Ophthalmic immunology

Protective mechanisms

Question.1

Question.2
Diversity Vs Tolerance

Tolerance
Clonal Deletion Receptor editing Anergy Ignorance Downregulation by: Treg

Diversity Vs Tolerance

Mechanisms of immune privilege in the eye

First, the eye is filled with immunosuppressive factors including: neuropeptides melanocyte stimulating hormone somatostatin vasoactive intestinal peptide calcitonin gene related peptide cytokines (e.g. TGF-2) complement inhibitors inhibitor of NK cell activity (macrophage inhibitory factor) .

Mechanisms of immune privilege in the eye

Second, the low expression of MHC class II in the eye limits antigen presentation.

Mechanisms of immune privilege in the eye

Third, stromal cells from the iris, ciliary body and retina of the eye are able to convert immune T cells to regulatory (Treg) cells . Furthermore retinal pigment epithelial (RPE) cells that line the borders of the eye are able to directly inhibit primed T cells.

Mechanisms of immune privilege in the eye

Fourth, death inducing molecules like PDL-1 and FasL are expressed by stromal cells in the eye and induce apoptosis of immune cells that transgress ocular boundaries

Mechanisms of immune privilege in the eye

Fifth, Immobility of Dendritic Cells Within
the Anterior Chamber and Anterior Chamber Associated Immune Deviation

failure of these antigen-bearing cells to migrate to the local lymph nodes . The inability to migrate is consistent with the known lack of lymphatics within the eye Immune response without inflammation

Anterior chamber associated immune deviation

In this model, the placement of antigen into the anterior chamber of the eye induces a characteristic immune response that includes the absence of complement fixing antibodies and Th1 and Th2 immune responses specifically to that antigen. However, the animal remains perfectly capable of responding to the antigen.

Generation of Foxp3+ CD8+ Treg cells : T-cell receptor -chain fragments from apoptotic cells are presented in the class I pathway. This event generates CD8 killer cells, which are capable of deleting the CD4 T cells

Termination of Tolerance
a. Cross-Immunization b. Co-Stimulation of anergic clones by superantigen

Immunological Pathomechanisms

HLA-B27 arrestin

Conjunctivitis

Keratitis

Scleritits and Uveitis

Termination of Tolerance

Scleritits

Uveitis

Uveitis

Uveitis

Uveitis

Panuveitis
Presentation of auto antigen because of MHC II expression on melanocyte perhaps to viral infection

Uveitic condition in sympathic ophthalmia

 Inflammation of the pars plana, a part of the ciliary body.

Therapeutic implications
T celltargeting therapies such as: cyclosporine, FK-506, and rapamycin, which are already FDA approved and in clinical use and Humanized CD25-specific antibody (daclizumab) Anti-TNF therapy IFN- is being used with considerable success to treat uveitis in patients with Behet disease and has been approved in Europe Oral tolerance to arrestin IL-17 neutralization therapy Blockade of the chemokine receptors CXCR3 and CXCR5 VLA4-specific monoclonal antibody is an FDA approved treatment for multiple sclerosis and Crohn disease

 Why are mismatched cadaver cornea grafts accepted 6070% of the time in humans?
Post-transplant event: These events are local episodes of alloantigen independent inflammation, such as a loosened transplant suture, bacterial suture-associated infection, or herpetic infection recurrence. These lead to recruitment of alloreactive cells, angiogenesis, lymphangiogenesis, and upregulation of MHC molecules on the graft cells, and sequelae, which in combination lead to an acute onset rejection response.

When antigen injected into the anterior

chamber , vitreous or

sub-retinal space induces peripheral tolerance to that antigen.

Phcogenic Uveitis

AIDS
Because cotton-wool spots are an early sign of AIDS, the ophthalmologist may be the first physician to alert the patient to the existence of this serious disorder .