Intracellular sensors of immunity and allogeneic hematopoietic stem cell transplantation - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 421

FIGURE 18.1
Intracellular sensors and activators of the immune system that enhance alloresponses.

and scavenger receptors [9,10] . In this chapter we focus on and review only
the intracellular sensors of innate immunity and discuss their connection
to alloreactivity following allogeneic hematopoietic stem cell transplanta-
tion (HSCT). The roles and relevance of extracellular immune receptors and
cellular subsets have been discussed in the preceding chapters.

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Studies have uncovered several different types of intracellular sensors that
recognize both pathogen-derived (nonself ) and “self” substances that
have danger-associated molecular patterns and trigger divergent signal-
ing pathways leading to the activation of innate immune responses and the
subsequent adaptive immune responses. Most intracellular sensors typically
recognize various forms of nucleic acids, i.e., single-stranded (ss) DNA,
double-stranded (ds) DNA, ssRNA, and dsRNA, irrespective of their origin [9] .

Antigen-presenting cells (APCs), whether hematopoietic (host and donor) or
nonhematopoietic in origin, might be considered the sensors for graft-versus-
host disease (GVHD) following allogeneic HSCT [11,12] . The APCs sense the
damage- and microbial-associated patterns and also present the major histo-
compatibility complex (MHC)-disparate or minor histocompatibility antigen
(mHA)-disparate protein on their surface to donor T cells [12] . These cells may
also provide the critical secondary (costimulatory) and tertiary (cytokine) sig-
nals for activation of the alloreactive T cells, the mediators of GVHD [12] . APCs
sense allodisparity through MHC and peptide complexes that are present on
the cell surface. The intracellular sensors do not play a direct role in the pre-
sentation of the all-disparate antigens; however, they play a significant role in
modulating the overall presentation, context, and response of the allodispa-
rate antigens. The emerging roles and relevance of various intracellular sen-
sors in the regulation of alloreactivity after allogeneic HSCT are discussed here.

Intracellular sensors

The intracellular sensors include those that directly initiate immune
responses and those that indirectly modulate immunity by sensing metabolic