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Questions on Immunity & auto-immunity?
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Sun Feb 26, 2006 3:10 am    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Alf Christophersen wrote:
Quote:
On 3 Dec 2005 07:20:55 -0800, "kumar" <lordshiva5753@rediffmail.com
wrote:

"Cytolysis" occurs in a hypotonic environment, where water diffuses
into the cell to the fact that there is more solutes within the cell.
As the water continues to diffuse into the cell, the cell grows larger,
and will eventually burst if too much water enters. The cell membrane
is not powerful enough to prevent and stop the swelling of the cell.
The bursting of the cell is called cytolysis. The contents of the cell
are released, and the cytoplasm is ruptured as a result of cytolysis.
http://en.wikipedia.org/wiki/Cytolysis
"Crenation" occurs because in a hypertonic environment (that is, the
cell has less solutes than the extracellular fluid does) osmosis (the
diffusion of water) causes a net movement of the water outside of the
cell, causing the cytoplasm to decrease in size. As a result, the cell
also decreases in size.The effects of crenation are especially visible
in red blood cells, as they become distorted in shape rather than the
usual disc-like shape with the dimple that the usual blood cell has.
http://en.wikipedia.org/wiki/Crenation "

Whether cytolysis and Crenation do not happen in WBCs? Can't cell
membrane changes due to any disorder cause to happen cytolysis and
Crenation in WBCs?

Please search literature on taurine and osmotic swelling and
shrinking. Cells are releasing organic osmolytes in order to keep
constant cell volumes in hypotonic medium and pump in osmolytes in
hypotonic medium in case they exists in the medium. If not, the cell
make themselves, like making sorbitol using aldose reductase that
change glucose into sorbitol. The sorbitol in turn is dehydrogenated
by sorbitol dehydrogenase when not needed. But the reaction is slow
and meanwhile other osmolytes may need to be released to keep isotonic
conditions and thus constant cell volumes.

Taurine, betaine and several other amino acids form osmolytes that are
easily transported over membrane, while sorbitol and inositols are
osmolytes with much slower turnover times, both for synthesis and
decomposition and is more longterm cell volume regulators.

If a cell shrink too much even osmolytes are pumped in, apoptosis is
induced, while too much swelling induce cell division unless the dV/dt
is far too big (V for cell volume), in such cases the cell may die due
to necrosis and all cell content is emptied in the vicinity of the
cell.

There are lot of literature on cell volume regulation.

I have a feeling you may make an analogy to what is easily observable
in fruits that is being either put in sugar syrup or put in either
destilled water or alchohol. (in last case, it is not osmotic
mechanisms doing what is observed, but effects of membrane
derangements making cell membrane leaking and thus loosing cell
content and letting water in at same moment)

Thanks for the indications. I am also trying to check, whether so
thought auto-immunity can also be a natural postive mechanism to save
organism as a whole at the cost of some?
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Alf Christophersen
medicine forum Guru


Joined: 01 May 2005
Posts: 738

PostPosted: Fri Feb 24, 2006 4:34 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

On 3 Dec 2005 07:20:55 -0800, "kumar" <lordshiva5753@rediffmail.com>
wrote:

Quote:
"Cytolysis" occurs in a hypotonic environment, where water diffuses
into the cell to the fact that there is more solutes within the cell.
As the water continues to diffuse into the cell, the cell grows larger,
and will eventually burst if too much water enters. The cell membrane
is not powerful enough to prevent and stop the swelling of the cell.
The bursting of the cell is called cytolysis. The contents of the cell
are released, and the cytoplasm is ruptured as a result of cytolysis.
http://en.wikipedia.org/wiki/Cytolysis
"Crenation" occurs because in a hypertonic environment (that is, the
cell has less solutes than the extracellular fluid does) osmosis (the
diffusion of water) causes a net movement of the water outside of the
cell, causing the cytoplasm to decrease in size. As a result, the cell
also decreases in size.The effects of crenation are especially visible
in red blood cells, as they become distorted in shape rather than the
usual disc-like shape with the dimple that the usual blood cell has.
http://en.wikipedia.org/wiki/Crenation "

Whether cytolysis and Crenation do not happen in WBCs? Can't cell
membrane changes due to any disorder cause to happen cytolysis and
Crenation in WBCs?

