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Q: Immune System ( Answered,   0 Comments )
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Subject: Immune System
Category: Miscellaneous
Asked by: ccc10-ga
List Price: $20.00
Posted: 16 Jun 2003 12:27 PDT
Expires: 16 Jul 2003 12:27 PDT
Question ID: 218013
Describe the phagocytic actions of macrophages and the mechanisms of
antibody actions.  What are the roles of the thymus gland, bone
marrow, and lymph tissuein the development of mature, immunocompetent
lymphocytes.  What are the roles of the MHC proteins in the processing
and display of endogenous proteins (cancer proteins) and protein from
phagocytized microorganisms.  What is the role of helper T cell in bot
humoral and cell mediated immune responses.  What are cytokines and
growth factors, What type of actions characterize these molecules. 
What are the current hypotheses concerning the causes of autoimmune
diseases?

Request for Question Clarification by tutuzdad-ga on 16 Jun 2003 13:20 PDT
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Answer  
Subject: Re: Immune System
Answered By: synarchy-ga on 16 Jun 2003 16:37 PDT
 
Hello - you've asked for quite a bit in your question, so I will break
it into parts.

1) Phagocytic action of macrophages - macrophages are a type of white
blood cell - white blood cells serve as part of the body's immune
system.  Macrophages are produced in the bone marrow as monocytes
which migrate through the body until they take up residence in a
tissue, becoming macrophages (also known as tissue macrophages). 
Macrophages are phagocytic (they eat things) towards cellular debris,
foreign particles, parasites, and bacteria.  Macrophages are more
active towards particles/bacteria/etc that has been "opsonized" (this
means that antibodies have bound to the surface of the particle - the
antibody binds to the particle, called an antigen, through one end,
and binds to macrophages through the other end, the Fc region).  Once
ingested, a particle is contained within a "phagosome", a special
compartment within the macrophage which is acidified and into which
the macrophage dumps hydrogen peroxide and other toxins and enzymes
which break down proteins (proteases) to kill any bacteria or
parasites which it has ingested.  After digesting the ingested
particle, the macrophage will "display" segments of proteins which it
has ingested on MHC (major histocompatibility complex) proteins on
it's surface - T lymphocytes see these proteins bound to MHC and
"prime" the immune system to respond to foreign particles which have
these proteins (more on this later).

Macrophages take part in the body's immune and inflammatory reactions
and their numbers will increase during infection or injury.  They are
found throughout the body, and specialized macrophages are found in
many tissues such as Kuppfer cells in the liver, alveolar macrophage
cells in the lungs, peritoneal macrophages in the abdominal fluid, and
so on.


A nice general overview of macrophages with links to further
information:
http://nic.sav.sk/logos/books/scientific/node21.html
 
A very brief description of macrophages:
http://www.ndif.org/Terms/macrophage.html

Another short description:
http://www.hon.ch/Library/Theme/Allergy/Glossary/macrophage.html

A picture of a macrophage:
http://dunn1.path.ox.ac.uk/~cholt/sgWhatare.html

2) Mechanisms of antibody action - antibodies are produced by B cells
of the immune system.  B-cells (or B lymphocytes) originate in the
bone marrow and travel to the thymus during infancy and early
childhood to mature and to have self-reactive B-cells deleted. 
Afterwards, B-cells travel to lymph nodes throughout the body where
they wait to be activated by an activated T-cell that binds to their
receptors (which bind to the same target as the antibodies which they
will produce) - this binding causes the cells to proliferate and begin
producing antibodies which are secreted into the bloodstream. 
Antibodies come in many forms depending upon which proteins are used
to put them together - the various forms are also often found in
different locations througout the body.  IgA (immunoglobulin A) is
commonly found in the mucosae (mucous lining of nose, GI tract, etc),
IgD (immunoglobulin D) is a component of the B-cell receptor on the
surface of the B-cell, IgE (immunoglobulin E) in the skin, IgG and IgM
in the blood (IgM first, followed by IgG).  Antibodies bind to their
targets in the body, thereby opsonizing them for ingestion by
macrophages (see above).  Antibodies also can activate the complement
system which recruits cell killing proteins to the surface of the cell
- these proteins assemble around the antibody and poke holes into the
cell membrane, killing the antibody-bound cell.  Antibodies can also
neutralize bacterial toxins and viruses within the bloodstream.

A nice overview, titled "What the heck is an antibody" covering the
structure of antibodies (two light chains and two heavy chains - the
heavy chains contain the Fc region which binds to macrophages, the
other end of the heavy chain as well as the light chains form two
separate antigen binding sites, the Fab region), and basic B-cell
physiology:
http://people.ku.edu/~jbrown/antibody.html

Another thorough overview of antibodies:
http://gsbs.utmb.edu/microbook/ch001c.htm

A simple schematic showing the process of macrophage ingestion,
through antigen presentation, to T-cell activation, to B-cell
activation and antibody production:
http://www.cellsalive.com/antibody.htm

Another overview which begins to lead into one of your further
questions regarding autoimmune disease:
http://www.ljpc.com/tolerance_tech_bcell_tolerance.html

A simple schematic showing antibody production and a possible
treatment for complications of HIV infection:
http://www.appliedbiomed.org/iab_uarp_3.pdf

3) Development of lymphocytes from the bone marrow to the thymus to
the lymph nodes - lymphocytes are formed within the bone marrow and
mature in the thymus.  Maturation in the thymus removes "bad" T and B
lymphocytes - "bad" lymphocytes fall into two categories - either they
do not have the correct proteins on them, which would render them
non-functional as immune cells, or they are "bad" because they react
to proteins naturally in the body; if left unchecked this would lead
to auto-immune response in which these lymphocytes would attack the
cells of the body.  After leaving the thymus, lymphocytes travel to
the lymph nodes where they await presentation of antigens in the lymph
which drains from parts of the body, through these lymph nodes.  If an
antigen, or antigen-presenting cell, arrives in the lymph node, to
which the lymphocyte is reactive, the lymphocyte will proliferate and
begin to seek out the antigen (T-cells) or make antibodies (B-cells).

