Cellular Immune Processes Research Articles

Lung and Blood Lymphocyte Subsets in Asbestosis and in Mixed Dust Pneumoconiosis

To study the local distribution of lymphocyte subsets in inorganic dust diseases, bronchoalveolar lavage (BAL) was performed in seven patients with asbestosis, and in 13 patients with mixed dust pneumoconiosis (anthracosidero-silicosis). Lymphocyte subsets in BAL and blood were determined by the monoclonal antibodies OKT3 (pan T), OKT4 (helper/inducer), OKT8 (suppressor/cytotoxic), B1 (B-cells), OKIa (HLA-DR antigens), and Leu-7 (natural killer). The BAL lymphocytes were moderately elevated to 15 +/- 8 percent (mean +/- SD) in mixed dust pneumoconiosis, and even more markedly increased to 28 +/- 21 percent in asbestosis. The OKT4/OKT8 ratio in BAL was significantly increased to 4.5 +/- 2.1 in asbestosis, and significantly reduced to 0.9 +/- 0.8 in mixed dust pneumoconiosis. In blood, the ratio of T-cell subsets remained unchanged, though total lymphocytes were decreased in asbestosis. These results suggest altered cellular immune processes in the lungs of patients with pneumoconiosis and may indicate different immunoregulatory changes depending on the nature of the inhaled dust.

Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis.

Gamma interferon (IFN gamma) is a potent immune mediator that plays a central role in enhancing cellular immune processes. This study demonstrates that while lung mononuclear cells from normal individuals spontaneously release little or no interferon (less than 10 U/10(6) cells per 24 h), those from patients with pulmonary sarcoidosis spontaneously release considerable amounts (65 +/- 20 U/10(6) cells per 24 h, P less than 0.02 compared to normals). Furthermore, cells from patients with active disease release far more interferon than those from patients with inactive disease (101 +/- 36 compared to 24 +/- 8 U/10(6) cells per 24 h, P less than 0.02). Characterization of this interferon using acid sensitivity, specific antibody inhibition, and target cell specificity criteria demonstrated that it was almost entirely IFN gamma. This spontaneous release of IFN gamma appeared to be compartmentalized to the lung of these patients in that their blood mononuclear cells spontaneously released little or no IFN gamma (P less than 0.02, compared to sarcoidosis lung mononuclear cells) and no IFN gamma was detected in their serum. Both lung T lymphocytes and alveolar macrophages contributed to the spontaneous release of IFN gamma by lung mononuclear cells from sarcoid patients; purified preparations of T lymphocytes and alveolar macrophages from these patients spontaneously released similar amounts of IFN gamma (56 +/- 21 and 32 +/- 11 U/10(6) cells per 24 h, respectively, P greater than 0.3). At least one role for IFN gamma in the pathogenesis of sarcoidosis appeared to be related to activation of alveolar macrophages, as alveolar macrophages recovered from patients with active disease spontaneously killed [3H]uridine-labeled tumor cell targets (17.7 +/- 4.5% cytotoxicity compared with 2.8 +/- 0.9% in normals, P less than 0.02) and purified IFN gamma enhanced the ability of alveolar macrophages from sarcoidosis patients with inactive disease to kill similar targets (P less than 0.001, compared to alveolar macrophages cultured in medium alone). Treatment of sarcoid patients with corticosteroids, a therapy known to suppress the activity of the disease, caused a marked reduction in the level of spontaneous IFN gamma release by lung mononuclear cells compared with untreated patients (P less than 0.02), which suggests that the effectiveness of corticosteroid therapy in controlling active pulmonary sarcoidosis may, at least in part, be due to suppression of IFN gamma release.

Autoimmune diseases of the kidney.

