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Lymphocytes
and immune system organ development
Considering all vertebrates produce some form of antibody they
must have the cells to produce it. These cells are called B cells
and they are a class that is part of the lymphocyte cell family.
However, many defence mechanisms, particularly those against viruses
or graft intolerance, are carried out by the T lymphocyte cell
class.
When we described the cellular defenses in coelemocytes (worms)
we described "immunocytes" that seem to have similarities
with both T and B cells. We also know there are lymphocyte-like
cells in echinoderms and possibly an unusual family of animals
called the protochordates. While we know that all vertebrates
possess B cells we are less confident about the presence of T
cells. Lampreys, members of the simple Agatha fish family, are
able to reject skin grafts and this suggests some form of T cell
function must be present. Most likely, lampreys have very simple
lymphocytes that lack the specialization of our lymphocytes. It
may be that each lamprey lymphocyte cell is capable of carrying
out both T and B cells functions.
When looking for T and B cell function we must be aware that
in mammals these cells are inextricably linked to the presence
of lymphoid organs such as the bone marrow, thymus, spleen, and
lymph nodes. The most basic lymphoid organs that we have are the
liver and kidneys, which help to clean the blood. The liver has
large numbers of modified phagocyte cells (which we will go into
detail about later) but very few lymphocytes are present. The
simplest lymphoid organ where lymphocytes dominate is "gut
associated lymphoid tissue" (GALT). GALT refers to congregations
of lymphocytes in nodes along the length of the intestines.
In invertebrates there are no true lymphoid organs. Cells of
their defence system merely float around the system and do not
congregate into specific areas that might be described as simple
lymphoid organs. In agnathan fish B cells are produced from the
intestines so they do have GALT tissue and they also have kidneys.
However, careful examination has failed to find any other lymphoid
organs.
Looking at the Teleostei advanced fish family we find a big
jump in the development of the immune system. Lymphocytes are
still produced by intestinal GALT tissue, there is still no presence
of bone marrow, but there is a clear distinction between the function
of T cells and B cell production of antibody. Teleostei have kidneys
and spleens. Most importantly, we see the first presence of a
key lymphoid organ, the thymus. So advanced fish are showing compartmentalization
of the immune system into specialized organs and use of specialized
cell types to defend against different pathogen challenges.
Amphibians also have immune cells arranged into organs. They
have a fully functional thymus, spleen and GALT. They also have
areas which look like primitive lymph nodes in the kidney, liver,
gills and elsewhere. Some, but by no means all, amphibian species
have bone marrow. So while some species produce their lymphocytes
in from stomach GALT, others have progressed to producing blood
cells in the better protected bone marrow regions. We also see
the subdivision of T cells into different specialist functional
ability. While T cells that destroy pathogens (cytotoxic T cells)
are present in fish and amphibians, we now see the development
of T helper cells. These cells, as we shall find out later, help
cytotoxic T cells by producing chemicals (cytokines) that stimulate
them. It is essentially your typical wrestling match (except it's
not fixed!) With a few dukeing it out in the ring and a large
audience shouting encouragement.
Reptiles have a very similar immun system structure. With T
helper and cytotoxic cells, B cells and presence of a thymus,
spleen and GALT. Several species of snakes and lizards have basic
lymphnodes that might be capable of functioning as our own.
Birds are quite close to mammals with a highly developed vertebrate
immune system. They have all the immune system organs that we
have, spleen, thymus, GALT, and bone marrow. Not all birds have
lymphnodes though. Sea birds and shore waders have a lymph node
network but birds such as chickens do not. Birds do have an additional
organ that we do not, the bursa of fabricius. This organ develops
in the embryo close to the intestines. However, the organ only
survives in a functional form for around one month. The bursa
of Fabricius was first recognized by Hieronymus Fabricius in the
sixteenth century, however its function was not understood until
1956. Unique to birds, this organ is where immature B cells migrate
after being produced in the bone marrow. Here, they mature into
fully functional cells before entering the blood stream. In mammals
the B cells mature in the bone marrow and then directly enter
the blood stream.
Here is a convenient end point and link to the next subject
of immune cells, how they develop and what they do in mammals.
Conclusions
The immune system developed as a form of protection from aggressive
life forms. The overall intention was to ensure survival of the
individual to reproductive age and consequently ensure survival
of the species. It would seem that the invertebrate defense system
developed from eating and digestive processes present in single
and multicellular organisms. Invertebrate species have developed
a wide range of different defense responses for protection, each
of them satisfactory for that species survival. Defense may include
not only the cellular and humoral responses that we traditionally
regard as a form of immune system, but may also involve such things
as rapidly reaching reproductive age and producing large numbers
of offspring. In this way, invertebrate species operate as a collective
where sacrifice of some individuals to pathogens is acceptable to
ensure overall species survival.
In contrast vertebrates have taken a very different approach.
We can still see the vestiges of some forms of invertebrate immune
defense present in mammals, including ourselves, such as phagocytosis,
use of enzymes in the gut or tears, and the existence of the complement
system. We have also moved away from rapid maturity and production
of many offspring. We can see through the natural history of vertebrates
that where production of many offspring was dominant in fish, amphibians
and reptiles, offspring numbers are much reduced in mammals. This
shift from survival of the species to survival of the individual
has required a change in the defense systems' objectives. The immune
systems' priorities are now to the individual rather than the species'
collective survival.
The vertebrate immune systems' development is obscure but seems
to have developed from gut tissue. The vertebrate system uses groups
of cells and humoral factors with different specialist capabilities.
This variety collectively allows a more comprehensive defense against
aggressive pathogens and longer survival of the individual. We can
see the different areas of the mammalian immune system develop through
different levels of vertebrates. From fish with some lymphocytes
and the ability to produce one form of antibody to at least some
types of antigen, through amphibians, reptiles and birds, we arrive
at the most advanced vertebrate immune system in primates. The primate
immune system has the ability to produce five types of antibody
and can target thousands of antigens. We have a comprehensive lymphocyte
population capable of targeting numerous parasites, bacteria and
viruses.
There are still gaps in our defense, particularly against some
types of virus. New challenges are encountered by our immune system
from viruses like HIV to prions causing Creutzfeld Jacob disease
(mad cow disease). Some of our old enemies still have the upper
hand and seem to be as successful as ever in penetrating our defense
shield such as malaria and tuberculosis.
Our immune system is dynamic, still under construction. Science
may artificially promote its development, traditionally with the
use of vaccines and in the future perhaps with gene therapy. Our
immune system may also have a few tricks of its own with the recent
reporting of some individuals as resistant to HIV infection. The
immune system is not limitless in its ability to respond and protect
but it is flexible and has the potential to adapt. It is a kind
of "bolt on" structure incorporating the old operating
systems like phagocytosis into the new. We may soon have the ability
to "bolt on" additional accessories of our own design.
The next step will be to go on and look at the components of the
mammalian immune system before looking at how they interact to protect
us. There is much that we don't understand and much more we have
yet to find out about the immune system.
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