Immunology and the Eye Flashcards
What is the role of lysozyme on the eye surface?
Active against gram -ve bacteria, fungi (destroy bacteria cell wall)
What is the role of lactoferrin and transferrin on the eye surface?
Active against gram +ve bacteria
What is the role of tear lipids on the eye surface?
Antibacterial to cell membranes/scavenger of bacterial products
What is the role of angiogenin on the eye surface?
Antibacterial to cell membranes/scavenger of bacterial products
What is the role of secretory IgA on the eye surface?
Prevents attachment
What is the role of IL-6, IL-7 and MIP on the eye surface?
Antimicrobial molecules that recruit leucocytes
What is the role of neutrophils in the eye?
Scavengers- release free radicals and enzymes
What is the role of macrophages in the eye?
Phagocytosis of damaged cells
Help to trigger adaptive immune system
What is the role of conjunctival mast cells in the eye?
Vasoactive mediators
What are the three components of the adaptive immune system
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 is the role of langerhans cells in the eye?
Principle APC for external eye
Rich in class II MHC molecules
Where are langerhans cells present?
Abundant in corneo-scleral limbus
Less in peripheral cornea
Absent from 1/3rd of conjunctiva
Which part of the eye has lymphatic drainage?
Conjunctiva
What does the conjunctiva contain to allow lymphatic drainage?
Specialised endothelial venues for regulated migration of lymphoid cells
What lymphoid populations are found in the conjunctiva?
CD4+T cells, CD8+T cells, IgA secreting plasma cells
What cells frequent the conjunctiva (MALT) of the eye?
Macrophages, langerhans cells and mast cells
Neutrophils only if recruited
Commensal bacteria
Describe the structure of the cornea and sclera
Tough collagen coat
Avascular
No lymphatics/lymphoid tissue
Describe the immune presence of the cornea and sclera
Lack of APCs
Langerhans only in peripheral cornea
Down-regulated environment
Which immune cells are found in the lacrimal gland?
Plasma IgA cells, CD8+T cells
What cells are found around intralobar ducts in the lacrimal gland?
T cells in small groups
What is rarely observed in the lacrimal gland?
Resting lymphoid cells
What provides the drainage of the lacrimal gland?
Diffuse lymphoid tissue and follicles (40-50%)
Describe the immune environment of the vitreous, choroid and retina
Blood-ocular barrier
Relative lack of APCs
Downregulated immune environment
Which parts of the body have immune privilege?
Brain/CNS
testes
Placenta/foetus
Eyes
What is immune privilege?
Able to tolerate the introduction of antigens without eliciting an inflammatory response
Which sites in the eye have immune privilege?
Cornea Anterior chamber Lens Vitreous Cavity Sub retinal space
What is ACAID?
Anterior Chamber Associated Immune Deviation
Protects eye and visual axis from collateral damage of an immune response to infection by suppressing a future response
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
Describe Separation (Immunological ignorance)
Corneal cells have reduced expression of MHC I molecules and do not express MHC II molecules
Normal cornea lacks blood and lymphatic vessels
Describe inhibition (development of an intracular immunosuppressive microenvironment)
Local factors within the eye inhibit components of the immune system to reinforce protection of immune privilege
Describe regulation (peripheral tolerance to ocular antigen)
ACAID
What is sympathetic ophthalmia?
Rare, bilateral granulomatous uveitis due to trauma (common) or surgery (less common) to one eye
What are the primary mediators of sympathetic ophthalmia?
T cells
What is the initial infiltrative wave in sympathetic ophthalmia?
CD4+ helper T cells
What is the later infiltrative wave in sympathetic ophthalmia?
CD8 + cytotoxic T cells
What are the injured and fellow eye known as in sympathetic ophthalmia?
Injured=exciting eye
Fellow= sympathising eye
What are the hazards of immunity in the eye?
Recurrent Infection
Inadvertent injury to normal host tissues
Allergy
Hypersensitivity reactions
Autoimmune disease
CAncer
Transplant/graft rejection
What is autoimmune uveoretinitis?
Inflammation of the uvea and retina
What is a dalen-fuchs nodule?
epithelial cells cluster in retinal layers
What is keratoconjunctivitis sicca?
Dry eyes
Describe mast cells in type 1 immediate hypersensitivity reactions
Mast cells express receptors for Fc region of IgE antibody on surface, when
encounter allergen, B cells produce antigen-specific IgE antibody
What happens on re-encounter with antigen in type 1 reactions?
residual IgE antibodies bind to circulating mast cells via Fc receptors
on 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 an example of a type 1 immune reaction in the eye
acute allergic conjunctivitis,
causes chemosis= oedema of the conjunctiva
What are the killing cells in type 2 immune reactions?
Macrophages/NK cells
Complement (MAC)
Give an example of Type 2 immune reaction in the eye
Ocular cicatricial pemphigoid
utoimmune conjunctivitis: blistering and scarring of the conjunctiva
What are type 3 immune reactions mediated by?
Formation of antigen-antibody complexes
Give an example of Type 3 immune reaction in the eye
autoimmune corneal melting,
outer layer of cornea melting: inner layer bulging forward,
possible perforation
Describe type 4 autoimmune reactions
T helper cells activated by intracellular pathogens
clonal expansion
when re-exposed, macrophages attracted
exaggerated immune response
Give an example of a type 4 immune reaction in the eye?
Corneal graft rejection
Which diseases- thought to be age related- are now thought to have an immune component?
adult macular degeneration (AMD), glaucoma, diabetic retinopathy
What is the proposed aetiology of immunity in age related diseases?
ocular immune priviledge combined with a lack of age-related antigens within the target tissue dampen what could otherwise be overt inflammation into the para-inflammation (slow, insidious) that characterises age-related neurodegenerative disease
