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  <head>
    <title>093-01 Innate barriers, pattern recognition, inflammation, phagocytes, and antiviral defence</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Innate barriers, recognition, phagocytes, antiviral defence">
      <outline text="Barriers and epithelium">
        <outline text="Goals: contain, remove damage, recruit, restore">
          <outline text="Without inflammation becoming the injury"/>
        </outline>
        <outline text="Skin: keratin, junctions, lipids, acidity, peptides"/>
        <outline text="Mucosa: mucus, cilia, flow, acid, secretory antibody"/>
        <outline text="Commensals occupy niches and educate immunity">
          <outline text="Defence is chemical and ecological"/>
        </outline>
        <outline text="Epithelia sense and release alarmins, peptides">
          <outline text="Paneth defensins, mucociliary defence, urinary flow"/>
        </outline>
        <outline text="Disruption exposes matrix and permits invasion"/>
        <outline text="Excessive repair causes fibrosis"/>
      </outline>
      <outline text="Pattern recognition">
        <outline text="Pathogen and damage patterns detected"/>
        <outline text="Toll-like receptors on membrane or endosomes"/>
        <outline text="Cytosolic NOD, RIG-I, cGAS-STING sensors">
          <outline text="Misplaced nucleic acid signals danger"/>
        </outline>
        <outline text="Adaptors link to NF-kappa B, AP-1, IRFs">
          <outline text="TNF, chemokines, type-one interferons"/>
        </outline>
        <outline text="Convergence with distinct timing and cells"/>
        <outline text="Repeat stimulation: tolerance or priming"/>
      </outline>
      <outline text="Inflammation and recruitment">
        <outline text="Mediators dilate vessels, open endothelium">
          <outline text="Histamine, nitric oxide, prostaglandins"/>
        </outline>
        <outline text="Exudate delivers antibody, complement, clotting">
          <outline text="But causes swelling"/>
        </outline>
        <outline text="Fever: hypothalamic prostaglandin signalling"/>
        <outline text="Selectins mediate transient rolling"/>
        <outline text="Chemokines activate leukocyte integrins">
          <outline text="Firm adhesion to immunoglobulin-family molecules"/>
        </outline>
        <outline text="Defects: high blood neutrophils, little pus"/>
      </outline>
      <outline text="Neutrophils and macrophages">
        <outline text="Neutrophils: rapid, short-lived, bacteria, fungi"/>
        <outline text="Phagosome fuses with granules">
          <outline text="NADPH oxidase generates superoxide"/>
          <outline text="Myeloperoxidase forms hypochlorous chemistry"/>
        </outline>
        <outline text="Extracellular granules damage host tissue"/>
        <outline text="Extracellular traps immobilise microbes">
          <outline text="Excess: thrombosis and autoantigen exposure"/>
        </outline>
        <outline text="Persistent inflammation: protease destruction"/>
        <outline text="From monocytes or embryonic precursors"/>
        <outline text="Present antigen, regulate iron, coordinate repair"/>
        <outline text="M1 versus M2 captures only extremes"/>
      </outline>
      <outline text="Phagocytosis and its disorders">
        <outline text="Opsonins: IgG, complement, lectins, pentraxins"/>
        <outline text="Receptor clustering drives actin engulfment"/>
        <outline text="Killing: acid, enzymes, oxidants, nutrient limits"/>
        <outline text="Chronic granulomatous disease: no respiratory burst">
          <outline text="Recurrent bacterial, fungal infection, granulomas"/>
        </outline>
        <outline text="Myeloperoxidase deficiency often mild"/>
        <outline text="Localise: arrive, engulf, oxidise, activate"/>
      </outline>
      <outline text="Inflammasomes">
        <outline text="Cytosolic platforms activate caspase one"/>
        <outline text="NLRP3 senses ion flux, crystals, lysosomal damage"/>
        <outline text="Caspase one matures interleukin-1 beta and 18"/>
        <outline text="Gasdermin D pores drive pyroptosis"/>
        <outline text="Urate or cholesterol crystals activate NLRP3"/>
        <outline text="Gain-of-function variants: periodic fevers">
          <outline text="Respond to interleukin-1 blockade"/>
        </outline>
      </outline>
      <outline text="Antiviral defence and sentinel cells">
        <outline text="Type-one interferons induced by viral nucleic acid">
          <outline text="JAK-STAT induces hundreds of antiviral genes"/>
          <outline text="Excess causes interferonopathies"/>
        </outline>
        <outline text="Natural killer balance: stress ligands, class one">
          <outline text="Lost class one removes inhibition"/>
          <outline text="Perforin, granzymes, interferon gamma"/>
        </outline>
        <outline text="CD16 enables antibody-dependent cytotoxicity"/>
        <outline text="Innate lymphoid cells mirror helper cytokines">
          <outline text="No rearranged antigen receptors"/>
        </outline>
        <outline text="Dendritic cells link sensing to naive T cells">
          <outline text="Maturation favours migration, costimulation"/>
        </outline>
      </outline>
      <outline text="Systemic response and sepsis">
        <outline text="Interleukins 6 and 1, TNF drive acute phase"/>
        <outline text="Liver raises CRP, fibrinogen, hepcidin">
          <outline text="Hepcidin degrades ferroportin"/>
          <outline text="Contributes to anaemia of inflammation"/>
        </outline>
        <outline text="Markers sensitive but not cause-specific"/>
        <outline text="Sepsis: dysregulated response, organ dysfunction">
          <outline text="Leak, coagulation, immune suppression"/>
        </outline>
        <outline text="Treat both trigger and physiology"/>
      </outline>
      <outline text="Resolution, memory, and sterile damage">
        <outline text="Resolution is an active programme"/>
        <outline text="Efferocytosis suppresses inflammation">
          <outline text="Failure: secondary necrosis, autoantigens"/>
        </outline>
        <outline text="Trained immunity: epigenetic, metabolic change"/>
        <outline text="Endotoxin tolerance dampens repeat responses"/>
        <outline text="Sterile necrosis releases DNA, ATP, urate"/>
        <outline text="Fever and neutrophils do not prove infection">
          <outline text="Microbiology, anatomy, timing, response"/>
        </outline>
      </outline>
    </outline>
  </body>
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