Structure of the Skin & Cutaneous Immunology 2022 Flashcards
1
Q
- In atopic dermatitis, lamellar granules release lipid contents into the intercellular space to
form a hydrophobic lipid seal that impedes transepidermal water loss.
In which layer of the skin is this hydrophobic lipid seal found?
A. Dermoepidermal junction
B. Epidermis
C. Papillary dermis
D. Reticular dermis
A
- B, Epidermis, p. 511.
The most abundant cell in the epidermis is the keratinocyte. Keratinocytes are continually
renewing cells that are roughly divided into four types: basal (stratum germinativum), spinous
(stratum spinosum), granular (stratum granulosum), and cornified (stratum corneum). The
hydrophobic lipid seal is at the interface of the granular and cornified layers of the epidermis.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
2
Q
- A 78-year-old man with bullous pemphigoid presents with tense blisters that have evolved
over 10 weeks from areas of itching and redness. The blisters have clear fluid centers on the
axillae and the flexural surfaces of his arms.
Which structure affected is vital for the attachment of basal keratinocytes to the lamina densa?
A. Anchoring plaque
B. Desmosome
C. Filaggrin
D. Hemidesmosome
A
- D, Hemidesmosome, p.512-3.
Bullous pemphigoid is an autoimmune blistering disease with autoantibodies against BPAG1
and BPAG2, affecting the hemidesmosome and lamina lucida. Hemidesmosomes, which are
composed of BPAG1, BPAG2, plectin, and alph6beta4 integrin, attach the plasma membrane of the basal keratinocyte to the basement membrane. There are three layers to the dermoepidermal junction: the hemidesmosome-anchoring filament (including the lamina lucida), the basement membrane (lamina densa), and the anchoring fibril layers.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
3
Q
- A 44-year-old woman with systemic sclerosis presents with progressive skin thickening,
digital vasculopathy, and joint contractures.
What cell found most in the papillary dermis synthesizes and degrades extracellular matrix
proteins including collagen, elastin, proteoglycans, and fibronectin?
A. Dermal dendritic cell
B. Dermal fibroblast
C. Dermal macrophage
D. Langerhans cell
A
- B, Dermal fibroblast, p. 514.
Mesenchyme-derived dermal fibroblasts synthesize and degrade extracellular matrix proteins
including collagen, elastin, proteoglycans, and fibronectin. Activity is increased during wound
healing. The fibroblasts also secrete various soluble mediators involved in the immune response when stimulated by cytokines. An example of a soluble mediator and this process is noted in Middelton’s (9th ed) where “eotaxin is produced by fibroblasts in response to IL-4 stimulation. Stem cell factor expression by fibroblasts may also contribute to normal cutaneous mast cell development”.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
4
Q
- You are studying a drug for an additional indication. The drug targets free nerve endings of
fibers that innervate all vital layers of the epidermis. These fibers can sense pain, itch, noxious
stimuli, temperature, and pressure.
What nerve fibers would you target to provide relief of severe pruritis due to atopic dermatitis?
A. Aβ fibers and Aδ fibers
B. Aβ fibers and C fibers
C. Aβ fibers, Aδ fibers, and C fibers
D. Aδ fibers and C fibers
A
- D, Aδ fibers and C fibers, p. 516.
The Adelta and polymodal C fiber free nerve endings innervate all vital layers of the epidermis and can sense pain, itch, noxious stimuli, temperature, and pressure. Polymodal C fibers can be stimulated by histamine, chloroquine, and cowhage. Bhlbb5 is a transcription factor that
modulates itch through its inhibitor function in the dorsal root ganglia. Loss of this transcription
factor can lead to chronic itch.
Sensation of itch is mediated by TRP (transient receptor potential) channels, neuromediators,
kinins, eicosanoids, neuropeptides, neurotrophins, proteases, and opioids. Inflammatory Th2
cytokines can both sensitize and stimulate itch-specific type C fibers through Jak1 signaling.
