Autoimmunity and Autoimmune Diseases

Autoimmunity and Autoimmune Diseases

Autoimmunity and Autoimmune Diseases

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Autoimmunity Basics - Tolerance Lost Saga

Autoimmunity: Immune system attack on self-tissues from lost self-tolerance.

  • Self-Tolerance: Unresponsiveness to self-antigens.
    • Central: Thymus (T-cells), Bone Marrow (B-cells). AIRE gene key for thymic self-Ag expression.
    • Peripheral: Secondary lymphoid organs. Anergy, Tregs suppression, deletion. 📌 Tregs Actively Suppress Peripherally.
  • Breakdown Mechanisms:
    • Molecular Mimicry: Pathogen mimics self.
    • Epitope Spreading: Response widens to new self-epitopes.
    • Polyclonal B-cell Activation: Non-specific.
    • Bystander Activation: Microbe-activated APCs present self-Ag.
    • Sequestered Antigens: Released from privileged sites.
    • Neoantigens: Altered self-antigens.

Mechanisms of Autoimmunity

⭐ The AIRE gene is crucial for central tolerance by promoting expression of tissue-specific antigens in the thymus.

Autoimmunity Factors - The Trigger Trio

Key factors contributing to autoimmunity:

  • 1. Genetic Susceptibility:
    • Gene Polymorphisms: PTPN22, CTLA4, IL-2RA.
    • HLA Associations:
      HLAAssociated Disease(s)Mnemonic 📌
      HLA-B27Ankylosing SpondylitisB27 seronegative spondyloarthropathies
      HLA-DR3/DR4Type 1 DM, SLEDR3/4 are bad for pancreas & more
      HLA-DR4Rheumatoid Arthritis

    ⭐ HLA-B27: strong link to ankylosing spondylitis (>90% patients positive).

  • 2. Environmental Factors:
    • Infections: Group A Strep & Rheumatic Fever (molecular mimicry).
    • Drugs: Procainamide & Drug-induced Lupus (alter self-antigens).
    • Others: UV radiation, smoking (tissue damage/inflammation).
  • 3. Hormonal Factors:
    • Estrogen: ↑ influence, may enhance autoimmunity.
    • Sex Bias: ↑ prevalence in females (e.g., SLE, RA).

Organ-Specific Diseases - Targeted Trouble

DiseaseTarget Organ(s)Key Autoantibody(ies)Key Clinical Feature(s)
Hashimoto's ThyroiditisThyroid GlandAnti-TPO, Anti-Tg Abs 📌 HashiMOTo - TPO AbChronic inflammation, hypothyroidism
Graves' DiseaseThyroid GlandAnti-TSHR Ab (TRAb)Diffuse goiter, hyperthyroidism, exophthalmos
Type 1 Diabetes MellitusPancreatic β-cellsAnti-GAD65, Anti-Islet cell (ICA)Insulin deficiency, hyperglycemia, ketoacidosis risk
Myasthenia GravisNeuromuscular Junction (NMJ)Anti-AChR AbsFluctuating muscle weakness, ptosis, diplopia
Goodpasture's SyndromeLungs (alveoli) & Kidneys (GBM)Anti-GBM Abs (Type IV collagen)Pulmonary hemorrhage, rapidly progressive glomerulonephritis
Pernicious AnemiaStomach (Parietal cells)Anti-Intrinsic Factor, Anti-Parietal cell AbsVitamin B12 deficiency, megaloblastic anemia, neuropathy

⭐ In Myasthenia Gravis, antibodies against acetylcholine receptors (AChR) lead to fluctuating muscle weakness, typically worsening with activity and improving with rest.

Systemic Diseases - Body-Wide Battle

Systemic autoimmune diseases involve immune responses against self-antigens, leading to widespread tissue damage across multiple organ systems.

DiseaseKey Autoantibody(ies)Major Systems AffectedHallmark Clinical Feature(s)
Systemic Lupus Erythematosus (SLE)ANA, Anti-dsDNA, Anti-SmSkin, joints, kidneys, blood cells, CNSMalar rash, photosensitivity, arthritis
Rheumatoid Arthritis (RA)RF, Anti-CCPJoints (synovium), lungs, skin, cardiovascular systemChronic, symmetric polyarthritis; joint erosions
Sjögren's SyndromeAnti-Ro/SSA, Anti-La/SSBExocrine glands (salivary, lacrimal), joints, lungsDry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia)
Systemic Sclerosis (Scleroderma)Anti-Scl-70 (topoisomerase I), Anti-centromereSkin, lungs, GI tract, kidneys, heartSkin fibrosis, Raynaud's phenomenon
Polymyositis/ DermatomyositisAnti-Jo-1, Anti-Mi-2Muscles, skin (DM), lungsProximal muscle weakness; Gottron's papules, heliotrope rash (DM)

⭐ Anti-dsDNA and Anti-Sm antibodies are highly specific for Systemic Lupus Erythematosus (SLE).

📌 Remember SLE features with "SOAP BRAIN MD" (Serositis, Oral ulcers, Arthritis, Photosensitivity, Blood disorders, Renal involvement, ANA, Immunologic disorders, Neurologic disorder, Malar rash, Discoid rash).

High‑Yield Points - ⚡ Biggest Takeaways

  • Autoimmunity is a failure of self-tolerance, leading to immune reactions against self-antigens.
  • Molecular mimicry (e.g., Rheumatic fever after Strep infection) is a key pathogenic mechanism.
  • Strong HLA association is common: HLA-B27 (Ankylosing Spondylitis), HLA-DR3/DR4 (Type 1 DM, RA).
  • Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease with ANA and anti-dsDNA antibodies.
  • Organ-specific examples include Hashimoto's thyroiditis (anti-TPO) and Myasthenia Gravis (anti-AChR).

Practice Questions: Autoimmunity and Autoimmune Diseases

Test your understanding with these related questions

Which of the following auto antibodies is most likely to be present in a patient with systemic lupus erythematosus?

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Flashcards: Autoimmunity and Autoimmune Diseases

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An immune ring (Wesseley) may be seen around the fungal  ulcer due to deposition of the _____

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An immune ring (Wesseley) may be seen around the fungal  ulcer due to deposition of the _____

immune complexes

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