An overview of the function of these various organs in the immune
system can be found here:
http://www.keratin.com/am/am014.shtml
 
A much longer explanation of the cells of the immune system detailing
their organs of origin:
http://www.med.sc.edu:85/bowers/immune%20cells.htm

4) Roles of MHC proteins - MHC can be broken down into two categories,
MHC class I and class II.  Class I proteins are expressed on cells
which are likely to first see foreign antigens, like macrophages. 
These cells are known as antigen-presenting cells, because after
digesting the foreign antigens, they "present" them on the cell
surface in a complex with their MHC class I proteins.  T lymphocytes
which express MHC class II molecules bind to MHC class I only when it
is bound to the antigen for which the MHC class II molecule is
specific.  MHC class II specificity is selected for in the thymus, and
auto-reactive MHC class II expressing T lymphocytes are deleted.  Some
self-proteins are not commonly seen on the cell surface - in some
cancers, however, these proteins can be expressed on the surface - the
immune system can therefore respond to these self-antigens and only
destroy the cancer without harming normal cells.

A long overview of MHC molecules:
http://www.med.sc.edu:85/bowers/mhc.htm

And a much shorter overview (search for MHC to find relevant section):
http://gsbs.utmb.edu/microbook/ch001a.htm

5) Helper T-cells in humoral and cell-mediated immunity - T helper
cells recognize MHC class II antigen bound cells and help to activate
T and B cells which are specific for this antigen.  There are two
categories of T helper cells, Th1 helper cells help to activate T
lymphocytes (cell mediated immunity)and Th2 helper cells help to
activate B lymphocytes (humoral immunity).

Search for T-helper in this document for a short description:
http://gsbs.utmb.edu/microbook/ch001a.htm

Two slides in a presentation illustrating the central role of T helper
cells in coordinating the immune response:
http://www.aegis.com/ni/pubs/slideshow_1/sld011.htm

6) Cytokines and growth factors - cytokines and growth factors are
proteins secreted by cells.  These proteins interact with receptors on
other cells, activating signaling pathways within the target cells
that change the action of those cells.  Growth factors, as the name
suggests, cause cells to grow and proliferate (interleukin-2, IL-2,
causes the proliferation of both T and B cells).  This is useful in
the immune response to increase the population of cells which have a
specificty towards an invading organism (thereby you get many, many
cells which target that particular organism).  Cytokines tend to alter
the activity level of cells in the immune system (IL-8 leads to
activation of neutrophils).  Cells which first detect infection or
inflammation release cytokines to alert other cells of the immune
system to the need to respond.

A complete chart of cytokines and growth factors involved in the
immune system can be found at the bottom of this page:
http://www.med.sc.edu:85/bowers/cell-mediated.htm

A schematic showing the growth promoting effects of IL-2, IL-4, IL-7:
http://www.med.sc.edu:85/bowers/cyt-tcell-9.jpg

7) Causes of autoimmune disease: Auto-immune diseases are those
diseases in which the immune system damages or destroys normal tissue.
 These diseases can either be organ specific (hemolytic anemia,
Goodpasture's, Grave's) or non-organ specific such as SLE (systemic
lupus erythematosus).  Cross-reactive antibodies (an antibody to a
viral or bacterial protein that can also bind to normal tissue could
be selected for by an infection, which, once gone would leave behind
reactive antibodies and/or T cells which would then attack the normal
tissue with a similar "looking" antigen - this could also happen with
certain drugs - if the drug is bound to a normal protein, it could
result in a different antigen being seen by the immune system) are
thought to be a potential cause of many autoimmune diseases (and has
been shown to happen, for instance with syphillis leading to hemolytic
anemia).  Ineffective deletion of self-reactive lymphocytes may also
play a role.  Similarly, lymphocytes could be stimulated by some other
substance (drug or otherwise - bacterial cell wall components such as
lipopolysaccharide (LPS) have been shown to do this) so that they
proliferate without proper antigen stimulation, thereby enlarging a
population of cells which normally would be deleted.

A short review of autoimmunity:
http://ntri.tamuk.edu/immunology/autoimmunity.html

A good general overview of autoimmunity:
http://edcenter.med.cornell.edu/CUMC_PathNotes/Immunopathology/Immuno_03.html



General:

A very nice online text summarizing immunology:
http://www.med.sc.edu:85/book/immunol-sta.htm


Please let me know if you have further questions.

synarchy

Search strategy:
macrophages 
lymphocyte development
leukocyte development
immunology review
immunology online
MHC review
MHC immunology
immunology cytokine
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