|
Humoral
type defense of self
As for vertebrates, invertebrates have humoral mechanisms of
defense. For more complex organisms, fluids are distributed by
a form of circulatory system but for simple animals the cells
are merely bathed in fluid that percolates through the body. Limited
research in this area gives us little to go on. However, the basic
requirement of defense of all areas of the body remains the same
regardless of the size, shape or structure of the animal. Any
humoral factors must be small and readily diffuse throughout the
body.
Land based snails use "agglutinin" as their humoral
defense and produce it from their stomachs. If bacteria are injected
into a snail, the bacteria is rapidly removed in a few hours.
Part of the defense uses phagocytosis. Agglutinin helps Phagocyte
cells to ingest the bacteria by acting as a coagulant for the
bacteria. By binding bacteria to each other, agglutinin stops
bacteria from circulating through the snail's system. The large
clumps of bacteria are also much easier for the phagocytes to
ingest and remove from the snail's system. Agglutinin can be found
in many invertebrates in some shape or form. Its structure is
that of a glycoprotein which is able to target various carbohydrate
molecules.
Agglutinin is a product that is always present. the levels do
not increase or decrease in response to the level of pathogenic
threat. There are however humoral defense mechanisms which are
specifically released when needed to defend against infection.
Being in Maine I can't leave invertebrate defense mechanisms without
mentioning the lobster. When lobsters are infected with bacteria
they respond with production of "bactericidin". Bactericidin
increases in concentration over two days after infection and seems
to act in a similar way to agglutinin by clumping bacteria together,
taking them out of the system and aiding phagocytosis. No one
has analyzed what exactly bactericidin is but it seems to be quite
limited in its reactivity and will only target just a few carbohydrate
structures.
We could go on to describe another interesting mechanism of
invertebrate defense called the complement system. However, this
method of defense is employed in humans in modified form. Because
the complement system has a complex structure, we will deal with
it separately later.
Cellular
type defense of self - passive defense
Cellular defense can be passive or aggressive. In 1923 Kepner
and Reynold described an experiment using a single celled animal
called Difflugia. Difflugia, a protozoan, can be found lurking in
the mud of stagnant ponds. The single cell forms a pear shape shell
made of particles it picks up (so its first mechanism of defense
is a simple protective covering). The shell has a single hole at
the bottom through which the cell sends out projections called pseudopodia
from the Greek pseudes=false and podus=foot. These arms and legs
are used to move around and find food.
Kepner and co. cut off these feet and observed that the separated
body and feet would move towards each other and fuse back together
again. If they cut the feet off two Difflugia and swopped the feet
over they saw that the feet would still fuse with the other body.
However, this would only occur if the two Difflugia came from the
same pond source. Feet from Difflugia in one pond could not fuse
with a body of Difflugia from another pond. They also saw that the
feet would not fuse with any other species of protozoa even if they
came from the same pond. So even at this very basic evolutionary
level, single cells have some ability to recognize different species
and avoid them. They can also recognize cells from different populations
but of their own species. This is a form of passive cellular defense
intended to keep different cell types separate from each other and
to avoid assimilation.
Sponges are sedentary aquatic animals that have been the focus
of attention for some time. In 1907 HV Wilson did an experiment
famous in immunological circles. He cut up a sponge and strained
the pieces to make a single cell suspension in a glass bottle. He
then observed that as the cells settle onto the bottom of the bottle,
they start to move around and when they come into contact with another
cell they will attach to each other. They eventually clump together
and if left for several days the cells will reconstitute themselves
into several new, fully functioning sponges (Hmm, now which horror
movie did I see that happen in?). Next he took two sponges from
different species, mashed them up and mixed the cells of the two
together. Left to their own devices the cells will settle and migrate
around looking for other cells. However, the cells will only attach
to other cells from the same individual. If two cells, one from
each sponge come into contact with each other they are immediately
repelled and move away from each other. The eventual result is lots
of little sponges, some entirely composed of cells from one donor
and other sponges composed of cells entirely from the second donor.
The donor cells do not mix and will not function together. So sponges,
like protozoans are able to differentiate between different species.
Corals are sedentary polyps encased in a soft skeleton structure.
If two branches of a living coral are tied together they will fuse.
