Question on hyperacute graft rejection...type II or III?

[Transformers]

Uworld had a classic case of a "mottled, kidney graft" with the answer being "antibody mediated hypersensitivity" but there was another option that had immune complex...so I'm a bit confused about the path of hyperacute rejection. One thing is for sure...it is antibody mediated and the classic buzzword is "thrombosis with fibrinoid necrosis of blood vessels" However, when you break down the scenarios, my understanding is:

1.) I agree that it is type II in the context of a blood cell [non-febrile RBC-surface antigen or febrile WBC-HLA antigen mismatch (i.e.- in a blood transfusion) where the attack would occur asap)

2.) But in terms of organ transplants, isn't this type III? Isn't this essentially an Arthus reaction with immune complexes forming and depositing in the renal artery to be specific causing this thrombosis? If so, I'm just a bit indecisive once again about whether Hyperacute rejection is Type II or Type III given this context of the UWorld question.

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[hardee17]

2

 

[Rac65]

Let us not forget that the ABO antigens are also present on cells other than RBCs. (such as the endothelium)

 

[Transposony]

You are confusing between hyperacute and acute rejection.

Hyperacute rejection is due to preexisting cytotoxic antibodies (Type 2) whereas Acute rejection is cell mediated (a Type 4) reaction.

Hyperacute rejection (Type II)

Initiated by preexisting humoral immunity, hyperacute rejection manifests within minutes after transplant, and if tissue is left implanted brings systemic inflammatory response syndrome. Of high risk in kidney transplants is rapid clumping, namely agglutination, of red blood cells (RBCs or erythrocytes), as an antibody molecule binds multiple target cells at once.

Acute rejection (Type IV)

Developing with formation of cellular immunity, acute rejection occurs to some degree in all transplants, except between identical twins, unless immunosuppression is achieved (usually through drugs). Acute rejection begins as early as one week after transplant, the risk being highest in the first three months, though it can occur months to years later. Highly vascular tissues such as kidney or liver often host the earliest signs—particularly at endothelial cells lining blood vessels—though it eventually occurs in roughly 10 to 30% of liver transplants, and 50 to 60% of kidney transplants. A single episode of acute rejection can be recognized and promptly treated, usually preventing organ failure, but recurrent episodes lead to chronic rejection.

Chronic rejection (Type II & IV)

The term chronic rejection initially described long-term loss of function in transplanted organs via fibrosis of the transplanted tissue's blood vessels. This is now chronic allograft vasculopathy, however, leaving chronic rejection referring to rejection due to more patent aspects of immunity.

 

[Transformers]

Acute is T cell mediated dude...i mean my question is really how do you get thrombosis of a kidney graft from merely Type 2 in a hyperacute rejection? Uworld said that hyperacute has fibrinoid necrosis and the hallmark of fibrinoid necrosis (as is the case of Arthus reaction) is immune complex deposition of essels

 

[Rac65]

I'm not really sure about the mechanism myself and you really shouldn't be worried about it either - what you do need to know is that hyperacute rejection is associated with a humoral response (premade antibodies to graft antigens) and immediate thrombosis upon reestablishment is its most important feature.

If you want to try and decipher the mechanism behind the fibrinoid necrosis, you can try and look at it the following way (and I'm not going to look for any resources on this one, feel free to waste your time doing that yourself): the term itself, FIBRINOID, refers to the accumulation of fibrin-like material in the walls of the vessel (in the case of vascular involvement) which microscopically stains pink(ish) using standard stains (H&E); when you have antibodies bound to graft tissue activating complement and eventually causing vessel damage - it is natural for protein (of all sorts) to leak through the endothelium into the vessel wall; the accumulation of necrotic, proteinaceous material in the vessel wall is the definition of fibrinoid nercosis.

Although a good association to have (fibrinoid necrosis, type III HSR, vasculitidies), I'm pretty sure that if the question asked you about anything involving hyperacute rejection it would be the concept I started the post with. (feel free to mention the question number)

 

[Transposony]

Acute is T cell mediated dude...i mean my question is really how do you get thrombosis of a kidney graft from merely Type 2 in a hyperacute rejection? Uworld said that hyperacute has fibrinoid necrosis and the hallmark of fibrinoid necrosis (as is the case of Arthus reaction) is immune complex deposition of essels

You are right. I have edited my post accordingly.

Here is the mechanism of hyperacute rejection: The antigen-antibody complexes get deposited in the walls of arteries. They also activate the complement, causing massive thrombosis in the capillaries. Fibrin leaks out of the vessels leading to "fibrinoid" appearance (as explained beautifully by Rac65).

 

[Phloston]

Saw a question once on hyperacute rejection where they wanted you to know CD27 was best reflective of the process.

CD27 = plasma cell marker --> preformed antibodies

 

[Transposony]

Saw a question once on hyperacute rejection where they wanted you to know CD27 was best reflective of the process.

CD27 = plasma cell marker --> preformed antibodies

You never fail to amaze me, Phloston with your more than helpful attitude.

 

[theTruth_97]

You are confusing between hyperacute and acute rejection.

Hyperacute rejection is due to preexisting cytotoxic antibodies (Type 2) whereas Acute rejection is cell mediated (a Type 4) reaction.

Transposony- does Type II Hypersensitivity reaction always involve preexisting antibodies or is it just for certain cases? (this may be a really dumb question but I'm kind of confused by it)

 

[Transposony]

Transposony- does Type II Hypersensitivity reaction always involve preexisting antibodies or is it just for certain cases? (this may be a really dumb question but I'm kind of confused by it)

Always. It's like an "Open season" kind of situation.

 

[theTruth_97]

Always. It's like an "Open season" kind of situation.

And what about Type III hypersensitivity- does that involve pre-existing antibodies as well?
Thank you soooo much for your help Transposony- not only for these questions but you've answered quite a few of my questions in the past as well!

 

[Transposony]

All hypersensitivity reactions (by definition) require prior exposure to the antigen. Only the type of immune response varies.

In type III hypersensitivitiy, first exposure to antigen leads to the synthesis of antibodies and second exposure leads to formation of antigen-antibody complexes.

The key difference between Type II and Type III hypersensitivitiy is that the damage in Type III is system-wide. Once the immune complexes lodge in the small diameter blood vessels, they activate complement followed by recruitment of leukocytes by C5a and Fc receptors in that location which may be quite distant from their point of origin.
Hope this helps.

 

[theTruth_97]

All hypersensitivity reactions (by definition) require prior exposure to the antigen. Only the type of immune response varies.

In type III hypersensitivitiy, first exposure to antigen leads to the synthesis of antibodies and second exposure leads to formation of antigen-antibody complexes.

The key difference between Type II and Type III hypersensitivitiy is that the damage in Type III is system-wide. Once the immune complexes lodge in the small diameter blood vessels, they activate complement followed by recruitment of leukocytes by C5a and Fc receptors in that location which may be quite distant from their point of origin.
Hope this helps.

WOW that was amazing! Makes so much more sense now- Thanks again!