--- module: 004-01 language: en chapter: 4 title: "Inflammation, Healing, Immunity, and Infection" module_title: "Foundations" source_sha256: 57c969e97082ad8262098cf49a3e7d378185d2c74f9ba825dd1d773a5cda319b --- # Inflammation, healing, immunity, and infection ## Orientation ### Protective response to infection, injury, foreign material ### Excessive or prolonged response damages tissue ### Immunity adds specificity and memory ### Infection is one cause, not a synonym ## Recognition and immediate defence ### Physical barriers are the first defence #### Skin: keratin, lipids, resident microbes, shedding #### Mucus traps particles, cilia move them to pharynx #### Barrier damage creates entry points ### Innate cells sense microbial and damage signals #### Pattern-recognition receptors activate inflammasomes ### Histamine: arteriolar dilation, venular permeability ### Mediators coordinate vessels, pain, fever, recruitment ## Complement outputs ### Inactive circulating precursors, tightly regulated ### C3 convertase releases C3a, generates C3b #### Surface C3b enables opsonisation #### Target easier to ingest, not killed by the label ### C5 convertase generates C5a and C5b #### C5a: inflammatory and chemotactic signal #### C5b initiates, C6 to C9 form attack complex ### Recruit, label, perforate are separate operations #### Resisting one leaves vulnerability to another #### Activation does not mean direct lysis ## Acute inflammation ### Increased flow: redness and warmth ### Permeability: protein-rich fluid, swelling ### Classic signs are patterns, not requirements ### Leukocyte recruitment as flow slows #### Selectins support rolling #### Chemokine-activated integrins bind firmly ### Neutrophils early, monocytes become macrophages ### Phagocytosis: recognise, engulf, kill, digest #### Killing agents injure tissue if released ### Abscess walls off pus, may need drainage #### Poor antibiotic penetration, incomplete control ### Outcomes: resolution, scar, abscess, chronicity ## Adaptive immunity ### Dendritic cells link innate and adaptive ### Class one: intracellular peptides to CD8 ### Class two: extracellular peptides to CD4 ### Activation also needs co-stimulation, cytokines ### CD4 cells coordinate specialised patterns #### Macrophage activation for intracellular organisms #### Eosinophils and immunoglobulin E responses #### Regulatory T cells restrain, support tolerance ### CD8 cells kill infected or abnormal cells ### B cells become plasma or memory cells #### Immunoglobulin M early, activates complement #### Immunoglobulin G abundant, crosses placenta #### Immunoglobulin A protects mucosal surfaces #### Immunoglobulin E binds mast cells ### Memory speeds re-response, durability varies ## Immune injury and immune failure ### Immediate hypersensitivity: IgE and mast cells ### Immune complexes deposit, activate complement ### Delayed: T cells and activated macrophages ### Autoimmunity: failed tolerance, genes, environment #### Positive autoantibody is not a diagnosis ### Infection pattern suggests the failed component #### Neutropenia: invasive bacteria and fungi #### T-cell impairment: intracellular, opportunistic #### Antibody deficiency: encapsulated bacteria ## Fever and systemic inflammation ### Hypothalamic prostaglandin raises the set point #### Feels cold, vasoconstricts, may shiver #### Falling set point: vasodilation, sweating ### Hyperthermia: heat load exceeds loss capacity ### Liver makes acute-phase proteins, albumin falls ### Severe inflammation: capillary leak, coagulation ### Sepsis: organ dysfunction from dysregulated response #### Not defined by fever, may be normothermic #### Cultures, antimicrobials, source, perfusion ## Healing and fibrosis ### Haemostasis creates a provisional matrix ### Macrophages shift signalling toward repair ### Regeneration needs dividing cells and scaffold ### Scar dominates with extensive damage #### Fibroblasts make collagen, myofibroblasts contract #### Strength rises over months, rarely fully ### Delay: perfusion, infection, steroids, diabetes ### Excess repair: keloids, strictures, organ fibrosis ## Antimicrobial and anti-inflammatory logic ### Match organism, site, severity, host, resistance ### Source control: drainage, debridement, devices ### Anti-inflammatories modify the host response #### Non-steroidal drugs: gut, kidney, heart injury #### Glucocorticoids: infection, glucose, bone, adrenal