ABSTRACT
The acquisition of skin sensitization is dependent upon the initiation of an immune response, and specifi cally a cellmediated immune response. The relevant events and processes can be summarized briefl y as follows. Sensitization is induced when an inherently susceptible individual is exposed topically to an appropriate and suffi cient amount of contact allergen. Following entry into the skin, the chemical allergen either directly, or indirectly, associates with protein and is recognized and inter nalized by cutaneous dendritic cells, the most important of which in this context are epidermal Langerhans cells (LC). It is now clear that LC play several pivotal roles in the generation of cutaneous immune responses and the induction of skin sensitization; their most important responsibility being the transport of antigen, via the afferent lymphatics, to draining lymph nodes. During this migration from the skin, LC are subject to a functional maturation with the result that by the time of their arrival in lymph nodes they have acquired the characteristics of immunostimulatory antigen presenting cells (Cumberbatch et al., 2000, 2003, 2005; Griffi ths et al., 2005; Kimber et al., 1998a, 2000). In the lymph nodes, antigen is presented to T lymphocytes and responsive cells become activated and are stimulated to divide and differentiate. Cell division results in a selective clonal expansion of allergen-responsive T lymphocytes; this quantitative increase in specifi c T lymphocytes represents the cellular basis for sensitization and immunological memory. If the now sensitized subject is exposed again to the same chemical, at the same or a different site, then this expanded population of specifi c T lymphocytes will recognize and respond to allergen in the skin and trigger an accelerated and more aggressive secondary immune response, that in turn causes the cutaneous
infl ammation that is recognized clinically as allergic contact dermatitis. The molecular and cellular mechanisms that result in the induction and elicitation of contact allergy have been reviewed extensively elsewhere (Dearman and Kimber, 2003; Grabbe and Schwarz, 1998; Kimber et al., 2002; Kimber and Dearman, 2002, 2003). For the purposes of this chapter it is suffi cient to say that the ability of chemical allergens to induce the activation of skin draining lymph nodes and to stimulate lymph node cell (LNC), proliferative responses are the events upon which the local lymph node assay (LLNA) is founded.
