Current Immunology Reviews

ISSN: 1573-3955

Current Immunology Reviews
Volume 3, Number 2, May 2007

Contents


Pathogenesis of Type 1 Diabetes: Regulation of Adhesion Molecules and Immune Cell Trafficking Pp. 87-100
Jordana Cohen, Krishnan Sundar and David Bleich
[Abstract]


AIDS Vaccines and Reproductive Immunology Pp. 101-107
Aldar S. Bourinbaiar, Vichai Jirathitikal, Dmytro S. Silin, Nian-Qing Lu and Rivka Abulafia-Lapid
[Abstract]


Platelets as Potential Immunomodulators: Is There a Role for Platelet Toll-Like Receptors? Pp. 109-115
Fabrice Cognasse, John W. Semple and Olivier Garraud
[Abstract]


Cellular and Molecular Regulation of Inflammatory Pain, Nociception and Hyperalgesia - The Role of the Transcription Factor NF-κB as the Lynchpin Nocisensor: Hyperalgesic or Analgesic Effect? Pp. 117-131
John J. Haddad
[Abstract]


Bacterial Infections of the Central Nervous System: A Critical Role for Resident Glial Cells in the Initiation and Progression of Inflammation Pp. 133-143
Vinita S. Chauhan and Ian Marriott
[Abstract]


Lipid-Specific Immune Responses Against Tuberculosis: From Basic Science to Medical Applications Pp. 145-150
Isamu Matsunaga and Masahiko Sugita
[Abstract]




Abstracts

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Pathogenesis of Type 1 Diabetes: Regulation of Adhesion Molecules and Immune Cell Trafficking
Jordana Cohen, Krishnan Sundar and David Bleich

Targeted pancreatic β-cell destruction by activated immune cells is a hallmark of type 1 diabetes in human beings and rodents. Activated T-lymphocytes, B-lymphocytes and antigen presenting cells all migrate to the pancreatic islets and orchestrate a β-cell specific inflammatory immune response. While the timing and sequence of these invading, migratory cell populations are undoubtedly critical and fundamental to our understanding of this disease, many details of the process are still poorly understood. Here, we review our present knowledge of immune cell trafficking, adhesion molecules and matrix interactions as they relate to the pathogenesis of type 1 diabetes. Understanding the roles that adhesion molecules play in guiding the flux of immune cell populations between the pancreatic islets, the vascular endothelium, the pancreatic lymph nodes and other lymphoid tissues will provide us with new therapeutic targets for type 1 diabetes and insights into the pathogenesis of the disease.


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AIDS Vaccines and Reproductive Immunology
Aldar S. Bourinbaiar, Vichai Jirathitikal, Dmytro S. Silin, Nian-Qing Lu and Rivka Abulafia-Lapid

It may appear that problems of reproductive immunology have little in common with issues of treatment and prevention of AIDS. However, the certain aspects of HIV immunopathogenesis are closely related to problems faced by reproductive immunologists. The development of prophylactic and therapeutic AIDS vaccines would greatly benefit from acquired experience in immune regulation of reproductive dysfunction. The spermatozoa and HIV are foreign intruders that must enter the host cell, oocyte or T-lymphocyte, in order to start the replication process. The immune responses of the host organism against fertilized egg or HIV-impregnated lymphocyte must be similar, since in theory they are directed against alloantigens presented by such cells. This paper attempts to bring together the recent advances in AIDS field with progress made in the physiology and pathology of reproduction in humans, especially in the domain of immunotherapy and prevention of recurrent spontaneous abortions (RSA). It is our opinion that the lessons learned from alloimmunization trials of infertile women are relevant to prophylactic and therapeutic strategies for HIV infection.


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Platelets as Potential Immunomodulators: Is There a Role for Platelet Toll-Like Receptors?
Fabrice Cognasse, John W. Semple and Olivier Garraud

Platelets are anucleated cells that are fragments of megacaryocytes, and they play a unique role in primary haemostasis. As they also contain numerous secretory products, they can exert crucial roles in several aspects of haemostasis. Furthermore, they contain and secrete a variety of cytokines, chemokines and associated molecules, which behave as ligands for receptors/counterparts displayed by both endothelial cells lining the vessels and most leukocyte subsets. These latter observations have sparked debate whether platelets play an important role in innate as well as adaptative immunity, thus highlighting the potential for platelets to take part in immune regulation. Moreover, platelets display receptors for several types of cytokines/chemokines (and associated molecules) along with FcγRII receptors. Platelets not only express a large variety of Toll-like receptors with recently identified or as-yet unknown functions, but they have also been shown to express a key tandem pair of inflammatory and antigen presentation molecules (CD40 and CD40-ligand/CD154) making them the major purveyors of soluble CD40L in the plasma. It appears that platelets may be regarded as one of the neglected players in immune cell regulation, and so we propose that they contribute to bridging innate and adaptative immunity. This review will present experimentally-driven arguments in favour of a role of platelet TLRs in regulating certain immune activities.


