Autoimmunity

Autoimmunity

• Autoimmunity is a misdirected immune response that occurs when the immune system attacks the body itself.
• It is a hypersensitivity reaction triggered by self-antigens.
• Molecular mimicry is a mechanism that can lead to autoimmunity, where a foreign antigen initiates an immune response, and a T- or B-cell component cross-recognizes self-antigens, leading to an autoimmune disease.

Tolerance

• The body has mechanisms to remove self-reactive T- and B-cells to prevent autoimmunity.
• Central tolerance is the mechanism that deletes self-reacting lymphocytes in the early stages of lymphocyte development (in thymus or bone marrow).
• Peripheral tolerance is a "safety net" that removes self-reactive lymphocytes that have escaped central tolerance, induced in mature lymphocytes, and involves T-regulatory cells (Tregs) that suppress autoreactions.

Classification of Autoimmune Conditions

• Autoimmune conditions are classified similarly to hypersensitivity reactions, with the exception of type I hypersensitivity.
• There are three types of autoimmune conditions:
  • Antibody-mediated (Type II) hypersensitivity reactions
  • Immune-complex mediated (Type III) hypersensitivity reactions
  • Cell-mediated (Type IV) hypersensitivity reactions

Antibody-Mediated (Type II) Hypersensitivity Reactions

• Antibody-mediated reactions occur when an antibody reacts to self-antigens, binds to tissue/cells, and results in opsonisation and complement activation.
• Example: autoimmune haemolytic anaemia.

Immune-Complex Mediated (Type III) Hypersensitivity Reactions

• Immune-complex mediated reactions occur when immune complexes are not cleared rapidly, leading to inflammation and tissue damage.
• Example: systemic lupus erythematosus (SLE).

Cell-Mediated (Type IV) Hypersensitivity Reactions

• Cell-mediated reactions occur when autoimmune T-cell responses lead to inflammation and tissue damage.
• Examples: rheumatoid arthritis, type I diabetes mellitus.

Ocular Autoimmune Diseases

• Mooren's ulcer: a rare disorder characterized by a painful, relentless, chronic ulcerative keratitis.
• Sympathetic ophthalmia: a bilateral granulomatous uveitis that occurs after a penetrating injury to one eye, potentially blinding.

Systemic Autoimmune Diseases

• Keratoconjunctivitis sicca: a dry eye syndrome characterized by dryness, corneal examination may reveal punctate erosive keratopathy or filaments.
• Scleritis: inflammation of the sclera, characterized by pain, tenderness, and decreased vision.
• Rheumatoid arthritis: a chronic inflammatory disorder that affects the joints, skin, eyes, lungs, heart, and blood vessels.
• Sjögren's syndrome: an autoimmune condition characterized by dry eyes and a dry mouth, affecting the mucous membranes and moisture-secreting glands of eyes and mouth.
• Graves' disease: an autoimmune condition resulting in hyperthyroidism, characterized by inflammation and congestion of periocular and orbital soft tissue.
• Systemic lupus erythematosus (SLE): a chronic inflammatory disease that can affect multiple organ systems, including the eyes.

Autoimmunity

• Autoimmunity is a misdirected immune response that occurs when the immune system attacks the body itself.
• It is a hypersensitivity reaction triggered by self-antigens.
• Molecular mimicry is a mechanism that can lead to autoimmunity, where a foreign antigen initiates an immune response, and a T- or B-cell component cross-recognizes self-antigens, leading to an autoimmune disease.

Tolerance

• The body has mechanisms to remove self-reactive T- and B-cells to prevent autoimmunity.
• Central tolerance is the mechanism that deletes self-reacting lymphocytes in the early stages of lymphocyte development (in thymus or bone marrow).
• Peripheral tolerance is a "safety net" that removes self-reactive lymphocytes that have escaped central tolerance, induced in mature lymphocytes, and involves T-regulatory cells (Tregs) that suppress autoreactions.

Classification of Autoimmune Conditions

• Autoimmune conditions are classified similarly to hypersensitivity reactions, with the exception of type I hypersensitivity.
• There are three types of autoimmune conditions:
  • Antibody-mediated (Type II) hypersensitivity reactions
  • Immune-complex mediated (Type III) hypersensitivity reactions
  • Cell-mediated (Type IV) hypersensitivity reactions

Antibody-Mediated (Type II) Hypersensitivity Reactions

• Antibody-mediated reactions occur when an antibody reacts to self-antigens, binds to tissue/cells, and results in opsonisation and complement activation.
• Example: autoimmune haemolytic anaemia.

Immune-Complex Mediated (Type III) Hypersensitivity Reactions

• Immune-complex mediated reactions occur when immune complexes are not cleared rapidly, leading to inflammation and tissue damage.
• Example: systemic lupus erythematosus (SLE).

Cell-Mediated (Type IV) Hypersensitivity Reactions

• Cell-mediated reactions occur when autoimmune T-cell responses lead to inflammation and tissue damage.
• Examples: rheumatoid arthritis, type I diabetes mellitus.

Ocular Autoimmune Diseases

• Mooren's ulcer: a rare disorder characterized by a painful, relentless, chronic ulcerative keratitis.
• Sympathetic ophthalmia: a bilateral granulomatous uveitis that occurs after a penetrating injury to one eye, potentially blinding.

