Immune Defense Systems
Healthy humans protect themselves against foreign invaders by intricate systems of immune and nonimmune mechanisms. Together with physical and chemical barriers, Neutrophil, macrophages, and natural killer (NK) cells form the first line of defense against infection. Experimental evidence in vitro and in vivo confirms that phagocytic defenses are of paramount importance against mucosal infection. Lungs of experimental animals acutely exposed to Cryptococcus neoformans mount an acute neutrophil response followed by an influx of mononuclear cells . Oxidants and granule products from stimulated neutrophils can kill C albicans and A fumigatus, and bronchoalveolar macrophages are particularly relevant in defense against fungal conidia .
Antibody-dependent cell-mediated cytotoxicity regulated by natural killer (NK) cells, cytotoxic T lymphocytes, helper T lymphocytes, and antibody-producing B lymphocytes are central to adaptive immune responses against fungal infections. The constant interaction of the different components of the immune system ensures successful protection of the host. After phagocytosis, monocytes may act to trigger the release of cytokines, in particular interferon () and interleukin-2 (IL-2) that in turn activate effector cells to destroy the engulfed organism. Tumor necrosis factor () and granulocyte macrophagecolony- stimulating factor (GM-CSF) have also been reported to activate effector cells . In addition, antibodies released by B lymphocytes can coat pathogens and change the capsular structure to allow more effective phagocytosis. Although this occurs in bacterial infection, the importance in fungal disease apart from Cryptococcus is not well established.
Complement activation, either via the classic or alternative pathway, facilitates the opsonization of target organisms, thereby enhancing phagocytosis and subsequent killing. Chemotaxis of phagocytes, induction of acute inflammatory responses, increased capillary permeability, and release of inflammatory mediators also result from this activation. Unlike bacteria, complement does not cause direct lysis of fungal cells. However, opsonization of invading fungi with complement fragments or antibody coating is important to facilitate phagocytosis and killing in some but not all species. Binding of certain fungi to macrophages can also be facilitated by cellular receptors for yeast mannose and beta-glucans .
Course Number: V035B.043001
This CME Expires on July 1, 2003; no tests will be accepted after this date.
This course is accredited by
The University of Pittsburgh School of Medicine, Center for Continuing Education