Rudolf L. Baer

Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes

Abstract Ferritin-challenged skin sites and draining lymph nodes were studied in normal guinea pigs and in guinea pigs which had been passively sensitized to ferritin or peroxidase by lymphoid cell transfer to ascertain whether Langerhans cells can bind antigen in skin and carry it to lymph nodes. After intradermal challenge with amounts of ferritin as small at 5 μg, ferritin-containing Langerhans cells were seen by electron microscopy in the marginal sinus and cortex of draining lymph nodes in ferritinscnsitized animals and, to an apparently lesser degree, in control animals. Lymph nodes from unchallenged normal guinea pigs contained rare Langerhans cells, none of which had ferritin. The findings indicate that Langerhans cells may pick up antigen in skin and from there circulate to draining lymph nodes, thus carrying out a function analogous to macrophages. In this way they may exhibit antigen to lymphocytes both in skin and in lymph nodes.

Langerhans cells: Target cells in immune complex reactions

Abstract Skin of normal, cobra venom extract-treated, and C 4 -deficient guinea pigs was injected with ferritin-antiferritin or with peroxidase-antiperoxidase immune complexes. Skin and draining lymph nodes were studied to compare the phagocytosis of these immune complexes by Langerhans cells (LC) and by macrophages. When complement was present, immune complexes were damaging to LC, and uptake of the immune complexes, although present, was limited. When components of complement were absent or diminished, increased numbers of LC in lymph nodes were seen, but damage to LC was absent or decreased. However no detectable change in the amount of phagocytosis by LC was noted. Since some LC can carry antigen from skin to lymph nodes and may be involved in the presentation of antigen to lymphoid cells in some cell-mediated immune responses, impairment or abolition of LC function by immune complexes could represent a mechanism through which the local presence of antibodies might interfere with the induction and elicitation of cellular immunity by antigen. Moreover, damage to LC and subsequent release of intracellular (lysosomal?) substances may constitute a general mechanism of response in the skin to injury and may be an integral part of inflammatory and allergic skin reactions.

Subepidermal vesicular dermatosis and sensory peripheral neuropathy caused by pyridoxine abuse

A woman who had ingested 2 gm of pyridoxine (vitamin B6) daily for 2 years for menstrual water retention developed a subepidermal vesicular eruption on the dorsa of the hands and toes, as well as a sensory peripheral neuropathy. The cutaneous and neurologic manifestations subsided about 2 months after discontinuation of the pyridoxine. The possible relationship of subepidermal vesicular eruptions caused by pyridoxine abuse to epidermolysis bullosa acquisita is discussed.

Papillated squamous cell carcinoma in situ arising in a seborrheic keratosis

A 73-year-old man had developed a 27 x 60-mm seborrheic keratosis on his trunk. Some months previously, an 18 x 19-mm cauliflower-like area had developed within this seborrheic keratosis. Histologic examination showed a papillated squamous cell carcinoma in situ arising in a seborrheic keratosis. Seborrheic keratoses are the most common cutaneous neoplasms in man. Malignant changes are most unusual but should be suspected in lesions of unusual clinical appearance.

Reversal by lymphokines of the age-related hyporesponsiveness to contact sensitization and reduced Ia expression on Langerhans cells

SummaryContact sensitivity responses were evaluated in young adult (3–5 months) and aged (16–26 months) BALB/c mice which were systemically treated with interleukin-2 (IL-2), interferon-γ (IFN-γ) or saline. Mice older than 16 months of age have deficient numbers of Ia+ Langerhans cells in addition to their well-known impaired T cell functions. They also have an impaired cell-mediated response to contact sensitization with 1-chloro-2,4,6-trinitrobenzene. This hyporesponsiveness in aged mice can be almost completely reversed by ness in aged mice can be almost completely reversed by IL-2 and is marginally improved by IFN-γ. Exposure of skin from aged mice to interleukin-2 or interferon-γ, both in vivo and invvitro, causes increases in the density of Ia+ Langerhans cells to levels approximating those in young mice. Since IFN-γ causes partial restitution while IL-2 fully restores the contact hypersensitivity in aged animals, we conclude that the hyporesponsiveness in aged mice results both from defective Ia antigen expression on the antigen-presenting Langerhans cells and from deficient T cell function.

