Type IV or delayed type hypersensitivity (DTH), is most seriously manifested when antigens (for example those of tubercle bacilli) are trapped in a macrophage and cannot be cleared. T cells are then stimulated to elaborate lymphokines which mediate a range of inflammatory responses. Other aspects of DTH reactions are seen in graft rejection and allergic contact dermatitis. DTH is used as a general category to describe all those hypersensitivity reactions which take more than 12 hours to develop, and which involve cell-mediated immune reactions rather than humoral immune reactions. Whereas allergic reactions occur within seconds and minutes and immune complex reactions occur within several hours to one day, DTH reactions peak at 2 to 3 days.
Unlike other forms of hypersensitivity, type IV
hypersensitivity cannot be transferred from one animal to another
by serum, but can be transferred by T cells
(T
1 cells in mice).
In humans, transfer from a sensitized to a non-sensitized
individual can be also achieved only by T lymphocytes and,
interestingly, by a low molecular weight material extracted from
them ( transfer factor). Delayed type hypersensitivity is
obviously associated with T cell protective immunity but does not
necessarily run parallel with it -- there is not always a complete
correlation between delayed hypersensitivity and protective
immunity. The T cells necessary for producing the delayed response
are cells which have become specifically sensitized to the
particular antigen by a previous encounter, and they act by
recruiting other cell types to the site of the reaction.
Three types of delayed hypersensitivity reaction are recognized: Contact hypersensitivity and tuberculin-type hypersensitivity both occur within 72 hours of antigen challenge, whereas granulomatous reactions develop over a period of weeks. The granulomas are formed by the aggregation and proliferation of macrophages, and may persist for weeks. This reaction is, in terms of its clinical consequences, by far the most serious type of delayed type hypersensitivity response. The position is complicated because these different types of reaction may overlap, or occur sequentially following a single antigenic challenge.
The delayed type hypersensitivity reactions are probably important for host defence against intracellular parasites such as tuberculosis and certain viruses and are prevalent in certain disease such as sarcoidosis, Wegener's granulomatosis, and polymyositis. In some diseases, such as chronic granulomatous disease of childhood, granuloma formation can lead to obstruction of vital structures such as the esophagus or ureters. The contact dermatitis is caused by sensitization to certain simple chemicals.
Perhaps the best known example of cell-mediated hypersensitivity is the Mantoux reaction obtained by injection of tuberculin into the skin of an individual in whom previous infection with the mycobacterium had induced a state of cell-mediated immunity. The reaction is characterized by erythema and induration which appears only after several hours and reach a maximum at 24--48 hours, thereafter subsiding. Histologically the earliest phase of the reaction is seen as a perivascular cuffing with mononuclear cells followed by a more extensive exudation of mononuclear and polymorphonuclear cells. The latter soon migrate out of the lesion leaving behind a predominantly mononuclear cell infiltrate consisting of lymphocytes and cells of the monocyte - macrophage series. This contrasts with the essentially ''polymorph'' character of the Arthus reaction.