Please search literature on taurine and osmotic swelling and
shrinking. Cells are releasing organic osmolytes in order to keep
constant cell volumes in hypotonic medium and pump in osmolytes in
hypotonic medium in case they exists in the medium. If not, the cell
make themselves, like making sorbitol using aldose reductase that
change glucose into sorbitol. The sorbitol in turn is dehydrogenated
by sorbitol dehydrogenase when not needed. But the reaction is slow
and meanwhile other osmolytes may need to be released to keep isotonic
conditions and thus constant cell volumes.

Taurine, betaine and several other amino acids form osmolytes that are
easily transported over membrane, while sorbitol and inositols are
osmolytes with much slower turnover times, both for synthesis and
decomposition and is more longterm cell volume regulators.

If a cell shrink too much even osmolytes are pumped in, apoptosis is
induced, while too much swelling induce cell division unless the dV/dt
is far too big (V for cell volume), in such cases the cell may die due
to necrosis and all cell content is emptied in the vicinity of the
cell.

There are lot of literature on cell volume regulation.

I have a feeling you may make an analogy to what is easily observable
in fruits that is being either put in sugar syrup or put in either
destilled water or alchohol. (in last case, it is not osmotic
mechanisms doing what is observed, but effects of membrane
derangements making cell membrane leaking and thus loosing cell
content and letting water in at same moment)
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Sat Dec 03, 2005 3:20 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

"Cytolysis" occurs in a hypotonic environment, where water diffuses
into the cell to the fact that there is more solutes within the cell.
As the water continues to diffuse into the cell, the cell grows larger,
and will eventually burst if too much water enters. The cell membrane
is not powerful enough to prevent and stop the swelling of the cell.
The bursting of the cell is called cytolysis. The contents of the cell
are released, and the cytoplasm is ruptured as a result of cytolysis.
http://en.wikipedia.org/wiki/Cytolysis
"Crenation" occurs because in a hypertonic environment (that is, the
cell has less solutes than the extracellular fluid does) osmosis (the
diffusion of water) causes a net movement of the water outside of the
cell, causing the cytoplasm to decrease in size. As a result, the cell
also decreases in size.The effects of crenation are especially visible
in red blood cells, as they become distorted in shape rather than the
usual disc-like shape with the dimple that the usual blood cell has.
http://en.wikipedia.org/wiki/Crenation "

Whether cytolysis and Crenation do not happen in WBCs? Can't cell
membrane changes due to any disorder cause to happen cytolysis and
Crenation in WBCs?
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Fri Dec 02, 2005 4:08 am    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

"Most autoimmune responses are noticed when big problems crop up, and
not
when people are staying healthy. Doctors and scientists tend to focus
on
people with big problems because they are easy to measure, and often
provide good repeatable models across the population of people with the

same disorder."

Hello Mike,
This may be a problem in our perusal for handling a disorder. Why we
not design such models when disorders can be handled at very early
stage. Probably then we may be able to cure that not just treat that.
As suggested, I shall be going deep in to it but I want to understand
the basics that, can there be autoimmunity beneficial at their early
stages? I feel making a person not to eat due to some disorder can be
some kind of "self destruction" or initial autoimmunity. Fasting on
getting any disorder or aversion to some foods and activities, are long
been practiced natural mechanisms by most animals and usually they
recover from any disorder by practicing it. This may be a defense
mediated mechanism at most early stage. Behavioral changes are there as
in pre-diabetic stages--more and irregular eating habits etc. No doubt,
it can be difficult to maintain normal life in later stages and for
which one will need medications, but we should first know the prime
reasoning of getting autoimmunity. Mostly all our bodily functional
changes (not pathogenic--although I suspect some of these also) in
initial stages may be for some benefit but since we look later stages,
we take these as harmful. Look at tumor formations, latencies. All
these changes may be to arrest the problematic cells/bacteria to starve
then and to prepare defense system so strong which can handle them at
some later date or slowly. I feel that when a person gets acute
inflammations or infections--our body's defense mechanism increases
blood supply at the problem site whereas decreases on getting latencies
and tumors. To decrease it means to starve those cells/bacteria and for
which our body may adopt many inferior/indirect auto
immunities--anorexia, bleeding, problems in absorptions, low gastric
acid secretions, excess loss/excretions, cells destructions etc. So it
may be helpful if we can find prime purpose of getting early/inferior
auto immunities.

