From: kja@cbnewsf.cb.att.com (krista.j.anderson)
Subject: Re: lung transplants (and more questions)
Organization: AT&T
Date: Tue, 1 Sep 1992 20:20:51 GMT

Ruth Ginsberg wrote:
>
>1)If an organ donor was asthmatic & his/her lungs were transplanted, would the
>recipient then also develop asthma?
>

Since I'm still reading in this area I've been thinking about this
question.  Basically I agree that asthma would not be transferred
with 2 caveats:  (1) I'm assuming the lung is washed of all blood
cells and serum and (2) I'm assuming asthma doesn't result in
*permanent* damage to lung tissue.

When I was thinking about #1, I got to wondering what would happen
if there were a transfusion of B cells since they make antibodies
specific for an allergen.  I guess the idea behind bone marrow
transplants is to transfer stem cells that can mature into blood
cells, including B cells, that will then do their jobs in the new
person's body.  But now I'm wondering about 2 details:

a.  Will the new person then be able to manufacture new stem cells
like the transplanted ones or will the immunity fade as the
transferred cells come to the end of their life spans?  

b.  When stem cells differentiate into B cells, is it set at that
point which kind of antibody the B cells are capable of making?  Or
is it not determined what kind of antibody a B cell will make until
activated by a T cell at the time of infection and immune response?

The answers may not be known yet, but if anyone has a clue, I'd
appreciate hearing it.

On #2, I was just reading that asthma can cause *temporary* damage
to lung tissue.  Well, let me start more at the beginning.  The
inner lining of the bronchi is a mucous membrane with cilia and
there are capillaries in there that bring blood close to the
surface.  Around that membrane is a layer of smooth muscle and then
an outer covering that is a layer of tough fiber and cartilage. 

During an allergic response, IgE antibodies attach to the allergen
and to mast cells in the mucous membrane.  The mast cells then
release histamine and other mediating chemicals.  Histamine and
some of the other mediators cause smooth muscle contraction and
vasodilation with increased permeability of the blood vessels.
This second effect allows more fluid, antibodies and white blood
cells to leave the blood vessels and enter the tissue in what is
called the inflammation response. 

Among the other mediators that are released by mast cells are
leukotrienes and prostaglandins.  While some prostaglandins are
bronchodilators, others are bronchoconstrictors and 3 of the
leukotrienes are also bronchoconstrictors.

So, the muscle contraction of asthma is caused more by leukotrienes
and prostaglandins than histamine, which is why antihistamines
don't help asthma as well as they help other allergic symptoms.

In addition to mast cells (called basophils in the blood)
white blood cells called eosinophils are particularly implicated in
allergic reactions.  Like IgE, eosinophils are associated with
infestations of helminths (parasitic worms).  Eosinophils are
capable of releasing toxic chemicals against them.  In the case of
allergy, the target is an allergen such as a dust mite or a pollen
rather than a worm or its egg, and the allergic response causes
more problems than the inert allergen.  (I can understand why a
dust mite might be mistaken for a helminth, but pollen? *&$^#@&^*)

Another chemical released by mast cells is called Eosinophil
Chemotactic Factor of Anaphylaxis (ECF-A).  Here, anaphylaxis means
the Type I or immediate hypersensitivity, i.e. allergy.
Chemotactic means it attracts the cell to the site.  The exact
mechanism seems to be unknown but a proposed hypothesis is that the
cell sort of follows a trail of chemotaxin to its greatest
concentration.  Since the blood vessels are dilated at the
site, the cell easily enters the tissue.  Neutrophils, also white
blood cells, are attracted in similar manner.

In the tissue the eosinophil releases its helminth toxins which
damage cells of the mucous membranes in the bronchi.  In similar
fashion, eosinophils can damage tissue in the digestive tract, skin
and possibly joints. 

In the case of asthma, this damage leaves the bronchi in a
hyperreactive state, (I guess because it is still inflamed) easily
irritated by infection, exercise, cold air, fumes, odors, smoke and
changes in barametric pressure.  The book hypothesizes that this
tissue damage is one thing that causes intrinsic asthma (in the
absense of an allergen).

They talk about 2 phases of asthma with the first being within 30
minutes of exposure to an allergen and resulting from degranulation
of mast cells and the second being 4-12 hours later and resulting
from the actions of eosinophils and neutrophils.  The neutrophils
are phagocytes that will probably hang around until the debris from
the damaged cells and immune complexes is cleaned up.  (An immune
complex is an antibody bound to an antigen plus any bonded
complement proteins or a clump of several of these since an
antibody can bind to more than 1 antigen.)

The late response may also be caused by a Type III hypersensitivity
response involving IgG and IgM and their complement cascade.  I'm
not sure what antigen the IgG and IgM are responding to in this
case.  The book thinks both eosinophils and Type III mechanisms
cause the late response. 

It's also worth noting that high concentrations of IgE or IgA can
initiate an alternate pathway to the complement cascade.  The
complement cascade not only lyses the cell bound to the immune
complex (which in Type III may be a body cell), but also
releases some anaphylatoxins which cause mast cells/basophils to
degranulate.  Eosinophils also release an anaphylatoxin. 

So, I guess if there is tissue damage due to hypersensitivity in a
transplanted lung, there could be a temporary experience with
intrinsic asthma, but the problem should clear up once the tissue
was repaired by normal cellular functions.

What really gets me about transplants, is how do they get the
nervous system to "hook up" to the new organ?

Reference
1. _Understanding Allergy, Sensitivity & Immunity_, Janice
   Vickerstaff Joneja, PhD & Leonard Bielory, MD, NJ:Rutgers
   University Press, 1990.

(the best book of this type I've run into so far)
Newsgroups: sci.med