This review evaluates the available information on the effects of mainstream and environmental tobacco smoke on the immune system in animals and humans. The primary emphasis is on mainstream smoke since little information is available on the effects of environmental smoke. The effects of mainstream tobacco smoke on the immune system in humans and animals are similar. Animals exposed to mainstream tobacco smoke for periods of a few weeks generally exhibit a slight immunostimulation. However, subchronic and chronic exposure studies indicate that immunosuppressive changes develop. Lymphocyte proliferation in response to the mitogens PHA and LPS is decreased, suggesting compromise of cell function. Antibody production can be suppressed. Smoke-exposed animals that are challenged with metastasizing tumors or viruses have been shown to exhibit a higher incidence of tumorigenic and infectious diseases, respectively. Localized immunological changes in the lung can include reduction of bronchus-associated lymphoid tissue and immunoglobulin levels. Smoking-related changes in the peripheral immune system of humans have included elevated WBC counts, increased cytotoxic/suppressor and decreased inducer/helper T-cell numbers, slightly suppressed T-lymphocyte activity, significantly decreased natural killer cell activity, lowered circulating immunoglobin titers, except for IgE which is elevated, and increased susceptibility to infection. The effects of environmental tobacco smoke on the immune system, in contrast to mainstream tobacco smoke, have just begun to be investigated and information available in the literature, to date, is limited. Immunoreactive substances are known to be present in environmental tobacco smoke, but to date, environmental tobacco smoke has been more closely associated with irritation than sensitization. A few studies have indicated a potential for environmental smoke-induced hypersensitivity and suppression of immunoregulatory substances. In contrast, other investigators have failed to detect immunological or other biological changes associated with environmental smoke. Clearly, more research is needed to resolve these differences.

We have tested the hypothesis that conserved sequences in the intervening sequence (IVS) and 5'-flanking region of a yeast tRNALeu3 gene serve some function. Genes with deletions of 8, 10, 13 and 20 bp in the IVS are all active as templates in vitro. Yeast extracts produce mature tRNALeu3 from delta 8, delta 10 and delta 13 genes. Xenopus extracts do not detectably ligate the 5' and 3' half-molecules resulting from IVS excision. Neither extract is able to excise the IVS from delta 20 precursors. Genes with introns enlarged by 10, 21 or 30 bp of DNA produce mature tRNA. Insertion of 103 bp results in reduced levels of transcription, little if any end maturation, and no detectable mature product. A conserved 15 bp sequence is present at the 5'-end of the tRNA sequence. Replacement of yeast DNA up to position -22 leaves the tRNA gene transcriptionally active. With replacement extended to -2 the gene is active in Xenopus extracts but nearly inert in yeast extracts. We conclude that tRNA transcription in yeast is insensitive to IVS structure but can be positively influenced by 5'-flanking sequence.

A pentadecanucleotide sequence, TTTCAACAAATAAGT, contiguous with the 5′‐end of Saccharomyces cerevisiae tRNA‐Leu3 coding sequence acts as a positive modulator of transcription in a homologous in vitro system. To determine whether modulation also takes place in vivo, the amber suppressor forms of tRNA‐Leu3 genes with different 5′‐flanking sequences were generated by site‐specific mutagenesis and cloned into YCp19, a yeast vector maintained at 1‐2 copies per cell. These plasmids were transformed into S. cerevisiae strains marked with amber mutations lys2‐801, met8‐1, and tyr7‐1. The ability of the tRNA‐Leu3 amber suppressor genes (tDNA‐Leu3A) to suppress functionally lys2‐801 and tyr7‐1 mutations in the yeast host strain correlated well with template activities measured in vitro. We conclude that the plasmid‐borne tRNA gene acts as an effective suppressor from the plasmid and the conserved pentadecanucleotide sequence modulated the expression of yeast tRNA‐Leu3 in vivo as well as in vitro. This regulatory sequence if found associated with genes coding for a number of tRNAs which are abundant in yeast. We postulate that this sequence represents a mechanism by which production of specific tRNAs can be enhanced to match demand created by codon use preferences.