Through their innervation by Adelta fibers, Meissner corpuscles sense touch, Pacini corpuscles
sense vibration, and Ruffini corpuscles sense stretch.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
5
Q
- When reviewing the literature for different emerging monoclonal antibodies that may be
helpful for atopic dermatitis, you come across one whose target is a cytokine that is the key
initiator of cutaneous inducible immunity. This cytokine is preformed in the cytoplasm of
keratinocytes and is released into the skin if integrity is disturbed.
What is the cytokine?
A. IFN-
B. IL-6
C. IL-33
D. IL-1alpha
A
- D, IL-1alpha, p. 517-20.
A key initiator of cutaneous inducible innate immunity and a distinguishing feature of skin is the abundant preformed IL-1alpha stored in the cytoplasm of keratinocytes. If skin integrity is disturbed with concurrent disruption or stimulation of epidermal keratinocytes, IL-1alpha is directly liberated into the skin. Release of IL-1alpha, along with release of TNF-alpha, appears to be key in initiating a cascade of events. The principal molecules induced by IL-alpha include IL-1alpha, IL-1beta, TNF-alpha, IL-8, nitric oxide synthase, and cyclooxygenase. It also induces expression of ICAM-1, VCAM-1, and Eselectin.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
6
Q
6. You are consulted to see a premature baby in the NICU who is small for gestational age and had an abnormal number of TRECs (T-cell receptor excision circles) on his newborn screen. An autosomal recessive mutation in mitochondrial adenylate kinase 2 (AK2) is identified. With this mutation, there is a deficiency of a specific immune cell that can exit the skin through lymph vessels and proceed to draining lymph nodes. They migrate by modulating their adhesion molecules such as 6 integrin, CD44, E-cadherin and matrix metalloproteinases expression. What is this immune cell called? A. CLA+ T cell B. Langerhans cell C. Mast cell D. Naive T cells
A
- B, Langerhans cell, p. 519-21.
Migrating Langerhans cells that have endocytosed antigen and have been activated by the inducible innate immune response may directly present antigen in the skin to previously generated skin-resident effector T cells, or they may exit the skin through lymph vessels and proceed to the draining lymph node by modulating their adhesion molecule (eg, alpha-6 integrin, CD44, E-cadherin) and matrix metalloprotease (MMP-6, MMP-2) expression. In the lymph node, Langerhans cells process and present antigenic peptide to naïve T cells.
CLA+ T cells have been activated in a lymph node and can home to the site of cutaneous inflammation and extravasate into the skin. Reticular dysgenesis is caused by an autosomal recessive mutation in mitochondrial adenylate kinase 2 (AK2).
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
7
Q
- A 2-week-old male neonate is diagnosed with a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. Genetic sequencing finds an abnormality in an anti-inflammatory molecule.
Which anti-inflammatory molecule plays an important role in resolution of the immune reaction in the skin?
A. Interleukin-6 receptor antagonist (IL6RA) from fibroblasts
B. Interleukin-1 receptor antagonist (IL1RA) from keratinocytes
C. Laminin alpha5 from pericytes
D. Vascular endothelial growth factor (VEGF) from fibroblasts
A
- B, Interleukin-1 receptor antagonist (IL1RA) from keratinocytes, p. 522.
While levels of inflammatory cytokines and pathogen-derived antigens are principal in resolution of the inflammatory immune response, anti-inflammatory molecules are also important. Waning levels of inflammatory cytokines (IL-1alpha, TNF-alpha) and pathogen-derived antigens are principal in resolution of the inflammatory immune response. With no antigen, there is no triggering of innate immune system pattern recognition receptors or activation of acquired immune system cells. A proportional increase in anti-inflammatory molecules such as interleukin-1 receptor antagonist (IL1RA) from keratinocytes, IL-10 and TGF-beta from macrophages phagocytosing apoptotic cells, and from regulatory T cells contributes to downregulation of the inflammatory response. Laminin alpha-5 from pericytes is important for angiogenesis and tissue regeneration.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
8
Q
- Which option describes the rash and the proteins involved in pemphigus vulgaris?
