--- module: 004-02 language: en chapter: 4 title: "Inflammation, Healing, Immunity, and Infection" module_title: "Resolution, immune architecture, and repair under stress" source_sha256: 4f1b6eebf99962c513578d79d5521d11d6c61b3c394c023f72dd0c0ac2c5a336 --- # Resolution, immune architecture, and repair ## Inflammation as an active sequence ### Recognition, recruitment, then active resolution ### Failure possible at every stage #### Weak recognition permits microbial spread #### Excess recruitment damages host tissue #### Poor source control keeps the signal present #### Defective resolution leads to chronicity, fibrosis ### Tissue-resident cells set the first response ### Endothelium is not passive plumbing #### Controls which proteins and cells leave blood ## Overlapping mediators ### Prostaglandins: vasodilation, pain, temperature ### Leukotrienes: permeability, bronchi, recruitment ### Cytokines coordinate, chemokines give direction ### Redundancy makes defence robust #### Blocking one mediator may not suppress syndrome ## Complement pathways and deficiency ### Antibody, lectin, alternative pathways converge ### Fragments coat surfaces, aid phagocytosis ### Terminal pores against Gram-negative organisms ### Host regulators limit activation on own cells ### Deficiency patterns differ #### Early classical loss: autoimmune disease #### Terminal loss: invasive Neisseria infection #### Lost regulation: haemolysis, thrombosis, kidney ## Neutrophils and macrophages ### Neutrophils: engulfment, granules, oxidants, traps #### Effective confined, hazardous when widespread ### Count alone does not describe competence #### Reserve, migration, killing, tissue access ### Macrophages are more than late cleaners #### Clear, present antigen, remodel matrix, repair #### A signal-shaped spectrum, not two categories #### Apoptotic-cell clearance promotes repair #### Persisting microbes, crystals, foreign bodies sustain ## Antigen presentation and tolerance ### Peptide recognition plus co-stimulation, cytokines ### Antigen without context: unresponsive or regulatory #### Reduces activation against self or harmless material ### Central tolerance: thymus and bone marrow ### Peripheral: anergy, deletion, inhibition, regulation ### Autoimmunity needs several safeguards to fail ### T-cell help supports switching and memory #### Germinal centres select stronger binders #### Mutation risks autoreactivity, lymphoid malignancy ### Memory is not absolute protection ## Chronic inflammation and granulomas ### Injury, mononuclear infiltrate, destruction, repair ### Persistent infection, autoimmunity, toxins, foreign bodies ### Granuloma: organised activated macrophages #### Contains material hard to eradicate #### Narrows the differential, not one cause ### Systemic effects outlast the local trigger #### Anaemia via iron sequestration #### Muscle wasting, insulin resistance, thrombosis #### Treat the driver, not the marker ## Resolution and tissue repair ### Resolution is an active process #### Recruitment stops, neutrophils undergo apoptosis #### Lipid mediators suppress further recruitment #### Failed clearance keeps stimulating immunity ### Repair needs blood, cells, matrix, controlled stress ### New vessels are initially leaky and fragile ### Strength balances synthesis and degradation ## Wounds in context ### Clean apposed edges: smaller scar ### Contaminated, ischaemic wounds contract and scar more ### Edge redness may be normal inflammation ### Spreading erythema, pus, crepitus suggest infection ### Ischaemic tissue may show little redness ### Immunosuppression mutes fever and leukocytosis ## Source control and sampling ### Antimicrobials are only part of treatment ### Obstruction, necrosis, abscess, prosthesis keep seeding #### Source control lowers burden, restores anatomy ### Sample the infected site before antimicrobials #### Surface colonisers mislead #### Positive molecular test may be residual nucleic acid #### Negative culture after therapy or poor sampling ## Immune modulation and judgement ### Glucocorticoids impair glucose, repair, infection defence ### Biological therapies create characteristic infection risks ### Control the host response, keep enough immunity #### Sterile autoimmunity: suppression removes driver #### Infection: suppression without source control worsens #### Sepsis: address pathogen and host physiology ### Integrate more than fever and white cell count #### One improved number is not safety #### Slow marker normalisation is not failure