After recovery from the primary infection, resistance to the organism is mediated by cellular immunity (i.e., by CD4 positive T cells and macrophages). The CD4-positive T cells are Th-1 helper T cells.
Circulating antibodies also form, but they play no role in resistance and are not used for diagnostic purposes. Patients deficient in cellular immunity, such as patients with acquired immunodeficiency syndrome (AIDS), are at much higher risk for disseminated, life-threatening tuberculosis. Mutations in the interferon-γ receptor gene are another cause of defective cellular immunity that predisposes to severe tuberculosis. This emphasizes the importance of activation of macrophages by interferon-γ in the host defense against M. tuberculosis.
Prior infection can be detected by a positive tuberculin skin test result, which is due to a delayed hypersensitivity reaction. PPD is used as the antigen in the tuberculin skin test. The intermediate-strength preparation of PPD, which contains five tuberculin units, is usually used. The skin test is evaluated by measuring the diameter of the induration surrounding the skin test site (Figure 1). Note that induration (thickening), not simply erythema (reddening), must be observed.
Fig1. Tuberculin skin test. Purified protein derivative (PPD) was injected intradermally, and 48 hours later, the diameter of induration was measured with a caliper. (Reproduced with permission from Talaro KP: Foundations in Microbiology. 8th ed. New York, NY: McGraw Hill; 2011.)
The diameter required to judge the test as positive varies depending on the status of the individual being tested. Indu ration of 15 mm or more is positive in a person who has no known risk factors. Induration of 10 mm or more is positive in a person with high-risk factors, such as a homeless person, an intravenous drug user, or a nursing home resident. Induration of 5 mm or more is positive in a person who has deficient cell mediated immunity (e.g., AIDS patients) or has been in close contact with a person with active tuberculosis.
A positive skin test result indicates previous infection by the organism but not necessarily active disease. The tuberculin test becomes positive 4 to 6 weeks after infection. Immunization with bacillus Calmette-Guérin (BCG) vaccine can cause a positive test, but the reactions are usually only 5 to 10 mm and tend to decrease with time. People with PPD reactions of 15 mm or more are assumed to be infected with M. tuberculosis even if they have received the BCG vaccine. A positive skin test reverts to negative in about 5% to 10% of people. Reversion to negative is more common in the United States now than many years ago because now a person is less likely to be exposed to the organ ism and therefore less likely to receive a boost to the immune system.
The skin test itself does not induce a positive response in a per son who has not been exposed to the organism. It can, however, “boost” a weak or negative response in a person who has been exposed to produce a positive reaction. The clinical implications of this “booster effect” are beyond the scope of this book.
Tuberculin reactivity is mediated by the cellular arm of the immune system; it can be transferred by CD4-positive T cells but not by serum. Infection with measles virus can suppress cell-mediated immunity, resulting in a loss of tuberculin skin test reactivity and, in some instances, reactivation of dormant organisms and clinical disease.
