Immunology Flashcards
Why is the eye vulnerable to infection?
Give three solutions for this?
Eye doesn’t have a layer of skin to cover it so it’s very exposed and vulnerable. Not may commensal bacteria in the eye which makes it vulnerable.
- Blink reflex
- Physical and chemical properties of eye surface
- Limit exposure/size
What are the three immunological components of tears?
Briefly describe each.
- Physical
- Flushing
- Mucous layer = anti-adhesive – stops pathogens adhering to the eyes itself - Chemical properties of the eye surface
- Lysozyme, lactoferrin, lpid, angiogenin, secretory IgA, complement, IL-6, IL-8 - Immune cells in the eye
- Neutrophils
- Macrophages
- Conjunctival mast cells
What three things dos the adaptive immune system require?
- Antigen presenting cells (APC = dendritic cells, B cells, macrophages)
- Lymphatic drainage to lymph node
- Variety of effector cells (incl. CD4+ T cells, CD8+ T cells, B cells)
What is the main APC for the external eye?
- What type of cell is this?
- Rich in which type of molecule?
- Where are they abundant
Langerhans cell
- Type of macrophage
- Class II MHC
- 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?
Which cells are associated?
Conjunctiva
- Diffuse lymphoid populations in all conjunctival zones (CD4+ and CD8+ T cells, IgA-secreting plasma cells)
- Dendritic cells act as APCs
- Mucosa associated lymphoid tissue (MALT)
- Macrophages, Langerhans cells and mast cells - frequent the MALT, neutrophils/eosinophils only there if recruited
Which parts of the eye make up the “touch collagen coat”?
- Vascularity?
- Lymphatics?
- APCs?
- Langerhans cells?
Cornea + sclera
- Avascularity
- No lymphatics/lymphoid tissue
- Relative lack of APCs
- Langerhans cells only in peripheral cornea + limbus
Name one difference between lacrimal gland immunology to conjunctiva
More plasma cells (IgA) and CD8+ T cells in lacrimal gland compared to conjunctiva
Which structures act as the blood-ocular barrier?
What is immunology like here?
Vitreous, choroid, retina
- Relative lack of APCs
- Downregulated immune environment
What is an immune privileged site?
They are able to tolerate the introduction of antigens without eliciting an inflammatory immune response.
Name four immune privileged sites in the body
- Brain/CNS (controversial)
- Testes
- Placenta/foetus
- EYES
Name five sites in the eye which are immune privileged
- Cornea
- Anterior chamber
- Lens
- Vitreous cavity
- Subretinal space
Give three features of the eye which allow it to be immune privileged.
- 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.
If you put a foreign antigen in this space it can produce a whole body non-response to the antigen.
-> ‘Peripheral tolerance’ to ocular antigens
Give two active mechanisms which downregulate the immune response in the eye
- 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)
How does ACAID protect the eye and visual axis from collateral damage of an immune response to infection?
By suppressing a future potentially damaging response to infection
Give the three things which establish ocular immune privilege
- SEPARATION - anatomically and immunologically separate from the rest of the body
- 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
- > 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.
Uvea = middle layer of the eye, between retina and sclera – choroid, iris and ciliary body.
Granulomatous – white cell granulomas.
Sympathetic ophthalmia
- Aetiology?
Aetiology is not well understood – usually due to trauma, and can be surgical.
Thought to be secondary to development of an autoimmune reaction to ocular antigens which are 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).
What is the pathophysiology of sympathetic ophthalmia?
- Main immunology cell?
- Which eye is which?
Immune response occurs at elevated rates
- Primary mediators thought to be T cells
- Initial wave of infiltrative cells composed of CD4+ helper T cells
- Later wave of infiltrative cells are CD8+ cytotoxic T cells
- 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 is Gel and Coombs classification of hypersensitivity reaction?
Type I: Immediate hypersensitivity
Type II: Direct cell killing
Type III: Immune complex mediated
Type IV: Delayed type hypersensitivity
Decribe type I hypersensitivity
Give an optic example
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.
Example - Acute allergic conjunctivitis
- Chemosis = oedema of the conjunctiva
Describe Type II hypersensitivity
Give an optic example
Also known as antibody-mediated cytotoxicity. Cells killed either by: - Macrophages/natural killer (NK) cells - Complement (membrane attack complex) Example – Ocular Cicatrical Pemphigoid - Type of autoimmune conjunctivitis: - blistering and scarring of conjunctiva - Treated with steroids or immune modulators
Give an optic example of type III hypersensitivity
Autoimmune Corneal Swelling
- Outer layer of cornea melting; inner layer bulging forward -> possible perforation
- If perforates -> effectively have an open eye
Describe Type IV hypersensitivity
Give an optic example
Also known as cell-mediated cytotoxicity
- T helper cells activated by intracellular pathogens
- Clonal expansion
- When re-exposed, macrophages attracted
- Exaggerated immune response
Example – Corneal Graft Rejection
- Vascularisation of host cornea reaching the donor tissue
-> graft rejection
What are the main eye side effects of steroids?
Cataracts
Steroid-induced glaucoma
