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I&I WC1 > Organ-specific immunity: SKIN > Flashcards

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
Q

What is the papillary dermis?

A

It is highly vascularized and made up of a lot of loose connective tissue

25
Q

What is the vascularization pattern in the dermis?

A

Capillaries in papillary, arterioles and venules to arteries and veins in reticular dermis (thickest towards basal lamina)

26
Q

What is the dermis populated by?

A

Next to collagen and elastic fiber, also fibroblasts, endothelial cells and innate and adaptive immune cells

27
Q

Is the skin a passive barrier?

A

No

28
Q

How is homeostasis maintained in the skin by the microbiota?

A

They themselves produce AMPs and they interact with keratinocytes and immune cells

29
Q

How do keratinocytes aid in innate immunity of the skin?

A

They express TLRs, signal for AMPs, produce inflammatory cytokines and chemokines to facilitate direct killing and recruit and modulate immune cells

30
Q

What does CCR7 do?

A

Aids in migration of langerhans cells to the lymph nodes

31
Q

What does CCR6 do?

A

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
Q

What are inflammatory reactions of langerhans cells?

A
  • Cytokine secretion (IL-1ß, TNF-α, IL-6, IL-12)
  • Chemokine secretion (recruitment)
  • IL-23: Th17 development
33
Q

What are tolerance reactions of langerhans cells?

A

IL-10 and TGFß
Co-stimulatory receptor downregulation

34
Q

How does TGFß play a role in skin homeostasis?

A

Wound healing

34
Q

What cells represent the vast majority of dermal cells?

A

Phagocytes, mostly macrophages, but also dermal DCs and migrating and resident langerhans cells

35
Q

What do langerhans cells do in steady state?

A

They respond to commensals and self antigens by producing TGFß and IL-10 to induce antigen-specific Tregs

36
Q

What is CGRP?

A

It is a neurotransmitter produced by nerves in the skin that is produced when sensing fungi or bacteria.

37
Q

When is TAFA4 produced?

A

UV exposure by sensory neurons around hair follicles

38
Q

What does TAFA4 do?

A

Induces macrophage survival, induces IL-10 production which limits inflammatory response by newly arriving macrophages and induces healing

39
Q

What do mast cells do in the skin? (5)

A
  • Vaso-dilation and activation
  • Recruit inflammatory cells
  • Induce emigration and activation of resident leukocytes
  • Peptide degradation
  • Scratch reflex
40
Q

What ILC is involved in tissue repair?

A

ILC2

41
Q

What ILC plays a role in psoriasis?

A

ILC3 (Th17 does too)

42
Q

What cells play a role in contact hypersensitivity?

A

NKs and ILC1

43
Q

AMP production is increased or decreased in certain skin diseases, which ones?

A

Psoriasis: increased -> seldom bacterial infections
Atopic dermatitis: decreased -> higher susceptibility to infection and commensal imbalance

43
Q

Who produces AMPs in the skin?

A

Keratinocytes, leukocytes, adipocytes and commensals

44
Q

What is a chemokine receptor of T cells, B cells and DCs for homing to the skin?

A

CCR10

45
Q

What is the macroscopic hallmark of psoriasis?

A

Plaque formation

46
Q

What are munro’s microabscesses?

A

Collections of neutrophils in the stratum corneum during psoriasis

47
Q

What are the 4 histological features of psoriasis?

A
  • 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
Q

What happens during pre-psoriasis?

A

Innate and adaptive cell activation and recruitment, Th1, Th22 and Th17 -> AMP production

49
Q

What do epithelial cells do during psoriasis?

A

Hyperproliferation

50
Q

What triggers psoriasis?

A

Microorganisms, trauma, drugs combined with genetic susceptibility

51
Q

What cytokines are important in psoriasis plaque formation?

A

IL-23 and IL-17

52
Q

What type of treatment is effective against psoriasis?

A

Biologics targeting p19 subunit of IL-23, since p19 is specific for that cytokine

53
Q

What is atopic dermatitis initiated by?

A

Defective skin barrier in combination with genetic susceptibility

54
Q

What happens when the skin of an AD susceptible person is disrupted?

A

Activation -> Th2 type reaction including ILC2

55
Q

What T cells dominate the acute stage of atopic dermatitis?

A

Th2/Th22

56
Q

What T cells are activated as atopic dermatitis prgresses?

A

More Th2 and Th22 cells, but also Th1 and Th17

57
Q

What types of itching pathways are there?

A

Histamine dependent and histamine-independent

58
Q

How is the histamine-dependent pathway initiated?

A

Histamines interact directly with histamine receptors on sensory neurons

59
Q

How is the histamine-independent pathway initiated?

A

Cytokines produced by Th2 cells (IL-4, IL-13 and IL-31) interact with their respective receptors on sensory neurons

I&I WC1 (25 decks)

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