IgA protease

[Phloston]

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I'm a bit confused about how IgA protease works.

To my understanding, it cleaves the proline-rich hinge region of the IgA heavy chain, leaving only the Fab fragment attached to the bacterium. This not only protects the bacterium from phagocytosis, but enables its penetration of pharyngeal mucosa.

I had thought this is because complement normally binds to the CH2 region, which is cleaved off by IgA protease, but IgA doesn't bind complement (as you've mentioned, the hundredthone). So what's going on?

I had read elsewhere that the cleavage enables the organism to bind to Fc-receptors on the pharyngeal mucosa, which is why the penetration is enabled, but how does that happen? Isn't the Fc region of the IgA cleaved off?

 

[thehundredthone]

Only IgG and IgM can bind complement.

The Fc region of the IgA molecule getting cleaved has nothing to do with an organism binding to Fc receptors. (if that is in fact true) What mucosal cells have Fc receptors anyway, afaik only macrophages, neutrophils, eosinophils, monocytes and NK cells have Fc receptors.

 

[Phloston]

Only IgG and IgM can bind complement.

The Fc region of the IgA molecule getting cleaved has nothing to do with an organism binding to Fc receptors. (if that is in fact true) What mucosal cells have Fc receptors anyway, afaik only macrophages, neutrophils, eosinophils, monocytes and NK cells have Fc receptors.

According to Kaplan QBank: IgA protease cleaves IgA, leaving the just Fc region to coat the bacterium (doesn't make sense to me why it would be the Fc region bc wouldn't the Fab bind the bacterium?), enabling it to bind to Fc receptors on epithelial/mucosal cells. Therefore IgA protease facilitates attachment + colonization of respiratory mucosa.

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If IgA cannot bind complement, then what's the mechanism through which it actually leads to pathogens being killed (e.g. Giardia)?

(And just realized: IgM/G are complement-binders; IgG/C3b are opsonins.)

 

[loveoforganic2]

The point of IgA is that it doesn't kill and thus doesn't incite inflammation. Bad crap goes through the gut all the time - you don't want chronic inflammation there. To get rid of the bad stuff, you secrete IgA, it neutralizes it, and it's excreted. Same deal in the respiratory system

 

[Phloston]

The point of IgA is that it doesn't kill and thus doesn't incite inflammation. Bad crap goes through the gut all the time - you don't want chronic inflammation there. To get rid of the bad stuff, you secrete IgA, it neutralizes it, and it's excreted. Same deal in the respiratory system

That seems a bit incomplete to me. Let's say you have Giardia attached to the intestinal mucosa. IgA doesn't just magically induce its release.

And do you have any idea about the IgA protease?

 

[thehundredthone]

How will the Giardia attach to the mucosa when IgA is present on the cells?

According to wikipedia, IgA binds to Fc receptors and causes ADCC, but that's in the bloodstream.

An interesting tidbit is that increased levels of IgA promote Meningococcemia because the IgA coating the organism prevents IgM and IgG opsonistation.

IgA protease cleaves like papain, at the hinge. Perhaps a more complete version of the Kaplan expanation (paraphrased, of course, in case it's copyrighted) would be of use to understand what they're saying.

 

[Phloston]

How will the Giardia attach to the mucosa when IgA is present on the cells?

According to wikipedia, IgA binds to Fc receptors and causes ADCC, but that's in the bloodstream.

An interesting tidbit is that increased levels of IgA promote Meningococcemia because the IgA coating the organism prevents IgM and IgG opsonistation.

IgA protease cleaves like papain, at the hinge. Perhaps a more complete version of the Kaplan expanation (paraphrased, of course, in case it's copyrighted) would be of use to understand what they're saying.

Interestingly, I do remember that part about Meningococcus from Kaplan.

I'm glad you mentioned papain btw. For some reason, I had annotated the pepsin/papain difference in my FA wrong. Lucky I corrected it now vs never.

 

[loveoforganic2]

That seems a bit incomplete to me. Let's say you have Giardia attached to the intestinal mucosa. IgA doesn't just magically induce its release.

And do you have any idea about the IgA protease?

For your first point - the intestinal epithelium sloughs off fairly quickly.

For your second question - haven't done bacteriology yet

 

[Phloston]

For your first point - the intestinal epithelium sloughs off fairly quickly.

For your second question - haven't done bacteriology yet

Lol, well fortunately for you, Giardia's a protozoan 😉

 

[loveoforganic2]

And giardia has IgA protease?

...

 

[Phloston]

And giardia has IgA protease?

...

No. But IgA is the major defense against Giardia.

 

[loveoforganic2]

As is the high turnover of GI epithelium. My point is I was responding to your second question (concerning IgA protease) when I said I hadn't taken bacteriology