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Current Immunology
Reviews
ISSN: 1573-3955
Current Immunology Reviews
Volume 2, Number 2, May 2006
Contents
Regulation of Apoptosis by Gram-Positive Bacteria:
Mechanistic Diversity and Consequences for Immunity Pp.
119-141
Glen C. Ulett and Elisabeth E. Adderson
[Abstract]
Physiological and Non-Redundant Functions
of PKC Isotypes in T Lymphocytes Pp. 143-156
Nikolaus Thuille, Thomas Gruber, Christa Pfeifhofer,
Natascha Hermann-Kleiter, Christina Lutz-Nicoladoni, Thomas
Letschka, Veronika Kollmann, Michael Leitges and Gottfried
Baier
[Abstract]
Defining a Role for Mucosal Immunity in the Prevention
and Pathogenesis of Respiratory Allergic Diseases Pp.
157-167
Anthony A. Horner
[Abstract]
Molecular Advances Toward the Understanding of the Patho-Biology
of Idiopathic Myelofibrosis Pp. 169-186
Anna Rita Migliaccio, Alessandro Maria Vannucchi,
Giovanni Migliaccio and Ronald Hoffman
[Abstract]
IL-2 Receptor Targeted Immunomodulatory
Biologics: The Past, Present, and Future Pp. 187-208
Deanna D.H. Franke and Haval Shirwan
[Abstract]
Abstracts
[Back to top]
Regulation of Apoptosis by Gram-Positive Bacteria:
Mechanistic Diver-sity and Consequences for Immunity .
Glen C. Ulett and Elisabeth E. Adderson
Apoptosis, or programmed cell death (PCD), is an important
physiological mechanism, through which the human immune system
regulates homeostasis and responds to diverse forms of cellular
damage. PCD may also be involved in immune counteraction to
microbial infection. Over the past decade, the amount of research
on bacteria-induced PCD has grown tremendously, and the implications
of this mechanism on immunity are being elucidated. Some pathogenic
bacteria actively trigger the suicide response in critical
lineages of leukocytes that orchestrate both the innate and
adaptive immune responses; other bacteria proactively prevent
PCD to benefit their own survival and persistence. Currently,
the microbial virulence factors, which represent the keys
to unlocking the suicide response in host cells, are a primary
focus of this field. In this review, we discuss these bacterial
“apoptosis regulatory molecules” and the apoptotic
events they either trigger or prevent, the host target cells
of this regulatory activity, and the possible ramifications
for immunity to infection. Gram-positive pathogens including
Staphylococcus, Streptococcus, Bacillus, Listeria, and Clostridia
species are discussed as important agents of human infection
that modulate PCD pathways in eukaryotic cells.
[Back to top]
Physiological and Non-Redundant Functions of PKC Isotypes
in T Lymphocytes
Nikolaus Thuille, Thomas Gruber, Christa Pfeifhofer,
Natascha Hermann-Kleiter, Christina Lutz-Nicoladoni, Thomas
Letschka, Veronika Kollmann, Michael Leitges and Gottfried
Baier
This review is about the physiological and non-redundant
functions of the PKC gene products in hematopoietic cells,
particularly T cells. In spite of the large amount of information
on PKC functions in various cell types and tissues, the characterization
of the isotype selective functions of the entire PKC family
in lymphoid cell lineages is far from complete. Given the
established important role of PKC θ
as regulator of T cell fate and knowing that several other
PKC isotypes are also expressed in T cells at a high level,
we here summarize the physiological and non-redundant functions
of PKC α,
β, δ, ε,
ζ and
θ isotypes
in T cells (with emphasis on the ongoing mouse genetic studies).
Their known and/or suspected cellular regulation, effector
pathways as well as physiological functions are discussed.
While PKC β,
ε, δ
and ζ
appear to be dispensable during cellular activation of primary
CD3+ T cells, PKC α
and PKC θ
take critical parts in signaling pathways that are necessary
for full antigen receptor mediated T cell activation and T
lymphocyte immunity.
