Intracellular sensors of immunity and allogeneic hematopoietic stem cell transplantation - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 420

ch 18
Intracellular sensors of immunity
and allogeneic hematopoietic
stem cell transplantation
Yaping Sun, Pavan Reddy
Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Internal Medicine,
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA
425
Introduction
Living cells utilize several mechanisms to “sense” and “respond” to changes
in the external and internal environment that elicit or modulate inflamma-
tion and immunity. Immune responses are induced by moieties with certain
molecular patterns from either endogenous or exogenous sources or through
metabolic perturbation [1-3] . The inducers that are sensed and lead to a func-
tional immune response have been variously characterized as “danger” or
“damage” or “nonself” from promiscuous but biologically distinct molecular
patterns [4] . They include damaged tissues, chemicals, metabolites, nonself
antigens from microbes, and allogeneic tissues [5] . Typically, microbes, aller-
gens, and allogeneic antigens might be considered the exogenous inducers
of immunity. Additionally, there is mounting evidence of metabolic changes
that result in modulation of immunity [6-8] . The inducers of immunity,
regardless of whether they are exogenous or endogenous, have to be “sensed”
or “recognized” by sensors. The receptors that function as sensors are on spa-
tiotemporal “sentry duty.” Having acquired significant immunological com-
plexity and redundancies through the development of multiple molecules,
mammals have established both extracellular and intracellular sensors that
sense various inducers of immunity [1,2] .
Both the extracellular and the intracellular sensors are germ-line coded and
form critical components of the innate immunity [2] (see Figure 18.1 ). These
germ-line-encoded receptors generally recognize molecular patterns from
a variety of nonself microbes and also danger signals sent out by damaged
cells/tissues [2,3] . The innate immune receptors are critical for the initiation
and regulation of immune responses against infection, autoimmunity, and
alloreactivity [1] . The extracellular immune receptors, or sensors, include
soluble factors (complement and antibodies) and cell-surface receptors
such as certain Toll-like receptors (TLRs), C-lectin receptors, Fc receptors,