Confused about Type II versus Type III hypersensitivity...

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CBG23

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So, I am currently learning about glomerulonephritis and am reading about how immune complex formation/ deposition is one of the general mechanisms of injury for GN. I know that immune complexes can form in the circulation and deposit in the glomeruli OR antigen can deposit in the glomeruli and then antibody binds to the deposited antigen and forms complexes (in situ complex formation).

So, I am confused about whether the diseases caused by in situ complex formation are Type II or Type III hypersensitivity. You could say that it is Type III because immune complexes have to form to cause disease, BUT why wouldn't it be a Type II reaction? Antibodies are binding to an antigen present on host tissue and not forming in the circulation? Isn't that basically defined as a Type II reaction? I was thinking that maybe the distinction was in whether or not the antigen in the tissues was intrinsic or extrinsic but it seems that both Type II and Type III reactions can be triggered by intrinsic or extrinsic antigens.

Maybe I am just not understanding the difference between Type II versus Type III hypersensitivity?:confused:

Anyway, I couldn't figure it out even after consulting several sources so I thought I'd see if someone here maybe had a better idea or understanding of the distinction...

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These seem to be shades of gray. I always traditionally associated type III with complex formation and then deposition. Type II, on the other hand, you just get Ab inappropriately targeted at something, but not complex formation.

Wiki classifies type III as Ab and Ag being in equal amounts. If true, this could be an important classification used to differentiate type II and type III.

http://en.wikipedia.org/wiki/Type_III_hypersensitivity

Edit: also, wiki notes that in type III you have large complex that are not bound to cell surfaces (just big clusters of of Ag and Ab sticking out from a surface). In type II this isn't the case.
 
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Another distinction between Type II and III is in type II, there is tissue phagocytosis while in type III, there is tissue necrosis.
 
I think the main difference is Ig specificity.

Type II Hypersensitivity - Tissue-specific IgG response

ex. Goodpasture's Syndrome - IgG response is specific for Collagen IV in the Basal Membrane of Renal Glomeruli (and sometime pulmonary alveoli). The IgG deposition is smooth (as seen in fluorescence studies) and the complement cascade is activated.

Type III hypersensitivity - Non-tissue-specific IgG response

ex. Systemic Lupus Erythematosus - IgG response is non-specific, with formation of immune complexes throughout the body. Butterfly face rash results from immune complexes getting physically stuck in capillaries close to skin surface, and kidney damage (along with other tissue damage) results from immune complexes getting physically stuck in the renal glomeruli, with a lumpy deposition (as seen in fluorescence studies)

ex. Rheumatoid Arthritis - Rheumatoid Factor (RF) is a strange type of anti-IgG antibody which binds to IgG (mostly in synovial joints), forming immune complexes that damage the articular cartilage
 
I think the main difference is Ig specificity.

Type II Hypersensitivity - Tissue-specific IgG response

ex. Goodpasture's Syndrome - IgG response is specific for Collagen IV in the Basal Membrane of Renal Glomeruli (and sometime pulmonary alveoli). The IgG deposition is smooth (as seen in fluorescence studies) and the complement cascade is activated.

Type III hypersensitivity - Non-tissue-specific IgG response

ex. Systemic Lupus Erythematosus - IgG response is non-specific, with formation of immune complexes throughout the body. Butterfly face rash results from immune complexes getting physically stuck in capillaries close to skin surface, and kidney damage (along with other tissue damage) results from immune complexes getting physically stuck in the renal glomeruli, with a lumpy deposition (as seen in fluorescence studies)

ex. Rheumatoid Arthritis - Rheumatoid Factor (RF) is a strange type of anti-IgG antibody which binds to IgG (mostly in synovial joints), forming immune complexes that damage the articular cartilage

Good generalization.

What about poststreptococcal glomerulonephritis? Immune complexes form in response to presence of streptococcal antigens which can get planted in situ or the complex can form in the blood and get lodged in the glomeruli.
 
We were taught Type 2 is when the Antigen (Ag) is where it is suppose to be when the Ab combines with it. Type 3 is when the Ag is not where it is suppose to be.

Type 2 would be an Ag like wrong blood transfusion and the Ag (diff blood type) is in the blood (where it is suppose to be) and the Ab binds to it.

