type 3 HS

[aspiringmd1015]

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in type 3 HS, how do the immune complexes circulate? example SLE is against dsdna, how would the ag bind to it, and then circulate with ds dna? also some sources say after clearing infections, you can antigen and antibody complexes, how does this occur? help is much appreciated, thanks!

 

[SBR249]

why not? for antigens that are not surface bound or that do not have multiple epitopes they may not be able to crosslink IgG. Without crosslinking, you don't get aggregation so you can get circulation of Ig-Ag complexes. When these ICs then get to places like the glomerulus, they then deposit because concentrations increase (due to ultrafiltration) or velocity decreases or whatever and cause problems.

As for infections, sometimes ags remain the body after an infection for a while, for example, pieces of bacteria, viral proteins, etc. That can form ICs. For if there's mimicry, then the body's Igs will recognize a self-Ag and think it's from the infection.

 

[aspiringmd1015]

so the antigens themselves must be circulating initially themselves? any cell that is tissuebound would be type 2 right?

 

[dyspareunia]

in type 3 HS, how do the immune complexes circulate? example SLE is against dsdna, how would the ag bind to it, and then circulate with ds dna? also some sources say after clearing infections, you can antigen and antibody complexes, how does this occur? help is much appreciated, thanks!

The concept behind Type 3 HSR (versus Type 2) is that the autoantibody doesn't target a specific tissue. In the SLE example, anti-dsDNA is the autoantibody, and dsDNA is the antigen. Part of normal red cell development is extrusion of the nucleus. Normally that nuclear material is taken up by macrophages and destroyed, but in SLE patients the autoantibodies bind to it instead, thus forming Ab-Ag complexes. These complexes are free to circulate until they get stuck onto something. The classic signs/symptoms of SLE tell you where the common sites of adhesion are. Contrast that with a Type 2 HSR, such as Graves' dz in which the autoantibody is specific to the TSH receptor. The Ab-Ag complexes don't circulate because the TSH receptor is only found on the thyroid (and not in systemic circulation).

After clearing infections you can get Ag-Ab complexes because of cross reactivity. Meaning, the infectious Ag very closely resembles a self-Ag and the Ab you make in response to the infection cross react with self-Ab.

I'm not trying to be rude, but it seems like you don't understand the basic physiology of normal immune responses. You should learn that before you start trying to understand things like hypersensitivities and autoimmunity. You can't learn to write words before you know the alphabet.

 

[aspiringmd1015]

i did learn that, no offense taken, just trying to clear my concepts, i just didnt understand the circulating part of type 3 hs, and i know what molecular mimicry is, thanks!

 

[SBR249]

the way I heard it explained depends on the location of the antigen. In type 2 HS, the antigen is where it's supposed to be (in its tissue of origin, etc) and the antibody binds. In type 3 HS, the antigen (and the antibody) are not where they are supposed to be (SLE ICs in the kidney). That's one way to look at it I suppose.

 

[Psai]

How do you not understand the circulating part? where did you think antibodies go

 

[aspiringmd1015]

i understand that the ag ab complex are circulating, thats a dead given. What wasnt clear to me was if the ag was always circulating in the first place

 

[Psai]

,

 

[SBR249]

You will want to be careful with the circulating distinction though. For example, say your Ag is an RBC surface marker, or a circulating protein like SHBG or even albumin. Then the antibody and the antigen will be circulating. In the case of RBC, you may get agglutination. Those would probably be called type 2 HS despite them being circulating because the Ag is technically where they are supposed to be - in the blood.

 

[aspiringmd1015]

right, for example E fetalis

 

[aspiringmd1015]

thanks for the help guys, really appreciate it!