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Current Immunology
Reviews
ISSN: 1573-3955
Current Immunology Reviews
Volume 3, Number 4, November 2007
Contents
Regulation of Innate and Adaptive Immune Responses
by a Novel Pattern Recognition Molecule Mindin Pp.
233-239
David W. Draper and You-Wen He
[Abstract]
T Cell Memory Generation in the Face of Persistent
Antigen Presentation Pp. 240-250
Dawn M. Jelley-Gibbs and Susan L. Swain
[Abstract]
The Network of Fibroblastic Reticular Cells in the
Lymph Node: Functional Framework for Immune Surveillance
Pp. 251-257
Tomoya Katakai and Akira Shimizu
[Abstract]
To Be, or Not To Be: That is the Question-Lineage
Commitment in Hematopoiesis Pp. 258-268
Chia-Lin Hsu and Motonari Kondo
[Abstract]
Regulation of T Cell Signaling and Function by Cbl-b
Pp. 269-275
Christine B.F. Thien and Wallace Y. Langdon
[Abstract]
Mechanisms of Drosophila Immunity –
An Innate Immune System at Work Pp. 276-288
Ulrich Theopold and Mitchell S. Dushay
[Abstract]
Sjögren’s Syndrome and Lymphoma Development
Pp. 289-296
Lingli Dong, Yasufumi Masaki, Masao Tanaka, Toshihiro
Fukushima, Toshiro Okazaki and Hisanori Umehara
[Abstract]
Abstracts
[Back to top]
Regulation of Innate and Adaptive Immune
Responses by a Novel Pattern Recognition Molecule Mindin
David W. Draper and You-Wen He
Extracellular matrix proteins play important roles in many
different biological processes. Our recent work has discovered
important roles for the ECM protein mindin in both innate
and adaptive immune responses. Mindin is a member of the F-spondin
family of extracellular matrix proteins, which are classified
by the presence of an FS1/FS2 domain and one or more thrombospondin
type 1 (TSR) repeats. Mindin is highly conserved throughout
evolution and is broadly expressed in several organs including
central and peripheral lymphoid tissues. As a component of
the extracellular matrix, mindin exerts several important
functions in immune responses. Mindin functions as a pattern
recognition molecule for microbial pathogen recognition and
is required for effective macrophage activation as well as
phagocytosis of microbes. In addition, it promotes leukocyte
trafficking during inflammation in vivo. Mindin is
also essential for the adaptive immune response by inducing
small GTPase expression in dendritic cells which is required
for efficient T cell priming. These effects are largely mediated
through the interaction of mindin with multiple cell surface
integrins, which likely results in integrin clustering and
the induction of downstream signaling cascades. The focus
of this review is to highlight these recent discoveries that
demonstrate the necessary roles for mindin during innate and
adaptive immunity.
[Back to top]
T Cell Memory Generation in the Face of Persistent
Antigen Presentation
Dawn M. Jelley-Gibbs and Susan L. Swain
In the face of emerging infectious diseases, we are challenged
to develop innovative vaccine strategies that can protect
against rapidly evolving and highly virulent pathogens. Since
CD4 T cells are needed to generate and maintain protective
B cell and CD8 T cell immunity, new vaccines should ideally
elicit both T and B cell memory. In order to generate long-lived
immune memory in both T and B cell compartments, such vaccines
will need to induce cross-reactive memory against highly conserved
antigens within a given pathogen. Acute influenza infection
provides a model system whereby the generation of T cell memory
is influenced by residual antigen depots. These antigen depots
persist for months after live virus clearance, and provide
continued, low level T cell stimulation. Here we discuss the
impact and implications of residual pathogen-derived antigen
depots on the generation and maintenance of T cell immunity.
We propose that effective vaccines may need to include persistent
depots of conserved proteins to generate a functionally flexible
memory T cell pool that can confer protection against rapidly
evolving pathogens.
[Back to top]
The Network of Fibroblastic Reticular Cells in the
Lymph Node: Functional Framework for Immune Surveillance
Tomoya Katakai and Akira Shimizu
Lymph nodes (LNs) are crucial organs for triggering adaptive
immune responses, and are localized at key places in the network
of the lymphatic vascular system in order to filter tissue
fluid exudates containing antigens effectively. Within the
LN, immune cells are strategically compartmentalized to form
a unique tissue architecture that is mechanically and functionally
supported by several types of stromal cells of mesenchymal
origin. In particular, one of the stromal cell types known
as fibroblastic reticular cells (FRCs) produces extracellular
matrix fibers and constructs an elaborate network of reticulum
that serves as a foothold for immune cells’ movement.