Type 3 would be like in SLE where you get Ab-Ag being formed and then deposited in tissue (where it's not suppose to be).

Type 2 can have some glomerular parts being attacked (Goodpasture), but that's because the Ag (which is the glomerular basement membrane) is where it is suppose to be. No Ag-Ab complexes are deposited there...the Ag was already there to begin with.

Type 3 for post-strep would have the strep protein deposited in the glomeruli. Ab then binds. Then immune complex is made. That immune complex is being made where it should not be made.

Hopefully I understood your question and didn't say something you already knew. :/ I like to keep it simple.
 
Thanks 49ers and TexasMDtobehttp://more.studentdoctor.net/member.php?u=324727. I think both of your explanations cleared it up for me. None of the sources I looked at, including good old Robbins emphasized the whether or not the location of the antigen was native or not when antibody was bound to it. Thanks again,

We were taught Type 2 is when the Antigen (Ag) is where it is suppose to be when the Ab combines with it. Type 3 is when the Ag is not where it is suppose to be.

Type 2 would be an Ag like wrong blood transfusion and the Ag (diff blood type) is in the blood (where it is suppose to be) and the Ab binds to it.

Type 3 would be like in SLE where you get Ab-Ag being formed and then deposited in tissue (where it's not suppose to be).

Type 2 can have some glomerular parts being attacked (Goodpasture), but that's because the Ag (which is the glomerular basement membrane) is where it is suppose to be. No Ag-Ab complexes are deposited there...the Ag was already there to begin with.

Type 3 for post-strep would have the strep protein deposited in the glomeruli. Ab then binds. Then immune complex is made. That immune complex is being made where it should not be made.

Hopefully I understood your question and didn't say something you already knew. :/ I like to keep it simple.
 
ex. Rheumatoid Arthritis - Rheumatoid Factor (RF) is a strange type of anti-IgG antibody which binds to IgG (mostly in synovial joints), forming immune complexes that damage the articular cartilage

So here's one thing I don't quite get, which hopefully someone can clarify. RA is considered a Type III hypersensitivity. Which I can understand, because there is Ab-Ag complex deposition in the joints. But why is it not also Type II? It is predicated upon formation of an IgM auto-antibody to epitopes on one's own IgG - without that self-reactive IgM, RA wouldn't occur.

Any ideas?
 
In Type II hypersesitivity antigens bind to host cell, antibodies attaches to them and causes lysis of the cell by activating MEMBRANE ATTACK COMPLEX ( particular to type II)....in type III the SOLUBLE antigens form complexes with antibodies and the smaller ones diffuses in joints and small blood vessles resulting in a GENERAL inflammatory response..
 
In Type II hypersesitivity antigens bind to host cell, antibodies attaches to them and causes lysis of the cell by activating MEMBRANE ATTACK COMPLEX ( particular to type II)....in type III the SOLUBLE antigens form complexes with antibodies and the smaller ones diffuses in joints and small blood vessles resulting in a GENERAL inflammatory response..

Tissue transplantation would be a huge contradiction to your soluble antigen in type III theory. This is in which alloantigens in the tissue (HLA proteins) cause the type 3 hypersensitivity. There are exceptions in every case and I wouldn't get bogged down on determining factors. Look at diseases that have already been classified and try to discern the differences like 49erz was doing.
 
Tissue transplantation would be a huge contradiction to your soluble antigen in type III theory. This is in which alloantigens in the tissue (HLA proteins) cause the type 3 hypersensitivity. There are exceptions in every case and I wouldn't get bogged down on determining factors. Look at diseases that have already been classified and try to discern the differences like 49erz was doing.

2 years later.
 
type II hypersensitivity can involve either IgM or IgG antibodies, with IgM typically causing an intravascular hemolysis through complement mediated lysis or IgG opsonizing and splenic (or other) macrophages consuming them leading to extravascular hemolysis. IgM doesn't opsonize and is a more potent activator of complement (5 binding sites). To my knowledge, type III hypersensitivity involves antigens in plasma that are circulating and binding to antibodies, subsequently depositing in innocent tissues, leading to complement activation and residual damage of tissues due to degranulation of neutrophils (C5a) and general inflammation (C3a/C5a chemotaxis).
 
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