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The
vertebrate immune system
There is a large and unexplained gap between invertebrates and
the development of vertebrates. From the simplistic invertebrate
animals we suddenly encounter vertebrates. Even the simplest vertebrate
is quite alien in structure and function compared to invertebrates.
Correspondingly, we find a large gap between the defense mechanisms
of invertebrates and simple vertebrates. While the occasional
throwback to invertebrate defense mechanisms remain such as phagocytosis
of bacteria or the use of enzymes in secretions, overall the vertebrate
immune system is nothing like the invertebrate systems. We have
very little understanding of how the defense mechanisms of invertebrates
could give rise to the vertebrate system. We must therefore consider
that the vertebrate immune system developed entirely independently
of invertebrate defense mechanisms. We are going to look at the
specific components of the vertebrate immune system later. For
now I want to take a quick look at the differences in more primitive
vertebrates and advanced vertebrates.
Vertebrates popped into view in the Cambrian era almost 600
million years ago in the shape of primitive fish belonging to
a family called Agatha (jawless fish such as lampreys). These
eventually advanced into the more complex fish we have today.
Along the way in development of fish, the class of amphibians
split off around 400 million years ago of which a subsection developed
into reptiles. From here, a further subdivision gave rise to birds
and mammals around 100 million years ago. At least that's the
current thinking based on our fractious knowledge of natural history.
For our purposes we could expect that the vertebrate immune system
should develop from the rudimentary in fish to the most complex
in ourselves. Invertebrates exhibit a variety of defense mechanisms.
All vertebrates however, have generally the same immune system
which has developed in subtly different ways for different species.
The
vertebrate humoral immune system
Antibodies are the defense of choice in all vertebrates. Antibodies
are structurally unrelated to the humoral factors found in invertebrates.
They have much more flexibility and are much more potent in their
defense ability. In humans there are several different Subtypes
of antibodies with different functions. We will look at this later.
For now accept that humans have five main types of antibody called
IgG, IgA, IgM, IgE and IgD. We can see an advance in complexity
of response from simple to complex vertebrates. Simple vertebrate
agnathan fish do have a very primitive form of antibody. It looks
a little like our own in basic amino acid composition and structure
but there are more differences than similarities. Advanced, jawed
fish have just one form of antibody, IgM. It's produced by B cells
like our own but fish IgM is a little simpler in its structure than
the human form of IgM. Our IgM has more chemical bonds in it to
make it more robust and longer lasting.
Antibody
diversity
As well as a general increase in the number of different classes
of antibody present from simple to advanced vertebrates there is
also an improvement in the ability to make antibodies that target
a specific antigen. In fish, even advanced development fish (of
the class Teleostei e.g. carp) there is a limited ability to mount
an antibody response towards many invading pathogens. So far, researchers
have only identified around 25 types of antigens that fish antibodies
will bind to. The human antibody repertoire is able to collectively
target thousands of antigens.
Because of the limited research carried out on the fish immune
system, there are probably several more antigens that fish antibodies
can target but they have not yet been identified. Never-the-less
it is clear that some invading pathogens entirely escape the attention
of the fish humoral immune system.
Amphibians have a somewhat improved ability to mount a response
to foreign antigens but it is still very limited. Having three different
classes of antibody, IgM, IgX and IgY does help improve their chances
of defense against infection but it is clear that amphibians have
a significant problem mount an antibody response against what are
called "thymus dependant antigens". This type of antigen
needs to be destroyed by the combined efforts of antibodies and
lymphocytes. Although part of the problem is that amphibians have
a limited number of T cells, the main problem is a limited antibody
repertoire. Most thymus dependant antigens are viral antigens, so
amphibians are more susceptible to viral infections than humans.
Unfortunately that is as far as we can go in looking at the ability
of different vertebrates to mount an antibody response as so little
research has been done on reptiles and birds. It would seem that
from the few experiments that have been conducted that reptiles
and birds also have a limited antibody repertoire. Some types of
pathogen such as streptococcal bacteria will elicit a wide range
of antibodies against different antigen components on the surface
of the bacteria. The response is as good as that found in mice.
However, other forms of pathogen, particularly viral antigens again,
elicit a more limited production of antibodies.
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