Abstract
In human tuberculosis, cavities are commonly seen in the lungs and this phenomenon is a special feature of this disease and quite different from other infections. Why is the cavity so easily and f requntly formed in tuberculosis? Yamamura and coworkers' experiments demonstrated that a tuberculous cavity formation in the lungs was related to the cellular immune reaction between host and tubercle bacilli. The process of the cavity formation will be considered as follows. When tubercle bacilli are inhaled into the lungs, they are phagocytized and processed by macrophages (Mcb) and the antigenic information is transfered to T-lymphocytes (T-cell) and then many sensitized T-cells are formed with the aid of the adjuvanticity of these microorganisms. The number of T-cells begin to increase and when they contact with the mycobacteria or tuberculin-like substances, they release lmyphokine (LK). With the action of LK, many Mφ and monocytes accumulate to the lesion, are activated and phagocytize the bacteria vigorously. Having a difficulty in digesting mycobacteria, Mφ are injured and release the lysosomal enzymes, because the cell wall of mycobacteria is composed of mycolic acid-arabinogalactan-mucopeptide complex and Mφ has no enzyme to disintegrate the mycolic acid. The released lysosomal enzymes damage the adjacent lung tissue and cause necrosis, softening and liquefaction followed by the elimination through the drainage bronchus, thus the cavity is produced. Based on this theoretical consideration the present experiment was done to determine the roles of lymphokine and mycobacterial cell wall in the process of the cavity formation.
Methods and Results. Rabbits were injected into the lungs through the chest wall with the mixture of LK and BCG-cell wall skeleton (CWS). The LK was used to accumulate Mφ to the injection site and to let them activate and phagocytize CWS synchro-nously. The CWS or LK alone was also injected into the lungs as controls. After 7 days the animals were sacrificed and the lesions of the lungs were examined, The histo-logical findings showed that the lesions injected with CWS+LK had necrosis surrounded by mononuclear cells. On the other hand, no necrosis was detected in the lesions injected with CWS or LK alone.
In the mean time, those rabbits received an intradermal injection of both CWS and LK, or CWS, LK, killed M. tuberculosis, H37Rv alone. After six days, the injection sites were surgically removed under anesthesia and the dermal lesions were examined macro-scopically and histologically. With the injection of LK+CWS, necrosis and distinct tissue defects were found in the skin. With the injection of CWS or killed M. tuberc. alone, slight necrosis were detected, but most of the lesions were granulomatous. With the LK-injection, the accumulation of Mφ was observed and no necrosis was found. It seems likely that since CWS or killed mycobacteria alone did not induce the immune reaction in the host by day 6 and were gradually phagocytized by Mφ without LK, the release of the lysosomal enzymes from Mφ would have been insufficient to cause necrosis in the lung tissue.
Conclusion. From these results, it is concluded that the mechanism of tuberculous cavity formation is related to the cellular immune reaction between host and parasites in which the special structure of the cell wall of mycobacteria plays an important role.
