Henry N. Claman

How corticosteroids work

Corticosteroids are widely used in the treatment of allergic and inflammatory conditions. It is important to recognize that there are great species differences in the responses to glucocorticoids and that man is a steroid-resistant species. Steroids affect metabolism and distribution of T and B lymphocytes, but do not significantly affect antibody production in man. Steroids profoundly affect the inflammatory response by way of vasoconstriction, decreased chemotaxis, and interference with macrophages. Steroids affect types I, III, and IV mechanisms of immunologic injury. There are still enormous gaps in our knowledge of the actions of glucocorticosteroids.

Mast cells, T cells and abnormal fibrosis

Inflamed, fibrotic lesions containing mast cells are characteristic of several clinical disorders and have been noted in graft versus host disease. Here Henry Claman reviews recent insights into the interactions between mast cells, T lymphocytes and fibroblasts which may account for abnormal collagen deposition.

Salivary immunoglobulinand albumin: Development during the newborn period

Summary Salivary levels of γG, γA, γM globulins andalbumin were measured serially in saliva of newborn infants by electroimmunodiffusion. Salivary γA was not detected at birth but appeared beginning at one week of age. By 4 weeks of age 92 per cent of normal infants had “adult” levels of γA in their saliva. γM was not detected. γG and albumin were temporarily present in many salivary samples in appreciable amounts before 10 days of age but these proteins disappeared as γA appeared in saliva. Serial determinations of salivary γA may provide a simple rapid method for early detection of defects of immunoglobulin production. The temporary appearance of γG and albumin in saliva may represent “leakage” from serum and probably reflects the increased permeability to proteins of mucous membranes in the immediate postnatal period.

Natural suppressor (NS) cells members of the LGL regulatory family

Natural suppressor (NS) activity is defined as the ability of unprimed null cells to suppress the response of lymphocytes to immunogenic and mitogenic stimuli. Cells with this ability have been studied for a number of years(1-16). In this review, Tom Maier and his colleagues examine some aspects of non-specific suppression and relate them to NS activity. They also consider NS cells as part of a natural non-specific suppressor-cell family along with natural killer and natural cytotoxic cells. This family has the large granular lymphocyte (LGL) phenotype.

Thymectomy: Prolongation of Immunological Tolerance in the Adult Mouse

The loss of acquired immunological tolerance of mice to bovine gamma globulin depended on the presence of the thymus. Mice were repeatedly injected with bovine γ-globulin from birth until the age of 5 to 10 weeks and then thymectomized or sham operated. After 130 to 160 days without antigen, an accelerated (immune) disappearance of I125 bovine γ-globulin could be uniformly induced in controls while thymectomized mice remained tolerant. Adult thymectomized mice made tolerant by a single injection of bovine γ-globulin lost tolerance more slowly than sham-operated controls.

Salivary immunoglobulins: Normal adult values and dissociation between serum and salivary levels

Abstract Salivary immunoglobulin levels were measured by electroimmunodiffusion (EID) in adults in health and disease. Forty parotid fluid samples from 18 healthy adults showed no detectable γG (one exception), γM, or γD. γA was present in all samples (2.8 to 15 mg. per cent, median 9.5 mg. per cent). Serial samples from the same individual showed considerable variation. Simultaneous samples of right and left parotid fluids showed little differences. In general, parotid fluid γA levels were higher than mixed submandibular-sublingual fluid γA levels. Eight patients with congenital sex-linked hypogammaglobulinemia and 3 patients with dysgammaglobulinemia had no detectable serum or salivary γA. A number of patients had dissociation of serum and salivary γA with low serum γA but normal levels of parotid fluid γA. These data suggest that the serum and salivary immunoglobulin pools are under separate regulation.

Serum immunoglobulin measurement during the first year of life and in immunoglobulin-deficiency states.

Serum immunoglobulin concentrations at several age intervals during the first year of life have been determined by a capillary immunoprecipitation technique. Immunoglobulin G was present in cord sera and declined during the first six months of life, following which an increase to almost three-fourths of the normal adult level was observed in the next six months. Immunoglobulin A was absent in the cord serum and progressively increased, reaching a level by one year of age approximately one-fifth that of the adult. Immunoglobulin M was present in most cord sera studied and steadily rose to one-half of adult levels by 52 weeks of age. Serum immunoglobulin determinations for selected immunologic deficiency states are reported.

Glucocorticosteroids I: Anti-inflammatory Mechanisms

Although progress in understanding how steroids work has accelerated in the past few years, several important factors have eluded definitive analysis. Broadly, the mechanisms affect leukocyte traffic and function: Glucocorticoids inhibit the availability of leukocytes to the inflammatory site, interfere with their function at the site, and thus suppress the normal inflammatory response.

Experimental production of granulomatous pneumonitis. Comparison of immunological and morphological sequelae with particulate and soluble antigens administered via the respiratory route.

Rabbits were sensitized with either a soluble protein antigen (BSA) or a particulate thermophilic actinomycete antigen (Micropolyspora faeni) via the respiratory route, followed by monitoring of sequential morphologic changes and the humoral plus cellular immunologic response. Primary respiratory tract sensitization with BSA resulted in a humoral anti-BSA response, Arthus and delayed skin reactivity, and in some cases specific antigen-induced alveolar macrophage migration inhibition, all in the absence of pulmonary lesions. Lesions characterized by mild multifocal perivascular mononuclear cell infiltrates in the lungs developed only after secondary BSA aerosol challenge. In contrast to these findings, primary respiratory tract sensitization with M. faeni particulate antigen in saline solution resulted in the gradual development of extensive and progressive pulmonary interstitial and alveolar mononuclear cell infiltrates. These lesions were uniformly associated with specific serum precipitating antibody and delayed skin reactivity. Alveolar macrophage migration was significantly inhibited by Micropolyspora faeni in virtually of these animals. These results, while not excluding a primary irritant effect or Type II or III alergic tissue injury, suggest a role for delayed (cell-mediated) hypersensitivity in the pathogenesis of particulate actinomycete-induced pulmonary lesions. They also indicate that primary immunization with soluble purified protein antigens via the respiratory route can lead to systemic humoral and cell-mediated immunity without production of pulmonary lesions.

Clinical ecology: Approved by the executive committee of the American academy of allergy and immunology

Summary An objective evaluation of the diagnositic and therapeutic principles used to support the concept of clinical ecology indicates that it is an unproven and experimental methodology. It is time-consuming and places severe restrictions on the individuals life-style. Individuals who are being treated in this manner should be fully informed of its experimental nature. Advocates of this dogma should provide adequate clinical and immunologic studies supporting their concepts, which meet the usually accepted standards for scientific investigation.