Autoimmunity in Haematology

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.