THE FATE OF BCG AND ASSOCIATED CHANGES IN THE ORGANS OF RABBITS

For some time after intravenous inoculation into rabbits the BCG multiplies in various organs of the body. As with more virulent tubercle bacilli, the greater the primary deposition of bacilli the more rapid is their initial growth and the earlier is the beginning of their destruction. Destruction sets in synchronously with the development of definite hypersensitivity to tuberculin. With the smallest deposition destruction begins at once in the lung and liver without preliminary multiplication. However multiplication always takes place in the lymph nodes. It continues here and in the spleen at a time when other organs have acquired sufficient immunity to reduce the number of bacilli considerably. It is seen that the relative susceptibility of the lymphatic tissue is not due to such factors as drainage. Thus the local immunity acquired by the lymph nodes against the BCG is for a time less effective than that developed in the other organs. However by the end of the 4th week, simultaneously with the development of marked hypersensitivity to tuberculin, even these structures acquire sufficient immunity to bring about the all but complete annihilation of the bacilli. Isolated microorganisms persist in the lymph nodes even 14 months after inoculation. These bacilli do not acquire any added virulence because of their long residence in the body. As observed with more virulent strains in previous studies, the growth of the bacilli is associated with a local accumulation of mononuclears into nodules and their multiplication by mitosis, the destruction of the bacilli with the formation of epithelioid and giant cell tubercles. These changes may be extensive and at times involve a large part of the lung and lymph nodes. The secondary invasion of the tubercles by polymorphonuclears, their death, exudation of serum and cells into the alveoli of the lung, and caseation in the lymph nodes occur simultaneously and are synchronous with the development of hypersensitiveness to tuberculin. At this time the presence in the tissues of numbers of bacilli that previously were innocuous to the cells is associated with caseation. It is noteworthy that both caseation and the tuberculin reaction are not elicited in an early stage of the disease, but in a later stage they are induced in response to smaller quantities of bacilli or tuberculin. All the tuberculous changes, including the caseous foci in the lymph nodes, usually resolve completely by the end of the 2nd month after inoculation without leaving any fibrous scars, although perivascular accumulations of mononuclears may still remain. The few bacilli that persist in the lymph nodes after this period cause no tuberculous changes.