Autoimmune diseases are due to a breakdown of the tolerant state to autologous constituents. Some autoimmune diseases, including kidney diseases, can occur spontaneously in man. Our present understanding of the pathogenesis of human autoimmune diseases, however, is based mainly on the results of studies of diseases induced in laboratory animals by appropriate immunization. These diseases usually involve strong immunization such as incorporation of autologous tissue in “adjuvants,” like Freund's adjuvant, or immunization of animals with a similar tissue from a different species that shares cross-reactive antigens. Autoimmune reactions can be manifested by the production of autoantibodies and/or of autoreactive T cells. Thus, tissue damage may result from the reaction of antibodies with antigens present in the kidney, from tissue deposition of circulating immune complexes, and from cellular immune processes (1, 2). These mechanisms of hypersensitivity are not mutually exclusive. It is only for didactic reasons that we arbitrarily classify the various autoimmune renal diseases as if they were induced by a single pathogenic mechanism (Table I). In this review two groups of animal models of nephritis will be described. In the first group kidney lesions are induced by autoantibodies reacting with structural kidney antigens such as those of basement membranes or those present on the surface of cells. In immunofluorescence microscopy the immune reactants may be found along basement membranes in either a linear (e.g., in antibasement membrane nephritis) or a granular pattern (e.g., in Heymann glomerulonephritis). In the second group the nephropathies are conceivably the result of deposition in the kidney of circulating autologous immune complexes. The immune complexes accumulate in a granular pattern. Where possible, we will present evidence that similar diseases occur in man. Because insufficient solid data are available, a separate discussion of the role of autoreactive T cells in the development of kidney diseases is not included in this review.

The Experimental Aspects of Cancer

The Experimental Aspects of Cancer

Immunologic Aspects of Thyroid Disease

Graves' disease and Hashimoto's thyroiditis are autoimmune processes considered distinct diseases in light of current knowledge. In Graves' disease, antibodies directed against the thyrotropin receptor of the thyroid cell stimulate the gland to hyperfunction. The ophthalmopathy of Graves' disease may result from a different autoimmune reaction, directed against orbital tissue. In Hashimoto's thyroiditis, humoral and cellular immune processes are directed against elements of the thyroid cell and result in destruction and glandular hypofunction.

Analysis of Autoimmunity through Experimental Models of Thyroiditis and Allergic Encephalomyelitis

Publisher Summary This chapter presents the relationship between the normal state of self-tolerance and its abnormal corollary, autoimmunity. The several possible bases for loss of self-tolerance, including failure of immune regulation and abnormal presentation of potential self-antigens, are considered in terms of current understanding of cellular and humoral immune processes. A particularly thorough evaluation of suppressor cells and their possible role in self-tolerance and autoimmunity is presented. The pathogenic mechanisms that may be involved in autoimmune disease are examined in the light of two familiar experimental models, allergic encephalomyelitis and autoimmune thyroiditis. The pathogenic potential of cellular autoimmune responses in encephalomyelitis, on the one hand, and of autoantibody responses in thyroiditis, on the other, indicates the very different pathogeneses, which may operate in autoimmunity. The various mechanisms that are responsible for the loss of tolerance to self antigens can be divided into three general categories. First, abnormalities may occur in the regulatory mechanisms that control the normal immune response. Second, a component of self that was once sequestered and nonimmunogenic may become exposed and presented in an antigenic form to the immune system. Third, a normally tolerated self component may for some reason circumvent the prevailing regulatory mechanisms and activate one or more arms of a normal immune system. Numerous factors are involved in autoimmune diseases including genetic control at major histocompatibility complex (MHC) and non-MHC loci, immunologic regulatory mechanisms, self-nonself recognition, and logistics and/or nature of the target autoantigens.

The effects of malnutrition on secretory and cellular immune processes

About 15 million children under 5 years of age die each year due to suppressed immunity and the resulting increased infection. In severely malnourished children and animals some immune systems such as T-cell function, secretory IgA and complement are significantly suppressed. Other systems, such as the serum IgG or IgA, are normal or even elevated. Some of these changes are apparently caused by nutritional stress while others may be due to stimulation by increased incidence of infection and antigen load. On the other hand, marginal malnutrition stimulates increased phagocytosis and T-cell function with increased immunity to cancer but decreased resistance to certain microbial agents. The mechanisms of immune suppression by malnutrition, persistence of these effects after renutrition, and the effect of maternal malnutrition on newborn immunity are critically reviewed. Possible non-nutritional means of rapid immunological restoration of malnourished children are described.

Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse.