Let us look at one more aspect. Just look at latent infections and
cancer tumors. I have posted a separate topic on it previously. Can't
these be due to our defense system's oriented changes to arrest, starve
& control those bacteria/cancer cells on one hand and prepare for
needed immunity at some later date? If so, can one get some acute
symptoms of that disease (not all symptoms of that disease esp. no
weight loss) on getting strong immunity (by bring them out of their
cages to handle them)? Can we confuse by these symptoms and start
treating which probably our improved immune mechanism was doing? Can
these interferences weaken or discourage immunity to perform their work
suitably and naturally? We somehow have to look and trust, what nature
has given us? These are some of my confusions which I want to clear.
Thanks.
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Mike McWilliams
medicine forum beginner


Joined: 13 Jun 2005
Posts: 43

PostPosted: Thu Dec 01, 2005 10:26 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Bryan Heit wrote:
Quote:
Mike McWilliams wrote:

kumar, I reccommend studying the differences between B cells and T
cells. It's been awhile since I have, but here is a basic outline of
what I remember.


A good intro source is Kuby's Immunology. Unfortunately, Dr. Kuby died
a few years ago, so her book is a little out of date. But it's good for
the basics. Paul also has a good immunology text, but it isn't very
good for people who are just entering the field.


I think the Kuby book is so good, it should be made available for
cheaper than it is. It not only gives a decent first timer an overview,
it covers the CD nomenclature, and a few of the well understood
molecular biology (signalling) pathways which different immune cells use
to communicate with each other.

Not to mention an in depth covering of the genetics, and processes
responsible for antibody diversity, and countless historically important
experiments which established todays body of knowledge are covered.

did I mention it has great diagrams? they don't need anyone to sell that
textbook, it sells itself.

my short outline purposely left out details, as I find that with
immunology as with other subjects, it is best to leave some of the more
exotic details out the first time around.

that said, kumar is interested in beneficial autoimmunity, and will need
a complicated serving of the material.
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Bryan Heit
medicine forum Guru Wannabe


Joined: 17 Nov 2005
Posts: 105

PostPosted: Thu Dec 01, 2005 9:04 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Mike McWilliams wrote:

Quote:
kumar, I reccommend studying the differences between B cells and T
cells. It's been awhile since I have, but here is a basic outline of
what I remember.

A good intro source is Kuby's Immunology. Unfortunately, Dr. Kuby died
a few years ago, so her book is a little out of date. But it's good for
the basics. Paul also has a good immunology text, but it isn't very
good for people who are just entering the field.

Quote:
B cells produce antibodies (immune globulins), and these are part of
humoral mediated immunity.

Correct.

Quote:
humoral immunity is generally used to deal with extracellular pathogens
such as bacteria.

This is no longer thought to be the case. Humoral immunity can play
central roles in the clearance of intracellular pathogens (i.e. ones
whom live in our cells). This can be done by covering them with
antibodies when they are in the blood (which targets them for
destruction). It can also target immune cells to sites where the
pathogen is killing cells, as parts of the pathogen will be found
floating around in the intracellular space when this happens.


Quote:
T cells are cytotoxic (cell killing), and basically scan the bodies
cells using a universal protein called the MHC

A bit more complicated then this. Today there are generally thought to
be 4 different groups of T-cells, each group which comprises of multiple
sub-groups.:

1) CD4+ T-cells: These cells are the mediators of the immune response.
They identify antigens through the MHCII protein, which is expressed
only on certain "professional" antigen presenting cells (APC's). These
cells are not usually cytotoxic, but rather do tings like activate other
cytotoxic cells, activate B-cells, and regulate inflammatory reactions.
This activating process is often called "help". These are also the
cells which dampen immune responses, and are believed to the cells which
fail during an autoimmune disease.

