Acute Inflammation


The acute inflammatory response is activated by infectious agents and/or damaged tissues. These trigger vascular and cellular responses to deliver cells and proteins to the site of cell injury.

Key steps of acute inflammation:

1. Recognition of inflammatory agents by host cells.
2. Leukocyte and plasma protein recruitment from the blood to the tissues.
3. Leukocyte activation at the site of injury.
4. Control and termination of inflammation to avoid harming healthy cells.

1. Recognition of “bad” offending agents/Microbes

Receptors in the host cell are used to identify any "bad stuff" such as microbes or damage to the host cell.

  • Ex: Toll-like receptors (TLR) on the surface of microbes help the host to recognize these invading "bad" microbes.

We commonly think of the receptors on the plasma membrane surface of a cell, but receptors can also exist in endosomes, and the cytosol of host cells.

Cytosolic sensors help detect cellular damage

  • Ex: changes in concentration of uric acid (inc), ATP, intracellular K+ (reduced)

  • 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 foreign "bad" tissues 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.

2. Recruitment of plasma proteins and leukocytes from the bloodstream

Inflammatory mediators lead to VASODILATION and INCREASED VASCULAR PERMEABILITY which allows plasma proteins and fluid to exit the vessel (aka, exudation)

  • Inflammatory mediators = histamine, prostaglandins, platelet activating factor (PAF), thromboxane A2 (generated from prostaglandins), bradykinin, and leukotrienes)

  • Clinical correlation: fibrinous pericarditis is a form of acute inflammation; fibrin and leukocytes infiltrate the pericardium causing the characteristic "friction rub" heard on auscultation.

Details about the Neutrophil Recruitment Process

Neutrophil recruitment from the blood involves:

  1. Capture

  2. Rolling

  3. Adhesion

  4. Diapedesis

  5. Chemotaxic Migration.

1. Capture:

– Capture starts via expression of a type of cell adhesion molecule, called E-selectins, on the Endothelial lining (blood vessel wall), (due to the inflammatory cytokines TNF & IL-1)

Neutrophils/ PMNs contain P-selectins (PSGL-1 (P-selectin glycoprotein ligand -1), which recognize & bind with exposed E-selectins on the endothelial surface

2. Rolling:

P-selectins (on PMNs) & E-selectins (Endothelium) expression is upregulated by cytokines, thrombin, and histamine. The P & E-selecting binding is weak, but it allows the PMNs to slow down and "roll" across the endothelial surface until it can strongly bind (next step)

3. Adhesion:

– Firmer adhesion occurs when endothelial ICAM-1 (Intracellular Adhesion Molecule) binds with neutrophil LFA-1 ligand (Lymphocyte Function-Associated).

4. Diapedesis:

This is a fancy term to describe the movement of a leukocyte across the vessel wall typically occurs via the paracellular route, and is assisted by PECAM-1 (Platelet Endothelial Cell Adhesion Molecule).

5. Chemotaxic Migration:

Chemokines guide neutrophils to the site of inflammation along chemotactic gradients. Once outside of the vessel, neutrophils generate more cytokines, which further promotes the inflammatory response.

3. Phagocytosis and destruction of inflammatory agents

We'll use neutrophil destruction of microbes as an example to describe the overall process of phagocytosis & subsequent destruction of the "bad stuff".

  • Neutrophil recognizes the "bad guy" using one of its sensors (described previously).

  • The neutrophil engulfs/eats the microbe and moves it into a phagosome ("jail cell").

  • Lysosomes (filled with degradative enzymes - can be thought of as the contents used in "lethal injection") then come in and merge with the phagosome, to form a phagolysosome

  • The "bad guy" is then destroyed via lysosomal enzymes, production of reactive oxygen species (ROS, aka, reactive oxygen intermediates), and inducible nitric oxide (iNO)- aka death by "lethal injection".

NOTE: Inflammatory cytokines, such as interferon gamma, trigger the production of ROS and iNO within the lysosomes and phagolysosomes.

Neutrophils & NETs

In addition to phagocytosis, neutrophils can produce extracellular traps (aka, NETs) to destroy infectious pathogens. In this process, the neutrophil "exudes its nuclear materials to envelop the microbes in chromatin and concentrated antimicrobial peptides and enzymes".


Although neutrophils/PMNs are the primary WBC active in acute inflammation, macrophages & other cells can play important roles. Macrophages release both pro- and anti-inflammatory cytokines that mediate the inflammatory response; they also release growth factors and enzymes that promote tissue repair. Macrophages will be discussed in further detail in my post on chronic Inflammation.

4. Control and Termination of Inflammatory Response

Once the initial insult/injury is under control, there are methods in place to stop further inflammation & avoid destruction of healthy host cells.

Methods to control acute inflammation:

  • Neutrophils have short half-lives once they leave the blood stream

  • Lipoxins (secreted by neutrophils and macrophages) prohibit continued recruitment of new neutrophils.

  • Macrophages release various anti-inflammatory molecules

Possible outcomes of acute inflammation:

  1. Full resolution - return to normal tissue functioning is possible.

  2. Progression to chronic inflammation - results when inflammatory agents persist. Mediated by monocytes- mainly macrophages & lymphocytes (T-cells & B-cells)

  3. Scarring or fibrosis - damaged tissues are replaced by connective (fibrous) tissues

Classic signs of acute inflammation and their physiologic causes:

Redness (Rubor)

caused by vasodilation and increased blood flow to the inflamed area.

Heat (Calor)

result of vasodilation & pyrogens (fever-inducing substances that act at the hypothalamus to reset the body's basal temperature)

Swelling (Tumor)

result of vessel leakage and edema during leukocyte and plasma protein recruitment.

Pain (Dolor)

caused by the release of prostaglandins and bradykinin

Pharmacological correlation

NSAIDS – non-steroidal anti-inflammatory drugs aspirin & ibuprofenlimit inflammation and pain by inhibiting cyclooxygenase (COX), which is the enzyme responsible for prostaglandin synthesis (a potent vasodilator)


These notes were adapted and modified while studying from the awesome medical education website, This is a GREAT website for visual learners. Please subscribe to their website to view the complete lecture and see step by step drawings and charts.

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Ref: "Acute Inflammatory Response" Lecture. Accessed 3/21/19.