How Viruses Cause Autoimmunity

[Consul]

@halcyon thanks for the very good explanation! While i have you here i will ask another one that is in the periphery of autoimmunity but i dont see where else to ask it, i have been wondering about this recently.

If you have e.g a monocyte that is presenting an antigen on its MHC and then this mhc-antigen structure suddenly gets hit by an antibody to that antigen - will the monocyte then get eaten(phagocytosed) by e.g a phagocyte or attacked by something else from our immune system?

If the monocyte was instead a regular cell in our tissue it would get killed through antibody dependent cell cytotoxicity (ADCC). But what would happen to the monocyte, if it gets killed it wont be able to do its job which is to present the antigen to a T-cell (if i remember correctly...).

Thanks

 

[halcyon]

If you have e.g a monocyte that is presenting an antigen on its MHC and then this mhc-antigen structure suddenly gets hit by an antibody to that antigen - will the monocyte then get eaten(phagocytosed) by e.g a phagocyte or attacked by something else from our immune system?

Good question, I'm really not sure. MHC molecules and the T-cell receptor (TCR) are designed to work with peptide fragments, while immunoglobulin/the B-cell receptor (BCR) is designed to bind proteins. It may be that the antigen fragments loaded on MHC molecules aren't large enough or don't contain the correct remaining conformation for immunoglobulin to attach to it. I could be completely wrong though.

 

[Consul]

Yes it must be something like that, i just found a document that talks about these things so its all good.

 

[Pyrrhus]

Not able to read though all of the articles posted yet, but it seems they're mostly to do with T-cell autoimmunity?

Well, let's take a look at the different models of the development of autoimmunity:

• Molecular mimicry, where an immune response generated against a pathogen happens to cross-react against normal human tissue. This model is applicable to both B and T cells.
• Epitope spreading, where immune cells mistake human tissue that is near a pathogen as part of the infection, generating an autoimmune response against that human tissue. Often, the human tissue is an intracellular remnant from a cell destroyed in the infection. This model is applicable to both B and T cells.
• Bystander activation, which I'll skip because it results in non-specific inflammation, but no real autoimmunity. (no auto-reactive B or T cells)
• Cryptic antigens, where an inflammatory environment results in abnormal expression of normally un-expressed "self" proteins. This model is applicable to both B and T cells.
• Failure of Regulatory T cells, where the regulatory T cells (Treg) that normally suppress autoimmune cells fail to activate during inflammation. This model is specific to Treg cells.

interesting hypothesis paper about B-cell autoimmunity possibly being caused by increased TLR7 signaling. That immediately perked up my ears, and I imagine might perk up yours as well, given that TLR7 is one of several pattern recognition receptors that detects ssRNA.

Thanks so much for sharing that hypothesis paper. It is indeed interesting that TLR7 has "been implicated" in autoimmunity, but that could mean almost anything. It could be as simple as the fact that TLR7 detects ssRNA viruses, generating inflammation. Then, when people fail to find the virus, they simply chalk it up to "autoimmunity".

Personally, I am more interested in TLR3 because:

1. TLR3 detects dsRNA, and many persistent ssRNA virus infections utilize the dsRNA intermediate state as a de facto latent state. Therefore, TLR3 should detect persistent ssRNA virus infections in this quasi-latent dsRNA state.
2. I happen to have genetic mutations in my TLR3 gene, and at least one of these mutations have been linked to an increased susceptibility to ssRNA virus infections.

If you have e.g a monocyte that is presenting an antigen on its MHC and then this mhc-antigen structure suddenly gets hit by an antibody to that antigen - will the monocyte then get eaten(phagocytosed) by e.g a phagocyte or attacked by something else from our immune system?

If I remember my immunology correctly, the macrophage (monocyte) phagocytoses the antigen, but the antigen is not displayed on the surface of the macrophage until the macrophage leaves the infected tissue and arrives in the lymph node. Once the macrophage containing the antigen arrives in the lymph node, it then presents the antigen to lymphocytes to generate adaptive immunity.

 

[Consul]

If I remember my immunology correctly, the macrophage (monocyte) phagocytoses the antigen, but the antigen is not displayed on the surface of the macrophage until the macrophage leaves the infected tissue and arrives in the lymph node. Once the macrophage containing the antigen arrives in the lymph node, it then presents the antigen to lymphocytes to generate adaptive immunity.

Very nice, thanks! Complicated stuff the immune system.