Monthly Archives: February 2021

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.

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:

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?)

This was a little hard to bear, but it’s not wrong…

a better, more complete video is this one…

A final video is…

Lastly, some important points are:

-The names and functions of the three pathways

-The initiating molecules for each pathway

-The alternative pathway is often considered a spontaneous pathway, although there are some specific activators

-IgM activates complement better than other classes of antibody

-All three pathways converge at the formation of the C3 convertase

-Complement always results in the assembly of a Membrane Attack Complex (MAC) -lyses bacteria, enveloped viruses, and nucleated cells

-C3a, 35a, and to a lesser extent C4a are anaphylotoxins

I’ve written one or two other posts about Complement including this and this.

Why does it make sense that the antibody most capable of activating complement is IgM?