Autoimmunity

Macrophage response—follows neutrophil response

• Initiate inflammatory response in osteolysis or aseptic loosening (occurs in response to particles

  <1 µm in diameter)

  • Mast cells—activated by trauma, complement, or IgE cross-linking, releasing histamine granules

    • Histamine mediates the peripheral nerve axon reflex that results in vascular smooth muscle relaxation.

      • Excessive endothelial vasodilation with respiratory smooth muscle constriction is an emergency mediated by IgE–type I hypersensitivity reaction and can lead to shock and death.

      • Recognition of epitopes from the “self”

        • ANAs, which are seen in many disease processes

          • Anti-Sm—SLE

          • Anti-RNP—mixed connective tissue disease

          • Anti–scl-70—scleroderma

          • Anti-dsDNA—SLE; also implicated in SLE nephritis

          • Antihistone—drug-induced lupus

          • Anti-Ro and Anti-La—Sjögren syndrome

        • HLA gene on chromosome 6 can be rearranged to make an antigen-specific receptor on APCs for up

          to 1015 different epitopes.

          • HLA-B27 is associated with a variety of rheumatologic diseases (mnemonic: PAIR)

 

• Hypersensitivity reactions

  • Psoriatic arthritis

  • AS

  • Inflammatory bowel disease

  • Reactive arthritis (Reiter syndrome)

  • Also juvenile RA

• HLA-DR3: myasthenia gravis and SLE

• HLA-DR4: RA

  • Type I: mediated by IgE

    • Anaphylaxis or allergic response, immediate response, mast cell degranulation

    • Food allergy (milk, egg, peanut, seafood, etc.) and drug allergies

  • Type II: mediated by IgM or IgG, cytotoxic, antibody-mediated response

    • Heparin-induced thrombocytopenia

    • Rheumatic fever

    • Myasthenia gravis

  • Type III: immune complex mediated (antigen-antibody [e.g., IgG-Ag])

    • SLE

    • RA

  • Type IV: cell-mediated (no antibodies); helper T cells activate cytotoxic cells and macrophages to attack tissue; delayed response.

    • TB screening with PPD (purified protein derivative)/Mantoux test

    • Type 1 diabetes mellitus

    • Multiple sclerosis

    • Type IV response to metallic orthopaedic implants

    • Pseudotumor hypersensitivity response can occur years after THA.

• Cytokines

  • Low-molecular-weight proteins that bind to receptors and elicit cellular responses.

  • Each cytokine can serve a variety of functions:

    • IL-1—initiates acute phase response

      • Induces bone loss through activation of osteoclasts via RANK/RANKL pathway.

    • IL-2—promotes growth and activation of lymphocytes

    • IL-6—induces synthesis of acute-phase proteins from liver (e.g., CRP)

      • IL-6 is key to growth and survival of multiple myeloma (MM) cells.

        • Generated in autocrine (MM cells) and paracrine (bone marrow stromal cells and osteoblasts) fashion

    • IL-10—antiinflammatory

    • TNF-α—helps mediate inflammatory response to intracellular infections

    • TGF-β—limits inflammation and promotes fibrosis