PATTERNS OF REACTION OF THE SKIN TO INJURY 79 In all three of these varieties which are sometimes called delayed types of allergic reactions, eczema, tuberculin type and homograft rejection, the sensitization phenomenon is a systemic affair which under proper conditions has been passively transferred with lymphocytic cells to non- sensitive hosts. The systemic nature of eczematous allergy, in contrast to former beliefs that such sensitivities depend on antibodies firmly fixed in the skin, was clearly proved by'the Danish dermatologist Haxthausen in his classic skin transplantation experiments in identical twins. He found when a skin graft was taken from one of a pair of identical twins who was contact eczematously allergic to a particular compound and grafted into the nonallergic twin, that it failed to react to application of the al- lergen. However, normal skin from the nonsensitive twin did so react when grafted to the allergic twin. One might speculate that the general slow development of these types of reactions even when antigen is directly injected into the tissues is partly based upon the necessity for the migration, at first by chance, of antibody carrying cells to the site of antigen deposition. Later, of course, the re- action would be accelerated by chemotactic factors associated with in- flammation. Next, I would like to briefly mention what are called allergic fixed erup- tions in which for long periods of time only very circumscribed areas of the skin show specific allergic reactions on exposure to certain drugs or simple chemical allergens. These peculiar local skin allergies, if indeed some of such reactions be true allergies, may be of either the urticarial or eczematous type. In trying to fit these reactions into the over-all scheme of allergy already discussed, one would have to postulate some unique local property in the reactive skin sites. Possibly there is a unique local difference in protein structure in such areas so that the specific antigen formed after conjugation with the chemical in question is unique or possibly there may be present in such areas an unusually low physiologic threshold for re- sponses to relatively weak antigen-antibody reactions. Whatever the explanation, it is a fact that on occasion after transplanting reactive skin to nonreactive sites in the same individual, specific reactivity is preserved in the grafted skin. This, of course, is in sharp contrast to the graft ex- periments in twins with ordinary eczematous allergy in which such a local effect could not be shown. Lastly, in closing, attention should be called to the rather recently re- vived and modified version by Jerne and Talmage and Burner of Ehrlich's original natural selection theory for the mechanism of antibody formation. Although the supporting arguments for this theory cannot be considered here, it appears to have much merit and has certainly stimulated new lines of thought about immunologic mechanisms. Simply stated, this new natural selection theory views antibodies as a

80 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS very large diverse group of naturally occurring proteins each one being produced by a fixed line of mature lymphocytic type cell. This is in con- trast to the more orthodox view that antibodies are new species of proteins molded on either antigen or antigen-modified templates. The antigen according to this natural selection theory serves simply as a selective stim- ulus which brings about an increased rate of production of those particular naturally produced globulins with which it can react and which normally would otherwise be present only in such minute amounts as to be only rarely detectable by ordinary immunological techniques This selective stim- ulation has further been postulated to occur mainly at the cellular level through the selective stimulation of cell proliferation by the antigen-anti- body complex of only those antibody producing cells in the general popu- lation of such cells which can produce globulin configurations that match the configuration of the antigen in question THE SKIN AS A SENSORY ORGAN By R. K. WINKELMANN, M.D., Presented September 15-16, 1960, Seminar, Chicago STIMULI BOMBARD US continually, causing sensations that man has learned to call by names such as pain, touch, heat and cold. We have come to recognize that certain intensities of these sensations give pleasure, others discomfort. These sensations are different for each of us because in- dividual variations in the activity of the central and peripheral nervous systems produce perceptual differences. Such factors as attention, emotion and the physical state of the body condition the reception of a sensation in the brain. All sensations finally perceived must filter through the neuronal pathways of the spinal cord, where they may be modified by sensa- tions from other levels of the cord. The cutaneous receptors, which are the subject of this discussion are the point of origin for a major portion of the sensory load. The sensation as it is finally selected for recognition in the brain is the result of all these processes in the brain, spinal cord and skin. The skin is a physiologic paradox, for it serves two mutually exclusive functions: It provides protection from the environment, and it provides for a sensitive recording by the nervous system of the environment and its changes. Absolute protection means minimal sensory perception ab- * Mayo Clinic and Mayo Foundation, Rochester, Minn. This investigation was supported in part by Research Grant B-1755 from the Public Health Service.