First Aid, Chapter 5, Anatomy, Physiology, and Pathology, Skin Flashcards
Are keratinocytes and melanocytes important in adaptive immunity?
No
What do keratinocytes express and produce that plays a role in adaptive and innate immunity?
keratinocytes do express major histocompatability complex (MHC)-type II proteins and produce several molecules (IL-1, antimicrobial peptides, thymic stromal lymphopoietin [TSLP], and receptor activator of nuclear factor κ-B ligand [RANKL]) that contribute to both the adaptive and innate immune response, respectively. These cytokines also mediate cutaneous inflammation.
What are langerhans’ cells? Where are they located? What kind of processes do they have? What happens once they are stimulated?
Langerhans’ cells are immature dendritic cells of the cutaneous immune system located in the suprabasal portion of the epidermis.
o They have dendritic processes that enable them to capture antigens entering through the skin.
o On stimulation by proinflammatory cytokines, Langerhans’ cells retract their processes, lose their adhesiveness for epidermal cells, and migrate to the dermis.
o They subsequently migrate to lymph nodes through afferent lymphatic vessels.
What percent of skin-associated lymphocytes do epidermal lymphocytes constitute? What type of lymphocytes are they mostly? How broad is the diversity of antigen receptors on these?
Epidermal lymphocytes constitute only about 2% of skin-associated lymphocytes (the rest reside in dermis), and the majority are CD8+ T lymphocytes.
o Express a more restricted set of antigen receptors than T lymphocytes in most extracutaneous tissues.
o The majority express an effector or memory phenotype.
Describe Langerhans’ cell histiocytosis. What is it caused by? What is the clinical presentation?
Langerhans’ cell histiocytosis (LCH) is a rare disease caused by clonal proliferation of Langerhans’ cells. Clinical presentation involves a nonspecific inflammatory response (fever, lethargy, weight loss) and multifocal organ involvement, including bone, skin, bone marrow, lymph nodes, endocrine glands, and lungs.
What is the function of the dermoepidermal junction?
The dermoepidermal junction joins the epidermis to the dermis. Its function is to protect against mechanical shear and to serve as a semipermeable barrier.
What are the three layers of the basement membrane?
- Lamina lucida: Includes the extracellular portion of the hemidesmosomes and anchoring filaments
- Lamina densa: Includes collagen IV and laminin network
- Sublamina densa: Includes anchoring fibrils (collagen VII)
What cells are located in the dermis?
Fibroblasts, mast cells, macrophages, dermal dendritic cells, and derma T lymphocytes.
Describe the function of fibroblasts in the dermis.
Fibroblasts synthesize and degrade extracellular matrix proteins, collagen, and elastic fibers. They also secrete soluble mediators (e.g., eotaxin when stimulated by IL-4, as well as IL-1 and IL-6).
Describe the function of mast cells in the dermis.
Mast cells have granules containing both tryptase and chymase. Their development depends on c-kit receptor and its ligand stem cell factor (SCF).
Describe the function of macrophages in the dermis.
Macrophages in dermis have several functions, including phagocytosis, antigen presentation, wound healing, and secretory functions. They express CD68.
Describe the function of dermal dendritic cells in the dermis.
Dermal dendritic cells can be labeled by factor XIIIa, and can express DCSIGN/CD 209+, CD1b, CD1c, and CD11c. They play a role in antigen presentation.
Describe the function of dermal T lymphocytes in the dermis.
Dermal T lymphocytes (both CD4+ and CD8+ cells) are located predominantly in perivascular locations. They express phenotypic markers typical of activated or memory T lymphocytes. Many dermal T lymphocytes also express a carbohydrate epitope called cutaneous lymphocyte antigen (CLA)-1, which may play a role in homing to the skin.
Where are connective tissue mast cells found? What receptor do they have?
Connective tissue mast cells with tryptase and chymase (MCTC) are present in skin, conjunctiva, heart, and intestinal submucosa (and have the CD88 receptor for C5a anaphylatoxin).
Where are mucosal mast cells found?
Mucosal mast cells with tryptase (MCT) present in the surface of the alveolar wall, the respiratory epithelium, and the small intestinal mucosa
How do some T cells home to the skin?
Skin homing of memory, effector, and regulatory T-cell subtypes (CLA+) are programmed by skin-derived dendritic cells via cytokines, such as CCR4/CCL17 and CCR10/CCL27.
What role does filaggrin play in the skin? What does mutation cause?
Filaggrin (FLG) serves as the matrix protein promoting aggregation and disulfide bonding of keratin filaments. Mutations in the FLG gene have been linked to ichthyosis vulgaris and atopic eczema. Some of these mutations have also been associated with the propensity to develop asthma in eczema patients and asthma severity that is independent of eczema.
