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  • Review Article
  • Published:

Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence

Nature Reviews Immunology volume 8, pages 764–775 (2008)Cite this article

Key Points

  • Secondary lymphoid organs (SLOs) are the central organizing platform for the immune system's daily 'business': coping with infectious challenges from the environment.

  • The following functional building blocks represent the basic structural entities of SLOs: first, input channels for pathogens, lymphocytes, and antigen-presenting cells (APCs), second, distribution channels for the communication between third, the antigen-sampling zone, fourth, the T-cell zone and fifth, the B-cell zone.

  • The microenvironment within SLOs is required for productive lymphocyte–APC encounters, particularly when limited amounts of antigen and low precursor frequencies of cognate lymphocytes are available.

  • A bell-shaped correlation links inflammatory stimuli from microorganisms to lymphoid structure and immunocompetence: on the one hand, low-level stimulation through intestinal microorganisms fosters optimal morphological integrity and functionality of SLOs; whereas, on the other hand, overwhelming inflammatory stimuli can lead to the disruption of SLO integrity and to loss of immunocompentence.

  • SLOs are an excellent example of reciprocity between anatomical form and organ function. This plasticity, as the collective result of individual cellular decisions, gives the host the best chance to fight invading microorganisms and to survive.

Abstract

Secondary lymphoid organs (SLOs) are tissues that facilitate the induction of adaptive immune responses. These organs capture pathogens to limit their spread throughout the body, bring antigen-presenting cells into productive contact with their cognate lymphocytes and provide niches for the differentiation of immune effector cells. Therefore, the microanatomy of SLOs defines the ability of an organism to respond to pathogens. SLO microarchitecture is, at the same time, extremely adaptable to environmental changes. In this Review, we discuss recent insights into the function and plasticity of the SLO microenvironment with regards to antimicrobial immune defence.

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Figure 1: Functional building blocks of an SLO.
Figure 2: Microstructure of the antigen-sampling zones in lymph nodes and spleen.
Figure 3: The integrity of lymphoid microenvironments determines the immunocompetence of the host.
Figure 4: Inflammation alters the integrity of SLO microenvironments and the immunocompetence of the host.

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Acknowledgements

We thank S. Miller for expert help with immunohistology. This work received financial support from the Kanton of St. Gallen.

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Authors and Affiliations

  1. Novartis Institutes for BioMedical Research, Basel, 4002, Switzerland

    Tobias Junt

  2. Research Department, Kantonal Hospital St. Gallen, St. Gallen, 9007, Switzerland

    Elke Scandella & Burkhard Ludewig

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  1. Tobias Junt
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  2. Elke Scandella
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Correspondence to Tobias Junt or Burkhard Ludewig.

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Glossary

Isolated lymphoid follicles

Small (150 μm diameter) aggregations of lymphocytes, predominantly B cells and follicular dendritic cells, that are present on the antimesenteric wall of the mouse small intestine.

Tertiary lymphoid tissue

Ectopic lymphoid aggregates that are generated during the process of chronic immune stimulation and that exhibit the structural characteristics of secondary lymphoid organs.

Alymphoplasia

(aly). A spontaneous mutation that is characterized by the systemic absence of lymph nodes and Peyer's patches and an aberrant splenic microarchitecture. The gene responsible for this phenotype was shown to encode nuclear factor-κB-inducing kinase (NIK).

Arteriolar tree

The feed arteriole of lymph nodes and its branches.

Metallophilic macrophage

A macrophage that is located at the border of the white pulp and the marginal zone of the spleen. These cells are stained by silver impregnation, which explains the name.

Immune complexes

Large aggregates of antibodies with cognate antigen. Immune complexes may bind to receptors on antigen-presenting cells, directly or through complement proteins, to trigger immune-effector responses.

High endothelial venule

(HEV). A specialized venule with a cuboidal endothelial lining. HEVs are found in peripheral lymph nodes and Peyer's patches and are used by naive lymphocytes to enter lymphoid tissues.

Pattern-recognition receptor

A host receptor (such as Toll-like receptors) that can sense pathogen-associated molecular patterns and initiate signalling cascades (which involve activation of nuclear factor-κB) that lead to an innate immune response.

Paucity of lymph-node T cells

(plt). A mutation that leads to loss of expression of the chemokines CCL19 and CCL21 in lymphoid organs, resulting in disturbed migration of CCR7-expressing T cells and mature dendritic cells.

Cytokine storm

A sudden surge in the circulating levels of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, tumour-necrosis factor and interferon-γ.

Activation-induced cell death

(AICD). A form of regulated cell death that is induced during lymphocyte activation. During a normal immune response, most antigen-specific lymphocytes undergo AICD.

Germ-free mouse

A mouse that is born and raised in isolators, without exposure to microorganisms.

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Junt, T., Scandella, E. & Ludewig, B. Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence. Nat Rev Immunol 8, 764–775 (2008). https://doi.org/10.1038/nri2414

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