2) CD8+ T-cells: These cells recognize pathogen antigens via MHCI
(expressed on all cells). If they identify a pathogen's antigen they
will kill the infected cell. Hence, these are the cytotoxic immune
cells you alluded to. These cells are only cytotoxic if first activated
by a CD4+ cell (i.e. if they receive help).

3) NKT cells. NKT cells are not well understood, but appear to be a
highly cytotoxic cell which has characteristics of both NK and T cells.
The regulation of these cells in not well understood (by myself
anyways), but from what I understand these cells can be cytotoxic
without CD4+ cell help, but function better if they have been activated
by CD4's.

4) Gamma-deltas: Gamma-delta T-cells express an unusual T-cell receptor
(made of gamma and delta proteins, instead of the usual alpha-beta).
These cells exist predominantly in the gut, and are specialized cells
which recognize bacterial antigens. Whereas most T-cells identify
protein-based antigens, gamma-deltas tend to recognize other antigens
like lipids and polysaccharides. Some people believe that these are the
trigonal T-cells, and that the CD4+/CD8+ sets evolved from these. These
cells do not express CD4 or CD8, and do not recognize the normal MHC's.
Instead, they recognize specialized non-classical MHC's, which belong
to a family of proteins called the "CD1 family".


Quote:
there are special t cells which don't directly kill cells, they are
called t helpers.


No. T-helpers are the CD4+ cells which I talked about above. Cytotoxic
T-cells are usually just referred to as "CD8's".


Quote:
there is another special type called gamma delta t cells which are not
totally understood. apparently they mediate immunity against
mycobacterium tuberculosis in particular, and may play a role in immune
surveillance (something you appear overly interested in), as mice
lacking gamma delta cells get more cancers.

Actually, the cancer thing was a mistake. More recent gamma-delta
knockouts don't develop higher rates of cancer.


Quote:
B cells also are generated in the bone marrow, but they stay there
during their selection process, which is perhaps not quite as complicated.

It's not quite as complicated because we don't understand it. As far as
we can tell the selection process is similar to T-cells; the antibody
must recognize something, or the cell dies. But if the antibody
recognizes a self-protein too well it is destroyed. No one is really
sure how this process works, but we think the bacteria which live in
your gut is pretty important.

Quote:

from what I recall, b cells which recognize self in the marrow are
destroyed, and those that don't enter the bloodstream/lymphatic system.
Once in the bloodstream/lymphatic system, they may encounter antigen
such as viral coat proteins, bacterial cell wall... etc.

B-cells rarely enter the blood. Once they've finished developing
they'll move to a lymphatic organ (i.e. spleen, tonsils, lymph nodes),
which AFAIK occurs via the blood. But once in a lymphatic tissue they
stay put for the rest of their lives. The lymphatics will carry
antigens to these sites, where if the B-cell recognizes the antigen,
it'll develop into an antibody factory called a plasma cell.


Quote:
As far as you are concerned about auto immunity, I would recommend
looking at the potential problems in the selection steps. These occur
within defined organs (thymus and bone marrow), and therefore autoimmune
problems can probably be traced to errors in those stages.

This idea has fallen out of fashion. The problem is that self-reactive
cells seem to be normally found in every human on the earth. There is
some evidence which suggests that these self-reactive cells may even be
required for proper tissue healing after an infection. It is now
thought that the main source of autoimmunity is not the improper
formation of self-reactive cells, but rather a failure to properly
control these cells.

One idea is that these cells are involved in the healing process, and
thus are activated by infections. Autoimmunity may result if these
cells are not shut off after an infection.


Quote:
also keep in mind that in nature, humans are meant to survive perhaps
40-50 years. We haven't evolved for natural longevity (sans medical
treatment) like turtles and trees, so most of us are probably destined
to die young from lapses in our biology, and a fair portion will be from
autoimmune disorders.

