The role of macrophages in
autoimmune pathology
Immunopathology lecture 11
Andrew Dick
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The Role of Macrophages in Autoimmune Pathology: Function, Differentiation, and Regulation, Study notes of Biotechnology
The role of macrophages in autoimmune pathology, discussing their functions during infection, inflammation, repair, and tissue homeostasis. The text also covers the regulation of macrophage function, their heterogeneity, and the impact of macrophages on various autoimmune diseases such as ocular granulomata, sarcoidosis, and experimental autoimmune uveitis (eau).
Typology: Study notes
2010/2011
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The role of macrophages inautoimmune pathology
Immunopathology lecture 11 Andrew Dick
Macrophages ^
Multi-potential role
^
During infection ^
During inflammation ^
During repair ^
Tissue-specific(?) homeostasis Evidence for tight regulation of function in tissue? Are macrophages heterogeneous or do they show plasticity
during course of inflammation, degeneration or repair?
Differentiation, distribution and activation of macrophages
in vivo
Resident Tissue Macrophages ^
Parenchymal ^
Slow turnover ^
Regulate homeostasis
^
Perivascular ^
Turnover every 2-3weeks ^
Immunogenic
Retinal APC are directed at limiting cellresponses
Ford et al
JI
1995;
J Exp Med
^1996
Microglia, unlike perivascular macrophages induce
T cell apoptosis on presentation
Gregerson et al
J Leuk Biol
2004;
J
Immunol
^2004
Allogeneic APC adoptive transfer showed thatrecruited APC were essential not resident cells. Retinal APC only weakly induced b-gal TCR T cellproliferation and not naïve T cells.
Ocular Granulomata
Granulomata can form throughout the eye ^
Granuloma in vitreousas a consequence ofchronic fungal infectionin an intravenous drugabuser
^
Granulomata inconjunctiva of a patientwith sarcoidosis
Sarcoidosis ^
Multisystem granulomatousdisease characterised by ^
Langhan’s cells and epitheliodcells Lung, skin, eye, heart, liver, brain.
Lung granuloma
Acute stage^ Granuloma And fibrosis in Healing phase
Innate and Humoral activation
β -glucanReceptorDECTIN-
Fc receptors TLR
NO ROS
IFN
α/β ΤΝ
F
Cytolytic activity
Classical vs alternative activation
NO ROS
Upregulation of MHC class II
TNF, IL-6, IL-
IFN
−γ
receptor
Classical
Trigger -LPS
TGF-
β /IL-4/IL-13receptor
Alternative
Ag endocytosis (Mannan-dependent) MHC class II upregulation
Experimental Autoimmune
Uveitis (EAU)
•^
Rat model of posterior uveitis
-^
Target organ destruction of retinalrod photoreceptors
-^
CD
+^
T cell mediated
•^
M
φ^
and CD
+^
T cell infiltrate
•^
Delete m
φ^
=> reduced disease
ROS RPE Choroid
Experimental autoimmune
uveoretinitis (EAU)
-^
Chronic,monophasic
-^
CD
+^ T cell mediated
-^
IRBP orIRBP peptidespecific
Macrophages respond in response toenvironment they are conditioned by:
They respond hierarchically to cytokinesgenerated to^
Respond to remove danger (autoimmune orinfectious stimuli) – by generating cytotoxicity orphagocytosis
Facilitate repair of tissue
Maintain homeostasis
Increased MG numbers during
neurodegeneration
Day^3 Day^14
WT
RDS
No Nitrite No peroxynitrite Depleting MG Had no Effect on Degeneration or Photoreceptor Apoptosis
Hughes et al
IOVS
Exp Eye Res