Sensitization phase

A large variety of antigens may induce delayed-type hypersensitivity (DTH). Usually, particulate antigens, such as bacteria, viruses or parasites, seem particularly to favor this type of hypersensitivity. Intradermal injection of foreign proteins or application on the skin of reactive chemical substances of low molecular weight, capable of forming conjugates with autologous carrier proteins, also frequently induce DTH. Polysaccharides, on the other hand, are less prone to cause DTH. The mode of administration of antigen also seems to play a role. Intravenous injection is usually not efficacious in inducing DTH. The incorporation of antigen in some adjuvants, in particular in complete Freund's adjuvants containing mycobacteria, is very favorable for establishing DTH. The role of macrophages in antigenic presentation is also important. Failure to provide proper antigenic presentation by macrophages usually leads to lesser induction of DTH, even if antibodies may be formed. The fate of antigen in the organism, for example after application on or injection into the skin, probably also plays an important role in induction of sensitivity. It has been shown that the integrity of afferent lymphatic channels and of regional lymph nodes is needed for establishment of DTH. It is therefore very likely that the first recognition of antigen and presentation to T lymphocytes occurs in the regional lymph nodes. However, to this concept of 'central sensitization' can also be added examples of 'peripheral sensitization'. In the induction of contact eczema or in skin transplantation, it has been shown that local persistence of antigen for a while is required for the induction of the process, even when large amounts of soluble antigens quickly reach the regional lymph nodes. In that case, antigen presentation and recognition may occur at the level of local antigen deposits by T lymphocytes and macrophages freely moving through tissues and returning through afferent lymphatic channels to the regional lymph nodes. The role of dendritic cells in the epidermis (Langerhans cells), which possess several macrophage-like properties, has been particularly emphasized.

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