A Burning Question: Inflammation - Acute And Chronic

29.9.06

Inflammation
• Results from injury.
• Organised set of defence responses.

Cellular injury - causes
• Physical.
• Radiation.
• Chemical.
• Ischaemic.
• Free radicals.
• Infection - has elements of several of these.

Inflammation
• Acute - stimulus involved.
• Chronic - stimulus persists.

Acute inflammation
• Cardinal signs:
-swelling (tumor);
-heat (callor);
-redness (rubor);
-pain (dolor);
-loss of use.
• Vascular change:
-permeability;
-pressure.

Inflammatory mediators (chemotactic, chemokinetic)
• Plasma protein cascades:
-complement;
-kinins;
-blood clotting;
-fibrinolytic.
• Intracellular, sorted, released on demand:
-histamine (vasoactive) from mast cells;
-serotonin: platelets and enterochromaffin cells (not mast cells);
-lysosomal enzymes (proteases).
• Synthesised and released from cells:
-prostaglandins (peroxidation of arachidonic acid) - pain and fever in inflammation;
-leukotrienes (lipo-oxygenase pathway) - activate Neutrophils (adhesion, free-radicals, enzymes);
-platelet activating factor;
-cytokines:
§interleukins (IL1-IL15) - IL1 and IL6: systemic acute phase responses;
§interferons (α, β, γ);
§cytotoxins (TNF-α and lymphotoxin).

Complement
• Opsonisation.
• Membrane attack complex (cell lysis).
• Proteolysis.
• Mediators for vascular and cellular pathways (anaphylatoxins C3a and C5a - cause histamine release).
• Classical pathway: antibody-mediated.
• Alternative pathway: LPS-mediated.

Kinins
• Hageman factor (factor XII) activates:
-factor XI to initiate clotting;
-plasminogen proactivator (fibrinolytic);
-prekallikein cleaved → kallikrein;
-kininogen → bradykinin;
-short-lived, but:
§increased vascular permeability;
§and something else, but nobody got it because he moved onto the next slide far too quickly.

Phagocytosis
• Neutrophils adapted for bacterial ingestion.
• Opsonisation by complement/specific immunoglobulin.
• Oxidation of organism by superoxide anion, H2O2, OH• radical and HOCl. Presence of myeloperoxidase required.
• Macrophages attack larger particles (but also some bacteria).

Defence against invasion
• Complement system.
• Non-specific defences.
• Immune system.
• Phagocytosis - opsonisation.

Chronic inflammation
• The immune system - lymphocytes, plasma cells.