Begell House Inc.
Critical Reviews⢠in Immunology
CRI
1040-8401
26
2
2006
Mechanisms of Calcium Signaling and Function in Lymphocytes
97-112
10.1615/CritRevImmunol.v26.i2.10
Bruce D.
Freedman
University of Pennsylvania, School of Veterinary Medicine, Department of Pathobiology, Philadelphia, PA 19104
The multifunctional role for calcium during lymphocyte activation and differentiation is well established; yet how fate-specific changes in calcium concentration are produced, and how these signals are translated into distinct cellular responses, is not known. A critical role has been identified for store-operated calcium release-activated calcium (CRAC) channels; however, the lack of information concerning the structure and mechanism of store-dependent activation has limited our ability to define CRAC's role in the range of calcium-dependent responses of lymphocytes. Moreover, additional calcium-permeant cation channels have been recently identified in lymphocytes. These channels regulate functions distinct from those attributed to CRAC channels. Consequently, this review summarizes well-established mechanisms of calcium signaling and also considers recent findings which suggest that diverse and interacting pathways encode functionally specific calcium signals in lymphocytes. Speculation is also offered about how distinct patterns of calcium signaling are translated into diverse transcriptional responses.
The Role of Protein Kinase A and A-Kinase Anchoring Proteins in Modulating T-Cell Activation: Progress and Future Directions
113-132
10.1615/CritRevImmunol.v26.i2.20
Robynn V.
Schillace
Veterans Affairs Medical Center, Department of Neuroscience, Oregon Health & Science University, Portland, OR 97239
Daniel W.
Carr
Department of Medicine, Oregon Health & Science University, Portland, OR 97239
Protein kinase A (PKA) is a broad-specificity serine/threonine protein kinase whose spatial and temporal regulation is maintained through interactions with A-kinase anchoring proteins (AKAPs). Subcellular localization of AKAPs through unique targeting domains provides a mechanism by which PKA can respond to localized microdomains of cyclic AMP (cAMP) and phosphorylate nearby substrates.1 For nearly 40 years, cAMP has been known to be a potent modulator of the immune system. cAMP levels are regulated by G-proteinâcoupled receptors, adenylyl cyclases (AC), and phosphodiesterases (PDEs). This review discusses recent progress made in the discovery of PKA substrates in T lymphocytes and in the identification of AKAPs in T lymphocytes. Because PKA is activated by cAMP, generation and maintenance of cAMP in T cells is also discussed. These findings are framed in the context of understanding the complexity of cAMP and, thus, PKA signaling and are intended to provide the reader with an overview of current literature, as well as an awareness of questions and concerns to consider.
Caspase Function and the Immune System
133-148
10.1615/CritRevImmunol.v26.i2.30
Sarita
Sehra
Departments of Pediatrics and HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202
Alexander L.
Dent
Department of Microbiology and Immunology and The Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202; The Walther Cancer Institute, Indianapolis, IN 46208
Caspases are key effector components of apoptosis, the process of programmed cell death. However, a large body of recent work has shown that caspase activity is necessary for several nonapoptotic cellular functions, such as proliferation, differentiation, survival, and the regulation of cytokine expression. In this review, we concentrate on the nonapoptotic functions of caspases and, in particular, on nonapoptotic roles of caspases in the immune system. Because of the involvement of caspases in promoting cell death, as well as cell proliferation and other nonapoptotic functions, studies involving the inhibition of caspases in vivo must be interpreted with caution.
Innate and Adaptive Immune Responses of the Central Nervous System
149-188
10.1615/CritRevImmunol.v26.i2.40
Samantha L.
Bailey
Department of Microbiology-Immunology and The Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; Authors contributed equally to this review
Pamela A.
Carpentier
Department of Microbiology-Immunology and The Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; Authors contributed equally to this review
Eileen J.
McMahon
Biology Department, Westmont College, 955 LaPaz Rd., Santa Barbara, CA 93108
Wendy Smith
Begolka
Department of Microbiology-Immunology and The Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611
Stephen D.
Miller
Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611
The central nervous system (CNS) is an immunologically specialized organ. The blood-brain barrier regulates the passage of molecules and cells into the CNS. Robust immune responses occur in the CNS even though there is normally an absence of MHC molecules, lack of normal lymphatic drainage, and reduced immune surveillance. This review discusses the immunological elements of the healthy CNS and the pattern of responses that evolve during innate and adaptive immunity in this organ. We also discuss the contribution of astrocytes, cerebrovascular endothelial cells, microglia, macrophages, and dendritic cells to the integrity and pathology of the CNS during CD4+ Т-cell autoimmune responses directed against neuroantigens.