Key points

■ The epidermis has a powerful innate immune system

■ Keratinocytes are immunologically active cells, able to identify and kill invading microbes by recognizing highly conserved structures of the pathogens (pathogen-associated molecular patterns; PAMPs)

They activate "pattern recognition receptors" (PRRs) resulting in the secretion of antimicrobial and pro-inflammatory mediators

■ Antimicrobial peptides, effector molecules of innate immunity, also act as regulators of acquired immune responses, inflammation and wound repair

■ Secondary bacterial colonization of HS can intensify chronic inflammation

■ PRR expression in the epidermis may play a role in host defense of the skin and in chronic inflammation

Contents

13.1

13.2

13.3

Introduction .

.100

Ancient and Modern: Innate and Acquired Immunity

.101

TLR/IL-1R Superfamily and their Signaling Pathways in the Skin 102

13.4 Members of the TLR Family Expressed by Keratinocytes 102

13.5 IL-1 Receptors in the Skin 104

13.6 Signaling Pathways via TLR/IL-1R 104

13.6.1 MyD88-Dependent Signaling Pathway .. 104

13.6.2 MyD88-Independent Signaling Pathway 105

13.7 Keratinocyte-Derived Effector Molecules in the Innate Immune System of the Skin 105

13.8 Antimicrobial Peptides 105

13.9 ß-Defensins 106

13.10 Cathelicidins 106

13.11 RNase7 107

13.12 Antileukoprotease (ALP) 107

13.13 Pro-Inflammatory Chemokines 107

13.14 Pro-Inflammatory Cytokines 108

13.15 TLR Recognition and the Commensal Microbiota of the Skin 109

13.16 Skin Infections and Innate Immune ResponsesoftheEpidermis 110

13.17 Hidradenitis Suppurativa and the Skin Immune System 110

13.18 Conclusions 112

References 112

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