⚡ Acute inflammation immediate · innate
- Innate immunity response to injury or infection
- Duration: hours to days (self‑limiting in normal host)
- Cardinal signs: rubor, calor, tumor, dolor, functio laesa
- Three pillars: hemodynamic changes, neutrophil emigration, chemical mediators
Trigger→
Vasodilation→
Increased permeability→
Stasis / margination
- High‑yield: acute inflammation is neutrophil‑predominant; chronic is mononuclear.
🔄 Hemodynamic changes
- Transient vasoconstriction (seconds) → rapid vasodilation
- Vasodilators: histamine, bradykinin, prostaglandins
- Increased permeability → exudation of protein‑rich fluid
- Mechanisms of permeability:
- Endothelial contraction (histamine, bradykinin, leukotrienes)
- Direct endothelial injury (toxins, burns)
- Leukocyte‑mediated injury
- Stasis: slowed flow → increased viscosity → margination
- Exam trap: vasodilation and increased permeability are mediated by different pathways; both occur early.
🧬 Neutrophils (PMNs)
- Tissue lifespan: 1‑2 days
- Primary (azurophilic) granules:
- Myeloperoxidase, elastase, defensins, BPI, lysozyme, acid hydrolases
- Secondary (specific) granules:
- Lactoferrin, lysozyme, collagenase, LAP, vitamin B12‑binding protein
- Adhesion cascade:
- Selectin upregulation (E‑selectin, P‑selectin) → rolling
- Chemokine stimulation → integrin activation (LFA‑1)
- Integrin‑ICAM/VCAM binding → firm adhesion
- Defects: LAD (autosomal recessive), diabetes, steroids, alcohol
| Step | Molecule | Location |
|---|---|---|
| Rolling | P‑/E‑selectin | Endothelium |
| Firm adhesion | Integrin (LFA‑1) | Neutrophil |
| Counter‑receptor | ICAM‑1 / VCAM‑1 | Endothelium |
- Phagocytosis:
- Opsonins: IgG, C3b, collectins
- Engulfment → phagosome → lysosome fusion
- Killing: oxygen‑dependent (NADPH oxidase → superoxide, H₂O₂, HOCl) and oxygen‑independent (lysozyme, defensins, BPI)
- CGD: NADPH oxidase defect → catalase‑positive organisms; NBT test negative.
🧪 Chemical mediators
- Vasoactive amines
- Histamine (mast cells, basophils, platelets)
- Serotonin (platelets)
- Kinin system
- Factor XII → kallikrein → bradykinin
- Bradykinin: pain, vasodilation, permeability
- Arachidonic acid
- COX: TXA₂ (platelet, vasoconstrictor), PGI₂ (endothelium, vasodilator), PGE₂ (pain)
- LOX: LTB₄ (chemotaxis), LTC₄/D₄/E₄ (vasoconstriction), lipoxins (anti‑inflammatory)
- Complement: C3a, C5a (anaphylatoxins), C5a (chemotaxis), C3b (opsonin), C5b‑9 (MAC)
- Cytokines: IL‑1, TNF (fever, acute phase, adhesion), IL‑8 (neutrophil chemoattractant)
- Pain mediators: bradykinin + prostaglandins (PGE₂).
⏳ Chronic inflammation
- Causes: unresolved acute, persistent infections, autoimmunity, foreign material, malignancy
- Key cells: macrophages (monocyte‑derived), lymphocytes (T/B/plasma), eosinophils, mast cells
- Macrophage chemotaxis: C5a, MCP‑1, MIP‑1α, PDGF, TGF‑β
- Eosinophil: parasitic, IgE‑mediated; major basic protein; eotaxin
- Basophil/mast cell: IgE‑mediated, histamine release
Monocyte→
Tissue macrophage→
Epithelioid cell(IFN‑γ)
- Lymphotoxin = lymphocyte chemokine.
🧫 Granulomatous inflammation
- Focal aggregate of epithelioid macrophages + multinucleated giant cells + peripheral lymphocytes
- Epithelioid cells: enlarged, abundant pink cytoplasm (IFN‑γ driven)
- Giant cells: Langhans (peripheral nuclei), foreign‑body (haphazard)
- Caseating necrosis: common in TB, fungi; suspect TB until proven otherwise
- TNF‑α inhibitors (infliximab): screen for latent TB (PPD) before therapy
| Disease | Granuloma type |
|---|---|
| Tuberculosis | Caseating |
| Sarcoidosis | Non‑caseating |
| Cat‑scratch | Suppurative |
| Foreign body | Non‑caseating |
🦠 Tissue responses to infections
- Exudative – neutrophil‑rich: bacterial meningitis, bronchopneumonia, abscess
- Necrotizing – virulent organisms: necrotizing fasciitis, pharyngitis
- Granulomatous – slow‑growing: mycobacteria, fungi, parasites
- Interstitial – mononuclear infiltrate: viral myocarditis, hepatitis
- Cytopathic/cytoproliferative – inclusions, syncytia, apoptosis: CMV (owl eye), rabies (Negri), RSV
- No inflammation – severe immunosuppression (AIDS, primary immunodeficiency)
- Histologic patterns correlate with organism type and host immune status.