Skin Immune System Flashcards
immune functions of keratinocytes
- form the epithelial barrier
- produce antimicrobial peptides (AMPs)
- initiate INNATE immune responses
pilosebaceous units
sweat + sebaceous glands
- produce AMPs
- produce superficial aqueous-lipid layer
langerhans cells
intra-epidermal dendritic cells
TOLEROGENIC
- promote function of regulatory T cells
dermal interstitial dendritic cells
present in the perivascular locations in the dermis
IMMUNOGENIC
- promote pro-inflammatory response
what are the main components of the skin’s immune function
- epithelial and keratinocyte microenvironment
- APCs (LCs, DCs, macrophages)
- skin-homing Tem cells
- dermal microvascular units
- skin draining LNs
do keratinocytes provide innate or adaptive immune activity
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)
what is the skin microbiome
commensal bacteria and fungi that live on the skin without triggering an immune response
maintained by Treg cells
T regulatory cells
cells that recognize commensal bacteria and release anti-inflammatory cytokines to prevent an autoimmune response
- mediated by langerhans cells
- recognition occurs early in life
what is the epithelial barrier and does it contribute to innate or adaptive immunity
keratinocytes + pilosebaceous units
INNATE immunity:
- produce AMPs
- produce aqueous lipid layer
function of the aqueous lipid layer
traps AMPs on the surface to create a protective barrier
sebaceous adenitits
immune mediated destruction of sebaceous glands by activated T cells and dendritic cells
how does sebaceous adenitis occur
- aqueous lipid layer gets compromised
- prevents AMPs from being trapped on surface
- decreased skin barrier
adaptive immunity in the skin
- CD1 (langerhans) cells present skin oils to Th22 T cells
- Th22 T cells produce IL-22
- IL-22 promotes keratinocyte and AMP proliferation
- maintains skin homeostasis
how is adaptive immune function compromised in sebaceous adenitits
when an endogenous lipid is presented to the Th22 T cells, they initiate an autoimmune response instead of releasing IL-22 for skin homeostasis
clinical signs of sebaceous adenitis
- keratinization defects: hyperkeratosis, follicular plugging, alopecia
- increased susceptibility to infections: folliculitis, pyoderma
what are the major skin histiocytes
- dermal macrophages
- dendritic cells (langerhans and dermal DCs)
function of dermal macrophages
scavenging roles
- express adhesion molecules (integrins)
- express scavenger receptors
function of skin dendritic cells
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
langerhans cell function
TOLEROGENIC
- promote anti-inflammatory response
- slow turnover
- locally renewed
- abundant adhesion molecules
- few TLRs, CRs, and inflammatory mediators
resting langerhans cells
induce activation and proliferation of Treg cells to maintain tolerance in normal skin
activated langerhans cells
induce activation and proliferation of memory T cells (Tem)
limit activation of Treg cells
dermal dendritic cell function
IMMUNOGENIC
- promote pro-inflammatory response
- fast turnover
- renewed by bone marrow precursors
- abundant TLRs, CRs, and inflammatory mediators
- few adhesion molecules
canine X linked SCID
severe combined immunodeficiency
mutations in the IL-2R submit in six yc-cytokine receptors
common in basset hounds and corgis
function of yc-cytokine receptors
B, NK, T and dendritic cell function
mutation –> decreased function of most immune cells –> immunodeficiency
function of CD8+ T cells against CPV-2 in healthy dogs
langerhans cells induce CD8+ memory T cells via IL-15 autocrine loop
CD8+ memory T cells regress CPV-2 lesions
why are X-SCID dogs prone to developing CPV-2 infections
lack of yc-cytokine receptor –> decreased T cell function –> inability to activate CD8+ memory T cells –> increased susceptibility to CPV-2
CPV-2
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
are T or B cells more common on the skin surface
T cells (resident and migratory memory T cells, regulatory T cells)
B cells only recruited during inflammation
can any T cell migrate to the skin surface
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
homing receptors
cutaneous lymphocyte antigen that binds to a vascular addressin (E-selectin)
what vessel do cells use to travel from skin to lymph nodes
lymphatics
what vessel do cells use to travel from lymph nodes to skin
blood
steps of traveling from skin to LNs
- LCs/DCs express CCR7 to bind to CCL21 in lymphatic endothelium –> LN
- CCR7 binds to CC21 in lymph node paracortex
- 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
steps of traveling from LN to skin
- effector memory T cell traffics in blood to skin
- CCR4 binds to CCL17 on skin surface
- homing receptor binds addressin on the skin
- adhesion ligand binds adhesion receptor
resident memory T cells (Trm)
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
migrating memory T cells (Tmm)
migrate ONLY to skin draining lymph nodes via the lymphatics
central memory T cells (Tcm)
migrate to ALL lymph nodes in the body
- generated in local immune responses
- less effective in local protection because migrates
malignancy: sezary syndrome
