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Neutrophils as primary responders to pathogens / injury

20 Feb

Neutrophils are the first responding immune cells following exposure to pathogens.

This is due to several characteristics of these cells. Primarily, these cells are very populous in the blood. In fact, they are the most common type of circulating leukocyte, so no matter where in the body there is an insult/injury, there will be neutrophils close by to respond. Secondly, these cells are primed to respond to chemoattractants elicited by complement and from pathogens themselves.

One immediate response that will occur following an injury is the cleavage of complement molecules as they react with invading pathogens. Complement may be activated in three ways, spontaneously (i.e., the alternative pathway), by pathogen-associated carbohydrates (i.e., the lectin pathway), and by antibody (i.e., the classical pathway). In all three pathways, C3 convertase is a common element where the complement protein, C3, is cleaved into C3b, which precipitates onto the membrane of the invading cell, and C3a, which diffuses away and acts as a powerful anaphylotoxin.

C3a has a number of effects, notably activating vasculature to dilate (thus slowing blood flow in the area), upregulating adhesion molecules for cells to attach to, and promoting permeability, making it easy to Neutrophils to extravasate (leave circulation and enter the tissue). Neutrophils are quick to respond and to all of these cues and will further be attracted to the C3a gradients themselves.

a neutrophil responding to a moving chemoattractive gradient

Once in the vicinity of an infection, neutrophils will become more attracted by more specific attractants, such as those secreted by the pathogens themselves. One beautiful example of this kind of chemoattraction can be seen in the video of a neutrophil pursuing a bacterium in vitro:

a neutrophil following a chemoattractive trail emanating from a bacterium

Consider the following:

If you were given any (antibody or other) reagents you wished, how might you determine whether the neutrophil pursuing the bacterium was following a trail of fMLF? (what is fMLF? Why might this particular chemoattractant be relevant to this example? How do you determine specificity?)

 
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Posted by on February 20, 2021 in Uncategorized

 

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