Allergic contact sensitization to iron

Abstract A case is reported of allergic contact dermatitis due to iron in a toolmaker. This is only the second case of iron contact allergy published in the literature. The possible reasons for the rarity of contact allergy due to iron are considered, among them the development of tolerance due to exposure to iron-containing compounds during fetal life.

Papaverine therapy in atopic dermatitis

Papaverine hydrochloride taken by mouth in doses of 100 mg four to six times daily or in 150-mg timed-release capsules two or three times daily is often effective in significantly decreasing itching in patients with atopic dermatitis. When used orally, as described here, it does not appear to have beneficial effects in other itchy dermatoses. It should be used as adjuvant treatment in combination with other accepted forms of therapy, since it alone cannot reverse the chronic skin changes brought about by months or years of scratching and rubbing.

Differential cell counts in the blister fluid of allergic eczematous and irritant bullous lesions

A CONSIDERABLE amount of evidence has been accumulated in animal experiments which shows that lymphocytes, monocytes, and plasma cellsr play an important role as carriers of the presumptive antibodies which mediate allergic skin hypersensitivity of the tuberculin type and contact type (LandSteiner and Chase,l Chase,2 and others). More recently H. S. Lawrence3a reported that he was able to passively transfer tuberculin-type sensitivity in human beings with leukocyte suspensions, indicating, here too, that the leukocytes play an important role, at least as carriers of these presumptive antibodies. Chase has demonstrated in guinea pigs that the intensity of the passively transferred hypersensitivity varies with the number of white cells and the degree of sensitivit,y of the cell donor, a finding which received considerable support from the work of H. S. Lawrence in human beings. The possibility of passive transfer of allergic eczematous contact-type sensitivity in man by means of white cell suspensions is suggested by the experimental results of Baer and Sulzberger.3b In the experimental animal it has not yet been possible to produce an exact morphologic replica of the eczematous response as it is seen in human beings, yet allergic contact dermatitis in animals is in an immunologic sense sufficiently close to allergic eczematous contact type dermatitis in man to make it appear very likely that, also in human beings, the mononuclear cells play an important role as the carriers of the presumptive antibodies. Nexmandl found in consonance wit,h this theory that mononuclear cells are predominant in the blister fluid of allergic eczematous reactions, and that in contradistinction polymorphonuclear leukocytes predominate in the blister fluid of reactions produced by primary irritant substances. In more recent studies with nitrogen mustard, Nexmand5 demonstrated that this difference exists even

Immunologic functions of Langerhans cells.

It is a great privilege and pleasure for me to be invited to speak at this session which honors my good friend Professor Toshiaki Yasuda. Since my remarks today will concentrate on the immunologic aspects of Langerhans cell functions, I shall not discuss the nonimmunologic functions which have been suggested for these cells. After making some general remarks about Langerhans cells, I shall present the evidence favoring a close similarity between the functions of Langerhans cells and of those macrophages which are now usually referred to as monocytic phagocytes, emphasizing those properties which enable monocytic phagocytes and Langerhans cells to serve as antigen-presenting cells. I shall also relate our observations in allergic contact dermatitis in guinea pigs to the immunologic functions of Langerhans cells. In 1868 at the age of 21, when he was a medical student, Paul Langerhans published his discovery of the cells which now carry his name (1). He described their suprabasal location and dendritic nature. Why did it take one hundred years before major advances were made in knowledge of these cells? The explanation lies largely in the fact that in conventional stains of skin sections, for example in hematoxylin-eosin stains, one sees only two varieties of cells in the epidermis, namely keratinocytes and clear cells, i.e. melanocytes. This, despite the fact that according to present estimates the epidermal cell population consists

Selected aspects of penicillin allergy.

SUMMARY.— Skin tests for immediate hypersensitivity with penicillin derivatives and haemagglutination tests for penicilloyl‐specific IgG and IgM antibodies are useful in the prevention, diagnosis and management of clinical adverse reactions mediated by IgE antibodies. In rare instances, the skin tests themselves may cause clinical adverse reactions. Under suitable conditions, hyposensitization or temporary loss of skin sensitivity can be successfully brought about, even in individuals with a high degree of immediate hypersensitivity.