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  <head>
    <title>093-02 Antigen processing, major histocompatibility complexes, and lymphocyte activation</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Antigen processing, MHC, and lymphocyte activation">
      <outline text="Adaptive recognition and HLA">
        <outline text="Clonal receptors from somatic rearrangement"/>
        <outline text="T cells see presented peptide, B cells native antigen"/>
        <outline text="Costimulation and cytokines supply context"/>
        <outline text="HLA encoded on chromosome six">
          <outline text="Class one: HLA-A, B, C"/>
          <outline text="Class two: HLA-DP, DQ, DR"/>
        </outline>
        <outline text="Polymorphism aids population pathogen recognition">
          <outline text="Complicates transplantation and disease links"/>
        </outline>
        <outline text="Co-dominant expression of inherited alleles"/>
      </outline>
      <outline text="MHC class one pathway">
        <outline text="Heavy chain, beta-two microglobulin, peptide"/>
        <outline text="Nearly all nucleated cells and platelets"/>
        <outline text="Closed groove holds short peptides"/>
        <outline text="CD8 T cells survey for intracellular change"/>
        <outline text="Proteasome, immunoproteasome in inflammation"/>
        <outline text="TAP carries peptides into the ER"/>
        <outline text="Chaperones load, edit, trim"/>
        <outline text="Stable complexes travel via Golgi to surface"/>
        <outline text="Defects impair antiviral defence"/>
      </outline>
      <outline text="Evasion and cross-presentation">
        <outline text="Viruses block proteasome, TAP, loading, surface"/>
        <outline text="Low class one removes natural killer inhibition">
          <outline text="Evolutionary tension"/>
        </outline>
        <outline text="Dendritic cells present external antigen on class one">
          <outline text="Primes killers against non-infecting viruses, tumours"/>
        </outline>
      </outline>
      <outline text="MHC class two pathway">
        <outline text="Alpha and beta chains"/>
        <outline text="Professional presenting cells, inducible elsewhere"/>
        <outline text="Open groove binds longer peptides"/>
        <outline text="Invariant chain blocks groove, routes to endosomes">
          <outline text="Degraded to CLIP fragment"/>
          <outline text="HLA-DM removes CLIP and edits loading"/>
          <outline text="HLA-DO modulates in selected cells"/>
        </outline>
        <outline text="Autophagy delivers intracellular antigen"/>
        <outline text="B cells present peptides of captured antigen">
          <outline text="Linked recognition explains carrier effects"/>
        </outline>
        <outline text="CD4 T cells coordinate responses"/>
      </outline>
      <outline text="T-cell activation">
        <outline text="Alpha-beta receptor with CD3 chains"/>
        <outline text="Recognises combined peptide-MHC surface"/>
        <outline text="CD4 binds class two, CD8 class one"/>
        <outline text="Modest affinity, sensitive via microclusters"/>
        <outline text="CD28 binds B7 as costimulation">
          <outline text="Without it: anergy, deletion, tolerance"/>
        </outline>
        <outline text="CTLA4 and PD1 restrain activation"/>
        <outline text="Calcineurin-NFAT, MAP kinase, NF-kappa B">
          <outline text="Induce interleukin 2 and high-affinity receptor"/>
          <outline text="Drugs target calcineurin, mTOR, nucleotides"/>
        </outline>
      </outline>
      <outline text="Trafficking and T-cell fates">
        <outline text="Enter nodes via high endothelial venules"/>
        <outline text="Unactivated cells exit on S1P gradients"/>
        <outline text="Activation retains, then changes homing"/>
        <outline text="Type 1: interferon gamma, intracellular pathogens"/>
        <outline text="Type 2: interleukins 4, 5, 13, helminths"/>
        <outline text="Type 17: interleukins 17, 22, barriers"/>
        <outline text="Follicular helpers give CD40 ligand"/>
        <outline text="FOXP3 regulatory cells suppress"/>
        <outline text="Categories flexible, mixed states occur"/>
        <outline text="CD8 kill via perforin, granzyme, death receptors"/>
        <outline text="Chronic antigen causes exhaustion">
          <outline text="Checkpoint blockade reinvigorates, risks inflammation"/>
        </outline>
      </outline>
      <outline text="B-cell activation">
        <outline text="Membrane immunoglobulin binds native antigen"/>
        <outline text="CD19 co-receptor amplifies complement-tagged signal"/>
        <outline text="T-dependent: present peptide to follicular helpers">
          <outline text="Extrafollicular: plasmablasts and IgM"/>
          <outline text="Germinal centres: affinity, switching, memory"/>
        </outline>
        <outline text="T-independent: rapid but little memory">
          <outline text="Especially weak in young children"/>
          <outline text="Protein conjugation recruits T-cell help"/>
        </outline>
      </outline>
      <outline text="Expansion, memory, and synapse">
        <outline text="Clonal expansion then contraction"/>
        <outline text="Memory alters threshold, location, metabolism"/>
        <outline text="Memory need not be sterilising"/>
        <outline text="Synapse: LFA1-ICAM stabilises contact"/>
        <outline text="Granules polarised to limit bystander damage"/>
      </outline>
      <outline text="Broad activation, HLA, and context">
        <outline text="Superantigens crosslink outside peptide groove">
          <outline text="Many clones, massive cytokine release"/>
        </outline>
        <outline text="HLA associations neither necessary nor sufficient">
          <outline text="Typing guides transplantation, drug safety"/>
        </outline>
        <outline text="Dose, persistence, route shape fate"/>
        <outline text="Adjuvants activate sensors, not specificity"/>
        <outline text="Specificity, danger, programme, destination, duration"/>
      </outline>
    </outline>
  </body>
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