Evidence from divergent sources suggests that some forms of interstitial pulmonary disease are associated with abnormalities of the cellular immune system. To evaluate whether cellular immune processes are necessary determinants for the development of parenchymal alveolitis and fibrosis secondary to bleomycin, we examined the effect of bleomycin on the NIH, outbred white mouse as compared to the homozygous nude, athymic mouse on the NIH outbred background. The nude mouse has virtually no detectable cell-mediated immune function; we therefore hypothesized that if this component of the immune system were necessary for the development of bleomycin-induced interstitial disease, bleomycin would not induce the same pulmonary lesion in the nude mouse as in the white mouse. However, both white and nude mice developed alveolitis and fibrosis after intraperitoneal administration of bleomycin. Comparison of the frequency and severity of these lesions in the 2 groups revealed no significant differences. These findings suggest that the presence of an intact cell-mediated immune system is not an absolute requirement for the development of bleomycin-induced interstitial disease in the mouse. To the extent that this model is an appropriate approximation of human bleomycin-induced pulmonary disease, these results are consistent with the hypothesis that T-lymphocyte mediated processes are not primary determinants of this lesion.

Antibody-dependent cellular protection against herpes simplex virus dissemination as revealed by viral plauqe and infectivity assays

Mouse nonimmune peripheral blood lymphocytes (PBL) plus antibody to herpes simplex virus inhibited virus dissemination in herpes simplex virus-infected 3T3 cell culture as revealed by development of viral plaque, size of immunofluorescent foci, appearance of polycaryocytes, and viral infectivity appearing in the culture. These nonimmune PBL did not act alone in inibiting virus dissemination, but did act synergistically in combination with antibody. The ratio of PBL to target monolayer cells needed to produce this effect was 20. Splenic lymphocytes had weak activity, whereas thymocytes were without effect, even in the presence of antibody. Neither interferon nor lymphotoxin was detected in this lymphocyte-mediated response. These findings support previous observations, based on cytotoxicity assays, that antibody-dependent cellular immune processes could be important in control of and recovery from herpesvirus infection.

The Effect of Lowered Body Temperature on Lifespan and Immune and Non-Immune Processes

The effect of lowered body temperature on lifespan and immune and nonimmune processes in invertebrates and vertebrates are reviewed. Decreasing the environmental temperature tends to increase lifespan of invertebrates and poikilothermic vertebrates. Thermolabile homeotherms appear to live longer than comparably-sized species which do not undergo periodic, natural lowering of their body temperature. Even a mild lowering of temperature suppresses both humoral and cellular immune processes in poikilotherms. On the other hand, metabolic and biochemical responses to decreased body temperature in poikilotherms are quite varied. With mild or moderate hypothermia (30–35°C), indications are that for most homeotherms, there would not be a major inhibition of nonimmune biochemical or metabolic processes. Initial studies aimed at inducing mild, chronic or intermittent hypothermia in mice with chloropromazine and marihuana derivatives are described.

Arthritis and psoriasis: the effects of antipsoriatic agents in the adjuvant-induced arthritic rat.

SummaryIn summary, we have shown that two topically useful antipsoriatic agents, anthralin and anthralin triacetate, both exert potent anti-inflammatory effects on oral administration. Anthralin further shows antiarthritic activity, inhibiting the cellular mediated immune processes as evidenced by suppression of both secondary lesions and skin wheal in the rat model. These data are preliminary in nature and further studies are in progress to elaborate on the biological profile of these two agents.

ROLE OF THE THYMUS IN HUMORAL IMMUNITY: Observations in Complete or Partial Congenital Absence of the Thymus

Congenital absence of the thymus in man has been associated with markedly defective humoral immune responses in spite of normal immunoglobulin production. This is probably due to lack of thymus-dependent antigen-reactive cells. Some infants with incomplete defects in embryogenesis of the third and fourth pharyngeal pouches have very small thymus glands which are histologically normal but inadequate for optimal immunological function. Such individuals appear to have a significant but very limited pool of competent antigen-reactive cells. This situation seems to be almost identical to that found after neonatal thymectomy in rodents and fowl, or after reconstitution of irradiated thymectomised animals with bone-marrow. The nearly normal antibody responses to some antigens in such animals and in infants with partial defects is not considered to be evidence for a separate class of antigen-reactive cells independent of thymic function. Available data support the contention that at least a few thymus-dependent antigen-reactive lymphocytes are required for initiating production of any specific antibody. When thymic function is greatly reduced, however, it is proposed that the humoral immune response is limited primarily by the availability of competent thymus-independent (”bursal equivalent” precursors of antibody-forming cells. Thus the ”two-component” concept of immunological development is regarded as reconcilable with evidence that thymus-dependent antigen-reactive cells are needed to initiate both humoral and cellular immune processes.