Skin Immune System

Question 1

immune functions of keratinocytes

Answer 1

• form the epithelial barrier
• produce antimicrobial peptides (AMPs)
• initiate INNATE immune responses

Question 2

pilosebaceous units

Answer 2

sweat + sebaceous glands

• produce AMPs
• produce superficial aqueous-lipid layer

Question 3

langerhans cells

Answer 3

intra-epidermal dendritic cells

TOLEROGENIC
- promote function of regulatory T cells

Question 4

dermal interstitial dendritic cells

Answer 4

present in the perivascular locations in the dermis

IMMUNOGENIC
- promote pro-inflammatory response

Question 5

what are the main components of the skin’s immune function

Answer 5

1. epithelial and keratinocyte microenvironment
2. APCs (LCs, DCs, macrophages)
3. skin-homing Tem cells
4. dermal microvascular units
5. skin draining LNs

Question 6

do keratinocytes provide innate or adaptive immune activity

Answer 6

INNATE
- act as APCs (express MHC I and II)
- release growth factors and chemokines
- express TLRs that recognize PAMPs
- express inflammasomes that recognize DAMPs (activates IL-1 –> pro inflammatory)

Question 7

what is the skin microbiome

Answer 7

commensal bacteria and fungi that live on the skin without triggering an immune response

maintained by Treg cells

Question 8

T regulatory cells

Answer 8

cells that recognize commensal bacteria and release anti-inflammatory cytokines to prevent an autoimmune response

• mediated by langerhans cells
• recognition occurs early in life

Question 9

what is the epithelial barrier and does it contribute to innate or adaptive immunity

Answer 9

keratinocytes + pilosebaceous units

INNATE immunity:
- produce AMPs
- produce aqueous lipid layer

Question 10

function of the aqueous lipid layer

Answer 10

traps AMPs on the surface to create a protective barrier

Question 11

sebaceous adenitits

Answer 11

immune mediated destruction of sebaceous glands by activated T cells and dendritic cells

Question 12

how does sebaceous adenitis occur

Answer 12

1. aqueous lipid layer gets compromised
2. prevents AMPs from being trapped on surface
3. decreased skin barrier

Question 13

adaptive immunity in the skin

Answer 13

1. CD1 (langerhans) cells present skin oils to Th22 T cells
2. Th22 T cells produce IL-22
3. IL-22 promotes keratinocyte and AMP proliferation
4. maintains skin homeostasis

Question 14

how is adaptive immune function compromised in sebaceous adenitits

Answer 14

when an endogenous lipid is presented to the Th22 T cells, they initiate an autoimmune response instead of releasing IL-22 for skin homeostasis

Question 15

clinical signs of sebaceous adenitis

Answer 15

1. keratinization defects: hyperkeratosis, follicular plugging, alopecia
2. increased susceptibility to infections: folliculitis, pyoderma

Question 16

what are the major skin histiocytes

Answer 16

1. dermal macrophages
2. dendritic cells (langerhans and dermal DCs)

Question 17

function of dermal macrophages

Answer 17

scavenging roles
- express adhesion molecules (integrins)
- express scavenger receptors

Question 18

function of skin dendritic cells

Answer 18

maintain skin homeostasis and respond to infection

act as APCs for T cells
- express CD1, MHC I, MHC II
- express adhesion molecules
- migratory - travel to skin draining LNs
- instruct naive T cells

Question 19

langerhans cell function

Answer 19

TOLEROGENIC
- promote anti-inflammatory response
- slow turnover
- locally renewed
- abundant adhesion molecules
- few TLRs, CRs, and inflammatory mediators

Question 20

resting langerhans cells

Answer 20

induce activation and proliferation of Treg cells to maintain tolerance in normal skin

Question 21

activated langerhans cells

Answer 21

induce activation and proliferation of memory T cells (Tem)

limit activation of Treg cells

Question 22

dermal dendritic cell function

Answer 22

IMMUNOGENIC
- promote pro-inflammatory response
- fast turnover
- renewed by bone marrow precursors
- abundant TLRs, CRs, and inflammatory mediators
- few adhesion molecules

Question 23

canine X linked SCID

Answer 23

severe combined immunodeficiency

mutations in the IL-2R submit in six yc-cytokine receptors

common in basset hounds and corgis

Question 24

function of yc-cytokine receptors

Answer 24

B, NK, T and dendritic cell function

mutation –> decreased function of most immune cells –> immunodeficiency

Question 25

function of CD8+ T cells against CPV-2 in healthy dogs

Answer 25

langerhans cells induce CD8+ memory T cells via IL-15 autocrine loop CD8+ memory T cells regress CPV-2 lesions

Question 26

why are X-SCID dogs prone to developing CPV-2 infections

Answer 26

lack of yc-cytokine receptor --> decreased T cell function --> inability to activate CD8+ memory T cells --> increased susceptibility to CPV-2

Question 27

CPV-2

Answer 27

canine papilloma virus 2 oncogenic - often progresses to squamous cell carcinomas suppresses innate immune function of the skin by down regulating keratinocyte release of pro-inflammatory cytokines

Question 28

are T or B cells more common on the skin surface

Answer 28

T cells (resident and migratory memory T cells, regulatory T cells) B cells only recruited during inflammation

Question 29

can any T cell migrate to the skin surface

Answer 29

NO - requires specific effector memory T cells that have been presented antigen by LCs or DCs T cell must have homing receptors and chemokine receptors that match chemokine ligands on the skin surface

Question 30

homing receptors

Answer 30

cutaneous lymphocyte antigen that binds to a vascular addressin (E-selectin)

Question 31

what vessel do cells use to travel from skin to lymph nodes

Answer 31

lymphatics

Question 32

what vessel do cells use to travel from lymph nodes to skin

Answer 32

blood

Question 33

steps of traveling from skin to LNs

Answer 33

1. LCs/DCs express CCR7 to bind to CCL21 in lymphatic endothelium --> LN 2. CCR7 binds to CC21 in lymph node paracortex 3. LC/DCs present antigen to naive T cells by binding MHC to TCR --> induces T cell to replace CCR7 with CCR4 --> becomes memory T cell

Question 34

steps of traveling from LN to skin

Answer 34

1. effector memory T cell traffics in blood to skin 2. CCR4 binds to CCL17 on skin surface 3. homing receptor binds addressin on the skin 4. adhesion ligand binds adhesion receptor

Question 35

resident memory T cells (Trm)

Answer 35

do not leave the skin (mostly) - generated in local immune responses - globally protects skin - rapid protection inflammation: atopic dermatitis, psoriasis malignancy: epitheliotropic cutaneous T cell lymphoma

Question 36

migrating memory T cells (Tmm)

Answer 36

migrate ONLY to skin draining lymph nodes via the lymphatics

Question 37

central memory T cells (Tcm)

Answer 37

migrate to ALL lymph nodes in the body - generated in local immune responses - less effective in local protection because migrates malignancy: sezary syndrome