[Back to top]
Defining a Role for Mucosal Immunity in the Prevention
and Pathogenesis of Respiratory Allergic Diseases
Anthony A. Horner
While it has long been recognized that the mucosal and systemic
immune systems function semi-independently, until fairly recently,
understanding of aeroallergen hypersensitivities derived principally
from studies of systemic immune regulation. Nonetheless, tolerance
and hypersensitivities to airborne allergens are likely to
be driven primarily, if not exclusively, by immunological
events taking place within the lungs and their associated
lymphoid tissues. Therefore, this review will focus on the
role of the airways in the prevention, development, and treatment
of respiratory allergic diseases. I will first consider how
the immunological immaturity of infancy may contribute to
the genesis of respiratory allergic diseases. Current understanding
of the mechanisms that promote airway allergen tolerance and
those that mediate CD4 cell differentiation will then be discussed.
Subsequent sections will review how airway exposures to allergens
and man made and natural adjuvants influence local immune
homeostasis and host risk for developing respiratory allergic
diseases. Finally, I will consider how interventions that
target airway immunity might be utilized for the prevention
and treatment of aeroallergen hypersensitivities.
[Back to top]
Molecular Advances Toward the Understanding of the Patho-Biology
of Idiopathic Myelofibrosis
Anna Rita Migliaccio, Alessandro Maria Vannucchi,
Giovanni Migliaccio and Ronald Hoffman
Chronic idiopathic myelofibrosis (IM) is a chronic myeloproliferative
disorder characterized by splenomegaly, a leukoerythroblastic
blood picture, teardrop poikilocytosis, marrow fibrosis, osteosclerosis,
marrow neo-vascularization, abnormal stem/progenitor cell
trafficking and extramedullary hematopoiesis. The disease
may eventually evolve into acute leukemia. This Philadelphia
chromosome negative disorder is thought to originate from
a somatic mutation at the level of the multipotent hematopoietic
stem cell, the most visible consequence of which is a profound
hyperplasia associated with increased proliferation but abnormal
differentiation of the megakaryocytes (MKs). The pathobiology
of the disease, however, involves not only abnormal hematopoietic
stem/progenitor cells functions, but also a defective marrow
microenvironment. The molecular nature of the genetic defect
in IM and how this defect might induce so many pleiotropic
consequences remains unknown. Many of the features of the
human disease can be reproduced in mice by genetic alterations
that induce MK abnormalities similar to those found in patients.
Unfortunately, none of the mutations causing the disease in
mice has been detected in the human disease. These animal
models, however, allow one to dissect the patho-biological
pathway that establishes the complex features of IM. Furthermore,
these models also shed light on the cross-talk between stem/progenitor
cells and microenvironment in normal hematopoiesis.
[Back to top]
IL-2 Receptor Targeted Immuno-modulatory Biologics:
The Past, Present, and Future
Deanna D.H. Franke and Haval Shirwan
The interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R)
system plays a central role in both the innate and adaptive
arms of the immune response. Of major importance is the function
of IL-2/IL-2R in the activation, differentiation, expansion,
and maintenance of T cells that are critical to adaptive immunity.
Clinically, the IL-2/IL-2R axis has been linked to the development
and persistence of hematopoietic malignancies, autoimmune
disorders, and allograft rejection. As such, the IL-2/IL-2R
system has been extensively studied and exploited for T-cell
directed immunotherapy. Several immunomodulatory approaches
targeting this receptor system have been developed that include
antibody-based ligands and radioisotopes, as well as immunoglobulin
and cytokine chimeric biologics, which contain toxins and
apoptosis-inducing proteins. While some of these biologics
are already in clinical practice others are either in transition
to the clinic or under development. We herein review the effectiveness
and limitations of these biologics and discuss new strategies
that could minimize the limitations and improve on the efficacy
of IL-2R-targeted immunotherapy.
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