Macrophages and lysosomal contents

[notbobtrustme]

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Just had this Uworld question that threw me for a loop. Basically, the question asks what mechanism is responsible for creating abscesses.

The correct answer was "Lysosomal content release by macrophages". THere are a few things wrong with this statement, but the explanation is the real kicker, the explanation groups neutrophils and macrophages together and talk about how collateral damage to the parenchyma forms an abscess.

There are a few things wrong with this question, IMO. Macrophages don't release their lysosomal contents, they fuse the lysosome with the phagosome, keeping their contents fully sequestered the entire time. Secondly, the lumping of neutrophils and macrophages together doesn't make sense mechanistically. If the answer stem was "lysosomal content release by neutrophils" I would have had no problem picking that answer choice because that's pretty much what neutrophils do.

Anyone else feel the same way I do or am I missing the mark.

 

[ChessMaster3000]

Just had this Uworld question that threw me for a loop. Basically, the question asks what mechanism is responsible for creating abscesses.

The correct answer was "Lysosomal content release by macrophages". THere are a few things wrong with this statement, but the explanation is the real kicker, the explanation groups neutrophils and macrophages together and talk about how collateral damage to the parenchyma forms an abscess.

There are a few things wrong with this question, IMO. Macrophages don't release their lysosomal contents, they fuse the lysosome with the phagosome, keeping their contents fully sequestered the entire time. Secondly, the lumping of neutrophils and macrophages together doesn't make sense mechanistically. If the answer stem was "lysosomal content release by neutrophils" I would have had no problem picking that answer choice because that's pretty much what neutrophils do.

Anyone else feel the same way I do or am I missing the mark.

Yeah i do also, missed that question a few days ago. I don't understand it, even if UW is wrong, I think there is an important point they are trying to make and id like to figure out what it is. Do you have the qid? I can go back to it at some point

 

[notbobtrustme]

Yeah i do also, missed that question a few days ago. I don't understand it, even if UW is wrong, I think there is an important point they are trying to make and id like to figure out what it is. Do you have the qid? I can go back to it at some point

ya the QID is 0302.

 

[Myxedema]

There are a few things wrong with this question, IMO. Macrophages don't release their lysosomal contents, they fuse the lysosome with the phagosome, keeping their contents fully sequestered the entire time. Secondly, the lumping of neutrophils and macrophages together doesn't make sense mechanistically. If the answer stem was "lysosomal content release by neutrophils" I would have had no problem picking that answer choice because that's pretty much what neutrophils do.

Robbins PBOD, 8th Ed., Chapter 2 [link]: "...During activation and phagocytosis, neutrophils and macrophages release microbicidal and other products not only within the phagolysosome but also into the extracellular space. The most important of these substances are lysosomal enzymes, present in the granules, and reactive oxygen and nitrogen species. These released substances are capable of damaging normal cells and vascular endothelium, and may thus amplify the effects of the initial injurious agent. In fact, if unchecked or inappropriately directed against host tissues, the leukocyte infiltrate itself becomes the offender, and indeed leukocyte-dependent tissue injury underlies many acute and chronic human disease. This fact becomes evident in the discussion of specific disorders throughout the book."

Robbins Basic Pathology, 9th Ed., Chapter 2, p. 39: "Secretion of Microbicidal Substances - The microbicidal mechanisms of phagocytes are largely sequestered within phagolysosomes in order to protect the leukocytes from damaging themselves. Leukocytes also actively secrete granule components including enzymes such as elastase, which destroy and digest extracellular microbes and dead tissues, as well as antimicrobial peptides. The contents of lysosomal granules are secreted by leukocytes into the extracellular milieu by several mechanisms:

• The phagocytic vacuole may remain transiently open to the outside before complete closure of the phagolysosome (regurgitation during feeding).
• If cells encounter materials that cannot be easily ingested, such as immune complexes deposited on immovable surfaces (e.g., glomerular basement membrane), the attempt to phagocytose these substances (frustrated phagocytosis) triggers strong leukocyte activation, and lysosomal enzymes are released into the surrounding tissue or lumen.
• The membrane of the phagolysosome may be damaged if potentially injurious substances, such as silica particles, are phagocytosed."

