Role of microbiota and barrier factors
The normal skin microflora forms a biofilm consisting of bacteria themselves and the exopolysaccharides they secrete. These commensal microorganisms actively participate in protection: they occupy receptors, compete with dangerous microbes for nutrients, and secrete special substances — bacteriocins.
Pathogen proliferation is also restrained by a whole arsenal of physico-chemical 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, as well as 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 guarding immunity
The epidermis is the front line of defense. Its main cells, keratinocytes, act as "sentinels". Thanks to pattern-recognition receptors (e.g., TLRs), they are the first to notice foreign microbial structures (PAMPs) or damaged tissue molecules (DAMPs) and immediately release pro-inflammatory cytokines (e.g., 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: an arsenal of immunocompetent cells
Beneath the epidermis lies the dermis, which features a much greater diversity of immune cells. Based 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, which provide the framework and repair.
It is this rich cellular composition that allows the dermis to deploy a powerful inflammatory and cytotoxic response.
Langerhans cell cycle and homing
The initiation of adaptive immunity in the skin follows a clear scenario:
- 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 become mature dendritic cells and present the antigen to naive T lymphocytes (using MHC and costimulatory molecules).
- Activation and homing: Activated T cells trigger a further cascade of reactions. Thanks to the CLA-1 receptor, which binds to vascular E-selectin, they purposefully return back to the skin to destroy the infection.
Upon arrival at the site, $\gamma\delta$ 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 the tissue recover after inflammation. They produce crucial 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.
Briefly: answers to topical questions
Which microorganisms are the main representatives of the resident skin microflora?
The main representatives of the resident skin microflora include:
- Propionibacteria (Propionibacteriaceae) — gram-positive bacteria.
- Coryneform bacteria (Corynebacteriaceae) — gram-positive bacteria.
- Epidermal staphylococci (Staphylococcus epidermidis and other coagulase-negative ones) — gram-positive bacteria.
- Micrococci (Micrococcaceae) — gram-positive bacteria.
- Streptococci and peptostreptococci — gram-positive bacteria.
- Dermabacter hominis — gram-positive bacteria.
- Acinetobacter (Acinetobacter) — gram-negative bacteria.
- Yeast-like fungi of the genus Malassezia.
What types of pattern-recognition receptors (PRRs) are present on keratinocytes?
Keratinocytes, which act as danger sensors in the epidermis, feature pattern-recognition receptors of the Toll-like receptor family.
- Toll-like receptors (TLR) are receptors that ensure the interaction between cells of the immune system and microbes. They are responsible for the rapid recognition of infectious agents (microbial patterns, PAMPs) and damage-associated molecular patterns (DAMPs), and also trigger signaling regarding pathogen invasion.
What pro-inflammatory cytokines do keratinocytes secrete upon activation?
Upon activation, keratinocytes secrete interleukin-1 beta and other pro-inflammatory cytokines.
- Interleukin-1 beta (IL-1$\beta$) is a pro-inflammatory cytokine whose synthesis is triggered in response to the recognition of microbial patterns (PAMPs) and damage molecules (DAMPs) by pattern-recognition receptors.
In addition, keratinocytes are capable of spontaneous expression of homeostatic cytokines, such as interleukin-7 (IL-7).
Class and exam questions
What is the sensory function of keratinocytes?
Keratinocytes have special receptors (TLRs) through which they recognize microbial patterns (PAMPs) and damage signals (DAMPs), after which they trigger inflammation by releasing cytokines (e.g., IL-1β).
What is skin lymphocyte homing?
This is the process of targeted return of T lymphocytes trained in the lymph nodes back to the skin tissue. It is mediated by the interaction of the CLA-1 receptor on the lymphocyte surface with E-selectin on the endothelium of skin blood vessels.
Which skin cells act as antigen-presenting cells?
Langerhans cells play the primary role in the epidermis. After capturing the antigen, they migrate to the lymph nodes, where they present it to T lymphocytes.
What else to study on this topic
- The mechanism of terminal keratinocyte differentiation
- Structure and composition of the intercellular lipid matrix (ceramides)
- Molecular mechanisms of perforin- and granzyme B-induced apoptosis
- Clinical significance: skin components as autoantigens (bullous dermatoses)
Study the full topic in the «Microbiology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Skin Immune System" and 4,383 more pages on the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 141 video lectures on the subject
Other topics in the section "Features of immunity in various locations..."
Free video lessons: microbiologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.