Why should two biopsies be performed with all suspected immunobullous diseases?
In all suspected immunobullous diseases, it is best to obtain two biopsies for diagnosis. One shave biopsy of an intact vesicle or bulla for routine hematoxylin and eosin (H&E) stain; and a second biopsy of perilesional tissue for direct immunofluorescence. (Note: Immunoreactants may not be present in lesional tissue.)
What is Nikolsky’s sign?
Nikolsky’s sign is the formation of erosion from shearing pressure applied on normalappearing skin.
What is the clinical presentation of pemphigus vulgaris? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Flaccid>tense bullae Crusting Nikolsky’s sign present Affects scalp, chest, intertriginous areas, and oral mucosa
Serum autoantibodies: IgG autoantibodies to desmoglein 1 and 3
Tissue Immunofluorescence: Epidermal IgG and C3 cell surface staining of the suprabasal layers
What is the clinical presentation of pemphigus foliaceous? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Superficial bullae Erosions Scale with crusting Nikolsky’s sign present
Serum autoantibodies: IgG autoantibodies to desmoglein 1
Tissue immunofluorescence:
Epidermal IgG and C3 cell surface staining of the granular layer
What is the clinical presentation of paraneoplastic pemphigus? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Flaccid bullae Lichenoid or erythema multiforme-like lesions Affects mucosa Nikolsky’s sign present
Serum autoantibodies: IgG autoantibodies to plakin proteins and desmoglein 1 and 3
Tissue immunofluorescence: Epidermal IgG and C3 cell surface and basement membrane zone staining
What is the clinical presentation of IgA pemphigus? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Pustules, erythema, and flaccid lakes of pus
Serum autoantibodies:
IgA autoantibodies to desmoglein 3, desmocollin 1
Tissue immunofluorescence:
Epidermal IgA cell surface staining
What is the clinical presentation of bullous pemphigoid? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Tense > flaccid bullae Prominent pruritus Nikolsky’s sign in some (~10%)
Serum autoantibodies:
IgG autoantibodies to BP180 and BP 230
Tissue immunofluorscense:
Linear basement membrane zone IgG and C3
What is the clinical presentation of Cicatricial pemphigoid? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Erosions, rare vesicles or bullae Scarring sequelae
Serum autoantibodies: IgG autoantibodies to integrins, BP180, and laminins
Tissue immunofluorescence: Linear basement membrane zone IgG and C3
What is the clinical presentation of herpes gestationis? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: bullae Onset in second trimester pregnancy Pruritus
Serum autoantibodies: Complement fixing, basement membrane zone, and epidermal; Autoantibody to BP180
Tissue immunofluorescence: Linear basement membrane zone C3
What is the clinical presentation of Epidermolysis bullosa acquisita? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Tense bullae, erosions, and scarring Sites of trauma and oral mucosa
Serum autoantibodies: IgG autoantibody to collagen VII
Tissue immunofluorescence: Linear basement membrane zone IgG and C3
What is the clinical presentation of linear IgA bullous dermatosis? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Tense bullae Oral involvement common
Serum autoantibodies: IgA autoantibody LABD97, LAD-1, and others
Tissue immunofluorescence: Linear basement membrane zone IgA
What is the clinical presentation of dermatitis herpetiformis? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Small bullae on elbows and knees Markedly pruritic Associated with intestinal gluten sensitivity (celiac disease)
Serum autoantibodies: IgA autoantibody to epidermal transglutaminase
Tissue immunofluroescence: Granular basement membrane zone IgA with stippling in dermal papilla
What is the clinical presentation of bullous lupus erythematosus? What are the serum antibodies? What is seen on tissue immunofluorescence?
Clinical presentation: Tense bullae Photo distributed
Serum autantibodies: IgG autoantibody to collagen VII
Tissue immunofluorescence:
Linear basement membrane zone IgG; May show granular IgM and C3 basement membrane zone
Identify the diseases in figure 5-11. They must be known for the boards!
Figure 5-11. (A) Pemphigus vulgaris lesions on the mucosal surface of the lower lip. (B) Bullous pemphigoid. (C) Dermatitis herpetiformis on a four-year-old child with a vesiculo-papular skin eruption due to dermatitis herpetiformis.
Which condition, PV, BP, or DH, is most likely to show a positive Nikolsky’s sign?
Pemphigus vulgaris (PV). Only approximately 10% of individuals with BP will have a positive Nikolsky’s sign.
Which condition(s), PV, BP, and DH, is(are) extremely pruritic?
Dermatitis herpetiformis (DH) and bullous pemphigoid (BP)
In PV and BP, what two molecules react with antigens in the basement membrane zone?