If branches of two corals from different species are tied together
they will attempt to pull away from each other and grow to leave
a gap between the branches. The branches will not fuse. What we
are seeing in all these examples of a passive cellular response
is incompatibility. The key defense mechanism against the threat
of assimilation.
Cellular
type defense of self - aggressive defense
Well if you can't join them beat them. If assimilation is not
an option and resources are limited you have to fight the opposition
for the territory.
Aggression may take the simple form of rapid colony proliferation.
Among several species of sedentary marine animals, expanding in
size to cover more ground will protect against other species encroaching
on the area. Some animals such as corals may aggressively expand
into already populated areas. Their dominance allows them to strangle
the more slowly proliferating competition opposition. This action
is similar to that seen in the plant world.
Engulfment is one aggressive form of response that is apparent
in both invertebrates and vertebrates alike. There are three forms
of engulfment reaction. "Pinocytosis" occurs when a cell
"eats" a fluid (Greek pineo=drink, kytos=cell). When a
cell eats a solid particle it is called "phagocytosis"
(Greek phagein=to eat). When a particle is too big for a single
cell to eat then several cells will attempt to "encapsulate"
it.
Pinocytosis and phagocytosis can be seen in single celled organisms
as their mechanism of obtaining food. The cells in classic amoeba
fashion send out cytoplasmic strands around the particle. These
strands, or pseudopodia (our false feet again) fuse together around
the particle effectively absorbing the item into the cell. The engulfed
particle is now inside the cell but separated from it by a membrane
of protein and lipids (this was originally part of the cell wall
that was pinched off to contain the foreign particle). This is described
as a vacuole. The cell releases enzymes into the vacuole to digest
the food. Any valuable products are absorbed across the vacuole
wall into the cell. Any remaining material that the cell can't absorb
is expelled in a process called "exocytosis". The vacuole
moves to the cell wall and fuses with it releasing the foreign material
to the outside. The vacuole membrane becomes part of the cell wall
again.
The first observation of engulfment being used as a form of defense
was observed in an animal called Tehys Fimbria which is a mollusc
found in the Mediterranean Sea and Atlantic Ocean. If indigo dye
is injected into this, or any other mollusc, some of the blood cells
will engulf the foreign particle in this case by pinocytosis as
the dye is a liquid. Injected iron particles will also be engulfed
(phagocytosed) by some of the blood cells. The Blood cells in molluscs
are called hemocytes. They are neither the equivalent of red nor
white blood cells in vertebrates but seem to perform both functions
of carrying oxygen and primitive defense.
As well as pinocytosis and phagocytosis, hemocytes will also undertake
encapsulation. If a particle too large to be engulfed is surgically
inserted into a mollusc, hemocytes will swarm around it. They form
into layers of cells, called lamellae, around the particle entirely
encapsulating it. The inner layers of the capsule die off to form
an impenetrable wall. The particle is effectively entombed. This
mechanism is very useful for protecting against large parasites.
The tomb stops the parasite from obtaining nutrients from the host
and it also stops the immune system from being further stimulated
by foreign antigenic material. As we will see when we examine the
mechanisms of defense against parasites in vertebrates, this can
sometimes be advantageous to some parasites.
Viral infection is not unique to vertebrates. Many invertebrates
also have their own forms of viruses to defend against. The only
real defense available against viruses is to destroy any cells that
become infected. The intention is to kill the virus inside the cell
before it can multiply and spread to other cells. This applies both
to both vertebrates and invertebrates alike and the mechanism of
cell destruction is carried out by cells called "cytotoxic
cells" (sometimes you may hear these cells described as killer,
cytolytic or effector cells but they are essentially the same thing).
Cytotoxic cells have the ability to recognize viral infected cells.
They will bind to the cell and cause changes in the cell wall which
make it more permeable to fluids. Fluids rush in to the cell, expanding
and bursting it. We will go into this in more detail when we talk
about cell types. This form of cell destruction is called "lysis".
This method of destruction will also occur if cells from a different
species is injected into an animal or tissue is transplanted between
different species.
Flat worms and earth worms have this property involving defense
using cytotoxic cells. The details are not known due to the limited
research done on in invertebrate immunology but these worms seem
to have cells that roughly work like cytotoxic lymphocytes invertebrates.