A. Flaccid bullae on noninflamed skin, crusting, and a positive Nikolsky sign. Desmoglein 1 and desmoglein 3 of the desmosome are the involved proteins
B. Small bullae on the extensor surfaces that are markedly pruritic with IgA endomysial and transglutaminase antibodies that tend to correlate with disease activity
C. Tense bullae, often on an urticarial base, with prominent pruritis. The proteins involved are BPAG1 and BPAG2 (bullous pemphigoid antigens 1 and 2)
D. Tense bullae that commonly occur in areas of trauma and in the oral mucous. The proteins involved include type VII collagen and anchoring fibrils
A
- A, Flaccid bullae on noninflamed skin, crusting, and a positive Nikolsky sign. Desmoglein 1 and desmoglein 3 of the desmosome are the involved proteins, p. 523, 525.
Answer choice A describes pemphigus vulgaris, an immunobullous skin disease. Tissue immunofluorescence would show epidermal IgG and C3 surface cell staining.
Answer B is
consistent with dermatitis herpetiformis, which is associated with intestinal gluten activity. Answer C is consistent with bullous pemphigoid. Answer D is consistent with epidermolysis
bullosa acquisita.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
9
Q
- You are obtaining a family history from a patient in allergy/immunology clinic. Her mother had a history of lupus erythematous as an adult but she can’t remember the specific type. The patient recalls her mother had autoantibodies to SSA-A/Ro and SS-B/La nuclear antigens.
What type of lupus erythematous did this patient’s mother likely have?
A. Discoid lupus erythematosus
B. Drug-induced lupus erythematosus
C. Subacute cutaneous lupus erythematosus
D. Systemic lupus erythematosus
A
- C, Subacute cutaneous lupus erythematosus, p. 524.
Subacute cutaneous lupus erythematosus and neonatal lupus erythematous are both associated with autoantibodies to SSA-A/Ro and SS-B/La nuclear antigens.
Usually, autoantibodies to nuclear antigens are not detected with discoid lupus erythematosus.
Autoantibodies to histones are detected with drug-induced lupus erythematosus.
Autoantibodies to SSA-A/Ro and SS-B/La nuclear antigens are also often found in cutaneous scleroderma and Sjogren syndrome, yet these conditions will not have deposits or changes at the basement membrane zone on direct immunofluorescence, as will lupus erythematosus.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
10
Q
- Which antimicrobial polypeptides of the skin are important for anti-viral defense?
A. Beta-defensin 1 and Beta-defensin 4 A (DEFB1 and DEFB4A)
B. Cathelicidin antimicrobial polypeptide (CAMP) and natural immunoglobulin M
C. IFN-α, IFN-β, IFN-κ
D. RNases and DNases
A
- C, IFN-α, IFN-β, IFN-κ, p. 517-9.
Interferon α (IFN-α), IFN-β, and IFN-κ are members of a class of antimicrobial polypeptides (ie, type 1 interferons) that are important in antiviral defense. Plasmacytoid dendritic cells secrete
large amounts of type 1 interferons in response to a viral infection.
The constitutive presence of protective antimicrobial polypeptides includes:
• Beta-defensin 1 and Beta-defensin 4 A (DEFB1 and DEFB4A)
• dermcidin
• iron-binding proteins
• lysozyme
• RNases
• DNases
• natural IgM
• cathelicidin antimicrobial polypeptide (CAMP)
These polypeptides enter the skin both from sweat and from keratinocytes entering their final stages of cornification. Similarly, some epidermal lipids such as sphingosine, keratinocyte-, and
sebum-derived fatty acids exhibit antimicrobial activity through their ability to reduce skin surface pH. Lactic acid excreted in eccrine sweat also lowers skin surface pH. Antimicrobial
peptides demonstrate other biologic properties, such as chemotactic activity for various immune cells.
Chapter 32: Structure of the Skin and Cutaneous Immunology
Middleton’s Allergy Principles and Practice, 9th Edition
