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Toll-Like Receptors

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Clinical and Basic Immunodermatology

Abstract

There are two major arms of the immune system: the innate immune response and the adaptive immune response. Innate immunity is the first line of defense against microbes and serves to limit infection within the early hours after exposure to a pathogen. It is classically associated with the recognition of pathogens by phagocytic cells via specific receptor recognition molecules or through complement fixation. Essential components of the innate immune response include neutrophils, natural killer cells, natural killer T cells, mast cells, complement, and antimicrobial peptides. Innate immune activation via pattern recognition receptors results in a specific expression of co-stimulatory molecules and cytokines. This inflammatory milieu shapes the subsequent adaptive response, which involves B cell activation and T cell-mediated recognition of foreign antigens presented on major compatibility complexes (MHC) I and II on the cell surface of antigen-presenting cells (APCs). Activated B and T lymphocytes then undergo clonal expansion to provide an antigen-specific immune response.

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Author information

Authors and Affiliations

  1. Department of Dermatology and Microbiology/Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA

    Jessica Shiu MSIV, PhD & Anthony A. Gaspari MD

Authors
  1. Jessica Shiu MSIV, PhD
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  2. Anthony A. Gaspari MD
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Corresponding author

Correspondence to Anthony A. Gaspari MD .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA

    Anthony A. Gaspari

  2. Department of Dermatology, University of Texas Health Science Center, Houston, Texas, USA

    Stephen K. Tyring

  3. Department of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Daniel H. Kaplan

Questions

Questions

  1. 1.

    Which of the following represent a negative regulator (inhibitor) of TLR function?

    1. A.

      IRAK-M

    2. B.

      TOLLIP

    3. C.

      SOCS-1

    4. D.

      All of the above

    5. E.

      None of the above

  • Correct answer: D-All of the above. IRAK-M, TOLLIP and SOCS-1 are all TLR negative regulators

  1. 2.

    Which skin disease have TLR negative regulators been associated?

    1. A.

      Non-melanoma skin cancer

    2. B.

      Psoriasis

    3. C.

      Atopic Dermatitis

    4. D.

      Cutaneous T-cell lymphoma

  • Correct answer: (C)-TOLLIP mutations have been associated with Atopic dermatitis. However, the exact role of these mutations in the pathophysiology of this common skin disease remains unclear

  1. 3.

    How do TLRs mediate pro-inflammatory cytokine production in acne vulgaris?

    1. A.

      PAMPs from P. acnes activate TLR2 and TLR4, inciting the production of pro-inflammatory cytokines

    2. B.

      PAMPs from S. aureus induce TLR2 activation

    3. C.

      TLRs are not involved in the pathophysiology of acne

    4. D.

      PAMPs from the pilosebacious unit activate TLR7,8,9

  • Correct answer: (A)-P. acnes microbial products such as LPS and peptidoglycan activate TLR2 and TLR4 to active the production of proinflammatory cytokines in the skin. It is thought that P. acnes strains in healthy controls may regulate TLR expression differently when compared to P. acnes strains in acne vulgaris patients

  1. 4.

    In allergic contact dermatitis (ACD), what is the predominant TLR involved in the pathophysiology of nickel allergy?

    1. A.

      TLR4

    2. B.

      TLR7

    3. C.

      TLR2

    4. D.

      TLR9

    5. E.

      None of the above

  • Correct answer: (A) Nickel, cobalt and palladium can bind and activate human TLR4s and activation of CHS. dependent on histidine residues that are specifically found in human TLR4, thus explaining why mice are naturally resistant to nickel-induced CHS

  1. 5.

    Why are mice genetically resistant to ACD to Nickel?

    1. A.

      Nickel does not penetrate mouse skin

    2. B.

      Their TLR are not activated by nickel

    3. C.

      Their Tregulatory cells suppress the response

    4. D.

      Mice have a high level of nickel in their diet

  • Correct answer: (B)-TLR4 in mice lacks the amino acid histidine in the extracellular domain. In humans, TLR4 normally expresses the amino acid histidine. TLR4 activation by nickel is dependent on histidine residues that are specifically found in human TLR4, thus explaining why mice are naturally resistant to nickel-induced CHS

  1. 6.

    How are TLRs involved in DNA repair?

    1. A.

      TLR sense DNA damage

    2. B.

      TLR activation directly induces a DNA repair response

    3. C.

      TLR activation triggers inflammation, which may stimulate DNA repair

    4. D.

      TLR7 agonists applied can increase DNA repair in the skin

    5. E.

      All of the above

    6. F.

      None of the above

  • Correct answer: (D)-TLR engagement may stimulate DNA repair by multiple mechanisms. This phenomenon is relevant to UV light exposure, and recovery of skin derived antigen presenting cells

  1. 7.

    Which of the following diseases is associated with impaired TLR signaling via TLR3?

    1. A.

      Discoid lupus

    2. B.

      Alopecia areata

    3. C.

      Psoriasis

    4. D.

      Xeroderma pigmentosa

  • Correct answer: (D)-XP patients NK cells are defective in IFN production in response to TLR3 stimulation

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Shiu, J., Gaspari, A.A. (2017). Toll-Like Receptors. In: Gaspari, A., Tyring, S., Kaplan, D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29785-9_2

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  • DOI: https://doi.org/10.1007/978-3-319-29785-9_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29783-5

  • Online ISBN: 978-3-319-29785-9

  • eBook Packages: MedicineMedicine (R0)

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