The Immune System: Structure, Function, and Roles in Skin Disease

Chapter
First Online:

Abstract

The skin is a complex defense system composed of both passive barriers and active immune responses mediated by specialized hematopoietic cells. Consequently, dysregulation of the immune system, namely, through increased or decreased activity of these cells, plays an important role in numerous diseases of the skin. In this chapter, we review the basic mechanisms of the immune system, the organization of defense in the skin, and the functions of the major immunologic effector cells (neutrophils, macrophages, dendritic cells, mast cells, eosinophils, basophils, natural killer cells, T lymphocytes, and B lymphocytes). We specifically emphasize the relationship between cell activity and skin pathology and organize skin conditions by the cell type most responsible for the characteristic pathophysiology. By highlighting these broad themes, we aim to provide a unique framework for understanding dermatologic disease.

Keywords

Innate immunity Adaptive immunity Hypersensitivity reaction Immunopathology Skin disease 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Medzhitov R, Janeway C. Innate immunity. N Engl J Med. 2000;343:338–44.CrossRefPubMedGoogle Scholar
  2. 2.
    Cooper MD, Alder MN. The evolution of adaptive immune systems. Cell. 2006;124:815–22.CrossRefPubMedGoogle Scholar
  3. 3.
    Medzhitov R. Approaching the asymptote: 20 years later. Immunity. 2009;30:766–75.CrossRefPubMedGoogle Scholar
  4. 4.
    Janeway CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):1–13.CrossRefPubMedGoogle Scholar
  5. 5.
    Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8:279–89.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell. 2002;109 Suppl:S45–55.CrossRefPubMedGoogle Scholar
  7. 7.
    Hodgkin PD, Heath WR, Baxter AG. The clonal selection theory: 50 years since the revolution. Nat Immunol. 2007;8:1019–26.CrossRefPubMedGoogle Scholar
  8. 8.
    Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132:631–44.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science (New York, NY). 2010;327:656–61.CrossRefGoogle Scholar
  10. 10.
    Schulz C, Gomez Perdiguero E, Chorro L, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science (New York, NY). 2012;336:86–90.CrossRefGoogle Scholar
  11. 11.
    Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–35.CrossRefPubMedGoogle Scholar
  12. 12.
    Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140(6):771.CrossRefPubMedGoogle Scholar
  13. 13.
    Pasparakis M, Haase I, Nestle FO. Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol. 2014;14:289–301.CrossRefPubMedGoogle Scholar
  14. 14.
    Gallo RL, Hooper LV. Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol. 2012;12:503–16.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Heath WR, Carbone FR. The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat Immunol. 2013;14:978–85.CrossRefPubMedGoogle Scholar
  16. 16.
    Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30:459–89.CrossRefPubMedGoogle Scholar
  17. 17.
    Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159–75.CrossRefPubMedGoogle Scholar
  18. 18.
    Gordon S. The macrophage: past, present and future. Eur J Immunol. 2007;37(Suppl 1):S9–17.CrossRefPubMedGoogle Scholar
  19. 19.
    Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–69.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604.CrossRefPubMedGoogle Scholar
  21. 21.
    Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604.CrossRefPubMedGoogle Scholar
  22. 22.
    Hammer GE, Ma A. Molecular control of steady-state dendritic cell maturation and immune homeostasis. Annu Rev Immunol. 2013;31:743–91.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010;10:440–52.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Voehringer D. Protective and pathological roles of mast cells and basophils. Nat Rev Immunol. 2013;13:362–75.CrossRefPubMedGoogle Scholar
  25. 25.
    Blanchard C, Rothenberg ME. Biology of the eosinophil. Adv Immunol. 2009;101:81–121.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Akuthota P, Weller PF. Eosinophils and disease pathogenesis. Semin Hematol. 2012;49:113–9.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13:9–22.CrossRefPubMedGoogle Scholar
  28. 28.
    Siracusa MC, Comeau MR, Artis D. New insights into basophil biology: initiators, regulators, and effectors of type 2 inflammation. Ann N Y Acad Sci. 2011;1217:166–77.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T. Nonredundant roles of basophils in immunity. Annu Rev Immunol. 2011;29:45–69.CrossRefPubMedGoogle Scholar
  30. 30.
    Capron M, Trottein F. Parasites and allergy. Basel; London: Karger; 2006.CrossRefGoogle Scholar
  31. 31.
    Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? The example of natural killer cells. Science (New York, NY). 2011;331:44–9.CrossRefGoogle Scholar
  32. 32.
    Held W, Kijima M, Angelov G, Bessoles S. The function of natural killer cells: education, reminders and some good memories. Curr Opin Immunol. 2011;23:228–33.CrossRefPubMedGoogle Scholar
  33. 33.
    Sojka DK, Plougastel-Douglas B, Yang L, et al. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. elife. 2014;3:e01659.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Spits H, Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol. 2012;30:647–75.CrossRefPubMedGoogle Scholar
  35. 35.
    Germain RN. T-cell development and the CD4-CD8 lineage decision. Nat Rev Immunol. 2002;2:309–22.CrossRefPubMedGoogle Scholar
  36. 36.
    Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591–619.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Zhang N, Bevan MJ. CD8(+) T cells: foot soldiers of the immune system. Immunity. 2011;35:161–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol. 2010;28:445–89.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.CrossRefPubMedGoogle Scholar
  40. 40.
    LeBien TW, Tedder TF. B lymphocytes: how they develop and function. Blood. 2008;112:1570–80.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kurosaki T, Shinohara H, Baba Y. B cell signaling and fate decision. Annu Rev Immunol. 2010;28:21–55.CrossRefPubMedGoogle Scholar
  42. 42.
    Stavnezer J, Guikema JEJ, Schrader CE. Mechanism and regulation of class switch recombination. Annu Rev Immunol. 2008;26:261–92.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Schroeder HW, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125:S41–52.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Uzzaman A, Cho SH. Chapter 28: classification of hypersensitivity reactions. Allergy Asthma Proc. 2012;33(Suppl 1):S96–9.CrossRefGoogle Scholar
  45. 45.
    Descotes J, Choquet-Kastylevsky G. Gell and Coombs’s classification: is it still valid? Toxicology. 2001;158:43–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyNorthwestern UniversityChicagoUSA
  2. 2.Department of DermatologyYale School of MedicineNew HavenUSA

Personalised recommendations