U01.04.016 Chronic inflammation

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Learning Objectives

Master the hallmarks of Chronic Inflammation and the shift from neutrophil-dominant to mononuclear infiltration. Understand the critical interaction between Macrophages and T-cells, and identify the long-term clinical consequences, including neoplastic transformation and amyloidosis.

1. Characteristics and Stimuli

Chronic inflammation is a prolonged response (weeks to years) where tissue destruction and repair (angiogenesis/fibrosis) occur simultaneously. Unlike the rapid onset of acute inflammation, this process is characterized by a “mononuclear” cellular profile.

Feature Description Clinical Stimuli
Primary Cells Macrophages, Lymphocytes, Plasma cells. Persistent infections (TB, Syphilis, Fungi).
Processes Angiogenesis (new vessels) and Fibrosis (scarring). Autoimmune diseases (SLE, RA).
Immune Link Often involves Type IV Hypersensitivity. Prolonged toxic exposure (Silica).

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2. Macrophage-T Cell Interaction

Macrophages are the dominant cells in chronic inflammation. Their function is dictated by the specific cytokines secreted by T-helper (Th) cells, leading to either a pro-inflammatory or a repair-focused state.

Pathway Mediators (Cytokines) Functional Outcome
Classical Activation Th1 cells secrete IFN-\gamma. Pro-inflammatory; enhanced microbicidal activity.
Alternative Activation Th2 cells secrete IL-4 and IL-13. Tissue repair, fibrosis, and anti-inflammatory effects.

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3. Long-Term Outcomes

Chronic inflammation creates a microenvironment that can eventually lead to irreversible structural changes or malignancy.

Outcome Mechanism / Association Examples
Neoplasia Continuous cell turnover + DNA damage. HCV → Hepatocellular Ca; H. pylori → Gastric Adeno Ca.
Amyloidosis High IL-6 → Serum Amyloid A (SAA). Secondary (AA) Amyloidosis.
Scarring Replacement of parenchyma with collagen. Organ dysfunction (e.g., Cirrhosis).

 

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High-Yield Mnemonics & Tips:

  • IFN-Gamma = Go: Think of IFN-\gamma as the signal that tells macrophages to “Go” and fight. It is the major activator of the classical pathway.
  • Cancer Link: Chronic inflammation is a hallmark of cancer. Whenever an organ is constantly “irritated” (e.g., by H. pylori or Hepatitis), the risk of carcinoma increases.
  • Fibrosis: Chronic inflammation almost always ends in a scar. If you see fibroblasts and new thin-walled blood vessels (angiogenesis) on a slide, you’re looking at the body trying to repair chronic damage.

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