Dermatology Flashcards
What are physiological functions of the skin? (9)
- Protection (physical & immune)
- Skin microbiome
- Thermoregulation
- Sensation
- Water storage
- Absorption
- Secretion
- Facial expression
- Synthesis of vitamin D
What is the most prominent innate immune cell subset of the skin?
Mast cells
Which part of the immune system can the skin be considered to be part of?
Innate immune system
What is the sex difference in immunity?
Androgen signalling in males skews skin immunity towards reduced inflammation
Women are more predisposed to auto-immune disease, but also better protected against infectious disease & tumours
What is a remarkable property of the skin in regards to its ability to induce an adaptive immune response?
All cells required to produce an antibody response are present in the skin -> lymph nodes not always necessary
Why is it important that the skin can quickly produce a humoral immune response without relying on lymph nodes?
Regulation of skin microbiota
[Infectious diseases/auto-immune diseases] of the skin usuallu have more systemic symptoms when compared to the other
Infectious diseases generally give more systemic symptoms than auto-immune diseases
How do susceptibility genes influence the chance of leprosy of the skin?
Genetic predisposition to stronger humoral immunity = higher bacterial load
Genetic predisposition to stronger cellular immunity = lower bacterial load
Why is cellular immunity important to lower leprosy bacterial load?
Leprosy = intracellular pathogen
Why is psoriasis protective for leprosy?
Psoriasis = overactive cellular immunity
Which cell type is especially prominent in combating fungal infections of the skin?
Th17-cells
Why do anti-IL-17 biologicals cause skin infections?
They inhibit the Th17 signalling important for preventing fungal disease (mainly Candida)
Which type of infection is frequently seen in patients using anti-IL-17 biologicals? Why?
Candida infections -> these biologicals block Th17 function, which is important to prevent fungal infection
What are essential roles of the skin microbiota? (3)
- Protection against invading pathogens
- Education of the immune system
- Breakdown of natural products
True or false: skin microbiota cannot enter hair follicles and glands of the skin
False; the hair follicles and glands form specific niches for microbiota
What kind of bioactive molecules are produced by skin commensals? (6)
- Antimicrobial peptides (AMPs)
- Free fatty acids (FFAs)
- Structural components
- Phenol-soluble modulins (PSMs)
- Cell wall components
- Antibiotics (produced by fungi)
What are important functions of the bioactive molecules produced by skin commensals? (3)
- Prevent pathogen invasion
- Activate keratinocytes to produce immune factors
- Stimulate mmune cells native to/passing through the skin
What are the characteristics of the skin micriobiome environment? (6)
- Low biomass
- High lipid
- High salt
- Dry
- Nutrient-poor
- pH 5
What are the characteristics of the gut micriobiome environment? (6)
- High biomass
- High saccharide
- Low salt
- Moist
- Nutrient-rich
- pH 7
In which part of the colon is the oxygen tension highest?
In the crypts
Skin microbiota in hair follicles [are secluded from the outside environment/intract with the outside environment]
Skin microbiota in hair follicles have little turnover with the outside world and stay in their specific niche
Gut microbiota in colonic crypts [are secluded from the outside environment/intract with the outside environment]
Gut microbiota in the crypts are actively turned over with the lumen
Which two classes of lipids are produced by the skin?
- Epidermal lipids
- Sebaceous lipids
By which cells/organs are epidermal lipids produced?
Keratinocytes
What is an important group of epidermal lipids?
Ceramide
By which cells/organs are sebaceous lipids produced?
Sebaceous glands
What are important groups of sebaceous lipids? (2)
- Squalene
- Wax esters
What are the three dominant skin lipids? (3)
- Cholesterol
- Triglycerides
- Free fatty acids
Where are free fatty acids of the skin produced?
These are produced by skin microbes
What are the effects of skin lipids on the microbiome?
- Antimicrobial activity
- Immunomodulatory effects
Which protein forms the majority of the skin protein biomass? Where is it found, and what is thought to be its function?
