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highlight the complexity of relationships that occur. It is clear that the nonlinear
integration of cell surface and cytokine signals from pathogen recognition, through
innate to adaptive immune responses bestows incredible complexity and flexibility
on and leads to the renewable recall capacity of the immune system.
Complex, dynamic nonlinear systems commonly produce unusual, non-
intuitive properties, so-called emergent properties. Emergence in this sense applies
where the activity of the parts does not simply sum to give the activity of the whole.
Therefore, ultimately, mathematical models will be required to help understand
immune function (Callard, George, and Stark 1999). Formulating such models
requires knowledge of the systems components and the rules that govern the system.
Some of the component details are known. For example, the vertebrate immune
system has evolved to comprise many specialist cell types, which themselves have
complex ontogenesis. These cell types reflect functional partitioning, with cells of
the myeloid lineage (monocyte/macrophage, neutrophils, eosinophils, and basophils)
functioning primarily in the innate, antigen-nonspecific immune response and cells
of the lymphoid lineage (T cells and B cells) functioning primarily in the adaptive
antigen-specific response. Other components are less well understood. For example,
gene expression programs and functional gene networks that manifest as different
immune cell phenotypes have not been defined. In this review we will discuss
aspects of how the host immune system functions in the recognition of pathogens
and begin to illustrate how plasticity in gene expression programs creates different
functional states in one of the pathogen-sensing components, the dendritic cell.
7.2 Dendritic Cells
The recognition and initial innate response to diverse pathogens is linked to an
effective adaptive immune response, with dendritic cells (DCs) providing the bridge
(Hoebe, Janssen, and Beutler 2004). Bone marrow-derived DCs in their “immature”
form are distributed at anatomical sites most likely to be breached by microbes. Here
they continuously sample their environment. When microbial antigens are
encountered, along with the presence of “danger signals” from locally infected cells,
DCs undergo a complex “maturation” process resulting in their migration out of
peripheral tissues and transit to secondary lymphoid tissues. Where mature, DCs
present processed microbial peptides on Major Histocompatibility complex (MHC)
molecules to T cells. Importantly, DCs express costimulatory molecules allowing
them to interact and prime antigen naïve T cells to proliferate. DCs are therefore able
to recognize and interpret the presence of different antigens, process the information
facilitating their own maturation, and present the processed information to T cells to
shape the adaptive immune response.
7.2.1 Recognizing Pathogens
7.2.1.1 Dendritic Cell Subsets
At least two, probably nonexclusive mechanisms can exist for differential
recognition of pathogens by DCs. First, distinct cell subsets specialize to recognize
particular pathogens. Second, cells can express different receptor molecule
repertoires that recognize specific pathogens. Evidence exists for both these
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