Effects on Adaptive Immunity

In contrast to adaptive immune function, fewer studies have examined effects of TCDD on the innate immune system. Furthermore, of the limited data available, much of it is inconsistent. For example, natural killer (NK) cell activity has been reported to be unaffected,80,93 diminished,94 and increased95 following exposure to TCDD. Although a thorough assessment of AhR expression in all innate cell lineages has not been conducted, neutrophils and macrophages express the AhR,8,96 and neutrophils are affected... 

The innate and the adaptive arms of the immune systems of higher organisms are bridged by a complex set of cellular and molecular mediators. The immunomodulatory activities of host defense peptides, such as the direct chemotactic activity, cytokine and chemokine induction, and the stimulation of differentiation and activation of effector cells, may contribute to this process. Host defense peptides may also influence the polarization of adaptive immune response, for example, through their effects on cytokine production. ... 

There are two protein replacement products available for A1AD, both pooled human plasma donor-derived products. Approval of these products was based upon replacement of serum AAT to the above-mentioned levels. Neither has been proven to prevent lung disease in a prospective, double-blinded placebo-controlled fashion, but retrospective registry data suggest a beneficial effect. However, protein replacement therapy has been very safe. Particularly remarkable has been the lack of an adaptive immune response by patients on therapy, which may relate to the genetic homogeneity of this A1AD population, in which approximately 95% have one particular missense mutant allele (PI Z). 

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