Diagnostics and Therapy in Veterinary Dermatology presents thorough coverage of the latest discoveries, drugs, and treatments for dermatologic conditions in animals. Chapters written by experts in each respective area of veterinary dermatology contain up-to-date information on new diagnostic tools and tests, autoimmune diseases, parasitic and fungal infections, medical management of acute and chronic conditions, alternative dermatologic therapies, and more.
Offering practical solutions for both specialist and general practice veterinarians dealing with dermatology cases, this wide-ranging resource also addresses antibiotic resistance and misuse, the availability of foods for elimination diet trials, problems with generic drugs, emerging infectious diseases, and other important problems currently facing the profession. Throughout the text, veterinary practitioners are provided with real-world guidance on improving how they work up their dermatology cases and strengthening communication between the primary care veterinarian and the dermatologist. Edited by a leading board-certified dermatologist, this volume:
Focuses on cats and dogs
Includes numerous high-quality clinical photographs illustrating all key concepts
Covers topics such as how to use your nursing staff to the fullest, the One Health movement, and how changing climate is increasing the spread of certain dermatologic diseases
Discusses approaches for building a better working relationship between clients, primary care veterinarians and dermatologists
Provides insights on the future of technology in the diagnosis and treatment of dermatologic diseases
Covering the very latest developments in the field, Diagnostics and Therapy in Veterinary Dermatology is essential reading for veterinary dermatologists, veterinary students, and any veterinary general practitioner with a dermatology caseload.
The Skin as an Immune Organ
Domenico Santoro and Megan Boyd
- 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, IL-13, CCL3, CCL4, IL-3, GM-CSF TLRs, NF-kB, NFAT, AP-1 Eosinophil Hypersensitivity reactions, vasodilation, chemotaxis, inflammation Dermis IL-3, IL-5, IL-8, IL-10, leukotrienes, GM-CSF, hydrolases Fc receptor Neutrophil Innate immunity, phagocytosis Dermis ROS, proteolytic enzymes TLRs, lectin receptor, mannose receptor M1 macrophage Phagocytosis, antigen presentation, bactericidal activity Dermis IL-6, IL-12, TNF, iNOS JAK1, JAK2, STAT1,
STAT2 M2 macrophage Phagocytosis, antigen presentation, regenerative effects Dermis IL-10, TGF, arginase-1 JAK1, JAK2, JAK3, STAT6 ILC (Innate lymphoid cell) Innate immunity Dermis IL-1, IL-23, IL-25, IL-33, TSLP Id2, T-bet, GATA 3, ROR Both innate and adaptive ?/d T cell Elimination of intracellular microorganisms and infected cells; cell death Dermis IL-17, IFN MHC- I Natural killer cell Innate immunity against viruses and intracellular bacteria Dermis IFN, GM-CSF, IL-3 MHC-I Natural killer T cell Elimination of lipid antigens Dermis IL-4, IL-17, IL-22, IFN MHC-1 Adaptive B lymphocyte Humoral response Dermis IL-2, IL-4, IL-6, IL-11, IL-13, TNF, BAFF Antibodies T-helper lymphocyte Coordinates immune function Dermis Various depending on the type of T-helper cell Various depending on the type of T-helper cell T-cytotoxic lymphocyte Elimination of intracellular microorganisms and infected cells Dermis IFN Perforin, granzyme, granulysin T-regulatory lymphocytes Control of immune response Dermis IL-10, TGF FoxP3, STAT5
Key: AMP, antimicrobial peptides; AP, activator protein; BAFF, B-cell activating factor; CCL, chemokine ligand; FoxP3, forkhead box P3 protein; GATA, transcription factor; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; ICAM, intercellular adhesion molecule; Id2, DNA binding protein inhibitor 2; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; JAK, Janus kinase; MHC, major histocompatibility complex; NFAT, nuclear factor of activated T cell; NF-kB, nuclear factor kappa B; ROR, retinoic acid-related orphan receptors; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; T-bet, T box transcription factor; TGF, transforming growth factor; TLR, Toll-like receptor; TNF, tumor necrosis factor; TSLP, thymic stromal lymphopoietin.
Figure 1.1 Innate skin immune system. 1. The innate immune system is activated when damage-associated molecular pattern (DAMP) molecules released by damaged cells or pathogen-associated molecular pattern (PAMP) molecules on pathogens are recognized by pattern-recognition receptors such as Toll-like receptors on both dendritic cells (Langerhans cells) and keratinocytes. 2. This leads to the activation of keratinocytes directly and the release of cytokines by the Langerhans cells that also activate the keratinocytes. 3. The activated keratinocyte releases various cytokines and AMPs to directly destroy the invading pathogen. 4. Neutrophils and macrophages are recruited to directly destroy the invaders. IFN, interferon; IL, interleukin; TNF, tumor necrosis factor.
Immune System of the Skin
The skin is a complex organ composed of an outermost layer, the epidermis; a middle layer, the dermis and cutaneous appendages; and an inner layer, the subcutis. Immune cells and inflammatory mediators are active in all these layers. It is important to understand that immune cells and inflammatory mediators are extremely interconnected and work in concert, as opposed to having isolated effects. If we compare the two branches of the immune system to an army, the innate immune system would be the entrenched peacekeeping force while the adaptive immune system...