Right and wrong. Our bodies are definitely built with a 40-year
lifespan built in. After that your immune system begins to weaken
(hence why the elderly are so suceptable to infection). But most
autoimmune disorders start when you are young; for women they occur
during the prime child-bearing years. Current thought is that
autoimmunity is the cost of a highly adaptive and active immune system.
From an evolutionary point of view, having a few members of the
species crap out due to autoimmune disease is a small price to pay if
the species can now survive deadly diseases.

Harsh, but probably true. The question is, can we control it?

Bryan
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Mike McWilliams
medicine forum beginner


Joined: 13 Jun 2005
Posts: 43

PostPosted: Thu Dec 01, 2005 3:29 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Kumar wrote:
Quote:
Hello Mike,

Thanks for detailed explaintions. However, I am more interested in
understanding that;

Can some (if not most) autoimmune disorder be "natural immune
responses" to control some big problem at the cost of some small
problems (temp. or permanent) created by it?

which also happens as per need. So pls try to find reasonings for "can
autoimmune resposes be natural responses for some indirect/net
benefits"? Best.


well, given my previous post, one could say that autoimmune responses
with a negative impact are a result of immune cell selection defects.
They would still be "natural immune responses", their targets would be
wrong.

The only suggestions I've heard toward autoimmune responses being
beneficial are the people who argue that the immune system helps to keep
cancer from arising.

In my previous post, I indicated that mice who lack gamma delta t cells
tend to develop cancer more readily.

So this would lend credence to the idea that an autoimmune response is
what is controlling cancerous proliferation through activity related to
the presence of gamma delta t cells.

The body of knowledge regarding beneficial autoimmune responses is
rather shallow from what I know, but then again, I don't have access to
countless online journals.

Most autoimmune responses are noticed when big problems crop up, and not
when people are staying healthy. Doctors and scientists tend to focus on
people with big problems because they are easy to measure, and often
provide good repeatable models across the population of people with the
same disorder.

If beneficial autoimmune responses are helping out other body systems,
(thyroid and pancreas as you suggested) then we probably won't know
about it for some time. But, positions researching immunity tend to be
well funded, so if you are looking for a career where you can live in
almost any large city, and pursue interesting and health improving
research, power to you. I don't work in the area of immunity, but it's
so important to understand to even a small degree that one ought to
spend at least half a year covering the basics.

I reccommend the textbooks by kuby.
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Thu Dec 01, 2005 5:01 am    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Hello Mike,

Thanks for detailed explaintions. However, I am more interested in
understanding that;

Can some (if not most) autoimmune disorder be "natural immune
responses" to control some big problem at the cost of some small
problems (temp. or permanent) created by it?

Examples of autoimmune (or autoimmune-related) disorders include:

Hashimoto's thyroiditis
pernicious anemia
Addison's disease
type I diabetes
rheumatoid arthritis
systemic lupus erythematosus
dermatomyositis
Sjogren's syndrome
lupus erythematosus
multiple sclerosis
myasthenia gravis
Reiter's syndrome
Grave's disease

Suppose, say for example, our body needs to control some latencies or
cancer in tumor by starving bacterias or cancer cells. Can't immune
response be towards pernicious anemia, RBCs destructions and changes in
their morphology on one hand, discouraging absorptions(anorexia),
bleeding, increased excretions on the other hand?

It may also be thought in case of diabetes & thyroid imbalances i.e.
to protect sugar/insulin's and thyroid hormone toxicities to body.
There may be some positive natural responses at initial stage of any
disorder but multiply and cause progressive permanent damages on
prolonged imbalances hich may be thought/considered as "negative immune
responses". It may be much important to understand first, the logic of
any response in body, probably may be natural and for the benefit in
suvival. Cells premature deaths/suicide can also meant for some purpose
which also happens as per need. So pls try to find reasonings for "can
autoimmune resposes be natural responses for some indirect/net
benefits"? Best.
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Thu Dec 01, 2005 4:12 am    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Hello Mike,

Thanks for detailed explaintions. However, I am more interested in
understanding that;

Can some (if not most) autoimmune disorder be "natural immune
responses" to control some big problem at the cost of some small
problems (temp. or permanent) created by it?

