Type 3 hypersensitivity is confusing?

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Discussion Overview

The discussion revolves around Type 3 hypersensitivity (T3H), exploring its mechanisms, including the formation of immune complexes, and the relevance of Arthus reaction and serum sickness as examples of this hypersensitivity type. Participants seek to clarify their understanding of these concepts and their interrelations.

Discussion Character

  • Exploratory
  • Technical explanation
  • Conceptual clarification
  • Debate/contested

Main Points Raised

  • Some participants describe T3H as involving excess antigen and insufficient antibody formation, leading to small immune complexes that are not phagocytized and can deposit in tissues.
  • Participants mention that the Arthus reaction is an experimental demonstration of T3H, where injecting antigen into an individual with specific antibodies leads to the formation of immune complexes at the injection site.
  • Serum sickness is discussed as a condition where large amounts of preformed antibodies are administered, potentially leading to an immune response against these antibodies and subsequent immune complex deposition.
  • There is a question about the clinical relevance of the Arthus reaction, with some participants noting it is primarily of historical interest.
  • Clarifications are made regarding the solubility of immune complexes in serum sickness versus their precipitation in the Arthus reaction, with some participants expressing confusion over the rationale for using excess antigen in the latter.
  • One participant notes that the deposition of antigen-antibody complexes can lead to complement fixation, contributing to vascular damage.

Areas of Agreement / Disagreement

Participants generally agree on the basic mechanisms of T3H and the roles of Arthus reaction and serum sickness, but there remains some confusion and debate regarding the clinical relevance of these examples and the specifics of immune complex behavior.

Contextual Notes

Some participants express uncertainty about the clinical implications of the Arthus reaction and the conditions under which immune complexes precipitate versus remain soluble. There are also references to historical context that may not be fully explored in the discussion.

sameeralord
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Hello guys,

I'm reading and trying to understand this and going no where. From what I gather in Type 3 hypersensitivity, there is too much antigen and small immune complexes are made, which are not phagocytosed and deposit in tissue causing tissue damage. Then what has Arthus reaction and serum sickness got to do with this concept (small immune complexes). I don't understand Arthus reaction and serum sickness, despite reading it for sometime now.
 
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sameeralord said:
Hello guys,

I'm reading and trying to understand this and going no where. From what I gather in Type 3 hypersensitivity, there is too much antigen and small immune complexes are made, which are not phagocytosed and deposit in tissue causing tissue damage. Then what has Arthus reaction and serum sickness got to do with this concept (small immune complexes). I don't understand Arthus reaction and serum sickness, despite reading it for sometime now.

These are simply examples of the type III reaction. What exactly are you unable to understand?
 
T3H is when you have excess antigen (Ag) and too little antibody (Ab) being formed. This results in small immune complexes being formed which aren't phagocytized and potential deposition along vasculature or basement membranes.

Arthus reaction is just an experimental way to demonstrate T3H. Its when you inject Ag into an individual with the specific Ab. At the injection site, there is excessive Ag which makes small immune complexes which deposit on the vasculature in the area leading to a red bump. Its not really relevant clinically.

In serum sickness, you have a patient being given large amounts of preformed antibodies hoping to give them passive immunity against the insulting substance. Such as antivenom or antitoxin. The host can make an immune response to these Ab's, but since you are giving such large amounts (as was often the case in WWII for soldiers being given anti-tetanus toxin) there is excess antigen. This results in the deposition along the vasculature and BM of glomeruli (glomerulinephritis).

The immune complexes cause local inflammation, histamine release, etc. That's why you get the red bump in Arthus, or the characteristic rashes of systemic lupus erythematosus.

Hope that helps
 
bobze said:
T3H is when you have excess antigen (Ag) and too little antibody (Ab) being formed. This results in small immune complexes being formed which aren't phagocytized and potential deposition along vasculature or basement membranes.

Arthus reaction is just an experimental way to demonstrate T3H. Its when you inject Ag into an individual with the specific Ab. At the injection site, there is excessive Ag which makes small immune complexes which deposit on the vasculature in the area leading to a red bump. Its not really relevant clinically.

In serum sickness, you have a patient being given large amounts of preformed antibodies hoping to give them passive immunity against the insulting substance. Such as antivenom or antitoxin. The host can make an immune response to these Ab's, but since you are giving such large amounts (as was often the case in WWII for soldiers being given anti-tetanus toxin) there is excess antigen. This results in the deposition along the vasculature and BM of glomeruli (glomerulinephritis).

The immune complexes cause local inflammation, histamine release, etc. That's why you get the red bump in Arthus, or the characteristic rashes of systemic lupus erythematosus.

Hope that helps

Thanks Bobze :smile: I understand serum sickness now. However arthus reaction, why are we giving excess antigen for no reason. Is it as you said just to demonstrate this effect. Also in Arthus reaction immune complexes seem to precipate unlike serum sickness where they are soluble. Why is that?
 
Correct, Arthus is just an experimental way to demonstrate a T3H. Like I said, its not useful clinically. Historically it was used to demonstrate the type 3 reaction. Around the turn of the 19th century I believe.

The immune complexes are still soluble. They are deposited in the small vasculature near the site of the injection, leading to vasculitis.

In serum sickness, you're giving the antivenom/toxin via IV administration. This circumvents the small vasculature that would lead to an Arthus reaction. However, your blood still passes through small vasculature which is why the effects are disseminated and the effects extend to areas like the glomeruli.
 
As an afterthought, The actual way you get vasculitis or vascular damage is because after deposition the Ag-Ab complex is capable of fixing complement.
 

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