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  <head>
    <title>004-02 Resolution, immune architecture, and repair under stress</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Resolution, immune architecture, and repair">
      <outline text="Inflammation as an active sequence">
        <outline text="Recognition, recruitment, then active resolution"/>
        <outline text="Failure possible at every stage">
          <outline text="Weak recognition permits microbial spread"/>
          <outline text="Excess recruitment damages host tissue"/>
          <outline text="Poor source control keeps the signal present"/>
          <outline text="Defective resolution leads to chronicity, fibrosis"/>
        </outline>
        <outline text="Tissue-resident cells set the first response"/>
        <outline text="Endothelium is not passive plumbing">
          <outline text="Controls which proteins and cells leave blood"/>
        </outline>
      </outline>
      <outline text="Overlapping mediators">
        <outline text="Prostaglandins: vasodilation, pain, temperature"/>
        <outline text="Leukotrienes: permeability, bronchi, recruitment"/>
        <outline text="Cytokines coordinate, chemokines give direction"/>
        <outline text="Redundancy makes defence robust">
          <outline text="Blocking one mediator may not suppress syndrome"/>
        </outline>
      </outline>
      <outline text="Complement pathways and deficiency">
        <outline text="Antibody, lectin, alternative pathways converge"/>
        <outline text="Fragments coat surfaces, aid phagocytosis"/>
        <outline text="Terminal pores against Gram-negative organisms"/>
        <outline text="Host regulators limit activation on own cells"/>
        <outline text="Deficiency patterns differ">
          <outline text="Early classical loss: autoimmune disease"/>
          <outline text="Terminal loss: invasive Neisseria infection"/>
          <outline text="Lost regulation: haemolysis, thrombosis, kidney"/>
        </outline>
      </outline>
      <outline text="Neutrophils and macrophages">
        <outline text="Neutrophils: engulfment, granules, oxidants, traps">
          <outline text="Effective confined, hazardous when widespread"/>
        </outline>
        <outline text="Count alone does not describe competence">
          <outline text="Reserve, migration, killing, tissue access"/>
        </outline>
        <outline text="Macrophages are more than late cleaners">
          <outline text="Clear, present antigen, remodel matrix, repair"/>
          <outline text="A signal-shaped spectrum, not two categories"/>
          <outline text="Apoptotic-cell clearance promotes repair"/>
          <outline text="Persisting microbes, crystals, foreign bodies sustain"/>
        </outline>
      </outline>
      <outline text="Antigen presentation and tolerance">
        <outline text="Peptide recognition plus co-stimulation, cytokines"/>
        <outline text="Antigen without context: unresponsive or regulatory">
          <outline text="Reduces activation against self or harmless material"/>
        </outline>
        <outline text="Central tolerance: thymus and bone marrow"/>
        <outline text="Peripheral: anergy, deletion, inhibition, regulation"/>
        <outline text="Autoimmunity needs several safeguards to fail"/>
        <outline text="T-cell help supports switching and memory">
          <outline text="Germinal centres select stronger binders"/>
          <outline text="Mutation risks autoreactivity, lymphoid malignancy"/>
        </outline>
        <outline text="Memory is not absolute protection"/>
      </outline>
      <outline text="Chronic inflammation and granulomas">
        <outline text="Injury, mononuclear infiltrate, destruction, repair"/>
        <outline text="Persistent infection, autoimmunity, toxins, foreign bodies"/>
        <outline text="Granuloma: organised activated macrophages">
          <outline text="Contains material hard to eradicate"/>
          <outline text="Narrows the differential, not one cause"/>
        </outline>
        <outline text="Systemic effects outlast the local trigger">
          <outline text="Anaemia via iron sequestration"/>
          <outline text="Muscle wasting, insulin resistance, thrombosis"/>
          <outline text="Treat the driver, not the marker"/>
        </outline>
      </outline>
      <outline text="Resolution and tissue repair">
        <outline text="Resolution is an active process">
          <outline text="Recruitment stops, neutrophils undergo apoptosis"/>
          <outline text="Lipid mediators suppress further recruitment"/>
          <outline text="Failed clearance keeps stimulating immunity"/>
        </outline>
        <outline text="Repair needs blood, cells, matrix, controlled stress"/>
        <outline text="New vessels are initially leaky and fragile"/>
        <outline text="Strength balances synthesis and degradation"/>
      </outline>
      <outline text="Wounds in context">
        <outline text="Clean apposed edges: smaller scar"/>
        <outline text="Contaminated, ischaemic wounds contract and scar more"/>
        <outline text="Edge redness may be normal inflammation"/>
        <outline text="Spreading erythema, pus, crepitus suggest infection"/>
        <outline text="Ischaemic tissue may show little redness"/>
        <outline text="Immunosuppression mutes fever and leukocytosis"/>
      </outline>
      <outline text="Source control and sampling">
        <outline text="Antimicrobials are only part of treatment"/>
        <outline text="Obstruction, necrosis, abscess, prosthesis keep seeding">
          <outline text="Source control lowers burden, restores anatomy"/>
        </outline>
        <outline text="Sample the infected site before antimicrobials">
          <outline text="Surface colonisers mislead"/>
          <outline text="Positive molecular test may be residual nucleic acid"/>
          <outline text="Negative culture after therapy or poor sampling"/>
        </outline>
      </outline>
      <outline text="Immune modulation and judgement">
        <outline text="Glucocorticoids impair glucose, repair, infection defence"/>
        <outline text="Biological therapies create characteristic infection risks"/>
        <outline text="Control the host response, keep enough immunity">
          <outline text="Sterile autoimmunity: suppression removes driver"/>
          <outline text="Infection: suppression without source control worsens"/>
          <outline text="Sepsis: address pathogen and host physiology"/>
        </outline>
        <outline text="Integrate more than fever and white cell count">
          <outline text="One improved number is not safety"/>
          <outline text="Slow marker normalisation is not failure"/>
        </outline>
      </outline>
    </outline>
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