Examples of autoimmune (or autoimmune-related) disorders include:

Hashimoto's thyroiditis
pernicious anemia
Addison's disease
type I diabetes
rheumatoid arthritis
systemic lupus erythematosus
dermatomyositis
Sjogren's syndrome
lupus erythematosus
multiple sclerosis
myasthenia gravis
Reiter's syndrome
Grave's disease

Suppose, say for example, our body needs to control some latencies or
cancer in tumor by starving bacterias or cancer cells. Can't immune
response be towards pernicious anemia, RBCs destructions and changes in
their morphology on one hand, discouraging absorptions(anorexia),
bleeding, increased excretions on the other hand?

It may also be thought in case of diabetes & thyroid imbalances i.e.
to protect sugar/insulin's and thyroid hormone toxicities to body.
There may be some positive natural responses at initial stage of any
disorder but multiply and cause progressive permanent damages on
prolonged imbalances hich may be thought/considered as "negative immune
responses". It may be much important to understand first, the logic of
any response in body, probably may be natural and for the benefit in
suvival. Cells premature deaths/suicide can also meant for some purpose
which also happens as per need. So pls try to find reasonings for "can
autoimmune resposes be natural responses for some indirect/net
benefits"? Best.
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Bryan Heit
medicine forum Guru Wannabe


Joined: 17 Nov 2005
Posts: 105

PostPosted: Wed Nov 30, 2005 10:14 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Mike McWilliams wrote:

Quote:

I meant cells which burst/lose their membrane integrity as opposed to
the blebs seen in apoptotic cells), and leak their contents into the
extracellular space/fluid. In this case, no processing for MHC display
would occur, and any malformed protein could be seen as antigen.

But in this case you'd get a B-cell antigen (i.e. intact protein which
can be Id'd by an antibody). However, in order to develop an immune
response against it you would need to induce a T-cell independent B-cell
response. This requires an antigen which is polymeric (i.e. has
multiple repeating identical domains). Although some bacterial antigens
can do this, I am unaware of any human protein which has been shown to
have this capability.

Bryan
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Mike McWilliams
medicine forum beginner


Joined: 13 Jun 2005
Posts: 43

PostPosted: Wed Nov 30, 2005 8:00 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

kumar wrote:
Quote:
Bryan Heit wrote:


"I guess you could get a B-cell antigen, but getting B-cell

activation to peptide antigens, without prior T-cell activation, is
nearly impossible. So I don't think this would work."


"Lymphocytes are a special type of white blood cell. B lymphocytes
(also called B cells) produce antibodies. Antibodies attach to a
specific antigen and make it easier for the phagocytes to destroy the
antigen. T lymphocytes (T cells) attack antigens directly, and provide
control of the immune response. B cells and T cells develop that are
specific for ONE antigen type. When you are exposed to a different
antigen, different B cells and T cells are formed.
http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm "
Bryan,
Sometimes I think, why B cells are evolved when T cells can attack
antigens directly? Can antigens basically be of two types? "Non Self
type" and "self type" , I mean "non self type" those ar easily
recognizable to T cells which kill them directly WHERAS "self type"
which are not easily recognizable to T cells so help of B cells are
needed. So the problem of autoimmunity should lie somewhere in
functioning of B cells. It is to be seen that B cells working is also
related to controlling "self body cells" for some reason as a natural
immune response or it will be by mistake.

kumar, I reccommend studying the differences between B cells and T

cells. It's been awhile since I have, but here is a basic outline of
what I remember.

B cells produce antibodies (immune globulins), and these are part of
humoral mediated immunity.

humoral immunity is generally used to deal with extracellular pathogens
such as bacteria. humoral immunity includes neutrophils and macrophage.
Some immune cells such as these have special receptors which allow them
to bind immune globulins, and make them into highly targeted phagocytic
cells. B cells make the immune globulins, other cells use them.

