Ocular Immune Privilege and Corneal Transplantation PDF

OCULAR IMMUNE Dr Leriska Haupt PRIVILEGE Haematologist CORNEAL Dept of Haematology TRANSPLANTATION and Cell Biology T: 051 401 9111 info...

OCULAR IMMUNE Dr Leriska Haupt PRIVILEGE Haematologist CORNEAL Dept of Haematology TRANSPLANTATION and Cell Biology T: 051 401 9111 [email protected] www.ufs.ac.za  CONTENT PART 1: Ocular immune privilege What is (ocular) immune privilege? Mechanisms of ocular immune privilege Anterior chamber-associated immune deviation PART 2: Corneal transplantation Immunological aspects of corneal transplantation Corneal graft rejection: – Different types – Mechanisms – Risk factors T: 051 401 9111 [email protected] www.ufs.ac.za PART 1: OCULAR IMMUNE PRIVILEGE IMMUNE PRIVILEGE Ability to tolerate the introduction of antigens without eliciting an inflammatory immune response. – Tissue grafts can survive for extended periods of time without rejection occurring. Function: – Protect vital structures from the potentially damaging effects of an inflammatory immune response. – Examples Inflammation in the brain or eye can lead to loss of organ function. Immune responses directed against a fetus can lead to the loss of the fetus. IMMUNE PRIVILEGE Immune privileged sites: – Eyes – Placenta and fetus – Testicles – Hair follicles – Brain OCULAR IMMUNE PRIVILEGE Lack of immune response when an allograft is transplanted into the eye microenvironment – Allograft: Transplant of an organ or tissue from one individual to another of the same species with a different genotype. Anterior chamber is immune privileged: – Cornea, the anterior chamber, the crystalline lens and the vitreous body Protected from immune reactions that are potentially dangerous. MECHANISMS Lack of lymphatic drainage Anatomical features – Blood barrier – No blood vessels or inflammatory cells – Protected by conjunctiva and eyelids Numerous inflammatory cells etc. Presence of immunosuppressive molecules or cell surface receptors – Inhibit T-cell proliferation – Suppress interferon secretion Lower expression of major histocompatibility (MHC) molecules Development of tolerance against antigens – Anterior chamber-associated immune deviation (ACAID) Membrane associated Tight junctions molecules leading to between cells prevent apoptosis/suppression of passage of cells from potentially harmful cells. the blood to the anterior eye. Soluble substances Regulation of immune leading to a response by ACAID. immunosuppressive environment. http://www.streilein-foundation.org/ocular_immunology.html  ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION (ACAID) Principles: Exposure of the anterior chamber to a foreign antigen induces suppressor immunity. Induction of antigen-specific suppressor CD8+ T-cells and regulatory T-cells (suppressor CD4+ T-cells). Induction of non-complement-fixing antibodies – Mediated by specific macrophages – Present inoculated antigen to a cluster of B-cells, NKT cells, CD4+ and CD8+ T cells in the spleen  ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION (ACAID) 1. Anterior chamber 4. Macrophage exposed to present antigen antigen in the spleen 5. Proliferation of T- regulatory cells specific to 2. Specific the antigen macrophages Suppresses the delayed activated type hypersensitivity (Type IV) response Lead to tolerance of the antigen by the body. https://mynotebook.labarchives.com/ 3. Macrophages share/Mutagenetix/OTIuM3wzMDgz LzcxL1RyZWVOb2RlLzE0fDIzNC4z travel through blood stream WHY IMMUNE PRIVILEGE? Normal symptoms of inflammation are redness, swelling and pain. If this occur in the eye it may lead to dysfunction, such as loss of vision – Disturbs the light path from the pupil to the retina. Certain circumstances (eg. trauma, infection, genetics) can lead to dysfunction of the regulatory mechanisms of the eye – Lead to immune inflammatory diseases of the eye PART 2: IMMUNOLOGY OF CORNEAL TRANSPLANTATION CORNEAL TRANSPLANTATION Also called penetrating keratoplasty Over 40 000 done per year in the USA Corneas removed from donor who has been declared dead Indications – Severe scarring of cornea – Cornea likely to break open – Severe damage involving cornea and lens WHY IS IT SUCCESSFUL? Due to the corneal immune privilege! 1. Absence of blood and lymph vessels in the graft and its bed 2. Absence of MHC class II+ antigen presenting cells in the graft 3. Reduced expression of MHC-antigens on graft cells 4. Immunosuppressive local microenvironment (aqueous humor) 5. Capacity of the graft to induce anterior chamber-associated immune deviation (ACAID) CORNEAL GRAFT REJECTION TYPES OF REJECTION Epithelial rejection – Host epithelium grows inward from remaining host cornea & limbus – Cover the graft Subepithelial rejection – Subepithelial infiltrates with leukocytes Both types – Steroid responsive – Generally self-limited – Tend not to cause visual disturbance – Asymptomatic or only of minimal irritation  CORNEAL GRAFT REJECTION IMMUNE MECHANISM Inflamed cornea contributes to erosion of immune privilege – Bone marrow-derived cells are recruited into cornea through limbal circulation. – These cells capable of processing & presenting antigens which may persist for months/years. – The greater the number of bone marrow-derived cells in host cornea at time of surgery, the higher the rejection rate. CORNEAL GRAFT REJECTION IMMUNE MECHANISM Antigen processing: – At cornea, ocular environs and draining lymph nodes – T-cells recognise donor MHC alloantigens – Leads to rejection by 2 mechanisms : Direct pathway: donor’s APCs are recognised directly by recipient’s T-cells – Acute graft rejection Indirect pathway: recipient’s APCs process antigen then present it to recipient’s T-cells – Delayed (Type IV) hypersensitivity – Chronic graft rejection (~ 2 weeks post transplant) CORNEAL GRAFT REJECTION CLINICAL PRESENTATION No specific symptoms May be asymptomatic Common complaints: – Decrease in visual acuity – Redness – Pain – Irritation – Photophobia CORNEAL GRAFT REJECTION RISK FACTORS Host corneal vascularisation Larger and eccentric grafts Presence of donor epithelium upon transplantation History of previous graft failure of any cause Bilateral penetrating keratoplasty Pre-transplantation corneal tissue media and preservation Host age (lower risk with age >60 y, much higher risk in infants) Human leukocyte antigen A (HLA-A) and human leukocyte antigen (HLA-B) and ABO blood type incompatibility – Contradictory results, require further studies QUESTIONS OR COMMENTS? T: 051 401 9111 [email protected] www.ufs.ac.za