A SPECTRUM OF IMMUNITY IN TUBERCULOSIS

Abstract

ABSTRACT The variable clinical presentation of tuberculosis would suggest a spectrum of host immune responses to the disease. To investigate this hypothesis, 30 hospitalized patients aged 19 to 61 years (moan 34.4 years) with bacteriologically-proven tuberculosis were studied prospectively clinically and with a representative range of in vivo and in vitro tests of immune function. 73% of patients had pulmonary disease, 70% originated from the Indian Subcontinent, and 50% were vegetarian. Responses were compared with those of healthy controls carefully matched for age, sex, ethnic group and diet. Before treatment, patients were profoundly malnourishedand had significant anaemia, hyponatraomia, hypoalbuminaemia, neutrophil leucocytosis, lymphocytopenia, (predominantly helper T-cell), monocytosis, elevation of sedimentation rate, serum alkaline phosphatase, total globulins and Immunoglobulins G and A. Accelerated skin reactions (6-8 hrs.) to intradermal tuberculin-purified protein derivative were significantly more frequent, and 48hr skin reactions were larger in the patients. Even allowing for the booster effect of repeated tuberculin testing seen in controls, chemotherapy was associated with an increase in tuberculin reactivity. Peripheral blood mononuclear cells from patients were less responsive in vitro to purified protein derivative, but not to potent mitogens. No inhibitory effect was observed when normal mononuclear cells were cultured in patients’ sera. Migration of mononuclear cells, judged by mean random locomotion and casein-stimulated chemotaxis in vitro wan impaired but no differences were observed between patients and controls in spontaneous and interferon-augmented Natural Killer cytotoxicity. No significant differences were found between patients and controls in titers of Interferon-a Induced by Newcastle Disease Virus. However, mononuclear cells from a subset of nine patients produced relatively low titers of Interferons in response to purified protein derivative. In comparison with other patients, this group wascharacterized by lower Interferon-a and Interferon-7 response to virus and mitogens respectively, relative energy to virus and mitogens respectively, relative energy to tuberculin skin testing, depressed in vitro mononuclear cell proliferative response to purified protein derivative, and neutrophil leukocytosis. Two patients, both alcoholic male Caucasians with extensive pulmonary disease, developed acute respiratory failure within two weeks of starting chemotherapy. One of them died. In all other patients, the initially abnormal measurements returned to normal limits for controls during chemotherapy, except that protein malnutrition permitted for at least as long as the nine-month regimen of treatment. It 1s proposed that patients be categorizedinto five groups according to their reactivity to tuberculin-purified protein derivative in the accelerated and delayed skin tests, mononuclear cell proliferation and lymphokine (Interferon-y) production assays. Responses to purified protein derivative were graduated and ranged from a state of hypersensitivity (Croup 1) to one of energy (Croup 5) In a continuous downward gradation. These immunological patterns showed only a weak association with nutritional status, but no association with age, radiological extent or duration of disease, serum antibodies, cell counts or erythrocyte sedimentation rate. These studies indicate a spectrum of Immunological responses In human tuberculosis, analogous to leprosy, but exclusive of a form equivalent to chronic lepromatous leprosy.