Mechanisms of the Skin's First Line of Defense: Mechanical and Biochemical Barriers
The skin serves as a robust first line of defense through integrated mechanical and biochemical barriers that work together to protect against external threats including pathogens, environmental toxins, and physical damage.
Structural Mechanical Barriers
The stratum corneum (10-20 μm thick) forms the primary mechanical barrier, consisting of flat, polyhedral-shaped corneocytes (dead cells) composed of insoluble bundled keratins surrounded by a cell envelope stabilized by cross-linked proteins and covalently bound lipids 1
Corneocytes are interconnected by polar structures called corneodesmosomes that contribute to stratum corneum cohesion, enhancing the physical barrier function 1
The intercellular lipid matrix in the stratum corneum, generated from lamellar bodies during keratinocyte differentiation, forms the only continuous domain and is essential for competent skin barrier function 1
The process of continuous cornification and desquamation maintains barrier integrity, with synthesis of the stratum corneum occurring at the same rate as loss 1
Biochemical Defense Mechanisms
The skin hosts a diverse microbiota that provides protection against pathogens, tunes immune responses, and fortifies the epithelium 2
Normal human skin is colonized with both resident flora (attached to deeper layers and resistant to removal) and transient flora (colonizing superficial layers and more amenable to removal) 1
Antimicrobial peptides (AMPs) are produced in deeper layers of the epidermis and transported to the stratum corneum, providing broad antibiotic-like activity against bacteria, fungi, and viruses 3, 4
AMPs not only directly kill pathogens but also balance immune responses, interfere in wound healing, cell differentiation, reepithelialization, and interact synergistically with the skin microflora 3
Langerhans cells in the epidermis play an important role in antigen presentation and immune responses 1
Integrated Defense System
The skin functions as an active organ capable of sensing danger signals and mounting adapted defense measures in response to invading pathogens 5
The skin barrier includes multiple interconnected levels: microbiome barrier, chemical barrier, physical barrier, and immune barrier 5
Melanocytes provide protection from harmful effects of ultraviolet radiation, contributing to the skin's defensive capabilities 1
The skin microbiome maintains diversity which is important for skin health and helps prevent microbial dysbiosis associated with various skin conditions 6, 2
Homeostatic Functions
The skin barrier prevents dehydration of the body through regulation of transepidermal water loss (TEWL) 1
The skin contains various receptors sensitive to pressure changes, pain, and temperature, which are essential for proper interaction with the environment 1
The skin barrier function is under homeostatic control, as demonstrated by epidermal responses to barrier perturbation 1
Disruption of the skin barrier (through extraction of skin lipids, physical stripping, or chemical irritation) leads to decreased barrier function as measured by increased TEWL 1
Clinical Implications
Peptides can enhance wound healing by promoting tissue repair without compromising host defenses 6
Maintaining skin barrier integrity is crucial for preventing invasion by pathogens and development of skin infections 7, 4
The host's immunological state is a determining factor for the type and severity of potential fungal infections 7
Anti-inflammatory peptides may help reduce microbial dysbiosis associated with skin conditions like atopic dermatitis 6