T cells are cytotoxic (cell killing), and basically scan the bodies
cells using a universal protein called the MHC

The MHC is present on almost every cell in the body (I think cornea
cells do not display MHC). The MHC sits on the outside of the cell, and
has a special pocket on it.

when a cell is infected by a virus or other intracellular pathogen,
little bits of foreign protein are put into these special pockets, and
the MHC is sent to the surface with the foreign bit, and waits for a t
cell to scan it. once a t cell scans it, it determines if the bit in the
pocket is foreign, and it it is, it encourages the rapid death of the
infected cell.


Both t and b cells go through a growth process which determines which b
and t cells will be allowed to survive in the body. part of this
selection process is whether or not the cells target self or target
non-self. cells that target self are destroyed.

there are special t cells which don't directly kill cells, they are
called t helpers.

there is another special type called gamma delta t cells which are not
totally understood. apparently they mediate immunity against
mycobacterium tuberculosis in particular, and may play a role in immune
surveillance (something you appear overly interested in), as mice
lacking gamma delta cells get more cancers.


when t cells are made, they migrate from the bone marrow to an organ
called the thymus (which is why they are called t cells) which is above
the heart. In the thymus they undergo two forms of selection.

Positive selection is: can they see MHC I molecules? If not, they die
can they see MHC II molecules? if not, they die

negative selection: they recognize a self peptide? they die
they can't recognize a self peptide? they live

after selection, they leave the thymus, and circulate in the blood and
lymphatic system.



see this animation
http://www.bio.davidson.edu/courses/Immunology/Flash/Main.html

B cells also are generated in the bone marrow, but they stay there
during their selection process, which is perhaps not quite as complicated.

from what I recall, b cells which recognize self in the marrow are
destroyed, and those that don't enter the bloodstream/lymphatic system.
Once in the bloodstream/lymphatic system, they may encounter antigen
such as viral coat proteins, bacterial cell wall... etc. if their
receptor is complementary to the antigen, they go throught a process
called clonal expansion where they fine-tune the shape of their receptor
through a process called somatic hypermutation (fun 5 syllable party
word), and they mature into secretory b cells who release stupendous
amounts of immune globulin specific to the antigen they have seen.

try this link

http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/humoral/antibodies/clonal/clonalan.html



As far as you are concerned about auto immunity, I would recommend
looking at the potential problems in the selection steps. These occur
within defined organs (thymus and bone marrow), and therefore autoimmune
problems can probably be traced to errors in those stages.


also keep in mind that in nature, humans are meant to survive perhaps
40-50 years. We haven't evolved for natural longevity (sans medical
treatment) like turtles and trees, so most of us are probably destined
to die young from lapses in our biology, and a fair portion will be from
autoimmune disorders.

cheers, mike
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Wed Nov 30, 2005 3:59 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Bryan Heit wrote:


"I guess you could get a B-cell antigen, but getting B-cell
Quote:
activation to peptide antigens, without prior T-cell activation, is
nearly impossible. So I don't think this would work."

"Lymphocytes are a special type of white blood cell. B lymphocytes
(also called B cells) produce antibodies. Antibodies attach to a
specific antigen and make it easier for the phagocytes to destroy the
antigen. T lymphocytes (T cells) attack antigens directly, and provide
control of the immune response. B cells and T cells develop that are
specific for ONE antigen type. When you are exposed to a different
antigen, different B cells and T cells are formed.
http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm "
Bryan,
Sometimes I think, why B cells are evolved when T cells can attack
antigens directly? Can antigens basically be of two types? "Non Self
type" and "self type" , I mean "non self type" those ar easily
recognizable to T cells which kill them directly WHERAS "self type"
which are not easily recognizable to T cells so help of B cells are
needed. So the problem of autoimmunity should lie somewhere in
functioning of B cells. It is to be seen that B cells working is also
related to controlling "self body cells" for some reason as a natural
immune response or it will be by mistake.
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Mike McWilliams
medicine forum beginner


Joined: 13 Jun 2005
Posts: 43

PostPosted: Wed Nov 30, 2005 3:43 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Bryan Heit wrote:
Quote:
Mike McWilliams wrote:

Bryan Heit wrote:

As for antigenicity, the answer is "probably not". The thing is that
all of the proteins expressed by cells, regardless of their age, are
self-proteins. As such our immune system is designed to ignore these
proteins. As such you shouldn't see age-specific changes in the
antigenicity of a cell as it ages. There is a cavete however; it is
conceivable that as a cell ages it's ability to break down and/or
recycle
old proteins may be impaired. If this occurred it is possible that you
may get mis-folded proteins which may have some antigenicity. But that
is pure speculation on my part; I was unable to find any scientific
literature supporting that in a quick search I did.



