|
Current Immunology
Reviews
ISSN: 1573-3955
Current Immunology Reviews
Volume 2, Number 4, November 2006
Contents
Hepatitis C Virus and Dendritic Cells Pp.
305-312
Babita Agrawal
[Abstract]
Immune Mechanisms of Sublingual Immunotherapy and
Mycobacterial Adjuvants in the Treatment of Allergic Disease
Pp. 313-318
Nerin N. Bahceciler and Isil B. Barlan
[Abstract]
The Long Pentraxin PTX3, a Soluble Pattern Recognition
Receptor Involved in Innate Immunity, Inflammation and Female
Fertility Pp. 319-329
Cecilia Garlanda, Virginia Maina, Federica Moalli, Alessia
Cotena, Livija Deban, Andrea Doni, Alessandro Montanelli,
Alberto Mantovani and Barbara Bottazzi
[Abstract]
Chemokines and Malaria Infection Pp.
331-344
Jenny Miu, Andrew J. Mitchell, Helen J. Ball and Nicholas
H. Hunt
[Abstract]
Role of Vitamin A in T Cell Homing to the Gut
Pp. 345-355
Makoto Iwata
[Abstract]
NF-κB
Activation by FcεRI-Mediated
Signal Transduction Pp. 357-360
Stefanie Klemm and Jürgen Ruland
[Abstract]
Regulation of Adaptive Immunity by the Neurotransmitter
Norepinephrine Pp. 361-370
Ian B. Fisher, Nicholas W. Kin, Jaclyn W. McAlees and
Virginia M. Sanders
[Abstract]
Immunological Impediments to Developing a Blood
Stage Malaria Vaccine Pp. 371-376
Michelle Wykes, Alberto Pinzon-Charry and Michael F.
Good
[Abstract]
Abstracts
[Back to top]
Hepatitis C Virus and Dendritic Cells
Babita Agrawal
A majority of hepatitis C virus (HCV) infected individuals
become chronically infected. There are approximately 175 million
patients chronically infected with HCV worldwide. Multispecific
and vigorous cellular immune responses against HCV antigens
have been suggested to play a significant role in viral clearance.
Patients with chronic HCV are unable to prime and/or maintain
vigorous T cell responses which are required to clear the
body of the viral infection. Dendritic cells (DCs) are the
professional antigen presenting cells which likely play a
dominant role in priming and maintaining vigorous T cell responses
in HCV infection. Furthermore, inefficient DCs function may
play an important role in progression to chronicity in HCV
infection. A number of reports have been published examining
the functional and phenotypic impairment of dendritic cells
in chronic HCV infection. However, these reports are difficult
to reconcile. In this article, studies examining the role
and modulation/regulation of dendritic cells in HCV infection
will be discussed. These elucidations are extremely important
for the rational design of vaccine and/or immunotherapy strategies
for chronic HCV infection.
[Back to top]
Immune Mechanisms of Sublingual Immunotherapy and
Mycobacterial Adjuvants in the Treatment of Allergic Disease
Nerin N. Bahceciler and Isil B. Barlan
While safety and efficacy of specific immunotherapy (SIT)
by the sublingual route in patients with allergic asthma/rhinitis
have now been largely documented, the immunological mechanisms
have only started to be investigated. Most likely, the allergen
captured within the oral mucosa by Langerhans-like dendritic
cells (DCs), subsequently mature and migrate to proximal draining
lymph nodes, which then induce T lymphocytes with regulatory
function. Animal experiments point to enhanced expansion of
TGF-β,
IL-10 and Fox p3 mRNA in CD4+ T cells, indicators of tolerance,
induced by mucosal vaccination. Meanwhile, although there
is still no firm proof in human, data on increase in allergen-induced
IL-10 and allergen-specific IgA secretion supports the possible
role of T regulatory cells in sublingual immunotherapy. Furthermore,
detection of high amounts of lipopolysacharide receptor CD14
on oral DCs support the idea of using adjuvants such as mycobacteria
along with allergen within the oral cavity, which may further
potentiate the immunomodulatory effect. Adjuvants that induce
the generation of allergen-specific T regulatory cells have
been suggested to increase the success of SIT. Supporting
this concept, Mycobacterium vaccae was demonstrated
to induce CD4+CD45RBlow
T regs that secrete IL-10 and TGF-β.
[Back to top]
The Long Pentraxin PTX3, a Soluble Pattern Recognition
Receptor Involved in Innate Immunity, Inflammation and Female
Fertility
Cecilia Garlanda, Virginia Maina, Federica Moalli, Alessia
Cotena, Livija Deban, Andrea Doni, Alessandro Montanelli,
Alberto Mantovani and Barbara Bottazzi
Pentraxins are a family of evolutionarily conserved multifunctional
pattern-recognition proteins characterized by a cyclic multimeric
structure. Based on the primary structure of the subunit,
the pentraxins are divided into two groups: short pentraxins
and long pentraxins. C-reactive protein (CRP) and serum amyloid
P-component (SAP) are the two short pentraxins. The prototype
protein of the long pentraxin group is pentraxin 3 (PTX3).
CRP and SAP are produced primarily in the liver in response
to IL-6, while PTX3 is produced by a variety of tissues and
cells and in particular, by innate immunity cells in response
to proinflammatory signals and Toll-like receptor (TLR) engagement.
PTX3 interacts with several ligands, including growth factors,
extracellular matrix components and selected pathogens, playing
a role in complement activation and facilitating pathogen
recognition by phagocytes, acting as a predecessor of antibodies.
In addition, PTX3 is essential in female fertility by acting
as a nodal point for the assembly of the cumulus oophorus
hyaluronan-rich extracellular matrix.
