Cell-mediated Immune reactions discussion

It must be stressed that the primary mechanism of many topical irritants (e.g., organic solvents, corrosives) is the impairment to the stratum corneum barrier properties discussed above, reflected by an increase in transepidermal loss (TEWL). If the stratum corneum barrier is perturbed, the feedback response mediated by cytokines (especially TNFa) may be initiated whereby regeneration of the barrier occurs. However, additional responses to these inflammatory mediators may in themselves launch an irritation response mediated by the keratinocytes or lead to an immune reaction if the antigen is recognized. Regardless of the initiating mechanism, the sequelae to many irritants is the same, namely, epidermal cell death. 

Synthetic retinoids have effects similar to those of natural retinoids. A number of different natural or synthetic retinoids have been used in the experiments discussed. Judging from the limited number of comparative studies, no dramatic differences between different retinoids are found. In the induction of cell-mediated cytotoxicity, retinoic acid, 13-cw-retinoic acid, retinyl palmitate, and etretinate all had quite comparable stimulatory effects (Lotan and Dennert, 1979). In the DTH reaction, retinyl palmitate, motretinid (F3), and 13-c -retinoic acid had stimulatory effects, but etretinate (FI) had no effect (Athanassiades, 1981). At present, it is therefore not clear what the molecular constraints on the retinoid molecule may be for stimulatory effects on the immune system. 

A variety of signals can be transmitted across membranes without the actual flow of a substance from one side of the membrane to the other. We saw in chapter 12 that some hormones bind to specific receptor sites on the outer surface of the plasma membrane, thereby triggering metabolic changes on the cytosolic side of the membrane. Hormonal systems that function in this way are discussed in greater detail in chapter 24. Other membrane proteins mediate specific cell-cell interactions. Sometimes these interactions merely stimulate particular types of cells to bind to one another, but often they also trigger reactions that result in proliferation or differentiation of the interacting cells. We discuss signals of this type when we consider the interaction between the B and T cells of the immune system (see Supplement 3). 

Many reactions to beta-lactam antibiotics are clearly not immune mediated. These include bleeding disorders, neurotoxicity, and most cases of diarrhea. In addition, many reactions, the pathogenesis of which is still being discussed, clearly depend on the daily and the cumulative dose of beta-lactam antibiotics and hence the duration of treatment. Although the rare, but well-understood, immune hemolysis after penicillin is seen mostly with high-dose and long-term treatment, dose dependency and time dependency point to direct toxicity rather than to immunological mechanisms. Indeed, direct toxic effects of beta-lactam antibiotics on eukaryotic cells and specific interactions with receptor proteins and enzymes have been shown (4) and may underlie particular reactions. 

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