Hypersensitivities and Autoimmunity

Study Notes

Hypersensitivity reactions are immune responses that cause tissue damage.
Four types of hypersensitivity reactions exist: Type 1, Type 2, Type 3, and Type 4.
Type 1: IgE-mediated mast cell degranulation (e.g., asthma, hay fever, peanut allergy).
Type 2: IgG response, antibody-mediated cell surface reactions causing cytotoxicity and complement activation (e.g., hemolytic anemia, HDFN).
Type 3: IgG response immune complex mediated, complement activation (e.g., arthus reaction).
Type 4: Cell-mediated, sensitized T cells, activated macrophages (e.g., contact dermatitis).
Immediate hypersensitivity reactions occur within minutes of exposure, while delayed-type reactions take 1-3 days.
Type 1 hypersensitivity is associated with histamine release.
Total serum IgE testing (RIST), skin prick testing, and allergen-specific laboratory tests are used to diagnose hypersensitivity reactions.

Autoimmune diseases occur when the immune system attacks the body's own tissues.
Several factors are associated with autoimmune disease development.
CD4+ T cells, CD8+ T cells, and B cells can be involved in autoimmune diseases.
HLA alleles can increase susceptibility to autoimmunity.
Sequestered antigens released by tissue damage can cause autoimmunity.
Molecular mimicry and polyclonal B cell activation can also trigger autoimmunity.

Autoimmune endocrine disorders (e.g., chronic autoimmune thyroiditis, Graves' disease, Addison's disease, type 1 diabetes mellitus) are associated with specific autoantibodies.
Chronic autoimmune thyroiditis is related to anti-thyroglobulin and anti-thyroid peroxidase autoantibodies (anti-TPO).
Graves' disease is connected to anti-TSH receptor antibodies.
Addison's disease has anti-21-hydroxylase autoantibodies.
Various autoimmune diseases have specific serological tests for their diagnosis.
Different hypersensitivity types cause different autoimmune disorders.

Rheumatoid arthritis and systemic lupus erythematosus (SLE) are common systemic autoimmune diseases.
Autoimmune rheumatologic diseases are often challenging to diagnose due to overlapping symptoms and lab test results.
FANA, ANA, and ENA tests assist in diagnosis (e.g., anti-dsDNA and anti-Sm are diagnostic for SLE).
Type 3 hypersensitivity is implicated in lupus.
FANA titers are important for diagnosis interpretation.
Certain diseases besides Lupus can show low positive FANA (e.g., Sjogren’s syndrome, scleroderma, mixed connective tissue disease).
Antihistone antibodies are associated with drug-induced lupus.
Lupus patients can have false positive syphilis tests, often treponemal.
Rheumatoid factor (RF) and anti-CCP help diagnose rheumatoid arthritis.