Organ-specific immunity: SKIN Flashcards
In what 4 ways does the skin act as a barrier?
Physical, microbiota, chemical, immune
Why do people that suffer from food allergy also often suffer from itchiness?
There is a skin-gut axis due to similar homing molecules
What are the main skin functions? (6)
- Protection/defense
- Signal reception
- Thermoregulation
- Communication
- Secretion
- Absorption
How does the skin thermally regulate the body?
Sweating, vasoconstriction/dilation
What is sebum?
A sticky, oily substance produced by the sebaceous glands
What can skin absorb?
Light, pharmaceutics
What are the three main layers of the skin?
Epidermis, dermis, hypodermis
What does the epidermis consist of?
Keratinocytes in 5 stratum layers:
- Corneum
- Lucidum
- Granulosum
- Spinosum
- Basale
Where are langerhans cells located?
The stratum spinosum
What does the stratum basale consist of?
Basal cells (stem-cell like keratinocyte precursors), Merkel cells and melanocytes
What do lamellar granules do in the skin
Play a role in keratinization
What is the function of the stratum lucidum?
Water resistance and barrier
What does the stratum corneum consist of?
Dead cells
What is the site of entry of microbiota?
The glands and hair follicles
What prevents invasion of microbiota into the hair follicles and glands?
Monocytes and Tregs
How do keratinocytes attach to the basal lamina?
Hemidesmosomes
What does the basal lamina consist of?
Type IV collagen, laminin and proteoglycans
What do desmosomes do?
They interconnect keratinocytes to each other, provide structural integrity but still allow passage of substances
How is transport of substances limited in the epidermis?
Tight junctions, particularly in the stratum granulosum, enforcing cytoplasmic uptake
Is all keratin expressed in skin cells the same?
No, different cells have different types of keratin made up of heterodimers of keratin with different functions (barrier, metabolism, differentiation, etc)
How is photoprotection provided?
- Melanocytes produce melanin and form melanosomes
- Melanosomes are exocytosed
- Melanosomes are endocytosed by keratinocytes
- Exposure to sunlight causes migration of melanosomes to apical side of keratinocytes to protect
What do Merkel cells do?
They are specialized epithelial cells especially present in thick skin. They are in close contact with sensory nerves and aid in perception of light touch
What is the reticular dermis?
Makes up the bulk of the dermis, made up of tight connective tissue
What are the two dermis layers?
Papillary dermis and reticular dermis
What is the papillary dermis?
It is highly vascularized and made up of a lot of loose connective tissue
What is the vascularization pattern in the dermis?
Capillaries in papillary, arterioles and venules to arteries and veins in reticular dermis (thickest towards basal lamina)
What is the dermis populated by?
Next to collagen and elastic fiber, also fibroblasts, endothelial cells and innate and adaptive immune cells
Is the skin a passive barrier?
No
How is homeostasis maintained in the skin by the microbiota?
They themselves produce AMPs and they interact with keratinocytes and immune cells
How do keratinocytes aid in innate immunity of the skin?
They express TLRs, signal for AMPs, produce inflammatory cytokines and chemokines to facilitate direct killing and recruit and modulate immune cells
What does CCR7 do?
Aids in migration of langerhans cells to the lymph nodes
What does CCR6 do?
It has CCL20 as a ligand, whch is produced by keratinocytes and other langerhans cells during inflammation to attract langerhans cells to the site
What are inflammatory reactions of langerhans cells?
- Cytokine secretion (IL-1ß, TNF-α, IL-6, IL-12)
- Chemokine secretion (recruitment)
- IL-23: Th17 development
What are tolerance reactions of langerhans cells?
IL-10 and TGFß
Co-stimulatory receptor downregulation
How does TGFß play a role in skin homeostasis?
Wound healing
What cells represent the vast majority of dermal cells?
Phagocytes, mostly macrophages, but also dermal DCs and migrating and resident langerhans cells
What do langerhans cells do in steady state?
They respond to commensals and self antigens by producing TGFß and IL-10 to induce antigen-specific Tregs
What is CGRP?
It is a neurotransmitter produced by nerves in the skin that is produced when sensing fungi or bacteria.
When is TAFA4 produced?
UV exposure by sensory neurons around hair follicles
What does TAFA4 do?
Induces macrophage survival, induces IL-10 production which limits inflammatory response by newly arriving macrophages and induces healing
What do mast cells do in the skin? (5)
- Vaso-dilation and activation
- Recruit inflammatory cells
- Induce emigration and activation of resident leukocytes
- Peptide degradation
- Scratch reflex
What ILC is involved in tissue repair?
ILC2
What ILC plays a role in psoriasis?
ILC3 (Th17 does too)
What cells play a role in contact hypersensitivity?
NKs and ILC1
AMP production is increased or decreased in certain skin diseases, which ones?
Psoriasis: increased -> seldom bacterial infections
Atopic dermatitis: decreased -> higher susceptibility to infection and commensal imbalance
Who produces AMPs in the skin?
Keratinocytes, leukocytes, adipocytes and commensals
What is a chemokine receptor of T cells, B cells and DCs for homing to the skin?
CCR10
What is the macroscopic hallmark of psoriasis?
Plaque formation
What are munro’s microabscesses?
Collections of neutrophils in the stratum corneum during psoriasis
What are the 4 histological features of psoriasis?
- Acanthosis: thickening of the skin
- Papillomatosis: Elongation of the epidermis into the papillary dermis
- Hypogranulosis: Loss of stratum granulosum
- Parakeratosis: Nuclei still present in stratum corneum cells
What happens during pre-psoriasis?
Innate and adaptive cell activation and recruitment, Th1, Th22 and Th17 -> AMP production
What do epithelial cells do during psoriasis?
Hyperproliferation
What triggers psoriasis?
Microorganisms, trauma, drugs combined with genetic susceptibility
What cytokines are important in psoriasis plaque formation?
IL-23 and IL-17
What type of treatment is effective against psoriasis?
Biologics targeting p19 subunit of IL-23, since p19 is specific for that cytokine
What is atopic dermatitis initiated by?
Defective skin barrier in combination with genetic susceptibility
What happens when the skin of an AD susceptible person is disrupted?
Activation -> Th2 type reaction including ILC2
What T cells dominate the acute stage of atopic dermatitis?
Th2/Th22
What T cells are activated as atopic dermatitis prgresses?
More Th2 and Th22 cells, but also Th1 and Th17
What types of itching pathways are there?
Histamine dependent and histamine-independent
How is the histamine-dependent pathway initiated?
Histamines interact directly with histamine receptors on sensory neurons
How is the histamine-independent pathway initiated?
Cytokines produced by Th2 cells (IL-4, IL-13 and IL-31) interact with their respective receptors on sensory neurons
