DEVELOPMENT OF AN ECZEMATOUS SENSI FIZ3_TION 37 an alien protein, the customary immunologic sequence of events would be that antibodies develop whose specificity is directed toward the protein conjugate. These antibodies would be found in the circulating gamma globulins. Actually, under appropriate circumstances, this can be shown to be so. Yet, it can be shown that, even though such antibodies exist, they have nothing to do with the development of the eczematous reaction. In fact, no circulating antibodies demonstrable by any techniques have been shown to be responsible for this type of reaction. This, then, raises the query as to the nature of the change which is responsible for the reaction. Some years ago, Burner (4), in an endeavor to explain the specific'ty of anti- body response, hypothesized that the antigen (alien protein) got to the site of globulin synthesis and there caused an enzymatic adaptation in the cells concerned with the synthesis of the globulin. As a consequence of this adaptation, these cells or the enzyme systems within them could utilize this new alien protein, but the globulin that they produced would be slightly different than that manufactured prior to the adaptation. This modification in the globulin would then be revealed by the attributes which are labeled as antibody properties. In view of the fact that each alien protein engenders a slightly different adaptation, the globulin synthes'zed by the adapted cell would be slightly different in each case, hence the specificity. Now, Burnet's views adequately take care of allergic situations in which there are circulating antibodies but offer no explanation for the type of reaction which is being considered here and in which, as has already been stated, circulating antibodies, if they exist at all, play no demonstrable role In an endeavor to explain the nature of the change in these types of reactions, Rostenberg and Brunner (5) extrapolated from Burnet's views. What they said in essence was that the basis of an allergic sensitization is the enzymatic adaptation to the antigen in question. If this adaptation takes place in a cell or system concerned with the synthesis of globulin, then there will be evidence of that adaptation in the form of circulating globulins with new properties which are labeled as antibodies. If, however, the adaptation takes place in a cell or system not concerned with the pro- duction of globulin, then there is, of course, no reason why there should be any evidence of that adaptation in the form of modified circulating globu- lins or, in other words, circulating antiboclies will either be not present, or, if they exist, can be shown to have nothing to do with the reaction in ques- tion however, the cell in which the enzymatic adaptation took place now displays a different reactivity toward the antigen (the material that caused the adaptation to take place) than the same cell did prior to this taking place. It is believed that in the delayed type of hypersensitivity, of which the eczematous reaction is one variety, the basis for the allergic state is an enzymatic adaptation in cells that are not concerned with the synthesis of globulin.

38 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Now, what are these cells, and where do they exist? Admittedly, no definitive statement can be made, but the evidence seems to point clearly to cells of the reticuloendothelial system as being the cells in which the altera- tion takes place. For a variety of reasons that I shall not go into here, it is thought that the primitive reticulum cell is a likely one in which the adapta- tion occurs. Of course, it is quite conceivable that the enzymatic adjust- ment can take place in several kinds of cells, but the primitive reticulum cell is the one I believe to be primarily responsible. This cell is rather ubiqui- tously distributed throughout the body and exists in the curls, as well as in the regional lymph nodes. There is circumstantial evidence to make one believe that the adaptation takes place in the curls or in the regional node or in both. An important point to realize about the enzymatic modification is that there is reason to believe that this type of adaptation is passed to the descendants of the cells in question. Consequently, the persistence of a sensitization over a period of time is explained. The next problem to be discussed is what happens to the cells in which the enzymatic adaptation has occurred? In the event that the adaptation has taken place in primi- tive reticulum cells situated either in the curls or in the regional nodes, there is, of course, no reason to believe that these cells move from their original locus but the primitive reticulum cell is the theoretical progenitor for the wide variety of cells, including many motile ones, such as macro- phages and lymphocytes. Such cells, when they are the descendants of a primitive reticulum cell with an adapted enzyme system, would then have the same modification and thus one would find cells with the specifically adapted system ubiquitously distributed throughout the body. When the eczematously sensitized individual is again exposed to the simple chemical in question, or to an immunologically equivalent material, there is reason to believe that, in order for a reaction to develop, the simple chemical has again to enter into the same sort of union that it did when the sensitizing application was originally done or, in other words, the same antigenic protein conjugate is formed in vivo as was formed initially. Just how the formation of this conjugate in the specifically sensitized in- dividual causes the development of the eczematous lesions is not known, but speculations which are at least in accord with the known facts can be advanced. First, in view of the fact that the conjugate is probably formed, as was already stated, within the epidermis, it would lie in proximity to the capillary loops coursing in the papillary bodies of the cutis. Theoretically, the in vivo formation of the conjugate would cause a trivial amount of damage which might mildly alter the permeability of the capillaries in ques- tion as a consequence of this alteration in permeability a few cells escape. In a person who possesses cells with an adapted enzyme system directed toward the antigenic conjugate which has been formed in the epidermis in