Autoimmune Diseases Flashcards
Autoimmune diseases are thought to occur via what “2-hit” mechanism?
Defective immunoregulation + environmental trigger (in a genetically susceptible person)
Failure to delete self-reactive B-cells in the bone marrow describes what kind of autoimmune-promoting problem?
Breakdown in central B-cell tolerance
Inappropriate T-cell activation of autoreactive B cells and defective B cell anergy are examples of what kind of autoimmune-promoting problem?
Breakdown in peripheral B-cell tolerance
Incomplete T cell deletion in the thymus is an example of what kind of autoimmune-promoting problem?
Breakdown in central T cell tolerance
A defect in what gene can cause incomplete presentation of self-antigens to T cells in the thymus, allowing autoreactive T cells to escape into the periphery?
AIRE
Inappropriate T cell co-stimulation and defects in clonal anergy due to low levels of CTLA-4 (which binds to B7 to inhibit the immune response) is an example of what kind of autoimmune-promoting problem?
Breakdown in peripheral T cell tolerance
What is the term for the way that some antigens in the body are sequestered in areas where they will not usually encounter lymphocytes? A breakdown in this protective mechanism due to trauma can cause effector T cells to be sensitized to self antigens.
Clonal ignorance
Inflammatory Th-17 cells refer to what kind of cells that secrete IL-17 in diseases like Crohn’s, RA, psoriasis, and allergic asthma?
CD4 T cells
What is the most important genetic factor in accounting for autoimmune susceptibility?
The HLA gene
What hormone seems to exacerbate autoimmune diseases, making them more common in women than in men?
Estrogen
What autoimmune condition is associated with HLA-B27 and infections?
Reiter’s syndrome or reactive arthritis (associated with infections such as Chlamydia, Shigella, Salmonella, Yersinia, Campylobacter, etc.)
Autoantibody-mediated autoimmunity corresponds to what type of hypersensitivity reaction? Does it tend to be organ-specific or systemic?
Type II hypersensitivity; organ-specific (the antibodies target a specific cell)
In autoimmune hemolytic anemia, what autoantigen does the antibody target?
Rh blood group antigens
In autoimmune thrombocytopenia purpura, what autoantigen does the antibody target?
Platelet integrin GpIIb/IIIa
In Grave’s disease, what autoantigen does the antibody target? Is the antibody an agonist or antagonist?
TSH (thyroid stimulating hormone) receptor; agonist (so it causes hyperthyroidism)
In myasthenia gravis, what autoantigen does the antibody target? Is the antibody an agonist or antagonist?
ACh receptor; antagonist (so it causes progresive muscle weakening)
Why is it that Grave’s disease, systemic lupus erythematosus, myasthenia gravis, hemolytic disease of the newborn, and thrombocytopenia purpura can all be transferred in utero?
Tthey all involve IgG which can cross the placenta
Systemic lupus erythematosus (SLE), subacute bacterial endocarditis, and mixed essential cryoglobulinemia are all examples of what kind of autoimmunity?
Type III/immune-complex-mediated
Immune-complex-mediated autoimmunity corresponds to what type of hypersensitivity reaction? Does it tend to be organ-specific or systemic?
Type III; systemic
What kind of antibodies are diagnostic for SLE?
Anti-dsDNA
Type I diabetes, rheumatoid arthritis, and multiple sclerosis are all examples of what kind of autoimmunity? Does it tend to be organ-specific or systemic?
Type IV/T-cell-mediated; mostly organ specific (because the T cells target specific tissue antigens)
Insulin-dependent diabetes mellitus or type I diabetes is associated with what kind of T cells directed against what antigen?
CD8 T cells; against GAD (glutamic acid decarboxylase) on pancreatic β-cells
Rheumatoid arthritis is associated with what kind of T cells directed against what antigen?
CD4 and CD8 T cells; targets the Fc region of IgG (the antibody is RF)
Multiple sclerosis is associated with what kind of T cells directed against what antigen?
TH1 CD4 cells; against antigens on the neuronal myelin sheaths
Autoimmune classifications can get fuzzy. Which 2 common diseases are variably classified as either type 3 or type 4 reactions?
SLE and rheumatoid arthritis.
In real life, T cells, B cells, and antibodies all play a role in every autoimmune disease pathogenesis. That being said, what is the primary mechanism of each of the following diseases: type 1 diabetes, SLE, myasthenia gravis, and multiple sclerosis?
Type 1 diabetes and multiple sclerosis are primarily T cells;
SLE is both T cells and antibodies;
Myasthenia gravis is primarily antibodies
Compare the mechanisms of autoimmune action for insulin-dependent and insulin-resistant diabetes.
Insulin-dependent diabetes is type 4/T-cell mediated against the pancreatic β-cell; insulin-resistant diabetes is type 2/antibody-mediated against the insulin receptor on tissue cells
Compare the mechanisms of insulin-resistant diabetes and antibody-mediated hypoglycemia.
Both involve antibodies for the insulin receptor, but the diabetes antibody is an antagonist while the hypoglycemia antibody is an agonist.
Compare the mechanisms of Grave’s disease hyperthyroidism with Hashimoto’s disease hypothyroidism.
Grave’s disease involves antibody agonists to the TSH receptor, while Hashimoto’s disease involves antibodies against the thyroid tissue itself (which leads to T-cell destruction of the thyroid)