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Cellular and Molecular Regulation of Inflammatory Pain, Nociception and Hyperalgesia - The Role of the Transcription Factor NF-κB as the Lynchpin Nocisensor: Hyperalgesic or Analgesic Effect?
John J. Haddad

The milieu of inflammatory cells and inflammatory mediators is crucially involved in the genesis, persistence and severity of pain following trauma, infection or nerve injury. The mechanisms and pathways mediating pain and nociception (hyperalgesia) are transcriptionally regulated. The transcriptional mediator nuclear factor (NF)-κB plays a major role in regulating inflammatory responses, ostensibly via the control of gene expression/suppression. An association has recently emerged to establish a possible link between NF-κB and pain/nociception, purportedly through the regulation of the inflammatory loop and the secretion (biosynthesis) of pro-inflammatory mediators. Current concepts conspicuously indicate that the effective inhibition of this transcription factor and associated upstream kinase(s) and the pathways that regulate its nuclear translocation could be major targets in a new strategy for the alleviation of inflammation and inflammatory-related pain. In contrast, recent evidence has implicated NF-κB in analgesic effects; the mechanisms are yet to be elucidated. To better understand this relationship, therefore, between NF-κB and the evolution of pain and hyperalgesia/nociception, it is imperative to unravel the molecular basis of this process. This survey integrates current themes pertaining to the pivotal role that NF-κB shares in regulating pain through the decoding of implicated molecular pathways and signaling mechanisms.


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Bacterial Infections of the Central Nervous System: A Critical Role for Resident Glial Cells in the Initiation and Progression of Inflammation
Vinita S. Chauhan and Ian Marriott

While bacterial infections of the central nervous system (CNS) constitute a group of serious and often life threatening diseases, the pathophysiology of these diseases remains poorly understood. Resident glia have traditionally been considered to be victim cells during bacterial infections, but it has become increasingly apparent that resident cells of the CNS have the potential to contribute to the initiation and/or progression of inflammatory host responses following bacterial invasion of the brain. Microglia and astrocytes have the ability to perceive bacterial pathogens and assume many of the functions of systemic immune cells following challenge. These responses include the production of large quantities of cytokines and chemokines that can precipitate recruitment of leukocytes into the CNS, and the expression of cell surface molecules that can initiate antigen-specific activation of these immune cells. In this article, we describe the most common clinical manifestations of bacterial infections in the brain and discuss the methods utilized by bacterial pathogens to breach the blood-brain-barrier. Furthermore, we outline the inflammatory responses associated with such infections, and discuss the potential role of resident glial cells in the pathogenesis of bacterially induced CNS disorders.


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Lipid-Specific Immune Responses Against Tuberculosis: From Basic Science to Medical Applications
Isamu Matsunaga and Masahiko Sugita

Mycobacteria are unique in that their thick cell wall contains a variety of lipid and glycolipid components that are critical for survival and virulence of the microbes. Studies over the past decade have established that our immune system has evolved an outstanding ability to elicit immune responses directed specifically against these highly hydrophorbic lipid antigens. Unlike MHC molecules that bind peptide antigens, human group 1 CD1 molecules (CD1a, CD1b, CD1c) bind mycobacteria-derived lipid antigens and present them to specific T cells that control mycobacterial infection. Presen-sitization of these CD1-restricted T cells with specific lipids results in protection against tuberculosis, underscoring the possibility that lipids may comprise a new biochemical class of vaccines against microbial infection. Further, the humoral immunity against certain glycolipids derived from the cell wall of mycobacteria has also been noted in patients with active tuberculosis, and the IgG antibody titers correlate with the disease activity. Thus, these lipid-specific immune responses have significant medical implications that have never been recognized previously.