Contemporary topics in immunobiology最新文献

Progress over the past five years has drawn attention to the fact that the anaplylatoxins are important factors in both leukocyte activation and regulation events. The C5 anaphylatoxin has been proposed to play major role in leukocyte aggregation and adherence phenomenon. Influences of C5a on the leukocyte may lead to clinical manifestations such as respiratory distress syndrome after trauma or postpump syndrome after cardiopulmonary bypass, both effects derived from leukocyte sequestration. Many other clinical conditions involving repeated transient sequestration of leukocytes, particularly in the pulmonary vasculature, may eventually be recognized as a complication of systemic complement activation. Dramatic pathologic changes observed in the lungs of animals exposed to either C3a or C5a emphasizes the potential damage that these factors may exert via cellular activation mechanisms (Huey et al., 1983). More recent evidence that the anaphylatoxins are potent immunoregulatory factors under in vitro conditions suggests a physiologic role for these humoral factors in nonspecific modulation of the immune response. It is an attractive hypothesis to suggest that once activated, complement is capable of relaying information to the cellular immune system via the anaphylatoxins. Other components of the complement system have long been known to exert regulatory influences on the immune system, and perhaps molecular description of such entities as the C3d-K fragment will serve to unravel this seemingly more complex effector system. In any case, as our understanding of both the chemical and biologic nature of factors derived from blood complement components advances, it has become apparent that a major function of complement may be to modulate the immune response. We have already demonstrated that these factors are selective both for cell type and for eliciting a variety of cellular responses. From this, one can infer that manipulation of the cellular events will eventually be possible. Hence a therapeutic value may be realized once involvement of these complement factors under in vivo conditions is better characterized.

Mononuclear phagocytes undergo dramatic changes during differentiation from bone marrow stem cells to resident tissue macrophages. Throughout differentiation, cells lose or acquire numerous morphologic, metabolic and functional capacities such that mature, resident macrophages of one tissue often bear little resemblance to resident cells of another. Superimposed on the intrinsic continuum of mononuclear phagocyte differentiation are the reactive changes in macrophages induced by endogenous and exogenous stimuli: the ability of mononuclear phagocytes to respond to a particular stimulus may also change with cell differentiation. This dynamic interaction of cell differentiation and response to a micro-environment, and the resulting heterogeneity among mononuclear phagocytes for many functional characteristics, is clearly illustrated by the effector activities of activated macrophages that we describe in this report. Despite the common regulatory events for induction and expression of transient nonspecific cytotoxic reactions effective against such diverse targets as rickettsiae, leishmania, schistosomula, and neoplastic cells, these effector functions can be dissociated by the cells that perform the effector activity, and the signals that regulate these activities. The differential susceptibility of the various targets to particular killing mechanisms induced by LK in responsive populations only adds to the complexity of these in vitro analyses. The details of effector functions of activated macrophages are unique for each target.