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  <head>
    <title>094-03 Vaccines, immunological assays, monoclonal therapies, and immune manipulation</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Vaccines, assays, and immune therapies">
      <outline text="Vaccine platforms">
        <outline text="Live attenuated: limited replication">
          <outline text="Strong humoral, cellular, mucosal memory"/>
          <outline text="Risk in severe immunodeficiency or pregnancy"/>
        </outline>
        <outline text="Inactivated whole organism cannot replicate">
          <outline text="Needs adjuvant and repeated doses"/>
        </outline>
        <outline text="Subunit and recombinant: safer, narrower epitopes"/>
        <outline text="Toxoid: antibodies against inactivated toxin"/>
        <outline text="Polysaccharide: T-independent, weak in young children">
          <outline text="Conjugation recruits helper T cells"/>
          <outline text="Class switching, memory, reduced carriage"/>
        </outline>
        <outline text="Viral vectors: class I and II presentation">
          <outline text="Vector immunity can reduce boosting"/>
        </outline>
        <outline text="mRNA in lipid particles, DNA as plasmid"/>
      </outline>
      <outline text="Shaping and judging vaccine responses">
        <outline text="Adjuvants activate innate sensors">
          <outline text="Aluminium salts favour antibody"/>
        </outline>
        <outline text="Reactogenicity is not protection"/>
        <outline text="Booster recruits memory, faster, higher affinity"/>
        <outline text="Longer intervals: maturation versus vulnerability"/>
        <outline text="Correlate versus mechanistic correlate of protection">
          <outline text="Waning antibody is not lost protection"/>
        </outline>
        <outline text="Sterilising versus disease-modifying immunity"/>
        <outline text="Herd protection not a fixed percentage"/>
      </outline>
      <outline text="Binding and imaging assays">
        <outline text="ELISA: indirect, sandwich, competitive">
          <outline text="Binding does not prove neutralisation"/>
          <outline text="Cut-offs trade sensitivity and specificity"/>
        </outline>
        <outline text="Immunoblot gives size plus binding"/>
        <outline text="Immunofluorescence localises antibody or antigen"/>
        <outline text="Immunohistochemistry depends on fixation and controls"/>
        <outline text="Agglutination visualises antigen-antibody lattice">
          <outline text="Prozone: antibody excess, false negative"/>
          <outline text="Dilution corrects prozone"/>
        </outline>
        <outline text="Nephelometry measures light scattering"/>
      </outline>
      <outline text="Cellular assays">
        <outline text="Flow cytometry measures single cells">
          <outline text="Gating, compensation, controls set boundaries"/>
          <outline text="Absolute counts need beads or blood count"/>
          <outline text="Marker presence is not function"/>
        </outline>
        <outline text="Intracellular staining after permeabilisation"/>
        <outline text="Tetramers find peptide-MHC-specific T cells"/>
        <outline text="Functional assays: neutralisation, killing, burst">
          <outline text="Neutralisation methods not interchangeable"/>
        </outline>
      </outline>
      <outline text="Complement and autoantibody testing">
        <outline text="Low classical, normal alternative: early classical"/>
        <outline text="Both low: C3, terminal deficiency, consumption"/>
        <outline text="Low alternative only: alternative defect"/>
        <outline text="Handling can activate complement in vitro"/>
        <outline text="Cell-based assays preserve membrane conformation"/>
        <outline text="Low positives without phenotype mislead"/>
      </outline>
      <outline text="Antibody and cellular therapies">
        <outline text="Monoclonals neutralise, block, deplete, deliver">
          <outline text="Fc region controls half-life and effector use"/>
          <outline text="Human sequence still allows anti-drug antibodies"/>
        </outline>
        <outline text="Anti-TNF raises tuberculosis risk"/>
        <outline text="B-cell depletion spares long-lived plasma cells"/>
        <outline text="Complement inhibitors: encapsulated bacteria risk"/>
        <outline text="Checkpoint inhibitors release peripheral restraint">
          <outline text="Immune adverse events in nearly any organ"/>
          <outline text="May appear after therapy stops"/>
        </outline>
        <outline text="CAR T cells recognise antigen without MHC">
          <outline text="Cytokine release, neurotoxicity, antigen escape"/>
        </outline>
      </outline>
      <outline text="Immunosuppression and tolerance induction">
        <outline text="Glucocorticoids: transcription and trafficking"/>
        <outline text="Calcineurin inhibitors block cytokine transcription"/>
        <outline text="mTOR inhibitors restrain growth"/>
        <outline text="Combination compounds infection and toxicity"/>
        <outline text="Desensitisation lasts only with exposure"/>
        <outline text="Allergen immunotherapy seeks lasting deviation"/>
      </outline>
      <outline text="Interpreting immune measurements">
        <outline text="Pretest probability comes first"/>
        <outline text="Predictive values depend on prevalence"/>
        <outline text="Drug monitoring: trough, anti-drug antibodies">
          <outline text="Targets not transferable between settings"/>
        </outline>
        <outline text="Measurements are imperfect proxies"/>
        <outline text="Conclusions need syndrome, method, controls"/>
      </outline>
    </outline>
  </body>
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