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  <head>
    <title>093-03 Antibodies, complement, Fc receptors, cytotoxic effectors, and immune-complex clearance</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Antibodies, complement, Fc receptors, cytotoxic effectors">
      <outline text="Effector overview">
        <outline text="Neutralise, opsonise, complement, kill, protect"/>
        <outline text="Antibodies give soluble specificity"/>
        <outline text="Complement amplifies by proteolytic cascades"/>
        <outline text="Fc receptors interpret isotype and context"/>
        <outline text="Deposited or misdirected products injure host"/>
      </outline>
      <outline text="Antibody structure">
        <outline text="Two heavy and two light chains"/>
        <outline text="Variable domains form two binding sites">
          <outline text="Complementarity-determining regions contact antigen"/>
        </outline>
        <outline text="Fc region binds receptors and complement"/>
        <outline text="Hinge permits binding at different angles"/>
        <outline text="Fab and Fc separable by proteolysis"/>
        <outline text="Affinity: one interaction; avidity: combined">
          <outline text="Low-affinity IgM gains high avidity"/>
        </outline>
      </outline>
      <outline text="Isotypes">
        <outline text="Class switch keeps the variable region"/>
        <outline text="IgM: pentamer, early, intravascular">
          <outline text="Timing limited by persistence, cross-reaction"/>
        </outline>
        <outline text="IgG: neutralises, opsonises, crosses placenta">
          <outline text="Neonatal Fc receptor extends half-life"/>
          <outline text="Maternal autoantibodies can transfer"/>
        </outline>
        <outline text="Secretory IgA crosses epithelium">
          <outline text="Secretory component resists proteolysis"/>
          <outline text="Neutralises with little inflammation"/>
        </outline>
        <outline text="IgE arms mast cells and basophils">
          <outline text="Specific IgE shows sensitisation only"/>
        </outline>
        <outline text="IgD: mainly naive B-cell receptor"/>
        <outline text="Kappa or lambda; light-chain restriction"/>
      </outline>
      <outline text="Neutralisation and opsonisation">
        <outline text="Neutralisation blocks attachment, entry, toxins">
          <outline text="Needs epitope access, not Fc"/>
          <outline text="Viruses escape by epitope change"/>
        </outline>
        <outline text="Mucosal prevents establishment, systemic limits spread"/>
        <outline text="Fc gamma receptors bind clustered IgG"/>
        <outline text="Complement receptors bind deposited C3 fragments"/>
        <outline text="Activating and inhibitory receptors balance"/>
        <outline text="Soluble monomeric IgG triggers weakly"/>
      </outline>
      <outline text="B-cell diversification">
        <outline text="Switching needs CD40 signalling and cytokines"/>
        <outline text="Intervening DNA deleted: largely irreversible">
          <outline text="Defects cause hyper-IgM syndromes"/>
        </outline>
        <outline text="Somatic hypermutation in germinal centres">
          <outline text="Clones compete for antigen and help"/>
          <outline text="Risks autoreactivity and translocation"/>
        </outline>
        <outline text="Plasma cells: abundant rough ER"/>
        <outline text="Long-lived cells in marrow or mucosal niches"/>
        <outline text="Serum level reflects production and catabolism"/>
      </outline>
      <outline text="Complement activation">
        <outline text="Classical: C1 binds antibody"/>
        <outline text="Lectin: mannose-binding lectin, ficolins"/>
        <outline text="Alternative: spontaneous C3 activation"/>
        <outline text="All form C3 convertases"/>
        <outline text="C3b opsonises and forms C5 convertase"/>
        <outline text="C5b to C9 membrane-attack complex">
          <outline text="Key against Neisseria"/>
        </outline>
        <outline text="C3a and C5a are anaphylatoxins"/>
        <outline text="Fragments lower B-cell activation threshold"/>
      </outline>
      <outline text="Complement regulation and deficiency">
        <outline text="C1 inhibitor restrains early and contact proteases">
          <outline text="Deficiency: bradykinin angioedema"/>
          <outline text="Antihistamines may be insufficient"/>
        </outline>
        <outline text="Factors H and I inactivate C3b"/>
        <outline text="DAF and membrane-cofactor protein"/>
        <outline text="CD59 blocks terminal pore formation"/>
        <outline text="Paroxysmal nocturnal haemoglobinuria">
          <outline text="GPI regulator loss: cell injury, thrombosis"/>
        </outline>
        <outline text="Early classical deficiency: lupus-like disease"/>
        <outline text="C3 deficiency: recurrent pyogenic infection"/>
        <outline text="Terminal deficiency: Neisseria infection"/>
        <outline text="Functional assays before single components"/>
      </outline>
      <outline text="Immune complexes and cytotoxicity">
        <outline text="Size, ratio, charge, flow set deposition"/>
        <outline text="Erythrocyte receptors carry them to liver, spleen"/>
        <outline text="Persistent complexes deposit in glomeruli, vessels"/>
        <outline text="CD16 antibody-dependent cellular cytotoxicity"/>
        <outline text="Eosinophils attack helminths too large to engulf"/>
        <outline text="Fc engineering alters potency, half-life"/>
        <outline text="Cytotoxic T cells: perforin-granzyme and Fas">
          <outline text="Defects cause haemophagocytic lymphohistiocytosis"/>
        </outline>
      </outline>
      <outline text="Access and amplification">
        <outline text="IgG in blood, IgA at mucosa, IgE in tissue"/>
        <outline text="Cytotoxic cells require contact"/>
        <outline text="Abundant defence fails without access"/>
        <outline text="Regulators protect host, clearance ends response"/>
        <outline text="Node failure: infection, allergy, autoimmunity"/>
      </outline>
    </outline>
  </body>
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