What is the purpose of inflammation?
To bring cells and molecules of host defense from the circulation to a site of tissue damage to remove the offending agents.
What are the two main participants in inflammation?
Blood vessels and leukocytes
Do leukocytes have short or long life spans in tissues?
What are the cardinal signs and symptoms of inflammation?
Rubor (redness), calor (heat), tumor (swelling), dolor (pain), functio laesa (loss of function)
What family of receptors senses the presence of foreign microbes?
Toll-like receptors (also, circulating antibodies and complement)
Intracellular sensors can sense what molecules that indicate possible damage to the cell?
ATP (indicating mitochondrial leakage), low potassium (indicating cellular leakage), uric acid (indicating DNA breakdown), DNA (indicating nuclear leakage)
Damage sensors in the cell trigger the formation of what structure?
What does the inflammasome produce?
What are the general steps of inflammation?
(1) Recognition of the injurious agent, (2) recruitment of leukocytes, (3) removal of the agent, (4) regulation of the response, (5) resolution and repair
What are the three major components of acute inflammation?
Dilation of small blood vessels, increased permeability of the microvasculature, migration of the leukocytes to the damaged tissues
Why do blood vessels dilate in inflammatory situations?
To increase blood flow to the area and slow down the blood flow
What is the principle inflammatory mediator leading to vasodilation?
Histamine (and also kinins)
What do endothelial cells increase expression of during the inflammatory response?
Adhesion molecules (for leukocyte attachment)
What is the most common method increased vascular permeability? What are other methods?
Endothelial cell shrinkage (increasing the interendothelial space); direct endothelial damage and necrosis, vascular endothelial growth factor
What vessels proliferate during inflammatory responses?
Blood and lymph vessels
Define lymphangitis. Define lymphadenitis.
Lymph vessel inflammation; lymph node inflammation
What is the cause of the red streaks seen coming from an infected wound?
What are the three steps of leukocyte migration in the blood vessel lumen?
Margination, rolling, and adhesion (all to activated endothelium)
What adhesion molecules assist leukocytes in the rolling phase?
What adhesion molecules assist leukocytes in the adhesion phase?
What is the name of the process by which leukocytes leave the blood vessel? What molecules assist in this process?
Diapedesis (also known as transmigration); PECAM-1 and CD31
When does chemotaxis occur?
After diapedesis when a leukocyte has entered the tissue space
What are the three principal chemokines involved in chemotaxis?
Interleukin-8, C5a, and leukotriene B4
What is the first responder in acute inflammation? What leukocyte will replace the first responder within 24-48 hours?
Neutrophils (more abundant, quicker, short half-life); macrophages (less abundant, slower, longer half-life, can proliferate in tissues)
What three drugs are especially effective in interfering with tumor necrosis factor and inhibiting harmful inflammation?
Etanercept, infliximab, adalimumab
What happens to the leukocytes post-chemotaxis once they reach the site of injury?
(1) They recognize the offending agents (toll-like receptors); (2) they become activated and phagocytic
What are the three steps of leukocyte phagocytosis?
Recognition, engulfment, and killing (or degradation)
What leukocyte receptors identify bacteria but not host cells?
What combines with the phagosome containing a phagocytosed bacteria or other agent within the leukocyte?
A lysosomal granule (containing reactive oxygen species and degradation enzymes)
How are foreign microbes killed within the body?
Mainly reactive oxygen species (the respiratory burst within the phagolysosome)