Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.

The dielectric loss factor and dielectric permittivity of 8–16 mol% solutions of chlorobenzene, o-dichlorobenzene, and 1-chloronaphthalene in cis-decalin; 50–60 mol% mixtures of pyridine with chlorobenzene, bromobenzene, 1-chloronaphthalene, and toluene; 50–60 mol% mixtures of tetrahydrofuran with bromobenzene and 1-chloronaphthalene; the pure liquids cis-decalin, o-terphenyl, iso-propylbenzene, propylene carbonate; and two fused salt systems, 45 mol% Ca(NO3)2–KNO3 mixture and Ca(NO3)2·4H2O have been measured from 50 Hz to 1 × 105 Hz from − 196° in the vitreous state to about 30° above their respective glass transition temperatures. The Tg's of the organic glasses have been measured by DTA. With the exception of propylene carbonate, all glasses show the presence of one secondary relaxation between − 196° and their respective Tg's either as a peak or shoulder in a tanδ–temperature plot at a single frequency, or in the dielectric loss spectrum. Arrhenius plots of the frequency of maximum loss against temperature in the main relaxation region for all systems are nonlinear, with the activation energy at the lowest temperature of our measurements ranging from 55 kcal/mol to 70 kcal/mol. The Arrhenius plots in the secondary relaxation region are linear and have activation energies between 5 and 12 kcal/mol. These glasses, most of which are composed of rigid molecules, show a remarkable similarity in their dielectric behavior to amorphous polymers. The results confirm the prediction made by one of the authors that the occurence of secondary relaxations is an intrinsic property of the glassy state.

Recent attempts have been made to assess the relative merits of the free volume and entropy theories of viscous flow in glass-forming liquids by accurate measurement of viscosity over wide temperature ranges, and subsequent comparison with the equations derived from these theories. In the author's view, this effort is misguided. The theories are crude and qualitative, and such tests are too stringent. It is better to make qualitative or semiquantitative comparison of a wide variety of physical phenomena; judged by this criterion, the entropy theory appears more successful. It is conjectured that further progress can be made by accepting the crude, naive character of any model we are likely to find tractable for the foreseeable future, and recognizing both the values and limitations of such models. A picture of the flow process in viscous liquids is proposed, in an attempt to answer certain questions about the molecular steps in flow either answered unsuccessfully or ignored by present theories, in the hope that it will lead a model closer to molecular reality but still sufficiently tractable to allow some range of predictive value. The model is based on the idea that in “viscous” liquids (shear relaxation time ≥10−9 sec) flow is dominated by potential barriers high compared to thermal energies, while at higher temperature, this will no longer be true. Certain concepts borrowed from the continuum theory of lattice defects are joined to a qualitative description of viscous flow due to Orowan, to provide a picture which leads to some qualitative predictions about flow and relaxation in the liquid and glassy states.

Mice with a targeted disruption in the f32-microglobulin (f32m) gene, which lack major histocompatibility complex class I molecules and consequently fail to develop functional CD8 T cells, provided a useful model for assessing the role ofclass I-restricted T cells in resistance to infection with virulent Mycobacterium tuberculosis. Ofmutant P2m-/-mice infected with virulent 106 M. tuberculosis, 70% were dead or moribund after 6 weeks, while all control mice expressing the P2m gene remained alive for >20 weeks. Granuloma formation occurred in mutant and control mice, but far greater numbers of tubercle bacilli were present in the lungs ofmutant mice than in controls, and caseating necrosis was seen only in P2m -/-lungs. In contrast, no differences were seen in the course of infection of mutant and control mice with an avirulent vaccine strain, bacille Calmette-Guirin (BCG). Immunization with BCG vaccine prolonged survival of I2m-/-mice after challenge with M. tuberculosis for 4 weeks but did not protect them from death. These data indicate that functional CD8 T cells, and possibly T cells bearing y6 antigen receptor, are a necessary component of a protective immune response to M. tuberculosis in mice.