Antibody question

[dnovikov]

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Question is as follows:
In cell #1, the addition of bivalent anti-insulin receptor antibodies induces a response without the addition of insulin. In cell #2, addition of a fragment anti-receptor antibody (monovalent) induces no response without insulin. To cell #2, antibodies against the monovalent anti-receptor antibodies are added. This will result in:

A. no response
B. decreased glucose uptake
C. increased CO2 production
D. increased insulin binding.


Explanation: The question tells us that the addition of bivalent anti-insulin receptor antibodies induces a response without insulin. The bivalent structure will induce cross-linking, leading to a clustering of insulin receptors. This conclusion is bolstered by the next sentence of the question which states that monovalent antibodies, which cannot produce cross-linking, do not induce a response in the absence of insulin. However, if we add antibodies against these monovalent antibodies/fragments, we should be able to induce cross-linking and thus clustering. Therefore, we should be able to induce an insulin-like response, which involves the promotion of glucose as a fuel. When glucose is oxidized, the carbons are released as carbon dioxide.


Ok so I am a little confused about the whole monovalent fragments and bivalent fragments and in general cross-linking in association with antibodies. Can someone explain the question and the explanation differently or make it more clear, I am still a little confused about the insulin receptor clustering; can't seem to picture it in my head. This question is from TBR Biology book 1 section 5 on immunology, page 316. Thanks and any help is much appreciated!

 

[MedPR]

Bivalent = can bind 2 epitopes (2 antigens).
Monovalent = can bind 1 antigen.

Bivalent antibodies bind 2 antigens and cross link them together. This makes a big clump = agglutination.

If you can only bind 1 antigen (monovalent), you can't cross link that antigen with anything because you have nothing to cross link it with.

 

[chiddler]

Bivalent = can bind 2 epitopes (2 antigens).
Monovalent = can bind 1 antigen.

Bivalent antibodies bind 2 antigens and cross link them together. This makes a big clump = agglutination.

If you can only bind 1 antigen (monovalent), you can't cross link that antigen with anything because you have nothing to cross link it with.

wa? where did you learn this!

 

[dnovikov]

Ok so in order to answer this question you just had to understand that adding antibodies in cell #2 to the monovalent antibodies mimics the process that was done in cell #1 due to clustering and so an insulin like response is induced?

 

[dnovikov]

wa? where did you learn this!

Seriously, TBR didn't go over this and I VAGUELY remember this from my immuno course... Nothing about clusters tho...

 

[MedPR]

wa? where did you learn this!

Not sure, but you should know the generic structure of an antibody. Two heavy chains, two light chains, and two variable regions. The two variable regions = bivalent = can bind two different antigens. There are some immunoglobulins, like IgM, that can bind more than 2 antigens, but that's another story.

Ok so in order to answer this question you just had to understand that adding antibodies in cell #2 to the monovalent antibodies mimics the process that was done in cell #1 due to clustering and so an insulin like response is induced?

Kind of. The question says that you add antibodies against the monovalent fragments. This means that the antibodies you are adding will bind two of the monovalent fragments, one at each variable region. Now you have 1 antibody (the one you added last) attached to two monovalent fragments. The monovalent fragments can still bind one antigen, but now they can also cross link because you have essentially made a new bivalent antibody (the one you added + two monovalents).

So the added antibody sees the monovalent antibodies as antigens. It binds two of them. The monovalent antibodies are still binding whatever they were binding before, only now they can cross link.

 

[MedPR]

Let me upload a picture. Drawn in paint so its really ugly, sorry.

Ok, this first picture is of cell 1 with the bivalent antibody. You can easily see that it can bind and cross-link two receptors, thus initiating the cascade of events that insulin would (they tell you this in the question). Red = bivalent antibody.

Now, this image is of the monovalent antibodies along with the antibody to those monovalent antibodies. The monovalent antibodies are shown in red. Yellow is the antibody against the monovalent antibodies. Initially you only have monovalent antibodies (red) that can bind the receptors, but do not cross link them. Thus, no cellular response. Now toss in the anti-monovalent antibody (yellow) and your receptors will be cross linked since the monovalent antibodies + the anti-monovalent antibody basically acts like a bivalent antibody for the receptors.

 

[dnovikov]

Wow great explanation and thanks for drawing the picture!! I completely understand now.

 

[hellocubed]

anti-insulin receptor antibodies

A question, what exactly does "anti-insulin receptor antibodies" mean?
Does it mean that the specific antibody signals the destruction of insulin?



