Ocular Immunity

Immune Privilege

IR can still occur, but strength of inflammatory/ adaptive response is reduced

Immune response in the eye

Highly regulated & not as strong/ long-lasting compared to rest of body

Factors that maintain immune privilege in eye

• absence of lymphatics

• Physical/anatomic barriers

• Active suppression of immune factors

The cornea, uvea, & retina has lymphatic vessels

False

Conjunctiva is well

Vascularized & has lymphatic vessels

Due to a sense of lymphatic drainage

• movement of immune cells & factors into the eye is limited

• Limits APCs movement out of the eye

MHC 1 & 2 expression in the eye

Very limited within the cells of the eye (except during autoimmune uveitis)

Nonclassical MHC 1 expression

Found on cells in the eye which protect these cells from NK cell killing

Physical/ anatomic barriers of immune privilege

• immune effectors blocked by blood-ocular barrier

• Tight junctions of epithelial barrier limits immune cells & molecules movement

Active Suppression of Immune Factors in Immune Privilege

Immunosuppressive factors produced by iris, ciliary body, retina, cornea, & aqueous humor, lead to an inhibitory ocular microenvironment

Expression of both FasL & PD-L1 on epithelial cells of iris & endothelial cells of anterior chamber

both FasL & PD-L1 include apoptosis of T cells, macrophages, & neutrophils if they enter the eye

PDL-1

Inhibits inflammatory cytokines in eye production (control ocular inflammation)

TRAIL expression

• TNF-related apoptosis inducing ligand (Corneal conjunctival endothelial cells)

• Induces apoptosis of T cells, macrophages, & neutrophils which express Fas

TGF-beta expression

• anterior chamber down regulates factors that stimulate T cells

• Immunosuppressive cytokine

• Limits T cell activation

• Inhibits NK cell function

• Limits of macrophages & neutrophils

• Inhibit AB production

• down regulates MHC expression

Tear Film

• not immune privileged

• Lubricates eye surface

• Optical surface maintenance

• Cellular & particulate debris removal

• Low level nourishment

• Eliminates pathogenic organisms

Three layers of Tear Film

• innermost, mucous layer

• Middle, aqueous layer

• Outer, lipid layer

Innermost, mucous layer

• Contains mucins which can inhibit binding of pathogens to epithelial cells

• Contains IgA produced in aqueous layer

Middle, aqueous layer

Lactoferrin, lysozyme, antimicrobial peptides, IgA

Outer, lipid layer

Decreases evaporation of underlying layers

Cornea

• immune privileged

• A vascular & lacks lymphatics preventing entry of pathogen, immune cells, or immune molecules

• Lack MHC expression

• FasL

• Complement regulatory proteins

• Complement proteins are present

• IgA, IgG, & IgM present

Conjunctiva

• mucosal immune system

  • Active immune responses (DC, lymphocytes, neutrophils, mast cells, IgG, IgA, AG presentation via MHC 1 & 2, Type 1 & 4 hypersensitivity rxns)

Sclera

• immune privileged (not well vascularized, few immune cells)

• Fibrous connective tissue that is continuous w/ cornea

• Complement, IgA & IgG present

Uvea

• immune privileged

• Iris, ciliary body, & choroid

• High vascularized (allows immune cell migration, complement IgA, IgG, & IgM present)

• Uveitis due to vascularization

• Type 1 & 4 hypersensitivity rxn

Uveitis

Inflammation in the uvea (tight junctions break down)

Retina

• immune privileged due to retinal-blood barrier

• Tight junctions between endothelial cells (Break down during uveitis)

• Immune mediators, immune cells, & pro-inflammatory cytokines can enter

Ankylosing Spondylitis

• type of arthritis that causes inflammation in joints & spine ligaments

• 40% develop uveitis

If cornea is avascular, how does the eye get oxygen?

Aqueous humor

Giant Cell Arteritis

• immune system attacks healthy arteries

• 50% experience visual symptoms unilateral visual blurring/ vision loss, often painless, or occasionally diplopia

• Partial field defect may progress to blindness over days

Most common cause of vision loss of GCA

• Anterior ischemic optic neuropathy (vasculitis of posterior ciliary artery)

• Optic disc shows chalky white pallor & edema, w/ or w/out splinter hemorrhages along disc margin

Myasthenia Gravis

• chronic autoimmune disease

• Auto-ABs form against nicotinic acetylcholine postsynaptic receptors @ neuromuscular junction of skeletal muscles

• Double vision

• Trouble focusing

• Drooping eyelids

What makes some thing immune privileged?

To be hidden from immune system

RA

• autoimmune disease that affects joints

• IgM ABs recognize Fc portion of IgG ABs (rheumatoid factor)

• RG creates large complexes which enter eye (type 3 hypersensitivity)

Ocular manifestations of RA

• 25% of ptss

• Dry eye

• Scleritis

• Peripheral Ulcerative Keratitis (PUK)

• Corneal perforation/ ruptured globe from scleritis

Peripheral Ulcerative Keratitis (PUK)

• crescent shaped destructive lesion of corneal stroma close to limbus

• Progressive thinning may lead to corneal perforation

• Immune complex activates complement > chemotaxis of inflammatory cells> release collagenase & protease that destroy corneal stroma

• Associated w/ RA, inflammatory bowel syndrome, SLE

Multiple Sclerosis Associated Uveitis

• autoimmune disease of CNS (Demyelinating disease)

• Uveitis in MS pts 0.4 to 26.9%

• Intermediate uveitis the most common presentation 60-80% pts

Thyroid Eye Disease

• graves opthalmopathy

• Bulging eyes (exophthalmos)

• Eyelid retraction

• Double vision

• Dry eyes

• Pain & inflammation around eyes

• Light sensitivity

• Blurred vision

• Immune system attacks muscles & tissues around eyes = inflammation & swelling