Ocular Surface Immunology
Dry Eye Disease
대전성모병원 노창래
• Angiogenic privilege of cornea
– (-) APC to the lymphoid compartment
• d/t lack of lymphatics
– (-) effector cell access to the cornea
• d/t lack of blood vessels
V
Aberrant activation of the innate
immune response
• General Stress response
– Increased osmolarity
• MAPK; p38, c-Jun, NF-kB
– Desiccating and osmotic stress
• MAPK, NF-kB
Aberrant activation of the innate
immune response
• Pathogen-associated receptors and
autoimmunity
– Pathogen recognizing receptors (TLR)
• Pathogen associated molecular pattern
• Endogenous danger signal; Host DNA/RNA from
dying (apoptotic or necrotic) or damaged cells
Aberrant activation of the innate
immune response
• Pathogen-associated receptors and
autoimmunity
– Pathogen recognizing receptors (TLR)
• Pathogen associated molecular pattern
• Endogenous danger signal; Host DNA/RNA from
dying (apoptotic or necrotic) or damaged cells
• 감사합니다.
• Uptake of material from apoptotic/necrotic cells or
small ribonuclear particles(snRNPs) that are
complexed with lupus anti-nuclear autoantibodies by
CD23+-plasmacytoid dendritic cells(pDC) leads to
the engagement of endosomal TLR 7/8 and
secretion of large amounts of autoimmune
response-promoting IFN-γ/β
• Uptake of choromatin, snRNPs, and related
immune complexes by B cells expressing BCR
antigen receptors with specificity to either the
antigenic moiety of the complexes or the Fc
moiety of the autoantibody leads to efficient B
cell activation and proliferation by endosomal
TLR (TLRs 7/8 or TLR 9)
• Sometimes the uptake of nucleic acid-containing
complexes by pDC and B cells can be further
promoted by the interaction of a DNA-bound
nuclear factor, termed high mobility group box-1
factor (HMBG-1), which is released extracellularly by
cells undergoing necrosis, using a cell surface
receptor for advanced glycation end-product termed
RAGE.
• Additionally, endosomal TLR9 can sense
otherwise inert self-DNA when it is
coupled with LL 37(coded by the CAMP
gene), the only mammalian cathelicidin
antimicrobial peptide, which is induced
early after skin injury.
• Finally, endogenous nucleic acids that
are taken up from apoptotic cells can,
under certain circumstances, induce type
I IFNs by engaging cytosolic helicases for
RNA or other not-yet-defined sensors for
B- and Z-forms of DNA and other
constituents.