AUTOIMMUNE DISEASES Flashcards
What is autoimmunity?
Autoimmunity means the presence of antibodies (made by B-cells) and T-cells directed toward normal components (self-antigens). The antibodies and T-cells that recognize autoantigens are called autoantibodies and autoreactive T-cells.
What are the characteristics of autoimmune diseases?
- Chronicity (self-antigen cannot be removed)
- Irreversible
- Affect females more than males, often beginning at 20-40 years of age
- Involve single or multiple organs (systemic diseases)
What role do genetic factors play in autoimmune diseases?
Many autoimmune diseases have a familial tendency that suggests genetic predisposition, mainly determined by MHC genes. For example, RA is associated with HLA-DR4, and ankylosing spondylitis is associated with HLA-B27.
How do hormonal factors influence autoimmune diseases?
About 90% of autoimmune diseases occur in women. For example, SLE appears or exacerbates during pregnancy or immediately postpartum.
What is molecular mimicry in the context of autoimmune diseases?
Molecular mimicry occurs when bacteria or viruses act as a source of cross-reacting antigens (they share epitopes with self-tissue) that trigger activation of autoreactive T-cells or B-cells. For example, the similarity of a 6-amino acid sequence between hepatitis B virus polymerase enzyme and human myelin basic protein may predispose to multiple sclerosis.
How can alteration of normal proteins lead to autoimmune diseases?
Some drugs may bind to normal proteins, changing them to become immunogenic, thus triggering an immune response. For example, procainamide can induce SLE.
What are hidden antigens, and how do they contribute to autoimmune diseases?
Hidden antigens, such as sperm, CNS, and lens, are normally sequestered from the immune system. Trauma to these tissues can release them into circulation, stimulating both humoral and cellular immune responses, leading to conditions like aspermatogenesis, encephalitis, or endophthalmitis.
What is the role of regulatory T-cells (Treg) in autoimmune diseases?
Treg cells (CD4+, CD25+, FoxP3+) produce IL-10, which suppresses the proinflammatory effect of Th1 cells. Any defect in these cells, such as a mutation in the FoxP3 gene, may lead to the development of autoimmune diseases.
What is polyclonal activation of lymphocytes, and how does it contribute to autoimmune diseases?
Polyclonal activation of lymphocytes can be caused by endotoxins, EBV, CMV, or AIDS, leading to high levels of interleukin production, which can contribute to autoimmune diseases.
How does inappropriate expression of MHC molecules lead to autoimmune diseases?
Inappropriate expression of MHC class II molecules on pancreatic beta cells (which normally should not be expressed) after a viral infection, with the release of IFNγ, may lead to insulin-dependent diabetes mellitus (IDDM).
What are the types of hypersensitivity reactions associated with autoimmune diseases?
• Type II: Antibodies react with bound cell surface antigens (e.g., autoimmune hemolytic anemia).
• Type III: Immune complexes are deposited in tissue, initiating complement activation and inflammation (e.g., SLE).
• Type IV: Mediated by CD8+ and CD4+ T-cells (e.g., celiac disease).