The cells are called "coelomocytes".
It is possible to transplant material between to members of the
same worm species. Indeed it is possible to graft complete heads
and tails of flat worms onto recipients to create multi-headed monsters.
However, when material from a different species, or a donor collected
from a different area than the recipient, is grafted onto a worm,
the graft is rejected. The rate of rejection is slow and does not
begin before 30 days post grafting. In earth worms the cells involved
in rejection apparently have a memory mechanism. If a second graft
is given to a recipient from the same donor, the graft will be rejected
much more quickly. However, compared to vertebrates the rate of
rejection is still very slow.
As animals have become more complex so have the defense systems
to protect against infection. Some mechanisms of defense, particularly
humoral ones probably developed from nutrient digestion. The simple
use of enzymes in secretory fluids to "digest" pathogens
may have been the first step. We also see the mechanism of phagocytosis
adapted from use to ingest food in single celled animals, to use
as a method to rapidly remove any invading microorganisms. As animals
increased in size, so a more compartmentalized structure was required.
The development of a circulatory system not only enabled distribution
of food to all areas but provided an efficient way of distributing
a rapid defense force, both humoral and cellular.
Simple defense systems of invertebrates show most of the basic
properties that our vertebrate immune system has. The invertebrates
have both humoral and cellular mechanisms of defense available.
However, these defense systems are very simple. Although almost
all animals are able to distinguish between self and non-self, the
ability to differentiate is unsophisticated. Defense systems of
many invertebrates can easily be confused by presenting them with
tissue or pathogens that have very similar antigens to the individual
animal.
For more complex animals we need a more complex defense system.
While vertebrates retain many similar defense functions of invertebrates
they have developed and specialized to improve protection of the
individual. A coordinated response requires regulation and its with
vertebrates that we first see the emergence of regulatory cells.
We see specialization of function taken to the extreme. With invertebrates,
each phagocytic cell or humoral factor could respond to a range
of different antigens. In vertebrates we see the development of
cells and antibodies that are each only able to target one, and
only one, antigen. This has required the expansion of the defense
system and the use of many more cells to ensure that all antigens
can be recognized by each vertebrate individual. Different parts
of the vertebrate immune system have different functions. As animals
have compartmentalized functions such as food intake, hormone production
etc. into different organs, so the immune system has been compartmentalized
into organs and further subdivided. Different immune organs carry
out specialized actions and cells and antibodies have been categorized
into subgroups each excelling at their specialist task. So now we
have lymphocytes that only target infected or dying self cells.
Other cells which standby and produce cytokines to help these cells.
More cells which oversee and regulate other cells. Certain antibodies
only target bacteria. Other types specialize in defending against
parasites.
An important point here. It would be impossible for most invertebrates
to ever develop a vertebrate type of immune system. Phagocytosis
and the use of enzymes can be used by a single cell for protection.
The vertebrate system however, requires the use of so many cells
that invertebrates would not have enough room to accommodate them
all. Invertebrates would have to give over their entire cell population
and then some to defense. There would be no cells left in their
body for any other function. So, there is a "size limitation"
imposed by the vertebrate immune system.
The vertebrate immune system has also enabled a change in the
mechanisms of survival for a species. For invertebrates survival
of the fittest is the order of the day. This has resulted in short
lived individual invertebrates that are not much more than reproductive
machines. Invertebrates make up for their defense limitations by
producing large numbers of progeny. Some may die from pathogens
but a few will survive. Their short life span means a reduced time
window of opportunity for parasites/microorganisms to invade. The
invertebrate defense system may be limited but if it gets the individual
from birth to reproductive age then it has done its job. It's GOOD
ENOUGH.
Vertebrates, and mammals in particular, have a different approach
to survival. We produce just a few progeny and reaching the reproductive
age takes a lot longer. Clearly we need an improved defense system
that will allow us to survive longer and reduce the threat of pathogens.
The intention of the immune system is still to get us to reproductive
age. What happens after that is of no "concern" to the
immune system. Once the genes have been passed on, the job is done.
This may be why we see so many thing go wrong with the immune system
in old age and why the immune response becomes weaker and more dysfunctional
the older we get. It was simply not designed to see us this far.
|
