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  <head>
    <title>004-01 Foundations</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Inflammation, healing, immunity, and infection">
      <outline text="Orientation">
        <outline text="Protective response to infection, injury, foreign material"/>
        <outline text="Excessive or prolonged response damages tissue"/>
        <outline text="Immunity adds specificity and memory"/>
        <outline text="Infection is one cause, not a synonym"/>
      </outline>
      <outline text="Recognition and immediate defence">
        <outline text="Physical barriers are the first defence">
          <outline text="Skin: keratin, lipids, resident microbes, shedding"/>
          <outline text="Mucus traps particles, cilia move them to pharynx"/>
          <outline text="Barrier damage creates entry points"/>
        </outline>
        <outline text="Innate cells sense microbial and damage signals">
          <outline text="Pattern-recognition receptors activate inflammasomes"/>
        </outline>
        <outline text="Histamine: arteriolar dilation, venular permeability"/>
        <outline text="Mediators coordinate vessels, pain, fever, recruitment"/>
      </outline>
      <outline text="Complement outputs">
        <outline text="Inactive circulating precursors, tightly regulated"/>
        <outline text="C3 convertase releases C3a, generates C3b">
          <outline text="Surface C3b enables opsonisation"/>
          <outline text="Target easier to ingest, not killed by the label"/>
        </outline>
        <outline text="C5 convertase generates C5a and C5b">
          <outline text="C5a: inflammatory and chemotactic signal"/>
          <outline text="C5b initiates, C6 to C9 form attack complex"/>
        </outline>
        <outline text="Recruit, label, perforate are separate operations">
          <outline text="Resisting one leaves vulnerability to another"/>
          <outline text="Activation does not mean direct lysis"/>
        </outline>
      </outline>
      <outline text="Acute inflammation">
        <outline text="Increased flow: redness and warmth"/>
        <outline text="Permeability: protein-rich fluid, swelling"/>
        <outline text="Classic signs are patterns, not requirements"/>
        <outline text="Leukocyte recruitment as flow slows">
          <outline text="Selectins support rolling"/>
          <outline text="Chemokine-activated integrins bind firmly"/>
        </outline>
        <outline text="Neutrophils early, monocytes become macrophages"/>
        <outline text="Phagocytosis: recognise, engulf, kill, digest">
          <outline text="Killing agents injure tissue if released"/>
        </outline>
        <outline text="Abscess walls off pus, may need drainage">
          <outline text="Poor antibiotic penetration, incomplete control"/>
        </outline>
        <outline text="Outcomes: resolution, scar, abscess, chronicity"/>
      </outline>
      <outline text="Adaptive immunity">
        <outline text="Dendritic cells link innate and adaptive"/>
        <outline text="Class one: intracellular peptides to CD8"/>
        <outline text="Class two: extracellular peptides to CD4"/>
        <outline text="Activation also needs co-stimulation, cytokines"/>
        <outline text="CD4 cells coordinate specialised patterns">
          <outline text="Macrophage activation for intracellular organisms"/>
          <outline text="Eosinophils and immunoglobulin E responses"/>
          <outline text="Regulatory T cells restrain, support tolerance"/>
        </outline>
        <outline text="CD8 cells kill infected or abnormal cells"/>
        <outline text="B cells become plasma or memory cells">
          <outline text="Immunoglobulin M early, activates complement"/>
          <outline text="Immunoglobulin G abundant, crosses placenta"/>
          <outline text="Immunoglobulin A protects mucosal surfaces"/>
          <outline text="Immunoglobulin E binds mast cells"/>
        </outline>
        <outline text="Memory speeds re-response, durability varies"/>
      </outline>
      <outline text="Immune injury and immune failure">
        <outline text="Immediate hypersensitivity: IgE and mast cells"/>
        <outline text="Immune complexes deposit, activate complement"/>
        <outline text="Delayed: T cells and activated macrophages"/>
        <outline text="Autoimmunity: failed tolerance, genes, environment">
          <outline text="Positive autoantibody is not a diagnosis"/>
        </outline>
        <outline text="Infection pattern suggests the failed component">
          <outline text="Neutropenia: invasive bacteria and fungi"/>
          <outline text="T-cell impairment: intracellular, opportunistic"/>
          <outline text="Antibody deficiency: encapsulated bacteria"/>
        </outline>
      </outline>
      <outline text="Fever and systemic inflammation">
        <outline text="Hypothalamic prostaglandin raises the set point">
          <outline text="Feels cold, vasoconstricts, may shiver"/>
          <outline text="Falling set point: vasodilation, sweating"/>
        </outline>
        <outline text="Hyperthermia: heat load exceeds loss capacity"/>
        <outline text="Liver makes acute-phase proteins, albumin falls"/>
        <outline text="Severe inflammation: capillary leak, coagulation"/>
        <outline text="Sepsis: organ dysfunction from dysregulated response">
          <outline text="Not defined by fever, may be normothermic"/>
          <outline text="Cultures, antimicrobials, source, perfusion"/>
        </outline>
      </outline>
      <outline text="Healing and fibrosis">
        <outline text="Haemostasis creates a provisional matrix"/>
        <outline text="Macrophages shift signalling toward repair"/>
        <outline text="Regeneration needs dividing cells and scaffold"/>
        <outline text="Scar dominates with extensive damage">
          <outline text="Fibroblasts make collagen, myofibroblasts contract"/>
          <outline text="Strength rises over months, rarely fully"/>
        </outline>
        <outline text="Delay: perfusion, infection, steroids, diabetes"/>
        <outline text="Excess repair: keloids, strictures, organ fibrosis"/>
      </outline>
      <outline text="Antimicrobial and anti-inflammatory logic">
        <outline text="Match organism, site, severity, host, resistance"/>
        <outline text="Source control: drainage, debridement, devices"/>
        <outline text="Anti-inflammatories modify the host response">
          <outline text="Non-steroidal drugs: gut, kidney, heart injury"/>
          <outline text="Glucocorticoids: infection, glucose, bone, adrenal"/>
        </outline>
      </outline>
    </outline>
  </body>
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