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The Mammalian Response: A Mosaic of Structures

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Endotoxin Detection and Control in Pharma, Limulus, and Mammalian Systems

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Abstract

The goal of this chapter is to provide the reader with a basic overview of the mechanisms that mammals use to detect and control endotoxin. This is an introductory chapter to support a more specialized knowledge in subsequent chapters. It should be evident that the structures used in higher organisms, especially mammals, have evolved from invertebrate precursors where, in many cases, the more ancient functionality (as reviewed in Chap. 18) has been combined into further specialized and differentiated structures. An overview of the adaptive immune system was given in Chap. 7. This chapter focuses on the innate immune response with the only adaptive discussion pertaining to the interface of antibody with the innate complement system.

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Notes

  1. 1.

    Not as descended from Limulus but from the last common ancestor of man and arthropods some 550 million years ago.

  2. 2.

    Native outer membrane vesicles.

  3. 3.

    LPS-depleted outer membrane vesicles.

  4. 4.

    N. meningitidis-LPS.

  5. 5.

    CDC is complement-dependent cytotoxicity.

  6. 6.

    ADCC is antibody-dependent cell cytotoxicity.

  7. 7.

    A polysaccharide coating associated most often with GNB but also with some GPB.

  8. 8.

    In this verbiage one cannot help but see the analogous activity of the release of antimicrobial as well as Limulus serine protease factors from amoebocyte large granulocytes.

  9. 9.

    Biologic administration is often preceded by the administration of anti-pyretic drugs in anticipation of fever.

  10. 10.

    SNP is single nucleotide polymorphism.

  11. 11.

    MPLA is monophosphoral lipid A.

  12. 12.

    Soluble MD-2.

  13. 13.

    GUV is “giant unilamellar vesicles”. See: Preparing giant unilamellar vesicles (GUVs) of complex lipid mixtures on demand: Mixing small unilamellar vesicles of compositionally heterogeneous mixtures, Bhatia et al., Biochimica et Biophysica Acta 1848 (2015) 3175–3180.

  14. 14.

    “…well-defined model membrane systems of a complexity that resembles biological membranes with rafts.”

  15. 15.

    DOPC is dioleoylphosphatidylcholine.

  16. 16.

    Sphingomyelin/cholesterol (6/4).

  17. 17.

    Liquid-crystalline phase.

  18. 18.

    Recently it’s been shown that five fit inside and the remaining one (in prototypical hexaacyl LPS) facilitates dimerization between TLR4–1 and TLR4–2.

  19. 19.

    Multivesicular bodies.

  20. 20.

    This may suggest a similar role for RP105 since it has no signaling ability.

  21. 21.

    However, if one were able to dig deeper, it might remove the “arbitrary” tag, as a mouse existing at the surface level (in the dirt) and feeding on scavenged foodstuffs may indeed benefit from different TLR activation in contrast to a human or a horse, for example.

  22. 22.

    TLR11 is non-functional in man whereas TLR10 in non-functional in mice. As the view is anthropocentric, TLR1–10 are human.

  23. 23.

    Necrotizing enterocolitis.

  24. 24.

    EC is epithelial cells.

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  1. bioMérieux Inc., Durham, NC, USA

    Kevin L. Williams

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    Kevin L. Williams

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Williams, K.L. (2019). The Mammalian Response: A Mosaic of Structures. In: Williams, K. (eds) Endotoxin Detection and Control in Pharma, Limulus, and Mammalian Systems. Springer, Cham. https://doi.org/10.1007/978-3-030-17148-3_20

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