Role of Microbiota and Barrier Factors
The normal skin microflora forms a biofilm consisting of bacteria themselves and exopolysaccharides they secrete. These commensal microorganisms actively participate in defense: they occupy receptors, compete with dangerous microbes for nutrients, and secrete special substances called bacteriocins.
Pathogen proliferation is also restrained by an arsenal of physicochemical properties of the skin:
- Environment: low pH and reduced temperature are uncomfortable for most pathogens (which prefer 37 °C and a neutral environment).
- Biochemistry: antimicrobial peptides, organic acids, transferrin, and immunoglobulins (IgA, IgG) destroy or suppress bacteria.
- Stratum corneum: corneocytes are held together by a lipid "cement" based on ceramides, cholesterol sulfate, and free fatty acids, which prevents the penetration of external agents.
Epidermal Cells on Immune Guard
The epidermis is the front line of defense. Its main cells, keratinocytes, act as "sentinels." Utilizing pattern-recognition receptors (such as TLRs), they are the first to notice foreign microbial structures (PAMPs) or damaged tissue molecules (DAMPs) and immediately release proinflammatory cytokines (such as IL-1$\beta$).
In addition to keratinocytes, the epidermis contains:
- Langerhans cells: specialized antigen-presenting cells that "patrol" the tissue.
- T lymphocytes: cytotoxic CD8+ lymphocytes are present in the basal and spinous layers.
- Merkel cells (responsible for touch) and melanocytes (protect against ultraviolet radiation).
Dermis: The Arsenal of Immunocompetent Cells
Beneath the epidermis lies the dermis, which features a much greater variety of immune cells. Stationed here are:
- Dendritic cells (dermal and plasmacytoid), which also participate in antigen recognition.
- Lymphocytes: various populations of CD4+ T helper cells ($T_H1$, $T_H2$, $T_H17$, regulatory), $\gamma\delta$ T lymphocytes, and NKT cells.
- Innate immune cells: macrophages, mast cells, and natural killer (NK) cells.
- Stromal elements: fibroblasts, providing structural framework and repair.
It is this rich cellular composition that allows the dermis to mount a powerful inflammatory and cytotoxic response.
Langerhans Cell Cycle and Homing
The initiation of adaptive immunity in the skin follows a precise sequence:
- Capture: Langerhans cells engulf the antigen directly in the epidermis.
- Migration: Transforming into "veiled cells," they migrate via lymphatic vessels to the regional lymph node.
- Presentation: In the paracortical zone of the node, they mature into dendritic cells and present the antigen to naive T lymphocytes (using MHC and costimulatory molecules).
- Activation and Homing: Activated T cells trigger further reaction cascades. Utilizing the CLA-1 receptor, which binds to vascular E-selectin, they purposefully return back to the skin to eliminate the infection.
Upon arrival, $\gamma\delta$ T lymphocytes and NKT cells perform surveillance and kill infected cells by releasing perforin and granzyme B.
Wound Healing and Repair
Skin lymphocytes (T cells and NKT cells) not only destroy enemies but also help tissue recover after inflammation. They produce essential growth factors:
- Keratinocyte growth factor (KGF);
- Fibroblast growth factor 9 (FGF9);
- Connective tissue growth factor (CTGF).
They also secrete cytokines (TNF, IFN-$\gamma$) that activate dermal dendritic cells, regulating the intensity of the immune response.