From what I recall you are right, cells which cannot complete
apoptosis appropriately can release old proteins which display
non-self conformations.



I've been thinking about this, and I don't think it's right anymore. The
antigens which are presented from dieing cells are nearly always
presented on MHCI or MHCII, and as such are only 8-12 amino acids in
length. Because of this the folding of the protein shouldn't be an
issue, as there isn't enough to fold (and MHC's hold the peptide
striaght). I guess you could get a B-cell antigen, but getting B-cell
activation to peptide antigens, without prior T-cell activation, is
nearly impossible. So I don't think this would work.

Bryan

I meant cells which burst/lose their membrane integrity as opposed to
the blebs seen in apoptotic cells), and leak their contents into the
extracellular space/fluid. In this case, no processing for MHC display
would occur, and any malformed protein could be seen as antigen.
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Bryan Heit
medicine forum Guru Wannabe


Joined: 17 Nov 2005
Posts: 105

PostPosted: Wed Nov 30, 2005 2:43 pm    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Mike McWilliams wrote:
Quote:
Bryan Heit wrote:
As for antigenicity, the answer is "probably not". The thing is that
all of the proteins expressed by cells, regardless of their age, are
self-proteins. As such our immune system is designed to ignore these
proteins. As such you shouldn't see age-specific changes in the
antigenicity of a cell as it ages. There is a cavete however; it is
conceivable that as a cell ages it's ability to break down and/or recycle
old proteins may be impaired. If this occurred it is possible that you
may get mis-folded proteins which may have some antigenicity. But that
is pure speculation on my part; I was unable to find any scientific
literature supporting that in a quick search I did.


From what I recall you are right, cells which cannot complete apoptosis
appropriately can release old proteins which display non-self
conformations.


I've been thinking about this, and I don't think it's right anymore.
The antigens which are presented from dieing cells are nearly always
presented on MHCI or MHCII, and as such are only 8-12 amino acids in
length. Because of this the folding of the protein shouldn't be an
issue, as there isn't enough to fold (and MHC's hold the peptide
striaght). I guess you could get a B-cell antigen, but getting B-cell
activation to peptide antigens, without prior T-cell activation, is
nearly impossible. So I don't think this would work.

Bryan
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Kumar
medicine forum Guru


Joined: 10 May 2005
Posts: 870

PostPosted: Wed Nov 30, 2005 10:21 am    Post subject: Re: Questions on Immunity & auto-immunity? Reply with quote

Bryan, nice explaination.

"Rather, autoimmune cells look to be very healthy and robust."

By your post, I could think two aspects; one, autoimmune cells can be
off any type, healthy/young or weak/older. Possibilty of antigenicity
due to old, non-functional cells is speculative. Why and how then
autoimmunity happens? Sometimes I think that can it be a nutural immune
response to save us from big damages at the cost of some temporary or
permanent inferior damages? Think about some anemia. The other
conditions which can be relavent to this "inferior damging immune
response" is on getting latent infections and tumors--cancer. So it can
be a great thought to check deeply--if this"inferior damging immune
response" can be a natural immune response meant for some beneficial
purpose? Any body response to "self cells or system" can be studied if
it is for benefit, otherwise for pathogens, it should be studied for
killing/removing them.

Reg; CaSO4, can it cause some damages if ingested in some monor
quantity? I don't feel that, you will agree from its reflection/energy
passing effects/benefits via it. This, we can think as photo may effect
somewhat alike a person can effect due to reflecting waves and
spectrum. Anyway we can take this possibilty at some other time.Very Happy
Best wishes.
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