The acute inflammatory response is activated in the presence of infectious agents and/or damaged tissues.
Acute inflammation triggers vascular and cellular responses that deliver cells and proteins to the site of cell injury.
Key steps of this process include:
– Recognition of inflammatory agents.
– Leukocyte and plasma protein recruitment from the blood to the tissues.
– Leukocyte activation.
– Control and termination of inflammatory reactions, which are otherwise harmful to healthy cells.
Recognition of offending agents
Microbes
Cellular receptors for microbes exist in the plasma membranes, endosomes, and cytosol of host cells.
For example: Toll-like receptors (TLR) enable dendritic and other "sentinel cells" to recognize invading microbes.
Host cell damage
Cytosolic sensors recognize various molecules, such as uric acid, ATP, DNA, and reduction of intracellular potassium concentrations, that indicate cellular damage.
For example: Multi-protein cytosolic complexes called inflammasomes respond to the cytosolic sensors and trigger the release of cytokines, which, as we'll see, are key mediators of the inflammatory response.
Circulating proteins act as pattern recognition molecules that recognize invaders by their display of abnormal, non-self patterns.
For example: mannose-binding lectin protein binds to mannose, which is a characteristic microbial sugar; after binding, MBL facilitates microbe ingestion and activates the immune system.
Plasma Protein and Leukocyte Recruitment
Recruitment of plasma proteins and leukocytes from the blood
Vasodilation and increased permeability of the vessel wall:
Triggered by inflammatory mediators, importantly: histamine, prostaglandins, platelet activating factor (PAF), thromboxane A2 (generated from prostaglandins), bradykinin, and leukotrienes.
Plasma proteins and fluid exit the vessel
Aka, exudation.
This process can lead to excess fluids in the interstitial tissues, a condition called "edema."
Clinical correlation: fibrinous pericarditis is a form of acute inflammation; as a result of the inflammatory response, fibrin and leukocytes infiltrate the pericardium (specifically the visceral pericardium, aka, the epicardium) and can cause "friction rub."
Neutrophil recruitment from the blood involves:
Capture, Rolling, Adhesion, Diapedesis, and Chemotaxic Migration.
Capture:
Capture occurs via E-selectins, which are a type of cell adhesion molecule.
Cytokines, specifically Tumor Necrosis Factor (TNF) and Interleukin-1, upregulate the expression of E-selectins on the endothelial lining of the vessel.
Correspondingly, neutrophils express PSGL-1 (P-selectin glycoprotein ligand -1), which binds with selectins.
Rolling:
Achieved via binding with P-selectins; their expression is upregulated by cytokines, thrombin, and histamine.
Adhesion:
Firmer adhesion occurs when endothelial ICAM-1 (Intracellular Adhesion Molecule) binds with neutrophil LFA-1 ligands (Lymphocyte Function-Associated).
Diapedesis:
The process of movement across the vessel wall typically occurs via the paracellular route, and is assisted by PECAM-1 (Platelet Endothelial Cell Adhesion Molecule).
Once outside of the vessel, neutrophils generate more cytokines, which further promotes the inflammatory response.
Chemotaxis:
Chemokines guide neutrophils to the site of inflammation along chemotactic gradients.
