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In-Depth Information
Chapter 7
Plasticity of Dendritic Cell Transcriptional Responses
to Antigen: Functional States of Dendritic Cells
Paul Kellam and Antonia Kwan
Department of Infection, University College L
UK, p.kellam@ucl.ac.uk
ondon, 46, Cleveland Street, London W1T 4JF,
Abstract.
The vertebrate immune system protects the host from harmful encounters with
pathogenic microorganisms and other dangerous components of the environment. To do this
the immune system must gather information about the 'nonself' pathogens and by processing
this information, initiate an appropriate immunological response. The immune system
represents an example of emergent behavior from a complex, multifactorial, adaptive system.
To understand emergent behavior we need to know the systems components and the rules that
govern the system. To identify the components, immunology research has catalogued and
characterized probably all major cell types involved in the innate and adaptive immune
response. In the postgenomic world, we are now able to further characterize global changes in
cellular gene expression and thereby identify and infer changes in the functional state of the
cells. Together this should allow modeling of immune system function. Dendritic cells
orchestrate the host immune response. By identifying a pathogen and processing this
information through a coordinated differentiation program, phenotypic changes effected in
dentritic cells allow appropriate information to be conveyed to the adaptive arm of the immune
system, thereby shaping downstream immunological responses. Transcriptional profiling of
human and mouse dendritic cell responses to different antigens have demonstrated this
functional plasticity. Understanding the regulation of these dendritic cell differentiation states
will contribute to computational models of the immune system, and our understanding of the
parameters that affect the immune system response to infection.
7.1 Introduction
The vertebrate immune system is remarkably versatile, functioning to protect
animals from pathogenic microorganisms and environmental toxins. The immune
system is also able to recognize and attack host cells that have become tumors. To
help understand many of the diverse functions required to fight pathogens the
immune system has been partitioned conceptually into a number of functionally
distinct components: recognition and response, innate and adaptive or effector and
memory. While theoretically simplifying the immune system, these divisions also
