Antibody Heavy Chain Determination

In summary: IgM heavy chain isotypes because of the presence of Switch regions at the 3' of any isotype gene exon. These Switch regions allow for cytokine secretion in response to Ag stimulation, and it is regulated largely by cytokines that are secreted upon Ag stimulation.
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None
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Dunno if anyone that reads these boards has a background with Immunology, but here goes.

As far as I understand it, heavy chain isotypes can switch on any given mature B cell due to the presence of Switch regions at the 3' of any isotype gene exon. This is regulated largely by cytokines that are secreted upon Ag stimulation.

Is it just regular old granulocytes that secrete these cytokines? And in response to what exactly, how does it know which isotype the antibodies should be?

Also, how does a placenta get the required antibodies to fight infection if IgG is the only placental transfer isotype. Is this due to chance? (though I highly doubt evolution would leave it at that)

Thanks in advance
None.
 
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"Also, how does a placenta get the required antibodies to fight infection if IgG is the only placental transfer isotype. Is this due to chance? (though I highly doubt evolution would leave it at that)"

First of all, I am not very familiar with immunology.

BUT

I will say this, evolution is not forward thinking, matter of fact it is not thinking at all, it is merely selection of nature upon phenotypes, which act upon genotypes, to change future allele frequency.

Based on the fact, that a placenta gets the required antibodies to fight infection, 100% of the time (or at least close enough), this has to be an acquired trait that is passed on from generation to generation. So there must be a mechanism in place. So to answer you question, NO, it can not be due to chance.

Nautica
 
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Thanks Nautica I agree...

This all sort of has to do with my initial question, what is regulating the cytokine secretion that is responsible for isotype switching? If I could figure that out, the rest would most likely be visible immediately.

None.
 
  • #4
Originally posted by None

Is it just regular old granulocytes that secrete these cytokines?

T helper cell and macropahge are the major cytokines producers but many more cell type (not restricted to immune system cells) can secrete cytokines which includes inteurleukins (IL), interferon (INF), lymphokines and tumor necrosis factors (TNF). Cytokines are excreted by various agents. IL-1 and TNF alpha are good example but it is a pain in the butt to explain plus I don't have my mechanism of pathogenecity notes.

Originally posted by None
And in response to what exactly, how does it know which isotype the antibodies should be?

The rearrangement appear to be random in the bone marrow. Mature B-cell exibit a single Ig with antigenic specificity but many different Ig-antigenic specifity are created at the same time (Lets call these cell 1, 2, 3, 4). Mature B-cell 1,2,3,4 get into contact with an antigen. Only Ig of B-cell 2 is immunospecific for this antigen. Then B-cell get "cloned" and produce memory cell and plasma cell.

Originally posted by None
how does a placenta get the required antibodies to fight infection if IgG is the only placental transfer isotype.

Antibodies are there more or less by chance. Immunoglobulin circulates through out the blood and lymp system and get transported into their tissues of preference once they get there. IgA is saliva breast milk, fluids of mucosa. IgG is the one that can cross the placenta and its 75% of all IgG. When Ig recognize an invaders/antigen it stimulates the immune system which migrates to the placenta or on the site of infection.
 
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I scan two page of notes

go to http://www.geocities.com/ytremb1/

and click on
B-Cell cloning and selection
Inflamation responce


Immunology is a hell hole. Everything activates everything and it gets complicated. Some books don't even aggree with each other.
 
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Thanks a lot for the scans iansmith, I'm not talking about proliferation of the B-Cells though, which is what that first slide is describing :smile:

The rearrangement appear to be random in the bone marrow. Mature B-cell exibit a single Ig with antigenic specificity but many different Ig-antigenic specifity are created at the same time (Lets call these cell 1, 2, 3, 4). Mature B-cell 1,2,3,4 get into contact with an antigen. Only Ig of B-cell 2 is immunospecific for this antigen. Then B-cell get "cloned" and produce memory cell and plasma cell.

Rearrangement is definitely not random!

Like you say in this paragraph, Mature B-Cell exhibit an Ig with a single antigenic specificity.. but it goes a little deeper, so far as I understand it anyways That single antigenic specificity is due to Combinatorial Diversity (basically the genes encoding the immunoglobulin heavy and light chains are arranged in exons that get spliced and matched up in tons of different ways). After this matching has occured, the antibodies will all be of either IgM or IgD heavy chain isotype, just because of the order of the rearrangements.

Mature B Cells in the bone marrow can display both IgD and IgM heavy chains, and in the periphery they can switch isotypes using the route

IgM ---> IgG --> IgA --> IgE

They will all have the same variable region however, that part of the rearrangement is permanent! (well sorta, mutations can occur but that gets a little complex). The important thing to remember is that it's only the Heavy chain isotype changing, not the antigenic specificity.

IgG is the one that can cross the placenta and its 75% of all Ig

Right! So basically what I'm asking is what if one Ig of the other 25% that isn't IgG happens to have the antigenic specificity we're looking for to identify infection? It can't cross the placenta and therefore can't reach the Antigen. This is why nautica so validly pointed out that it can't just be chance switching to get it through! There has to be some sort of mechanism involving the cytokines.

I'll explain some of these concepts if you non-immunology students are really interested. I've seen that iansmith has already started a tutorial
 
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Originally posted by None

Right! So basically what I'm asking is what if one Ig of the other 25% that isn't IgG happens to have the antigenic specificity we're looking for to identify infection? It can't cross the placenta and therefore can't reach the Antigen. This is why nautica so validly pointed out that it can't just be chance switching to get it through! There has to be some sort of mechanism involving the cytokines.

but the Ig circulates freely in the body. Your intestine is full of IgA but they do not specifcaly protect against some invaders. IgG is also supply by the mother and is only produce after the first infection. So technacilly the IgG will go randomly through the body seaching for invaders. When it come to contact with the placental cell intakes IgG and it cross the barrier. Their must have been an evolution presssure for IgG or any other type to cross the barrier but they are not call to the placenta. The process is far from perfect, many children get pre-natal infection due to latent invader in the mothers.

Subsequent step will call the specificity of immune system into the the site of infection.
 
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Originally posted by None
I'll explain some of these concepts if you non-immunology students are really interested. I've seen that iansmith has already started a tutorial
Hi None! This is great, welcome to the forums!

I wish I could talk along with immunology.. but at this point I can't really, but reading all this is really interesting :)
 

1. What is antibody heavy chain determination?

Antibody heavy chain determination is a laboratory technique used to identify and characterize the specific heavy chain subunits of antibodies. It involves isolating and analyzing the heavy chain portion of an antibody molecule to understand its structure and function.

2. How is antibody heavy chain determination performed?

Antibody heavy chain determination typically involves techniques such as electrophoresis, chromatography, and mass spectrometry. These methods allow for the separation and analysis of the heavy chain subunits of antibodies.

3. Why is antibody heavy chain determination important?

Antibody heavy chain determination is important because it helps researchers better understand the structure and function of antibodies. This information can be used to develop more effective therapeutic antibodies and improve our understanding of immune responses.

4. What are the applications of antibody heavy chain determination?

The applications of antibody heavy chain determination include antibody engineering, disease diagnosis, and drug development. It can also be used in research studies to investigate the role of specific antibody heavy chains in various biological processes.

5. Are there any limitations to antibody heavy chain determination?

Yes, there are some limitations to antibody heavy chain determination. For example, it may not be able to identify rare or unique heavy chain variants, and it may not provide information about the binding specificity of antibodies. Additionally, the process can be time-consuming and may require specialized equipment and expertise.

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