Integrating innate and adaptive immunity in the whole animal

Immunol Rev. 1999 Jun;169:225-39. doi: 10.1111/j.1600-065x.1999.tb01318.x.


The mammalian defense system can respond to a variety of threats, but this capability is not just a simple alarm system for triggering antigen-presenting cells and initiating cellular immunity. Instead, the body is an integrated system in which nearly every cell type can relay the alarm through the production of chemokines, which recruit specific inflammatory cells to the target tissues. This chemokine production is carefully regulated at several levels so that the kinetics and character of local tissue inflammation is tailored to the specific threat. First, the production of nuclear factor-kappa B-regulated chemokines can be modulated in non-bone marrow-derived cells through transcriptional repression mediated by RelB. RelB is also implicated in the differentiation of lymphoid dendritic cells, suggesting that this gene regulates the transition from acute inflammation to adaptive immunity. Second, tissue parenchymal cells, in their capacity as sentinel cells, are able to produce different patterns of chemokines in response to different alarm stimuli. Third, cells from different tissues also show distinct potentials for chemokine responses so that the non-specific damage from inflammation might be avoided in some cases. Finally, the differentiation of T-cell effectors allows for further regulation of local inflammation as their cytokines can also affect chemokine production. This integration of innate and adaptive immunity allows for both rapid responses and dynamic regulation of inflammation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Differentiation
  • Central Nervous System / immunology
  • Chemokine CCL11
  • Chemokines / immunology
  • Chemokines, CC*
  • Cytokines / biosynthesis
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Humans
  • Immunity*
  • Inflammation / immunology
  • Islets of Langerhans / immunology
  • Lung / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Proto-Oncogene Proteins / immunology
  • T-Lymphocytes / immunology
  • Transcription Factor RelB
  • Transcription Factors / immunology


  • CCL11 protein, human
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • Proto-Oncogene Proteins
  • RELB protein, human
  • Relb protein, mouse
  • Transcription Factors
  • Transcription Factor RelB