Symptoms of certain hyper sensitivity reactions appear after 24 to 72hours of exposure to allergen and such reactions are referred as delayed type hyper sensitivity reactions.

The term delayed hyper sensitivity was first coined by Koch in late nineteenth century, while studying immunity to tuberculosis. When certain antigens are injected into the skin of sensitized animals an inflammatory response develops after many hours of injection.

Several evidences suggest that, type IV reaction is important in host defense against parasites.

Unlike other forms of hyper sensitivity reactions Type IV hyper sensitivity cannot be transferred from one animal to another thorough serum, but can be transferred by T cells.


Three types of delayed hyper sensitivity reactions have been recognized (1) Contact hyper sensitivity (2) Tuberculin-Type hyper sensitivity (3) Granulomatus hyper sensitivity.

(1) Contact hyper sensitivity:

This kind of hyper sensitivity reaction produces eczematous response at the site of contact with the allergen which is generally a haptane like chemical. The small antigenic molecules (haptanes) penetrate epidermis and bind to the proteins inside and act as sensitizers.

The protein bound haptens are first internalized by epidermal langerhans cells and later carried to paracortical areas of lymphnodes by circulation and finally they are presented to T Cells. Release of lymphokines from the stimulated cells results in manifestation of clinical symptoms after 12 to 15hours of contact.


(2) Tuberculin Type hyper sensitivity (Mantoux Reactions):

When a small dose of tuberculin (antigen derived from the tubercle bacillus) is injected intradermally into a sensitized individual, hardening and swelling develops at the site of injection. Soluble antigens from a number of organisms including Mycobacterium tuberculosis, M leprae and Leishmania tropica induce similar type of reactions in sensitive people. Granulomatous reaction due to persistence of antigens in the tissues may be responsible for the development of lesions.

(3) Granulomatous hyper sensitivity:

It is the most important from of delayed hyper sensitivity reactions rooting many of the pathological effects. If macrophages fail to destroy the engulfed microbes or their Ag particles, the persistent immune complex induces epithelioid cell granuloma formation. In the same way granuloma formation occurs with a variety of foreign bodies or particulate agents, when macrophages fail to digest the inorganic matter of foreign agents or particulate matter. Epithelioid granuloma cells are large flattened cells
with increased endoplasmic reticulum. The region affected by Type IV hyper sensitivity reactions typically show a core of epithelioid cells and macrophages, with or without giant cells and the core is surrounded by a cuff of lymphocytes and a considerable fibrosis. Increased proliferation of fibroblasts and collagen synthesis ensue fibrosis in reaction areas. Delayed hyper sensitivity reaction manifests many chronic diseases in man. Some of the important diseases developed by delayed hyper sensitivity reactions are Tuberculosis, Leprosy, Leishmaniasis, Deep fungal infections and Helminth infections.