week 1 immunology of the eye Flashcards
two types of immune system?
innate, adaptive
things involved in innate immune response
immediate= Anti-microbial proteins, Complement, Mast cells, Macrophages, Inflammation,
Recruitment/activation of phagocytes
Inflammation
things involved in adaptive immune response
CD4, CD8, Bcells
innate IS of eye
- Blink reflex
- Physical and chemical properties of eye surface
- Limit exposure/size
what properties does the blink reflex possess to help Innate IS
TEARS – PHYSICAL
- Flushing out
- Mucous layer = anti-adhesive
what properties do the chemical properties of the eye possess to help Innate IS
TEARS – CHEMICAL
Lysozyme: v. gram –ve bacteria, fungi (destroy bacteria cell wall)
Lactoferrin and transferrin: v. gram +ve 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 leucocytes
what properties do the immune cells in the eye possess to help Innate IS
TEARS – CELLULAR
Neutrophils: -Attracted by chemotaxis -Scavengers – release free radicals, enzymes Macrophages: -Phagocytosis of damaged cells -Help to trigger adaptive immune system Conjunctival mast cells: -Vasoactive mediators
what three things does the adaptive IS require?
1-Antigen presenting cells (APC = dendritic cells, B cells, macrophages)
2-Lymphatic drainage to lymph node
3-Variety of effector cells (incl. CD4+ T cells, CD8+ T cells, B cells)
what type of cell are langerhans cells in the eye? function and how does it achieve this?
macrophages
Principle APC for external eye
Rich in Class II MHC molecules
where are langerhans cells in the eye found?
Abundant at corneo-scleral limbus, less in peripheral cornea, absent from central 1/3rd of cornea
what is the only part of the eye with lymphatic drainage?
conjunctiva
what allows regulated migration of lymphoid cells in conjunctiva?
Specialised endothelial venules
what do dendritic cells act as in conjunctiva?
APC’s
the conjunctiva is a MALT, what is this? what is found there?
Mucosa associated lymphoid tissue (MALT)
Macrophages, Langerhans cells and mast cells frequent the MALT, neutrophils/eosinophils only there if recruited
please note commensal bacteria are found on conjunctiva
what is described a being made from a tough collagen coat?
Cornea and Sclera
describe the IS in the Cornea and Sclera
Avascularity No lymphatics/lymphoid tissue Relative lack of APCs Langerhans cells only in peripheral cornea Downregulated immune environment
what does the lacrimal drainage system contain?
Diffuse lymphoid tissue and follicles (40-50%) in mucosa (MALT)
what does the lacrimal gland contain?
More plasma cells (IgA) and CD8+ T cells compared to conjunctiva
T cells in small groups around intralobar ducts
Resting lymphoid cells very rarely observed
describe the IS in the Vitreous, choroid & retina
Blood-ocular barrier
Relative lack of APCs
Downregulated immune environment
therefore lots of potential for damage to occur=”petri dish with protective covering”
what is immune privilege
They are able to tolerate the introduction of antigens without eliciting an inflammatory immune response
what sites have immune privilege?
Brain/CNS (controversial)
Testes
Placenta/foetus(EG: baby is foreign material but IS does not attack it)
EYES
what sites in the eye are immune-privileged?
Cornea Anterior chamber Lens Vitreous cavity Subretinal space
what are the ocular immune privilege mechanisms?
- Unique anatomical features of a blood-tissue barrier and a lack of direct lymphatic drainage
- Ocular microenvironment is rich in immunosuppressive molecules and inhibitory cell surface molecules that influence the reactivity of immune cells
- Anterior chamber-associated immune deviation (ACAID)
what is Anterior chamber-associated immune deviation (ACAID)?
- The placement of foreign antigen into the ocular microenvironment can induce a systemic form of tolerance to the foreign antigen = ACAID
- ‘Peripheral tolerance’ to ocular antigens
- Active mechanisms that downregulate the immune response within the eye
what are the immunological hallmarks of ACAID?
- Generation of primed CD4+ T and B cells that produce non-complement-fixing antibodies
- Inhibition of delayed-type hypersensitivity (CD4+ Th1) and B cells that secrete complement-fixing antibodies (inhibition of a cell-mediated immune response)
what is the function of ACAID?
ACAID protects the 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?
