Functional and clinical consequences of Fc receptor polymorphic and copy number variants.

Receptors for immunoglobulins (Fc receptors) play a central role during an immune response, as they mediate the specific recognition of antigens of almost infinite diversity by leucocytes, thereby linking the humoral and cellular components of immunity. Indeed, engagement of Fc receptors by immunoglobulins initiates a range of immunoregulatory processes that might also play a role in disease pathogenesis. In the circulation, five main types of immunoglobulins (Ig) exist - namely IgG, IgA, IgE, IgM and IgD and receptors with the ability to recognize and bind to IgG (Fc gamma receptor family), IgE (Fc epsilon RI and CD23), IgA (CD89; Fc alpha/microR) and IgM (Fc alpha/microR) have been identified and characterized. However, it is astonishing that nearly all the known human Fc receptors display extensive genetic variation with clear implications for their function, thus representing a substantial genetic risk factor for the pathogenesis of a range of chronic inflammatory disorders.

Defense and melanization depend on the eumelanin pathway, occur independently and are controlled differentially in developing Ceratitis capitata.

A defense mechanism in the hemocytes and cuticle of developing Ceratitis capitata has been demonstrated (Marmaras and Charalambidis, 1992; Marmaras et al., 1993a; Marmaras et al., 1993b). To elucidate further the mechanism and the regulation of defense reactions, we studied this process in relation to melanization in the major larval tissues, in two distinct developmental stages; the feeding and wandering larval stages. The results demonstrate that defense reaction depends on reactive tyrosine derivatives of either early or late stages of the sequence of reactions involved in eumelanin biosynthesis. However, defense and melanization occur independently e.g. hemocytes exhibit a high degree of Escherichia coli immobilization and entrapment, but not any ability to biosynthesize melanin. Serum on the other hand, showed a high degree of melanin formation in wandering stage larvae, but had not any ability for E. coli immobilization. In integuments of wandering stage larvae, both processes occur simultaneously. These findings suggest independent control mechanisms for these processes. Indeed, our results suggest that defense seems to be controlled by the presence of proteins responsible for nonself recognition and melanization by developmental regulation of dopachrome conversion factor.

Defense mechanisms in insects: certain integumental proteins and tyrosinase are responsible for nonself-recognition and immobilization of Escherichia coli in the cuticle of developing Ceratitis capitata.

A defense mechanism in the cuticle of developing C. capitata was demonstrated using an in vitro system consisting of isolated cuticular tyrosinase from C. capitata, cuticular tyrosinase-free proteins, tyrosine, and E. coli. The simultaneous presence of the above components resulted in the formation of large immobilized E. coli aggregates. By contrast, omission of any of the above components failed to produce such aggregates. In other words, E. coli retained their mobility and viability. The results indicate that certain cuticular proteins are responsible for the nonself-recognition, since they are able to bind to the E. coli surface in vitro, and a reactive tyrosine derivative is generated by the action of cuticular tyrosinase for the immobilization and probably killing of E. coli. Based on these studies the most likely explanation for the nonself-recognition and immobilization and/or killing of bacteria is the production of E. coli-protein complexes and their crosslinking through quinone intermediate.