Systemic Autoimmune Diseases

• Keratoconjunctivitis sicca: a dry eye syndrome characterized by dryness, corneal examination may reveal punctate erosive keratopathy or filaments.
• Scleritis: inflammation of the sclera, characterized by pain, tenderness, and decreased vision.
• Rheumatoid arthritis: a chronic inflammatory disorder that affects the joints, skin, eyes, lungs, heart, and blood vessels.
• Sjögren's syndrome: an autoimmune condition characterized by dry eyes and a dry mouth, affecting the mucous membranes and moisture-secreting glands of eyes and mouth.
• Graves' disease: an autoimmune condition resulting in hyperthyroidism, characterized by inflammation and congestion of periocular and orbital soft tissue.
• Systemic lupus erythematosus (SLE): a chronic inflammatory disease that can affect multiple organ systems, including the eyes.

Ocular Manifestations of Autoimmune Diseases

• Keratoconjunctivitis sicca is a common ocular manifestation of autoimmune diseases, particularly in women over 40 years old.
• Treatment of keratoconjunctivitis sicca is symptomatic.

Rheumatoid Arthritis (RA)

• RA is a chronic inflammatory disorder primarily affecting the joints, but also affecting the skin, eyes, lungs, heart, and blood vessels.
• It is a cell-mediated (type IV) hypersensitivity reaction.
• Approximately 25% of patients with RA will have ocular manifestations, including:
  • Keratoconjunctivitis sicca (most common, up to 25% of patients)
  • Scleritis/episcleritis (4-10% of patients with RA)
  • Keratitis
  • Peripheral corneal ulceration

Graves' Disease

• Graves' disease is an autoimmune condition resulting in hyperthyroidism (overproduction of thyroid hormones).
• Inflammation and congestion of periocular and orbital soft tissue occur in Graves' disease.
• Ocular manifestations of Graves' disease include:
  • Graves' ophthalmopathy
  • Exposure keratopathy
  • Diplopia
  • Compressive optic neuropathy

Systemic Lupus Erythematosus (SLE)

• SLE is an autoimmune disease that occurs more frequently in women, particularly those of childbearing age.
• Ocular disease occurs in 20% of SLE patients, with external ocular manifestations including:
  • Keratoconjunctivitis sicca
  • Conjunctivitis
  • Uveitis
  • Episcleritis and scleritis
  • Keratitis
  • Discoid lupus rash over the eyelids
• Intraocular manifestations of SLE include:
  • Microinfarction
  • Hemorrhage
  • Vasculitis in various locations
  • Optic neuritis/optic neuropathy

Sympathetic Ophthalmia

• Sympathetic ophthalmia is a rare, bilateral, granulomatous uveitis that occurs after a penetrating injury to one eye.
• It is a potentially blinding disease that involves both eyes.
• More frequent in men, with a possible association with HLA-A11.
• Predisposing factors include:
  • Penetrating injury (almost always occurs after a penetrating injury)
  • Ciliary region wounds = dangerous zone
• Pathogenesis involves multiple theories, including the "allergic theory" and molecular mimicry.

Keratoconjunctivitis Sicca

• Keratoconjunctivitis sicca is a dry eye syndrome.
• Symptoms include:
  • More prominent during the latter part of the day due to the evaporation of the tear film
  • Corneal examination (slit lamp) may reveal punctate erosive keratopathy or filaments

Scleritis and Episcleritis

• Scleritis and episcleritis are distinguished based on anatomy and appearance.
• Symptoms may be similar, with scleritis having more severe pain and tenderness to palpation of the globe.
• Scleritis is more common in patients with RA, and patients with scleritis and RA have a worse prognosis.

Diabetes Mellitus (Type 1)

• Diabetes mellitus is an autoimmune condition where the insulin-producing cells in the pancreas are destroyed.
• It leads to elevated blood glucose levels and damages the blood vessels in most organ systems, including the eye.
• Ocular complications include:
  • Diabetic retinopathy
  • Cataract formation
  • Glaucoma
• Prevention of complications involves controlling blood sugar levels and regular eye exams.

Sjögren's Syndrome

• Sjögren's syndrome is an autoimmune condition characterized by dry eyes and a dry mouth.
• It results in decreased production of tears and saliva due to molecular mimicry.

Classification of Autoimmune Conditions

• Autoimmune conditions are classified similarly to hypersensitivity reactions, with the exception of type I hypersensitivity.
• Types of autoimmune conditions include:
  • Antibody-mediated (type II) hypersensitivity reactions
  • Immune-complex mediated (type III) hypersensitivity reactions
  • Cell-mediated (type IV) hypersensitivity reactions

Mooren's Ulcer

• Mooren's ulcer is a rare disorder characterized by a painful, relentless, chronic ulcerative keratitis.
• It typically occurs in healthy, adult men, with no evidence of systemic disease.
• Etiology is unsure, but possible autoimmune reactions include exposure to infectious agents.

Autoimmunity

• Tolerance is the mechanism for preventing autoimmunity, where self-reactive T- and B-cells are removed.
• Autoimmunity occurs when the immune system goes awry and attacks the body itself, triggering hypersensitivity reactions to self-antigens.
• Molecular mimicry is a process where foreign antigens initiate an immune response, leading to cross-reactive immune responses against self-antigens.