SEPARATION: Immunological ignorance
Corneal cells have ↓ expression of MHC Class I molecules and do not express MHC Class II molecules
Normal cornea lacks blood and lymphatic vessels
INHIBITION: Development of an intraocular immunosuppressive microenvironment
Local factors within the eye inhibit components of the immune response to reinforce the protection provided by immune privilege
REGULATION: Peripheral tolerance to ocular antigens
ACAID
in short : The eye is ignorant to induction of non-self, the body is tolerant to the presence of ocular antigens, and the local environment within the eye supports these
what is Sympathetic Ophthalmia
Rare, bilateral, granulomatous uveitis due to trauma (more common) or surgery (less common) to one eye
what does Sympathetic Ophthalmia occur?
- Thought to be secondary to development of an autoimmune reaction to ocular antigens: exposed during the traumatic or surgical event
- Related to the physical and immunological isolation of the eye from the systemic immune system (disadvantage of immune privilege)
- Immune response occurs at elevated rates
what is the primary mediator in Sympathetic Ophthalmia?
T cells
Initial wave of infiltrative cells composed of CD4+ helper T cells
Later wave of infiltrative cells are CD8+ cytotoxic Tcells
what is the exciting eye and the sympathising eye? how to distinguish between the two?
The injured eye is the ‘exciting eye’ and the fellow eye is known as the ‘sympathising eye’
Clinically both eyes appear the same and it is only by history that one can identify which eye is the exciting eye
what can happen is IS goes wrong?
Recurrent infections Inadvertent injury to normal host tissues Allergy Hypersensitivity reactions Autoimmune disease Cancer Transplant/graft rejection
what are some AI diseases of the eye?
- Autoimmune uveoretinitis (inflammation of uvea & retina)
- Dalen-Fuchs nodule (epithelial cell clusters in retinal layers)
- Keratoconjunctivits sicca (‘dry eyes’)
- Lens-induced uveitis (reaction due to release of lens products)
- Retina autoantibodies (common in retinopathy associated with cancer/infection/degenerative disease)
- Sympathetic ophthalmia (bilateral granulomatous uveitis)
definition of a hypersensitivity reaction
Immune response that results in bystander damage to self
‘collateral damage’
Usually exaggeration of normal immune mechanisms
what is a type 1 HR
Immediate hypersensitivity
what is a type 2 HR
Direct cell killing
AKA:antibody-mediated cytotoxicity
what is a type 3 HR
Immune complex mediated
what is a type 4 HR
Delayed type hypersensitivity
AKA: cell-mediate cytotoxicity
pathogenesis of type 1 HR
mast cells express receptors for Fc region of IgE antibody on their surface →On encounter with allergen, B cells produce antigen-specific IgE antibody→allergen is cleared→Residual IgE antibodies bind to circulating mast cells via Fc receptors.
→No great consequence→After re-encounter with antigen:
-Allergen binds to IgE-coated mast cells and disrupts cell membrane
-Release of vasoactive mediators – histamine, tryptase etc
-Also increased cytokines and leukotriene transcription
give examples of type 1 HR of eye?
Acute allergic
conjunctivitis (chemosis=oedema of the conjunctiva can occur)
type 2 HR pathogenesis
Cells killed either by:
- Macrophages/natural killer (NK) cells
- Complement (membrane attack complex)
give examples of type 2 HR of eye?
Ocular cicatricial pemphigoid
(Type of autoimmune conjunctivitis:
blistering and scarring of conjunctiva)
give examples of type 3 HR of eye?
Autoimmune
corneal melting
(Outer layer of cornea melting; inner layer bulging forward possible perforation)
type 3 HR pathogenesis
accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes
type 4 HR pathogenesis
T helper cells activated by intracellular pathogens
Clonal expansion
When re-exposed, macrophages attracted
Exaggerated immune response
give examples of type 4 HR of eye?
Corneal graft
rejection
(Vascularisation of host cornea reaching the donor tissue
graft rejection)
what plays an important role in corneal transplants?
Immune privilege plays an important role
what factors help maintain immune privilege?
Reduced and impaired expression of MHC Class I and II molecules in corneal cells – the net antigenic load is reduced
Cornea lacks blood and lymph vessels – prevents antigenic information escaping from tissues and migration of APC
Central cornea is deficient in Langerhans cells – absence of APC lengthens the time for graft recognition
Secretion of molecules with immunosuppressive properties to inhibit macrophages, NK cells, DCs, T cells, B cells
Expression of surface molecules that inhibit immune effectors
ACAID in recipients
what are the ocular side effects of steroids?
Cataracts
Steroid-induced glaucoma
summary of IS in the eye
Eye has limited innate and adapted responses, some of which have been ‘modified’
Concept of immune privilege helps maintain ocular clarity and good vision, but responses can be extreme and sight-threatening - [Beware of ‘sympathetic ophthalmia’]
