Immunology Flashcards
Innate immune system of the eye
Blink reflex
Physical and chemical properties of eye surface
Limit exposure/ size
Blink reflex- tears
Tears: physical
- flushing
- mucous layer= anti-adhesive
Tears: chemical
- lysozyme, lactoferrin, transferrin
- tear lipids
- angiogenin
- secretory ILA
- complement
- Il-6, Il-8, MIP
Tears; cellular
- neutrophils
- macrophages
- conjunctival mast cells
Adaptive Immune system of eye
Antigen presenting cells (APCs)
- dendritic cells, B cells, macrophages
lymphatic drainage to. lymph node
Variety of effector cells
Langerhan Cells
Principle antigen presenting cell for external eye
Rich in class II MHC molecules
Abundant at corner-scleral limbus
Less in peripheral cornea
Absent from central ⅓ of cornea
Conjunctiva
Only part of the eye with lymphatic drainage
Specialised endothelial venues for regulated migration of lymphoid cells
Diffuse lymphoid populations in all conjunctival zones
- CD4+ & CD 8+ T cells, IgA secreting plasma
Dendritic cells act as APCs
Mucosa associated lymphoid tissue (MALT)
- macrophages, langerhans and mast cells
Commensal bacteria
Cornea and Sclera
‘Tough collagen coat’
Avascularity
No lymphatics or lymphoid tissue
Relative lack of APCs
langerhans cells only in peripheral cornea
Downregulated environment
Lacrimal Gland
More plasma cells (IgA) and CD8+ T cells compared to conjunctiva
T cells in small groups around interlobular ducts
Lacrimal Gland drainage system
Diffuse lymphoid tissue and follicles in mucosa (MALT)
Vitreous, Choroid and Retina
Blood-ocular barrier
Relative lack of APCs
Downregulated immune environment
Immune privilege site
Able to tolerate introduction of antigens without exciting an inflammatory response
Sites of immune privilege in eye
Cornea Anterior. chamber Lens Vitreous Cavity Sub-retinal space
Ocular immune privilege mechanisms
Unique anatomical features of blood-tissue barrier and lack of direct lymphatic drainage
Ocular environment is rich in immunosuppressive molecules and inhibitory cell surface molecules that influence the reactivity of immune cells
Anterior chamber associated immune deviation
- ACAID
Anterior chamber associated immune deviation
Placement of foreign antigen. into ocular microenvironment can induce a systemic form of tolerance to foreign antigen
‘Peripheral tolerance’ to ocular antigen
ACAID protects the eye and visual axis from collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection
Establishment of Ocular Immune Privilege
Separation
Inhibition
Regulation
Establishment of Ocular Immune Privilege: Separation
Immunological Ignorance
Corneal cells have decreased expression of MHC class I and do not express MHC class II
Cornea lacks blood and lymphatic vessels
Establishment of Ocular Immune Privilege : Inhibition
Development of an intraocular immunosuppressive microenvironment
Establishment of Ocular Immune Privilege : Regulation
Peripheral tolerance to ocular antigens
–> ACAID
Sympathetic Ophthalmia
Rare, bilateral, granulomatous uveitis due to trauma or surgery to one eye
Sympathetic Ophthalmia pathophysiology
Primary mediator: T cells
Initial wave of infiltrative cells composed of CD4+ helper T cells.
Later wave of infiltrative cells are CD8+ Cytotoxic T cells
Sympathetic Ophthalmia Clinical
Injured eye: ‘exciting’ eye
Fellow eye: ‘sympathising’ eye
Clinically. both eyes will appear the same
History is required to determine exciting eye
Ocular Autoimmune Diseases (5)
Autoimmune uveoretinities
- inflammation of urea and retina
Dalen-Fuchs Nodule
- Epithelial cells clusters in retinal layers
Jerato conjunctivitis Sicca
-dry eyes
lens-induced uveitis
- reaction due to release of lens products
Retina autoantibodies
- common in retinopathy associated with cancer/ infection/ degenerative disease
Hypersensitivity Reactions
Type I: Immediate Hypersensitivity
Type 2: Direct cell killing
Type 3: Immune complex mediated
Type 4: Delayed type hypersensitivity
Type 1 : Immediate hypersensitivity
Acute allergic conjunctivitis
- chemosis: oedema of conjunctivitis
Type 2: Direct Cell Killing
(Antibody mediated cytotoxicity)
Ocular Cicatricial Pemphigoid
- Type of autoimmune conjunctivitis
- BListering and scarring of conjunctiva
Type 3: Immune complex mediated
Outer layer of cornea melts and inner layer bulges forward: possible perforation
Type 4: Delayed hypersensitivity
Corneal Graft rejection
- vascularisation of host cornea reaching the donor tissue = graft rejection
Corneal Transplants and Immune Privilege
Factors that maintain immune privilege:
Reduced and impaired expression of MHC
Class I and Class II molecules in corneal cells
-reduced net antigenic load
Cornea lacks blood and lymph vessels
Central cornea is deficit in Langerhans Cells
Secretion of molecules with immunosuppressive properties
Expression of surface molecules that inhabit immune effectors
ACAID in recipients
