to b-2 receptors on smooth muscles to counter the smooth muscle contraction.