Oh my gosh I am so confused.

The antibody for antibodies is becoming insulin?

 

[chiddler]

A question, what exactly does "anti-insulin receptor antibodies" mean?
Does it mean that the specific antibody signals the destruction of insulin?



Oh my gosh I am so confused.

The antibody for antibodies is becoming insulin?

relax lol

anti-insulin just means that the antibody binds to insulin. yes it may signal the destruction of insulin. i'm not sure what your last sentence is saying but if still confused ask.

 

[Whiteshoes]

Let me upload a picture. Drawn in paint so its really ugly, sorry.

Ok, this first picture is of cell 1 with the bivalent antibody. You can easily see that it can bind and cross-link two receptors, thus initiating the cascade of events that insulin would (they tell you this in the question). Red = bivalent antibody.

Now, this image is of the monovalent antibodies along with the antibody to those monovalent antibodies. The monovalent antibodies are shown in red. Yellow is the antibody against the monovalent antibodies. Initially you only have monovalent antibodies (red) that can bind the receptors, but do not cross link them. Thus, no cellular response. Now toss in the anti-monovalent antibody (yellow) and your receptors will be cross linked since the monovalent antibodies + the anti-monovalent antibody basically acts like a bivalent antibody for the receptors.

Nice explanation.

what if the problem was the same but now it's "anti-glucagon" wouldn't CO2 still be produced since during a glucagon cascade your body needs to burn glucose since it is in stress? if so that's sort of counter intuitive because I would think an insulin cascade & glucagon cascade have opposite effects.

 

[MedPR]

A question, what exactly does "anti-insulin receptor antibodies" mean?
Does it mean that the specific antibody signals the destruction of insulin?



Oh my gosh I am so confused.

The antibody for antibodies is becoming insulin?

relax lol

anti-insulin just means that the antibody binds to insulin. yes it may signal the destruction of insulin. i'm not sure what your last sentence is saying but if still confused ask.

Be careful. The question is talking about "anti-insulin receptor antibody" not "anti-insulin antibody." The antibodies in this question simply bind to insulin receptors and activate the same cascade you would expect of insulin. In this situation you can consider the insulin receptor to be an "antigen." I use quotes because an antigen is defined as something that illicits an immune response. Based on the question stem, the antibodies are being added artificially as opposed to being created by plasma cells so there is no reason to believe there is an immune response involved.

If it helps you, you can think of the bivalent anti-insulin receptor antibody as an insulin agonist and the monovalent anti-insulin receptor antibody as a competitive inhibitor of insulin. These facts are a bit beyond what the question asks, and are probably one or two steps beyond what a typical MCAT question would ask, but its kind of a hat-trick like thought process!

 

[MedPR]

Nice explanation.

what if the problem was the same but now it's "anti-glucagon" wouldn't CO2 still be produced since during a glucagon cascade your body needs to burn glucose since it is in stress? if so that's sort of counter intuitive because I would think an insulin cascade & glucagon cascade have opposite effects.

Glucagon and insulin have opposite effects. Insulin = decrease blood glucose and glucagon = increase blood glucose. They basically are mediators of a feedback inhibition loop.

"Anti-glucagon" antibodies would result in very low blood glucose levels since glucagon would be tied up in the antibody and unable to bind its receptor to initiate the normal response/cascade. I assume CO2 production by glycolysis would be normal at first, then eventually hit 0. Why? There is some glucose stored in muscles, so initially they will be able to contribute to the increased ATP demand, but once the muscle uses up all its stored glucose and whatever glucose happens to be floating around in the blood, it will have no way to get more since glucagon is inactivated and thus not stimulating the liver to release glucose into the blood. No glucose = no glycolysis = no CO2 production (specifically by glycolysis). Whether or not overall CO2 production would decrease/increase I don't know.


Did you mean "anti-glucagon receptor" antibodies? In that case, assuming these antibodies were glucagon agonists (like they are insulin agonists in the OP question) they would also stimulate the glucagon cascade. The bivalent anti-receptor antibodies discussed in the question are nothing more than substitutes for insulin/glucagon. So bivalent anti-glucagon receptor antibody would stimulate the glycogenolysis in the liver (produce glucose from glycogen) and then release the glucose into the blood.

Assuming the information in the first sentence of the question is correct, the bivalent anti-receptor antibodies will result in the exact same stuff as normal person with normal insulin/glucagon levels and controls.