Thus, the prototypic long pentraxin PTX3 is a multifunctional
soluble pattern recognition receptor acting as a non-redundant
component of the humoral arm of innate immunity and involved
in tuning inflammation, in matrix deposition and female fertility.
[Back to top]
Chemokines and Malaria Infection
Jenny Miu, Andrew J. Mitchell, Helen J. Ball and Nicholas
H. Hunt
Malaria is a devastating disease of the tropics, with an estimated
3.2 billion people exposed to the threat of malaria. There
are 1-3 million deaths annually, mostly of children in sub-Saharan
Africa. Deaths due to malaria often arise from complications
of Plasmodium falciparum infection, particularly
cerebral malaria, but difficulties during pregnancy also contribute
to the high incidence of morbidity and mortality. Cytokines
are known to play a major role in the pathogenesis of severe
malaria, which is generally considered to be an immunopathological
process. Chemokines are a family of chemotactic cytokines,
with diverse roles that include cellular trafficking and neuronal
signaling. Studies on chemokines in malaria infection indicate
that they may be important mediators of the immune response
to malaria. There is also evidence to suggest that chemokines
are involved in the recruitment of leukocytes to the placenta
during pregnancy-associated malaria, and also to the brain
during cerebral malaria. Chemokines and infiltrating leukocytes
can contribute to the severe manifestations of malaria through
the actions of cytokines and other inflammatory mediators,
for example, low birth weight in placental malaria, and neurological
symptoms in cerebral malaria.
[Back to top]
Role of Vitamin A in T Cell Homing to the Gut
Makoto Iwata
Vitamin A supplementation significantly reduces infant mortality
in developing countries, largely by reducing persistent diarrhea
that is often aggravated by malnutrition. Vitamin A contributes
to maintaining the integrity of mucosal epithelia and enhancing
IgA responses in the gut. Recently, we found that vitamin
A is essential for the homing of T cells to gut tissues. Retinoic
acid (RA), an oxidative metabolite of retinol, even at 0.1
to 1 nM, enhances the expression of the gut-homing receptors,
the integrin α4β7
and the chemokine receptor CCR9, on T cells upon activation
in vitro, and grants them the capacity of migrating
to the small intestine. The RA receptors RARα
and/or β
are involved in this effect. Dendritic cells of the gut-associated
lymphoid organs, Peyer’s patches and mesenteric lymph
nodes, express the RA-producing enzymes, and can produce RA
from retinol (vitamin A). Antigenic stimulation of T cells
with these dendritic cells enhances α4β7
expression on T cells, depending on the production of RA by
dendritic cells and its binding to RAR in T cells. Therefore,
vitamin A-derived RA imprints T cells with the gut-homing
specificity. Possible roles of this effect in the development
of diseases and possible future treatments for them are discussed.
[Back to top]
NF-κB
Activation by FcεRI-Mediated
Signal Transduction
Stefanie Klemm and Jürgen Ruland
NF-κB
is a master transcription factor in immunity and inflammation.
It can be activated by a large variety of distinct cell surface
receptors in response to multiple stimuli. NF-κB
activation by the high affinity IgE receptor FcεRI
is critical for proinflammatory cytokine production during
mast cell activation and is crucial for allergic inflammatory
diseases. Recent studies have identified two adaptor proteins,
Bcl10 and Malt1, as essential regulators of FcεRI-mediated
NF-κB
activation. Bcl10 and Malt1 form a signaling complex that
operates downstream of PKC enzymes and regulates the production
of proinflammatory cytokines in response to FcεRI
signaling. Other PKC-dependent mast cell effector functions
like degranulation or leukotriene production are not controlled
by Bcl10 and Malt1. Thus, the Bcl10/Malt1 complex specifically
uncouples the pathway for transcription-dependent cytokine
production from degranulation events. This review will summarize
our current knowledge of the specific NF-κB
activation pathway that is selectively engaged by FcεRI
ligation in mast cells.
[Back to top]
Regulation of Adaptive Immunity by the Neurotransmitter
Norepinephrine
Ian B. Fisher, Nicholas W. Kin, Jaclyn W. McAlees and
Virginia M. Sanders
Endogenous physiological mechanisms are in place to regulate
cell activity in organ systems to maintain host homeostasis
when challenged. Antigenic exposure is an example of a challenge
that disrupts host homeostasis. During this challenge, activated
immune cells secrete cytokines that influence central nervous
system activity, which in turn activates the peripheral sympathetic
nervous system to release the neurotransmitter norepinephrine
from nerve terminals located within lymphoid tissues. Norepinephrine
binds to the beta2-adrenergic receptor expressed on immune
cells to regulate the level of gene expression and the magnitude
of an immune response. In this review, we will discuss both
in vitro and in vivo findings that indicate
the cellular and molecular mechanisms by which norepinephrine
stimulation of the beta2-adrenergic receptor on CD4+
T cells and B cells regulates the level of cellular activity
to maintain host homeostasis.
[Back to top]
Immunological Impediments to Developing a Blood Stage
Malaria Vaccine
Michelle Wykes, Alberto Pinzon-Charry and Michael F.
Good
There are 300-500 million cases of malaria each year and of
the more than one million people that die each year from malaria,
most are children under 5 years of age. The cloning of malaria
antigens in 1983 offered great hope of developing a viable
subunit vaccine. While some subunit vaccines have shown great
promise in model systems, an efficacious human vaccine is
still not available. Immunological studies have shown that
numerous factors such as parasite’s antigenic variation
and polymorphism, immunological non-responsiveness to individual
vaccine antigens, parasite-induced apoptosis of immune effector
and memory cells, immune deviation as a result of maternal
immunity and alterations of dendritic cell function can impede
the development of vaccines. These findings indicate that
alternative novel approaches are required to tackle the disease
and induce protection against malaria.
|
