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How/why The Immune System Reacts To Gluten?

Posted by mle_ii, 31 August 2006 · 210 views

Immune System and Celiac
NOTE: This is the start of going from point A to point B, the ingestion of gluten to damage of the mucosa, in Celiac Disease. Not saying that any of this is correct, but is my current and I'm sure changing understanding of the process. Any comments/corrections/additions would be greatly appreciated as this is a learning process for me and I'm new to the world of biochemistry, pathology and the immune system. So take any of this for what it's worth. :D

Tissue transglutaminase binds the glidian.

QUESTION: Why and what was bound to the glidian? Was it only the tTG or did the tTG bind something to the glidian?

B-Lymphocyte sees an antigen and via Endocytosis it absorbs the glidian and tissue transglutamise bound to it.

QUESTION: Why did the B Lymphocyte do this? Does it do it to random proteins? Did the protein do something it shouldn't? Did the protein try to enter the GI wall tissue?

Once the B Lymphocyte breaks down the glidian and tissue transglutamise it presents itself to the T Cell as an antigen via the MHC mechanism. If it finds a match then antibodies are produced by the B Cell.

QUESTION? Why is the glidian and ttg seen as antigens? Is this via HLA-DQ2 AND DQ8?
QUESTION? The glidian is forein so this I can understand, but why the ttg, why isn't this seen as part of the body? Perhaps since the ttg is bound to the glidian the B Cell it creates antibodies to all proteins that it took in.
QUESTION? Do the HLA mark the protein as forein or self? I'm guessing it's non self.

Antibodies are produced for the glidian and tissue transglutamise.

For the tissue transglutamise it produces IgA anti-tissue transglutaminase antibody (anti-tTG).
For the glidian it produces IgA and IgG anti-gliadin antibodies (AGA), IgG and IgA.

QUESTION? Why is the villi being destroyed? Is this an innate (unfocused) attack? Are the antibodies attacking the villi/mucosa or trying to get to something in the villi or mucosa? Perhaps since the bowel lining is high in tTG and thus the attack is on the bowel.

QUESTION? Where do the endomysium IgA anti-endomysial antibodies (EMA) come from? endomysium is part of the muscle, the connective tissue.
QUESTION? WHat about anti-reticulin antibodies? reticulin is part of the lymphatic tissues.

OTHER QUESTIONS:
Is Anergy the reason why Celiac isn't always turned on in everyone with the gene?
http://en.wikipedia.org/wiki/Anergy

What does glutamine have to do with anything? Specfically what does this mean?
http://www.ncbi.nlm....t_uids=10684852

What other pathogens look like gliadin? Have a similar ammino acid structure?
We have
Candida
Human type 12 adenovirus
http://www.ncbi.nlm....st_uids=1696236

Here we go, both innate and adaptive are invloved:
http://www.ncbi.nlm....t_uids=16230082
http://www.ncbi.nlm....l=pubmed_DocSum
That means that normally the immune system tollerates gluten, but once tollerance is broken all bets are off.

"Although at present it is unknown why tolerance in celiac disease is not established or broken, both environmental and genetic factors have been implicated. There is strong evidence for the existence of genes or gene variants on chromosomes 5, 6, and 19 that predispose to celiac disease. In addition, type I interferons have been implicated in development of several autoimmune disorders, including celiac disease. Thus, viral infection and/or tissue damage in the intestine may cause inflammation and induce protective Th1-mediated immunity leading to loss of tolerance for gluten. Once tolerance is broken, a broad gluten-reactive T cell repertoire may develop through determinant spreading."

1) [quote]Endocytosis is a process whereby cells absorb material (molecules such as proteins) from outside by engulfing it with their cell membrane.[/quote]
http://en.wikipedia....iki/Endocytosis

2) [quote]Tissue transglutaminase - binds proteins.[/quote] Among other things.
http://en.wikipedia....ransglutaminase
http://www.ncbi.nlm....t_uids=12366374
http://www.pubmedcen...mp;blobtype=pdf
http://www.ncbi.nlm....m.cgi?id=190196

3) [quote]Gliadin is a glycoprotein, present in wheat and some other cereals, best known for its role, along with glutenin, in the formation of gluten. [/quote]
http://en.wikipedia.org/wiki/Gliadin

4) [quote]Gluten is an amorphous ergastic protein found combined with starch in the endosperm of some cereals, notably wheat, rye, and barley. [/quote]
http://en.wikipedia.org/wiki/Gluten

5) [quote]The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells) that is responsible for recognizing antigens bound to major histocompatibility complexes (MHC).[/quote]
http://en.wikipedia....T_cell_receptor

6) [quote]The major histocompatibility complex (MHC) is a large genomic region or gene family found in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an important role in the immune system, autoimmunity, and reproductive success.[/quote]
http://en.wikipedia....ibility_complex

7) [quote]An antigen-presenting cell (APC) is a cell that displays foreign antigen complexed with MHC on its surface.[/quote]
http://en.wikipedia....resenting_cells

8) [quote]B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response).[/quote]
http://en.wikipedia.org/wiki/B-cells

9) [quote]Humoral immunity (HIR) is the aspect of immunity that is mediated by secreted antibodies, produced in the cells of the B lymphocyte lineage (B cell). [/quote]
http://en.wikipedia....umoral_immunity

10) [quote]The human leukocyte antigen system (sometimes human lymphocyte antigen) (HLA) is the general name of a group of genes in the human major histocompatibility complex (MHC) region on human chromosome 6 (mouse chromosome 17) that encodes the cell-surface antigen-presenting proteins.[/quote]
http://en.wikipedia....ukocyte_antigen

11) [quote]T cells are a type of white blood cell that play a central role in cell-mediated immunity.[/quote]
http://en.wikipedia....i/T_lymphocytes

12) [quote]T helper cells (also known as effector T cells or Th cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that play an important role in establishing and maximising the capabilities of the immune system. Th cells are involved in activating and directing other immune cells, and are particularly important in the acquired immune system.[/quote]
http://en.wikipedia....i/Helper_T_cell

13) [quote]Regulatory T cells (also known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self.[/quote]
http://en.wikipedia....ppressor_T_cell

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Mikey, I would not call these random ramblings! They are quite deliberate and technical. Random ramblings, for me is something that probably makes sense to me, but probably no-one else! But then if I look harder into what you are saying, then yes I probably don't understand, yet. I'm not trying to put you down, if anything I am putting my self down for not knowing enough.

Your comments are quite up there above my head and to be honest I can't help you with the answers, but good on you for trying to suss it all out. You have offered me a challenge, and I will sit down and study what you have said, and hopefully I will be enlightened.

The way I have handled coeliac thus far is, if I eat something and it makes me sick, that is that. I will not eat that again. I not so much look into why and how the reaction works, but I know it happens. As far as I know it is genetic, so it was going to happen to me, and all forms of gluten are out. At this point I am more concerned about how to prevent any more damage being done to my intestines. So really if I keep going like I am, hopefully and probably this is all that is required to keep my health.

But sometimes I like to think I have more brains than what I probably have, so I will read through your ramblings and see what I can figure out.

Thanks for the thinking.

Catherine
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