Immunology and the eye Flashcards
What is included in the innate immune system of the eye?
No physical barrier
Not many commensals
Chemical agents
Cell
How does the eye protect itself?
Blink reflex
Physical and chemical properties of eye surface
Limit exposure
How does the blink reflex protect the eye?
Physical tears
Flushing
Mucous layer
What is present in tears that allows them to act as a chemical barrier?
Lysozyme: protects against gram negative bacteria and fungi
Lactoferrin and transferrin: protective against gram positive bacteria
Tear lipids: antibacterial to cell membranes/ scavenger of bacterial products
Angiogenin: antimicrobial effect within tear film
Secretory IgA: prevents attachment
Complement
IL-6, IL-8, MIP: antimicrobial molecules that recruit leukocytes
What cells are present in tears that help them to act as a barrier?
Neutrophils: chemotaxic, scavengers
Macrophages: phagocytosis of damaged cells, helps to trigger adaptive immune system
Conjunctival mast cells: vasoactive mediators
What does the adaptive immune system require?
Antigen presenting cells - dendritic cells, B cells, macrophages
Lymphatic drainage to lymph nodes
Variety of effector cells (CD4+ T cells, CD8+ T cells, B cells)
What is the role of langerhans cells in the eye?
Principle APC for external eye Rich in class 2 MHC molecules Found at limbus
What immunological features can be found at the conjunctiva?
Only part with lymph drainage
Specialised endothelial venules for regulated migration of lymphoid cells
Diffuse lymphoid populations in all conjunctival zones (CD4+ CD8+ T cells, IgA plasma cells)
Dendritic cells as APC
MALT
Commensal bacteria
What immunological features can be found at the cornea and sclera?
Tough collagen coat Avascular No lymphatics Lack of APC Langerhans cells only in peripheral cornea Down Regulated immune environment
What is the role of the lacrimal gland in immune protection of eye?
More plasma (IgA) cells and CD8+ T cells than conjunctiva T cells in small groups around intralobular ducts Resting lymphoid cells very rarely observed
What is the role of the lacrimal drainage system in immune protection of the eye?
Diffuse lymphoid tissue and follicles in MALT
What are immune privilege sites in the body?
Brain/CNS
Testes
Placenta/ foetus
Eye
What sites in the eye are immune privileged?
Cornea Anterior chamber Lens Vitreous cavity Subretinal space
What is immune privilege?
Tolerate introduction of antigens without eliciting an inflammatory response
How does the eye have immune privilege?
Blood-tissue barrier with a lack of lymph drainage
Ocular microenvironment is rich in immunosuppressive molecules and inhibitor cell surface molecules that influence the reactivity of immune cells
Anterior chamber associated immune deviation
What is anterior chamber associated immune deviation (ACAID)?
Placement of foreign antigen into the ocular microenvironment can induce a systemic form of tolerance to the foreign antigen
Downregulates immune response within the eye
What are the hallmarks of ACAID?
Generation of primed CD4+ T and B cells that produce non-complement fixing antibodies
Inhibition of delayed type hypersensitivity (CD+Th1) and B cells that secrete complement fixing antibodies
What is the purpose of ACAID?
Protects eye and visual axis from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection
How is ocular immune privilege established?
SeparationL immunological ignorance; corneal cells have a decreased expression of MHC class 1 molecules and do not express MHC class 2 molecules
Normal cornea lacks blood and lymph
Inhibition: development of an intraocular immunosuppressive microenvironemt
Regulation: ACAID
What is sympathetic ophthalmia?
Rare, bilateral granulomatous uveitis due to trauma (more common) or surgery (less common) to one eye
Autoimmune reaction to ocular antigens
What immunological cells determine sympathetic ophthalmia?
Primary mediators are T cells
Initial wave of infiltrative cells composed of CD4+ helper T cells
Later wave of infiltrative cells at CD8+ cytotoxic T cells
What are hazards of immunity?
Recurrent infections Inadvertent injury to normal host tissue Allergy Hypersensitivity reactions Autoimmune disease Cancer Transplant/ graft rejection
What autoimmune diseases can affect the eye?
Autoimmune uveoretinitis Dalen-fuchs nodule Keratoconjunctivitis sicca Lens-induced uveitis Retina autoantibodies Sympathetic ophthalmia
Hypersensitivity reactions?
Type 1: immediate hypersensitivity
Type 2: direct cell killing
Type 3: immune complex mediated
Type 4: delayed type hypersensitivity
What are examples of ocular type 1 hypersensitivity reactions?
Acute allergic conjunctivitis with associated chemosis
What is chemosis?
Oedema of the conjunctiva
What mediated type 2 hypersensitivity?
Macrophages/ NK cells
Complement (MAC)
What is an example of ocular type 2 hypersensitivity reactions?
Ocular cicatricial pemphigoid
Blistering and scarring of conjunctiva
What is an example of ocular type 3 hypersensitivity reactions?
Autoimmune corneal melting: outer layer of corneal melting, inner layer bulging forward; possible perforation
What is an example of type 4 hypersensitivity reaction in the eye?
Corneal graft rejection - vascularisation of host cornea reaching donor tissue
What ocular side effects can occur with steroids?
Cataracts
Steroid-induced glaucoma