Loricrin (70% of protein biomass of the skin), found in keratinocytes. May have in important barrier function.
What is the outside structure of Gram- bacteria?
Two lipid layers + peptidoglycan cell wall
What is a major antigen found on Gram- bacteria? Where is it found?
LPS, found in the outer membrane
What is the most immunogenic part of LPS?
The O-region
What is the outside structure of Gram+ bacteria?
Inner lipid bilayer + thick peptidoglycan wall
True or false: all bacterial species use the same limited group of peptidoglycans
False; peptidoglycans are specific to different species and families
What is the outside structure of fungi?
Lipid bilayer membrane covered in chitin & β-glycan mesh
Which 4 types of human skin can be identified? What are examples of locations in which they can be found?
- Sebaceous (oily) -> forehead
- Moist -> anteroir antecubital fossa
- Dry -> volar forearm
- Foot -> toe web space
What is the relevance of the different types of human skin to the microbiome composition
Each skin type has a specific microbiome composition
How can the skin microbiome be identified?
Metagenomic sequencing
Which two strategies for metagenomic sequencing of the skin microbiome can be used?
- Amplicon sequencing
- Whole genome metagenomics
Which two amplicons can be used for amplicon sequencing of the skin microbiome?
- 16S rRNA sequencing (bacteria)
- Internal transcribed spacer 1 (ITS1)
Which bacterial (2), epithelial (1) and immunological (2) actions occur in the presence of S. aureus? What does this show?
Bacterial:
1. Production of antibiotics
2. Production of AMPs
Epithelium: production of AMPs
Immunological:
1. Production of AMPs
2. Production of cytokines for further immune activation
Shows crosstalk between the immune system & commensals in case of invading pathogenic bacteria
What are the major interfaces between mucosal surfaces and the outside world? (3)
- Intestines
- Respiratory tract
- Skin
Which immunological features are shared by all major interfaces between mucosal surfaces and the outside world? (3)
- Robust innate defence
- Presence of high amounts of adaptive immune cells
- Th17 cells in close apposition to epithelial barriers to act swiftly in case of epithelial breach
What is the role of Th1 in the defence of musocal surfaces?
Defence against intracellular pathogens
What is the role of Th2 in the defence of mucosal surfaces?
Defence against extracellular pathogens, mainly bacteria
What is the role of Th17 in the defence of mucosal surfaces?
Defence against extracellular pathogens, mainly fungi
What are the results of a disbalance of IL-17?
IL-17 too low = fungal overgrowth
IL-17 too high = bacterial overgrowth
In which inflammatory diseases is the Th17/IL-17 pathway implicated? (6)
- IBD
- Arthritis
- MS
- Periodontitis
- Psoriasis
- Uveitis
What are characteristics of pathogenic Th17 cells? (2) Which cytokines do they produce? (3)
Characteristics:
1. Presence of Runx1/2
2. Presence of T-bet
Cytokines produced:
1. TGF-β3
2. IFN-γ
3. IL-22
Which cells are capable of producing IL-17? (4)
- Th17
- ILCs
- iNKTs
- γδ T-cells
What is the structure of the IL-17 cytokine?
Can exist as homo- and heterodimers of IL-17A and IL-17F:
IL-17A/IL-17A
IL-17A/IL-17F
IL-17F/IL-17F
Which components make up the IL-17R? (2)
- IL-17RA
- IL-17RC
What is the intracellular signalling pathway of IL-17R activation? (5 steps)
ACT1 -> TRAF6 -> TAK1 -> IKK-complex -> NF-κB
On which types of cells does IL-17 mostly have effect?
Cells of the non-haematopoietic compartment
Which genes are regulated by IL-17?
- Inflammatory cytokines
- Chemokines
- AMPs
- Matrix metalloproteases (MMPs)
Which tools can be used to target the Th17/IL-17 pathway? (5)
- IL-17A targeting antibodies
- IL-17A/IL-17F targeting antibodies
- IL-17RA targeting antibodies
- Inhibitors of IL-17R signal transduction
- Inhibitors of Th17 generation
