Diagnostics and Therapy in Veterinary Dermatology. Группа авторов
Milena Carmona‐Gil, DVM, MSc DermaVet Centro de Dermatología Veterinaria, Medellín, Antioquia, Colombia
Catlin Contreary, DVM, DACVD Veterinary Dermatology Center, Maitland, FL, USA
Katherine Doerr, DVM, DACVD Veterinary Dermatology Center, Maitland, FL, USA
Valerie Fadok, DVM, DACVD, PhD Zoetis, Bellaire, TX, USA
Cecilia Friberg, DVM, DACVD Sodra Djursjukhuset, Stockholm, Sweden
Natalie Gedon, DVM University of North Carolina College of Veterinary Medicine, Raleigh, NC, USA
Darcie Kunder, VMD, DACVD Friendship Hospital for Animals, Washington, DC, USA
Judy Lethbridge, RVT (registered veterinary technician) Veterinary Dermatology Center, Maitland, FL, USA
Dawn Logas, DVM, DACVD Veterinary Dermatology Center, Maitland, FL, USA
Jacob Logas, MS CS Georgia Tech, PhD Georgia Institute of Technology School of Interactive Computing, Atlanta, GA, USA
Rosanna Marsella, DVM, DACVD University of Florida, Gainesville, FL, USA
Ralf Mueller, DVM, MANZCVSc (Canine Medicine), DACVD, FANZCVSc (Dermatology), DECVD Centre for Clinical Veterinary Medicine, LMU Munich, Germany
Luisito S. Pablo, DVM, MS, DACVAA College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
Mark G. Papich, DVM North Carolina State University, Raleigh, NC, USA
Jason B. Pieper, DVM, MS, DACVD Iowa State University, Ames, IA, USA
Domenico Santoro, DVM, MS, DrSc, PhD, DACVD, DECVD, DACVM (Bacteriology, Mycology, Immunology) University of Florida, Gainesville, FL, USA
JoAnn Stewart, RVT, CVPM, CCFP Executive Director, Collaborative Care Coalition, Gurnee, IL, USA
Rebekah Westermeyer, BSEd, DVM, DACVD, MRCVS Animal Allergy Specialists, Oahu, HI, USA Asia Veterinary Diagnostics, Kowloon, Hong Kong
Amelia White, DVM, MS, DACVD Auburn University College of Veterinary Medicine, Auburn, AL, USA
Michelle Woodward O’Gorman, DVM, DACVD Baton Rouge Veterinary Specialists, Baton Rouge, LA, USA
1
The Skin as an Immune Organ
Domenico Santoro and Megan Boyd
KEY POINTS
The skin is an extremely active immunologic organ.
The skin has many resident immunologically active cells.
The skin defense system includes a physical barrier (stratum corneum and hair), a chemical barrier (fatty acids and antimicrobial peptides), an immunologic barrier (innate and adaptive immune system), and a microbiological barrier (beneficial microorganisms).
Keratinocytes are the most immunologically active cells in the epidermis.
The skin is commonly affected by immune system disorders.
The skin is the largest organ in the body. It has long been known as the primary physical barrier between an organism and its environment, but since the early 1980s the skin has been recognized as an active immune organ with its own skin‐associated immune system. The skin’s defense system consists of physical, chemical, immunologic, and microbiologic components that protect the body against trauma, chemicals, toxins, and microorganisms.
The physical barrier represents the first line of defense against invaders. It is composed of keratinocytes tightly bonded together by a lipid‐rich mortar in the stratum corneum (top layers) and keratinocytes joined together by tight cell‐to‐cell junctions in the lower layers. The chemical barrier consists of compounds with active antimicrobial activity, including fatty acids and antimicrobial or host defense peptides secreted by sebaceous glands and keratinocytes. If the physical and chemical defenses of the skin are overcome by invaders, components of the innate and active immune system along with beneficial microorganisms in the skin microbiome become important. Beneficial microorganisms compete for the same niche as pathogens and actively secrete antimicrobial peptides (AMPs) that inhibit the proliferation of pathogenic competitors.
When pathogenic microorganisms breach the physical and chemical defenses of the skin, they activate the skin‐associated lymphoid tissue (SALT) (Table 1.1). SALT includes dendritic cells, mast cells, lymphocytes, and keratinocytes, and forms part of the innate immune system (Figure 1.1). Innate immunity, which is considered the most ancient branch of the body’s immune defenses, is characterized by a rapid onset of action (minutes to hours), a lack of specificity (it recognizes common microbial structures as opposed to specific organisms), and a lack of memory, which means the response does not improve with each exposure. Cells of the innate immune system include macrophages, dendritic cells, neutrophils, natural killer (NK) cells, mast cells, and keratinocytes. When innate immunity is overwhelmed, the adaptive branch of the immune system (Figure 1.2), primarily made of T and B lymphocytes, is activated. The adaptive immune response is characterized by a slow onset of action (days to weeks), high specificity (recognizes unique antigens), and memory, which means the speed and magnitude of the response improve with each exposure. The innate and adaptive branches of the immune system are highly interconnected. When cells of the innate immune system are activated, they secrete numerous inflammatory cytokines and chemokines that prime and direct the adaptive immune system’s response.
Table 1.1 Cells of the innate and adaptive immune system discussed in this chapter.
| Cell type | Functions | Location | Cytokines produced | Expressed molecules | |
|---|---|---|---|---|---|
| Innate | Keratinocyte | Mechanical barrier, epidermal production Immune function | Epidermis | IL‐1, IL‐6, TNF, IL‐8, IL‐10, IL‐12, IL‐15, IL‐18, IL‐19, IL‐20, TGF, IL‐20, IL‐23, GM‐CSF, G‐CSF | TLR, MHC‐I, MHC‐II, AMP |
| Langerhans cell | Antigen‐presenting cell | Epidermis | IL‐12, IL‐23, IL‐6, TNF | Fc and mannose receptors, ICAM‐1, IL‐12, MHC‐II | |
| Dermal dendritic cell | Antigen‐presenting cell | Dermis | IL‐12, IL‐23, IL‐6, TNF | Fc and mannose receptors, ICAM‐1, IL‐12, MHC‐II | |
| Mast cell | Hypersensitivity reactions, vasodilation, chemotaxis, inflammation | Dermis |
TNF, IL‐1, IL‐4, IL‐5, IL‐6, |