Organ-specific immunity: SKIN Flashcards

1
Q

In what 4 ways does the skin act as a barrier?

A

Physical, microbiota, chemical, immune

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2
Q

Why do people that suffer from food allergy also often suffer from itchiness?

A

There is a skin-gut axis due to similar homing molecules

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3
Q

What are the main skin functions? (6)

A
  • Protection/defense
  • Signal reception
  • Thermoregulation
  • Communication
  • Secretion
  • Absorption
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4
Q

How does the skin thermally regulate the body?

A

Sweating, vasoconstriction/dilation

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5
Q

What is sebum?

A

A sticky, oily substance produced by the sebaceous glands

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6
Q

What can skin absorb?

A

Light, pharmaceutics

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7
Q

What are the three main layers of the skin?

A

Epidermis, dermis, hypodermis

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8
Q

What does the epidermis consist of?

A

Keratinocytes in 5 stratum layers:
- Corneum
- Lucidum
- Granulosum
- Spinosum
- Basale

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9
Q

Where are langerhans cells located?

A

The stratum spinosum

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10
Q

What does the stratum basale consist of?

A

Basal cells (stem-cell like keratinocyte precursors), Merkel cells and melanocytes

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11
Q

What do lamellar granules do in the skin

A

Play a role in keratinization

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12
Q

What is the function of the stratum lucidum?

A

Water resistance and barrier

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13
Q

What does the stratum corneum consist of?

A

Dead cells

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14
Q

What is the site of entry of microbiota?

A

The glands and hair follicles

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15
Q

What prevents invasion of microbiota into the hair follicles and glands?

A

Monocytes and Tregs

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16
Q

How do keratinocytes attach to the basal lamina?

A

Hemidesmosomes

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17
Q

What does the basal lamina consist of?

A

Type IV collagen, laminin and proteoglycans

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18
Q

What do desmosomes do?

A

They interconnect keratinocytes to each other, provide structural integrity but still allow passage of substances

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19
Q

How is transport of substances limited in the epidermis?

A

Tight junctions, particularly in the stratum granulosum, enforcing cytoplasmic uptake

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20
Q

Is all keratin expressed in skin cells the same?

A

No, different cells have different types of keratin made up of heterodimers of keratin with different functions (barrier, metabolism, differentiation, etc)

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21
Q

How is photoprotection provided?

A
  • 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
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22
Q

What do Merkel cells do?

A

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

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23
Q

What is the reticular dermis?

A

Makes up the bulk of the dermis, made up of tight connective tissue

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23
Q

What are the two dermis layers?

A

Papillary dermis and reticular dermis

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24
What is the papillary dermis?
It is highly vascularized and made up of a lot of loose connective tissue
25
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)
26
What is the dermis populated by?
Next to collagen and elastic fiber, also fibroblasts, endothelial cells and innate and adaptive immune cells
27
Is the skin a passive barrier?
No
28
How is homeostasis maintained in the skin by the microbiota?
They themselves produce AMPs and they interact with keratinocytes and immune cells
29
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
30
What does CCR7 do?
Aids in migration of langerhans cells to the lymph nodes
31
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
32
What are inflammatory reactions of langerhans cells?
- Cytokine secretion (IL-1ß, TNF-α, IL-6, IL-12) - Chemokine secretion (recruitment) - IL-23: Th17 development
33
What are tolerance reactions of langerhans cells?
IL-10 and TGFß Co-stimulatory receptor downregulation
34
How does TGFß play a role in skin homeostasis?
Wound healing
34
What cells represent the vast majority of dermal cells?
Phagocytes, mostly macrophages, but also dermal DCs and migrating and resident langerhans cells
35
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
36
What is CGRP?
It is a neurotransmitter produced by nerves in the skin that is produced when sensing fungi or bacteria.
37
When is TAFA4 produced?
UV exposure by sensory neurons around hair follicles
38
What does TAFA4 do?
Induces macrophage survival, induces IL-10 production which limits inflammatory response by newly arriving macrophages and induces healing
39
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
40
What ILC is involved in tissue repair?
ILC2
41
What ILC plays a role in psoriasis?
ILC3 (Th17 does too)
42
What cells play a role in contact hypersensitivity?
NKs and ILC1
43
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
43
Who produces AMPs in the skin?
Keratinocytes, leukocytes, adipocytes and commensals
44
What is a chemokine receptor of T cells, B cells and DCs for homing to the skin?
CCR10
45
What is the macroscopic hallmark of psoriasis?
Plaque formation
46
What are munro’s microabscesses?
Collections of neutrophils in the stratum corneum during psoriasis
47
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
48
What happens during pre-psoriasis?
Innate and adaptive cell activation and recruitment, Th1, Th22 and Th17 -> AMP production
49
What do epithelial cells do during psoriasis?
Hyperproliferation
50
What triggers psoriasis?
Microorganisms, trauma, drugs combined with genetic susceptibility
51
What cytokines are important in psoriasis plaque formation?
IL-23 and IL-17
52
What type of treatment is effective against psoriasis?
Biologics targeting p19 subunit of IL-23, since p19 is specific for that cytokine
53
What is atopic dermatitis initiated by?
Defective skin barrier in combination with genetic susceptibility
54
What happens when the skin of an AD susceptible person is disrupted?
Activation -> Th2 type reaction including ILC2
55
What T cells dominate the acute stage of atopic dermatitis?
Th2/Th22
56
What T cells are activated as atopic dermatitis prgresses?
More Th2 and Th22 cells, but also Th1 and Th17
57
What types of itching pathways are there?
Histamine dependent and histamine-independent
58
How is the histamine-dependent pathway initiated?
Histamines interact directly with histamine receptors on sensory neurons
59
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