 

[notbobtrustme]

Robbins PBOD, 8th Ed., Chapter 2 [link]: "...During activation and phagocytosis, neutrophils and macrophages release microbicidal and other products not only within the phagolysosome but also into the extracellular space. The most important of these substances are lysosomal enzymes, present in the granules, and reactive oxygen and nitrogen species. These released substances are capable of damaging normal cells and vascular endothelium, and may thus amplify the effects of the initial injurious agent. In fact, if unchecked or inappropriately directed against host tissues, the leukocyte infiltrate itself becomes the offender, and indeed leukocyte-dependent tissue injury underlies many acute and chronic human disease. This fact becomes evident in the discussion of specific disorders throughout the book."

Robbins Basic Pathology, 9th Ed., Chapter 2, p. 39: "Secretion of Microbicidal Substances - The microbicidal mechanisms of phagocytes are largely sequestered within phagolysosomes in order to protect the leukocytes from damaging themselves. Leukocytes also actively secrete granule components including enzymes such as elastase, which destroy and digest extracellular microbes and dead tissues, as well as antimicrobial peptides. The contents of lysosomal granules are secreted by leukocytes into the extracellular milieu by several mechanisms:

• The phagocytic vacuole may remain transiently open to the outside before complete closure of the phagolysosome (regurgitation during feeding).
• If cells encounter materials that cannot be easily ingested, such as immune complexes deposited on immovable surfaces (e.g., glomerular basement membrane), the attempt to phagocytose these substances (frustrated phagocytosis) triggers strong leukocyte activation, and lysosomal enzymes are released into the surrounding tissue or lumen.
• The membrane of the phagolysosome may be damaged if potentially injurious substances, such as silica particles, are phagocytosed."

seems really nitpicky and was never made a point of emphasis in any class I've ever taken and I was literally getting a PhD in Immunology a couple years ago. Chalk that one up to Uworld weirdness.

 

[sanj238]

seems really nitpicky and was never made a point of emphasis in any class I've ever taken and I was literally getting a PhD in Immunology a couple years ago. Chalk that one up to Uworld weirdness.

what were the wrong choices please

 

[notbobtrustme]

what were the wrong choices please

major basic protein secretion by eosinophils
ifn-y from Th1 T cells
il-12 secretion from neutrophils
antibody binding to mast Fc receptors

I picked IFN-y from Th1 cells, since that would activate CD8+ T cells and macrophages, leading to damage causing an abscess.

 

[ChessMaster3000]

major basic protein secretion by eosinophils
ifn-y from Th1 T cells
il-12 secretion from neutrophils
antibody binding to mast Fc receptors

I picked IFN-y from Th1 cells, since that would activate CD8+ T cells and macrophages, leading to damage causing an abscess.

I picked the same thing--even if their answer choice is right, isn't ifn-y correct also? We know macrophages cause abscesses and ifn-y is released from th1 cells to activate macrophages...

 

[sanj238]

I picked the same thing--even if their answer choice is right, isn't ifn-y correct also? We know macrophages cause abscesses and ifn-y is released from th1 cells to activate macrophages...

I dont know...reading Kaplan I remember ifn gamma was for autoactivation of T cell - H1 type and for granuloma formations. I dont reall abscess formation via ifn gamma.....

 

[notbobtrustme]

I dont know...reading Kaplan I remember ifn gamma was for autoactivation of T cell - H1 type and for granuloma formations. I dont reall abscess formation via ifn gamma.....

and I've never seen the statement "lysosomal content release by macrophages" since that's not the way they've been described in the literature in the 5+ years I've studied Immunology.

At least with IFN-y, there's a viable mechanism via macrophage activation and CD8+ activation.

 

[Kingella]

Somehow I ended up on this thread after searching for something completely unrelated, but reading this reminds me of the question and thinking it was an odd one. It got me thinking about the process of answer selection in these MCQs.
In the end I think i was more sure about picking the macrophage lysosomal content release after remembering that in the goljan audio tapes he says something about "macrophages not having myeloperoxidases and chose to become couch potatoes but that they still have lysozyme to release."

Also this is the type of question where knowing less would probably lead to a better outcome. If you know the bit about it being due to released enzymes but not necessarily the distinctions between macrophage and neutrophil lysosome content then you would pick the right answer. Knowing too much ends up leading me to pick the wrong answer sometimes since I'll know enough to start questioning the fine distinction but in the end not enough to rule it out or in completely (which is rare unless you have all the major textbooks memorized lol).

 

[syoung]

i think also though that CD8 t cells wouldn't cause abscess? they are cytotoxic and cause the cells they target to apoptose right? this would then lead to orderly cell death instead of abscess

 

[Jabbed]

I think that the process discussed is called "frustrated phagocytosis". It's covered in Robbins.