This network of matrix fibers ensheathed by FRCs also functions
as a transport system for low molecular weight materials,
including lymph-borne soluble antigens. In addition, FRCs
potentially control the localization and homeostasis of immune
cells by producing various factors such as adhesion molecules,
chemokines, and cytokines. Therefore, this type of less-understood
stromal cell component in the LN plays a central role in the
spatiotemporal regulation of adaptive immune surveillance.
[Back to top]
To Be, or Not To Be: That is the Question-Lineage
Commitment in Hematopoiesis
Chia-Lin Hsu and Motonari Kondo
During hematopoiesis, hematopoietic stem cells (HSCs) gradually
lose their multi-potency and ultimately commit to a single
lineage at certain period in the maturation process. Before
entering the lineage commitment stage, progenitors have to
go through multiple specification steps. During this progression,
both external and internal cues may have effects on the cell
fates of progenitors. However, it is not clear how extrinsic
signals such as cytokines or growth factors from the microenvironment
and intrinsic cell differentiation programs are coordinated
and determined for lineage specification and commitment during
hematopoiesis. Nevertheless, it has been assumed that upon
lineage commitment, progenitors follow a hierarchical and
linear differentiation program. Recently, the issues of developmental
plasticity or latent differentiation potential in lineage-committed
progenitors have been documented, although lineage commitment
has been thought to be an irreversible event. Therefore, we
may need to revisit the issue of how “lineage commitment”
is determined in the hematopoietic system at the molecular
level. In this review, we would like to propose a revised
model for lineage commitment and give an overview of recent
advances in understanding how lineage decision is made.
[Back to top]
Regulation of T Cell Signaling and Function by Cbl-b
Christine B.F. Thien and Wallace Y. Langdon
The activation of intracellular signaling pathways by the
engagement of ligands with cell-surface receptors is a key
event in determining the fate and function of cells. While
these outcomes are primarily determined by the nature of the
ligand and its receptor, proteins that negatively regulate
the strength and duration of these signals are also critical
components in this process. In recent years the E3 ubiquitin
ligases c-Cbl and Cbl-b have emerged as prominent negative
regulators of signaling responses initiated from antigen receptors
on thymocytes and T cells respectively. In this review we
focus on the role of Cbl-b in regulating T cell signaling
and function and update new and exciting findings relating
to Cbl-b deficient T cells that promote the rejection of tumors.
[Back to top]
Mechanisms of Drosophila Immunity –
An Innate Immune System at Work
Ulrich Theopold and Mitchell S. Dushay
Insect immune systems which lack the type of adaptive immunity
known in vertebrates rely on several mechanisms including
solid barriers against the environment, rapid coagulation
of hemolymph after wounding, the formation of aggregates that
immobilize and kill foreign invaders, phagocytosis, and the
production of antimicrobial peptides. The mode of action and
the regulation of the expression of antimicrobial peptides
have been studied intensively for more than three decades
and are now increasingly well understood. In addition, the
characterization of several key molecules involved in other
branches of insect immunity has led to a deeper and much more
comprehensive understanding of innate immunity in insects.
Here we focus on the current status of our view of immunity
in the vinegar fly Drosophila melanogaster, the best
characterized insect model. We also discuss how evolutionary
and ecological forces may have shaped immune responses in
Drosophila as compared to other insect species. Finally,
several infection models reveal finely-tuned and pathogen-dependent
interactions between Drosophila immunity and fly
physiology.
[Back to top]
Sjögren’s Syndrome and Lymphoma Development
Lingli Dong, Yasufumi Masaki, Masao Tanaka, Toshihiro
Fukushima, Toshiro Okazaki and Hisanori Umehara
Primary Sjögren’s syndrome (pSS) is a systemic
as well as an organ-specific autoimmune disease characterized
by lymphocytic infiltration of the glandular epithelial tissue.
It has been reported that pSS patients have a relatively increased
risk for the development of lymphoma and various factors such
as cytokine stimulation, environmental exposures and viral
infections as well as genetic events may contribute to the
development of lymphoma in pSS patients. Over the past few
decades, numerous efforts have been undertaken to search for
the relationship between lymphoma and pSS, for example advances
in molecular biology for clonality analysis and well-linked
register cohort studies for the predictive value of clinical,
laboratory and histological findings. Despite this, mechanisms
and prediction of lymphoma development in pSS patients still
remain to be defined. In this review we have summarized the
current knowledge concerning incidence and risk factors of
lymphoma development in pSS patients. In addition, the most
recent discoveries in the emergence and treatment of lymphoma
in pSS patients and the possible mechanism of lymphoma development
are also discussed.
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