allergy feed back loop

[Guest guest]

Essential " Allergy Feedback Loop " Discovered By Hopkins Scientists

The Hopkins team documented this feedback loop in lab tests and, for the first

time, in patients, confirming what they had long suspected: that IgE antibodies

and IgE receptors wax and wane together, linked somehow in a complex dance.

" To stop allergies, you need to maintain low counts of both IgE antibodies and

IgE receptors,

http://www.sciencedaily.com/releases/1999/05/990505165340.htm

http://www.eurekalert.org/pub_releases/1999-05/JHMI-EFLD-050599.php

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Development of a Monoclonal Anti-Immunoglobulin E Antibody (Omalizumab) for the

Treatment of Allergic Respiratory Disorders

http://ajrccm.atsjournals.org/cgi/content/abstract/164/8/S1/S6

http://ajrccm.atsjournals.org/cgi/reprint/164/8/S1/S6

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AUTOIMMUNITY

The three most accepted theories are:

1. The release of sequestered antigen.

2. Molecular (or antigenic) mimicry.

3. Polyclonal B cell activation.

Release of Sequestered Antigen

Sequestered antigen is antigen that is normally hidden from the immune response.

A good example would be myelin basic protein (MBP) which is a large component of

the myelin sheath which surrounds nerves. This protein is unlikely to be in the

thymus to mediate negative selection of T cells but also it is unlikely to be

floating around in the circulation for presentation to T cells.

If, however, a viral infection damages the nervous tissue, now MBP could be

released in large quantities and under conditions of inflammation. The local

dendritic cells would now be seeing large amounts of a protein they are not used

to seeing in an environment where damage is occurring and an active anti-viral

immune response is being initiated. In this context the dendritic cells could

present the MBP antigen to T cells with the appropriate co-stimulation to

initiate an immune response to MBP. The immune response initiated would then

cause more damage to the nerves releasing more MBP antigen in the context of

more inflammation. This will result in a chronic response which will damage the

nerve sheath.

There is also evidence that the expression of " unexpected " antigens can lead to

autoimmunity, especially antigens out of sync with normal development.

http://immunology.medicine.dal.ca/bookcase/autoimmunity.htm

ANTIBODIES

http://immunology.medicine.dal.ca/bookcase/antibodies.htm

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Scientists Show Monoclonal Antibody Leads To Repair Of Myelin Sheath In

Laboratory Study Of Multiple Sclerosis.

http://www.medicalnewstoday.com/articles/85935.php

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Monoclonal Antibodies

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Monoclonals.html

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[Guest guest]

Molecular Mechanisms for Transcriptional Regulation of Human High-Affinity IgE

Receptor -Chain Gene Induced by GM-CSF1

Cells of limited types such as mast cells, basophils, eosinophils (1), monocytes

(2), Langerhans cells (3, 4), platelets (5, 6), and neutrophils (7) express the

high-affinity receptor for IgE (FcRI). FcRI plays an important role in

triggering IgE-mediated allergic reaction. Cross-linking of FcRI on effector

cells, for example mast cells, by Ag (allergen)-IgE complexes triggers allergic

reaction by activating intracellular signal cascades to induce not only the

release of chemical mediators in the early-phase reaction but also cytokine gene

expressions leading to the late-phase reaction. Moreover, FcRI on epidermal

Langerhans cells in the skin is known to be involved in the Ag presentation by

facilitating uptake of IgE-associated allergens, suggesting its pivotal role in

the pathophysiology of atopic dermatitis.

FcRI is composed of three different subunits, , , and , of which the -chain

directly binds IgE through its extracellular domain, while the - and -chains are

responsible for mediating intracellular signals. Although a functional receptor

is expressed both as tetramers (2) and trimers (2) in humans (8), intracellular

signals (9, 10), in addition to cell surface expression of the receptor (11),

were reported to be significantly amplified by -chain, indicating that -chain

increases cell activation sensitivity to the stimulation by allergens. Recently,

it was revealed that -chain amplified degranulation and leukotriene secretion

but suppressed cytokine production (12), indicating that -chain regulates

distinct intracellular signaling events in both positive and negative manners by

the same molecule of itself. Furthermore, an alternative splice variant which

encoded only an N-terminal portion of -chain was found to be expressed in human

mast cells (13). This truncation variant competed with full-length and

prevented FcRI surface expression by inhibiting -chain maturation (13). Because

all of these findings indicate that -chain is a fine regulator of FcRI-mediated

cell activation to precisely control the allergic reaction, elucidation of

regulatory mechanisms of -chain expression will make a meaningful contribution

to medical intervention for allergy. In addition, because -chain has only been

reported to associate with FcRIIIA except for FcRI (14) and its expression is

limited in the specific types of cells such as mast cells and basophils,

applications which are targeted for -chain are expected to exert cell

type-specific effects.

http://www.jimmunol.org/cgi/content/full/177/7/4605

> Essential " Allergy Feedback Loop " Discovered By Hopkins Scientists

>

> The Hopkins team documented this feedback loop in lab tests and, for the first

time, in patients, confirming what they had long suspected: that IgE antibodies

and IgE receptors wax and wane together, linked somehow in a complex dance.

> " To stop allergies, you need to maintain low counts of both IgE antibodies and

IgE receptors,

> http://www.sciencedaily.com/releases/1999/05/990505165340.htm

>

> http://www.eurekalert.org/pub_releases/1999-05/JHMI-EFLD-050599.php