Immunoglobulin G and C3 complement
What is the indirect immunofluorescence pattern of SLE? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence show?
Indirect Immunofluorescence Pattern (Serum):
Peripheral Homogeneous Nucleolar Speckled
Nuclear Antigens to Which Autoantibodies Are Directed:
nDNA or dsDNA, ssDNA, histones, nucleolar RNA, various ribonucleoproteins, cardiolipin, Sm (Smith), U1-snRNP, and HMG-17
Direct Immunofluorescence of Tissue: Two or more granular immunoglobulin and complement deposits at BMZ, IgG, IgM, and/or IgA with C3 in involved and uninvolved skin (lupus band)
What is the indirect immunofluorescence pattern of discoid lupus erythematous? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum):
No circulating antibodies
Nuclear Antigens to Which Autoantibodies Are Directed: Usually none detected
Direct Immunofluorescence of Tissue: Two or more granular immunoglobulin and complement deposits at BMZ, IgG, IgM, and/or IgA with C3 in involved skin
What is the indirect immunofluorescence pattern of Subacute cutaneous lupus erythematous? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum):
Speckled
Nuclear Antigens to Which Autoantibodies Are Directed: SS-A/Ro and SS-B/La
Direct Immunofluorescence of Tissue: Particulate intercellular staining with or without granular immune deposits at BMZ or lichenoid changes
What is the indirect immunofluorescence pattern of neonatal lupus erythematous? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum):
Speckled
Nuclear Antigens to Which Autoantibodies Are Directed: SS-A/Ro and SS-B/La
Direct Immunofluorescence of Tissue: Granular IgG (transplacental) at BMZ
What is the indirect immunofluorescence pattern of drug-induced lupus erythematous? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum):
Peripheral Homogeneous
Nuclear Antigens to Which Autoantibodies Are Directed: histones
Direct Immunofluorescence of Tissue: Granular immune deposits at the BMZ
What is the indirect immunofluorescence pattern of cutaneous scleroderma? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum): peripheral
Nuclear Antigens to Which Autoantibodies Are Directed: Scl-70, SS-A/Ro, and SSB/La
Direct Immunofluorescence of Tissue: No characteristic changes; vascular staining may be observed
What is the indirect immunofluorescence pattern of limited scleroderma (CREST)? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum): Centromere
Nuclear Antigens to Which Autoantibodies Are Directed: Centromere, Scl-70, U1snRNP, and HMG-17
Direct Immunofluorescence of Tissue: No characteristic changes; vascular staining may be observed
What is the indirect immunofluorescence pattern of progressive systemic sclerosis? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum): Nucleolar Speckled
Nuclear Antigens to Which Autoantibodies Are Directed: Scl-70, U1- and U3snRNP, fibrillarin, and RNA pol I, II, and III
Direct Immunofluorescence of Tissue: No characteristic changes; vascular staining may be observed
What is the indirect immunofluorescence pattern of dermatomyositis polymyositis? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum): Speckled Nucleolar
Nuclear Antigens to Which Autoantibodies Are Directed: Jo-1, PM-Scl, Mi-2, U1snRNP and SS-A/Ro s
Direct Immunofluorescence of Tissue: No characteristic changes; lichenoid features and vascular staining may be observed
What is the indirect immunofluorescence pattern of Sjogren’s syndrome? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum): Fine speckled Nucleolar
Nuclear Antigens to Which Autoantibodies Are Directed: SS-A/Ro, SS-B/La, histones, and U1-snRNP
Direct Immunofluorescence of Tissue:
No characteristic changes; vascular staining may be observed
What is the indirect immunofluorescence pattern of Mixed connective tissue disease (MCTD)? What are the nuclear antigens to which autoantibodies are directed? What does direct immunofluorescence
Indirect Immunofluorescence Pattern (Serum):
Speckled
Nuclear Antigens to Which Autoantibodies Are Directed: U1-snRNP and PM-scl
Direct Immunofluorescence of Tissue: No characteristic changes; granular immune deposits at the BMZ lichenoid features and vascular staining may be observed
What are defensins? What percent of all cellular proteins of human neutrophils do they comprise? What do they kill? What is their synthesis increased in response to?
Antimicrobial peptides (AMPs) in the skin. Defensins are cysteine-rich peptides made up of 29–34 amino acids that are present in skin. They are abundant in neutrophil granules and constitute about 5% of all cellular proteins of human neutrophils. Defensins are broad in spectrum, and kill a wide variety of bacteria and fungi. Synthesis of defensins is increased in response to inflammatory cytokines such as IL-1 and tumor necrosis factor (TNF), which are produced by macrophages and other cells in response to microbes.
