الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Dendritic cells are special type of leukocytes, which perform a
variety of activities. DCs have a long history of key observations made
more than 40 years ago. Although some original publications were
disregarded at first, the importance of DCs has been widely appreciated by
immunologists since the 1980s. They are a highly heterogeneous
population of immunocytes with diverse phenotypes and functions. It is
difficult to define DCs based on morphology, phenotypes, and functions
because DCs exhibit widespread plasticity both in vivo and in vitro. DCs
are defined based on a combination of parameters that include morphology,
phenotype, cytokine secretion, immunomodulatory capacity, expression of
chemokine and chemokine receptors, and migration in response to
chemotactic stimuli.
Dendritic cells are widely recognized as the most professional
antigen-presenting cells. Moreover, they are incorporated in the regulation
of the delicate balance between immunity and tolerance. By interacting
with other cells of the immune system through cell to cell contact or the
production of cytokines, DCs induce an appropriate answer to a specific
antigen. DCs can also prevent autoimmunity by inducing apoptosis of
autoreactive T cells in the thymus on one hand (i.e., central tolerance), and
by induction of anergy (desensitization), deletion, or tolerance through
cooperation with Treg in the periphery on the other hand (i.e., peripheral
tolerance). Consequently, it has been assumed that defects in the number,
phenotype, and/or function of DCs cause the development of autoimmune
diseases.
DCs originate from CD34+ hematopoietic progenitor cells in the
bone marrow and are generally classified in two groups: myeloid or
classical DCs and plasmacytoid DCs. The life cycle of DCs divided into
Summary
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two main stages: the immature and mature stage. The bone marrow
hematopoietic stem cells give rise to circulating DC precursors. They home
to the blood, the lymphoid and non-lymphoid tissues (skin, lungs…) where
they reside as immature cells. In the absence of microbial infection or other
influences, most DCs in the periphery display an immature phenotype and
are very potent in capturing antigen. Upon pathogen recognition, immature
DCs differentiate from an immature to a mature state where they function
as; Inducing T cell tolerance, prevention of auto immunity and induction
of long-lasting immune tolerance.
A substantial number of clinical trials have been conducted for the
treatment of cancer using DCs. Overall, tumor-specific immune responses
have been frequently observed in patients vaccinated with DCs, but durable
clinical responses were rare. In cancer patient, DC vaccination is feasible
and safe, since no or only mild and self-limiting adverse effects have been
reported in a small number of patients. DCs can be injected intradermally,
subcutaneously, intravenously, intralymphatically, intranodally and
intratumorally but pinpoint intradermal injection is the preferred method.
Until now the main focus of research in the field of DC-based
immunotherapy has been on optimizing the immunostimulatory potential
of injected vaccine DCs, aimed at boosting the activation and proliferation
of tumor-specific CTLs. Although Dc based vaccination alone in not
enough, Combination therapy has been shown to improve the clinical
efficacy of cell-based immunotherapy. This may be variously attributed to
several factors including: a) enhanced presentation of tumor-antigens and
other alterations in phenotype that facilitate immune-mediated killing b)
reduction of Tregs or suppressive cytokines and c) boosting of tumorspecific
effector cells.
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Dendritic cells participate profoundly in innate immune responses.
Much has been learned about their basic immunological functions and their
roles in various diseases. Comparatively little is still known about their role
in renal disease, despite their obvious potential to affect immune responses
in the kidney and immune responses that are directed against renal
components. Kidney dendritic cells form an abundant network in the renal
tubulointerstitium and constantly survey the environment for signs of
injury or infection, in order to alert the immune system to the need to
initiate defensive action. Recent studies have identified a role for dendritic
cells in several murine models of acute renal injury and chronic nephritis.
However, recent data are conflicting and at present, it is completely unclear
why kDCs were protective in some renal disease models and proinflammatory
in others.
The concept of immune therapy for treating different liver diseases
is a comparatively new one whereby various practical points have yet to be
optimized. Most immune-based therapies targeting liver disease have been
conducted in pilot studies or clinical trials. Patients with liver diseases
exhibit distorted immune responses to invading pathogens or cancer cells
or autoantigens. On the other hand, recovery from liver diseases is usually
associated with restoration of host immunity. By culturing DCs with viral
antigens or tumor-associated antigens or different cellular products,
immunogenic or tolerogenic DCs can be produced. When antigen-pulsed
DCs are administered, an increase in the functional capacities of cells of
innate immune system is observed. In addition, patients administered with
antigen-loaded DCs exhibit an augmentation of helper T cells, cytotoxic T
cells, and plasma cells activities. This should be aimed at fixing the
distorted immunity of patients with various liver diseases.
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Dendritic cells play a crucial role both in maintaining immune
tolerance and in inducing adaptive immune responses. Therefore, DCs are
the most sought in initiating autoimmunity and its responsibility to
autoimmune diseases. The emerging knowledge of the importance of DCs,
DC-derived cytokines, and intracellular signal transduction pathways in
mediating autoimmune diseases and in creating an inflammatory
environment provides a rationale for pursuing strategies to block these
inflammatory pathways for therapeutic purposes.