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  <head>
    <title>094-02 Hypersensitivity, autoimmunity, immune-complex disease, and transplantation</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Hypersensitivity, autoimmunity, and transplantation">
      <outline text="Classifying immune injury">
        <outline text="Type I: immediate, IgE-mediated"/>
        <outline text="Type II: antibody to cells, matrix, receptors"/>
        <outline text="Type III: soluble immune complexes"/>
        <outline text="Type IV: T-cell mediated"/>
        <outline text="Autoimmunity targets self, alloimmunity same species"/>
      </outline>
      <outline text="Type I hypersensitivity">
        <outline text="Sensitisation: IL-4 and IL-13 switch to IgE">
          <outline text="IgE binds high-affinity Fc epsilon receptors"/>
        </outline>
        <outline text="Re-exposure crosslinks IgE, degranulation"/>
        <outline text="Histamine: permeability, vasodilation, itch"/>
        <outline text="Leukotrienes: sustained bronchoconstriction"/>
        <outline text="Cytokines recruit eosinophils, late phase"/>
        <outline text="Anaphylaxis: airway oedema, leak, shock">
          <outline text="Intramuscular adrenaline first-line"/>
          <outline text="Antihistamines do not reliably reverse it"/>
        </outline>
        <outline text="Sensitisation does not prove clinical allergy">
          <outline text="Broad panels create false-positive labels"/>
        </outline>
      </outline>
      <outline text="Type II hypersensitivity">
        <outline text="IgG or IgM bind cells or matrix">
          <outline text="Complement, phagocytosis, cytotoxicity"/>
        </outline>
        <outline text="Haemolysis, thrombocytopenia, Goodpasture, pemphigus"/>
        <outline text="Antibodies can stimulate or block receptors">
          <outline text="Graves: TSH receptor activation"/>
          <outline text="Myasthenia: acetylcholine receptor impaired"/>
          <outline text="Maternal IgG makes neonatal disease transient"/>
        </outline>
        <outline text="Direct antiglobulin test: bound to red cells"/>
        <outline text="Indirect test: serum antibodies"/>
        <outline text="Binding may occur without active haemolysis"/>
      </outline>
      <outline text="Type III immune-complex disease">
        <outline text="Small complexes at antigen excess evade clearance"/>
        <outline text="Complement recruits neutrophils, damages vessels"/>
        <outline text="Serum sickness systemic, Arthus local"/>
        <outline text="Deposition: charge, size, permeability, filtration"/>
        <outline text="Complement consumption may lower C3 and C4"/>
        <outline text="Granular deposits versus linear antibody"/>
      </outline>
      <outline text="Type IV hypersensitivity">
        <outline text="T cells rather than antibody">
          <outline text="Th1 activate macrophages, Th17 neutrophils"/>
        </outline>
        <outline text="Delayed onset: recruitment and transcription"/>
        <outline text="Contact allergens act as haptens"/>
        <outline text="Patch test delayed, prick test immediate"/>
        <outline text="Irritant dermatitis mimics allergy"/>
        <outline text="Drug hypersensitivity can use any mechanism">
          <outline text="Rechallenge is not a casual test"/>
        </outline>
      </outline>
      <outline text="Autoimmune disease">
        <outline text="Organ-specific versus systemic targets"/>
        <outline text="Autoantibodies: pathogenic, marker, incidental">
          <outline text="Low-titre ANA common in healthy people"/>
          <outline text="Testing follows pretest probability"/>
        </outline>
        <outline text="Rheumatoid arthritis">
          <outline text="Rheumatoid factor binds Fc, not specific"/>
          <outline text="Anti-citrullinated antibodies more specific"/>
        </outline>
        <outline text="Tissue injury exposes new epitopes"/>
        <outline text="Lupus sustained by interferon and poor clearance"/>
      </outline>
      <outline text="Vasculitis and neurological disease">
        <outline text="Large-vessel disease: T cells and macrophages"/>
        <outline text="Antineutrophil antibodies in some small-vessel disease"/>
        <outline text="Vessel calibre predicts organs, not cause"/>
        <outline text="Surface-receptor antibodies respond to removal"/>
        <outline text="Intracellular antigens mark tumour T-cell injury"/>
        <outline text="Serum antibody needs specificity and phenotype"/>
      </outline>
      <outline text="Transplantation">
        <outline text="Direct recognition of intact donor HLA"/>
        <outline text="Indirect recognition of donor peptides"/>
        <outline text="High precursor frequency, strong responses"/>
        <outline text="Hyperacute rejection: preformed antibodies">
          <outline text="Complement, thrombosis, ischaemic necrosis"/>
          <outline text="Prevented by crossmatching and screening"/>
        </outline>
        <outline text="Acute rejection: T-cell and antibody-mediated"/>
        <outline text="Chronic rejection: narrowing and fibrosis">
          <outline text="No single marker captures it"/>
        </outline>
        <outline text="Graft-versus-host disease: donor T cells attack">
          <outline text="Skin, gut, liver, marrow"/>
          <outline text="Graft-versus-leukaemia benefit"/>
        </outline>
      </outline>
      <outline text="Treatment and synthesis">
        <outline text="Avoid triggers, block mediators, restrain cells"/>
        <outline text="Glucocorticoids alter transcription broadly"/>
        <outline text="Biologics target cytokines, B cells, complement"/>
        <outline text="Precision reduces, never eliminates, risk"/>
        <outline text="Diseases occupy several boxes, a network"/>
      </outline>
    </outline>
  </body>
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