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Introduction
Invertebrates do not generally have what we could describe as
organs involved in defense. Their immune cells can congregate
into loose structures which may resemble the precursors of lymph
nodes but for the most part invertebrate defense cells are diffusely
spread around the entire organism body. In chapter 2 we briefly
noted the evolutionary development of immune system organs from
simple vertebrates to ourselves as the most advanced form of vertebrate
immune system defense. We saw the gradual shift from an unordered
immune system into one that was highly specialized and compartmentalized
into specific structures and functions. Chapter 4 looks at the
lymphoid organs, what they look like and what they do.
There are two classes of lymphoid organs called primary (or
central) and secondary (or peripheral) organs. The primary organs
look after immature immune cells, either producing them or educating
them. Secondary lymphoid organs look after mature cells that are
an active part of the defense force.
Primary
organs of the immune system
In adult humans there are two primary organs the bone marrow and
the thymus. In some bird species there are three, the bone marrow,
thymus and bursa of Fabricius. We should also consider the development
of primary organs in our embryonic development where we find the
yolk sac and fetal liver are primary organs, albeit temporary ones.
Primary
organ embryonic development
Very early on in the development of embryos there is a requirement
to disseminate nutrients and oxygen and remove waste material and
CO2 around the system. This requires the development of blood cells
and we know that erythrocytes and white blood cells come from the
same source in adults. The same is true for embryos. Embryonic stem
cells that produce red blood cells can also produce white blood
cells.
This lymphocyte and erythrocyte formation first develops from
a few stem cells in the yolk sac. In birds and other vertebrates
that lay eggs the yolk sac is a very large structure compared to
the size of the embryo because of course the embryo is isolated
from the mother and unlike humans cannot obtain further nutrients
from her. The large size and developing externally outside any womb
enables easy examination and experimentation and much of what we
understand about the embryonic immune system is based on what we
see in bird eggs. The yolk sac of a chicken lasts from day zero
until after hatching and continues to be a source of blood cells
throughout although its activity diminishes as the yolk reduces
in size and the bone marrow develops to take over production of
blood cells.
In the first few days of development and embryonic chick is just
a thin circular patch of white cells on top of the yolk in an egg.
This layer of cells spreads out to enclose the yolk in the yolk
sac and within this sac blood vessels are formed and blood cells
can be migrating taking the yolk nutrients to the central developing
embryo.
Mammalian embryos including humans also have yolk sacs although
they are much smaller and don't last very long. Human yolk sacs
persist for up to 60 days from egg fertilization. They are the nutrient
source for early embryo development and to see it through migration
from the fallopian tubes to implantation in the womb wall and development
of an extensive placental connection to the mother.
Early embryonic development is very similar to birds and the embryo
develops from a thin layer of cells on top of the egg. Embryos form
by multiplication of the single egg cell. After several cell divisions
it becomes apparent that the ball of cells is developing into a
structure with two poles. At the top the layer of cells that will
form the embryo are situated. Beneath these a hollow cavity of cells
develops. This cavity (blastocyst cavity) is effectively the yolk
sac. Cells around the sac become vegetal in nature and form a loose
conglomeration. They will not directly contribute to the development
of the embryo rather they function as a nutrient supply - the yolk.
The yolk sac surrounding and forming the cavity develops into
a several layered structure. Cells in the middle layers start to
differentiate and collect together into small balls of cells. These
balls become "blood islands" The outer layer of the ball
forms into a blood vessel wall and the inner cells become stem cells
which multiply to make red and white blood cells. The blood islands
expand and elongate linking up with other blood islands to form
a capillary network over the yolky cells that will provide nutrients.
With development of the placenta the yolk sac quickly regresses
and becomes a vestigial attachment to the umbilical cord. With regression
so production of blood cells diminishes. To continue production
of blood cells the fetal liver takes over. It is actively producing
blood cells from around 40 days until about 160 days after fertilization.
While blood cell development in the yolk sac membrane was actually
inside the blood vessels themselves, the blood cell development
in the fetal liver occurs outside of the blood vessel walls. The
liver is formed from a protrusion from the embryonic gut which at
this stage opens into the yolk sac so blood cell production does
not move very far from the yolk sac.
The liver is a very complicated organ and develops from cells
coming together from a variety of sources. First the gut wall of
the embryo forms a protrusion which pushes out and elongates into
several solid strands of tissue called cords. These strands develop
into a complex meshwork which encloses around blood vessels in tissue
just below the heart. Gradually the tissue cells between the blood
vessels and within the meshwork differentiate into the specialized
liver cells. Some of these cells are temporarily stem cells producing
blood cells which then penetrate through the blood vessel walls
and into the blood stream.
Bone marrow tissue is the source of blood cells in adults and
gradually comes into production and full activity in human embryos
from around 75-80 days after fertilization. The collarbone/clavicle
is the first bone that develops marrow able to produce blood cells.
Bone and marrow develop from lose aggregations of "mesenchymal"
cells. Around the periphery of these aggregations the cells are
very loosely packed together. Cells toward the center rapidly multiply
to form a tightly packed accumulation of cells. These cells are
called chondroblasts (chonros is greek for cartilage and blastos
means germ). These chondroblasts start to secrete a products that
form into collagen fibers and an amorphous jelly like substance.
This "matrix" of material accumulates between the cells
(it is called an intercellular matrix) and pushes them apart. The
matrix matures into cartilage within which calcium salts start to
accumulate. Gradually the cartilage is calcified. While this is
happening the blood mesh network is expanding and penetrating into
the cartilage. Penetration is accomplished by blood and vessel wall
cells destroying any surviving cells and any uncalcified cartilage
leaving just the calcified meshwork built up by the deposition of
calcium salts.
These hollowed out spaces in the calcium salt meshwork are filled
up with capillaries, undifferentiated cells and cells called "osteoblasts"
which mature into bone forming cells. These cells excrete a highly
calcified material which forms on the still fragile meshwork laid
down previously. This deposition occurs from the center of the calcium/cartilage
matrix outwards to the edge of the bone. As the meshwork is filled
out with calcified bone material any calcified material deposited
in the center of the bone gets absorbed by "osteoclasts"
which are bone destroying cells. Effectively they are taking down
the internal scaffolding once the outer bone wall has been constructed.
The reabsorbed calcium gets redistributed to the outer edges of
the growing bone to strengthen the exterior.
All this happens as a continuum from the center of the bone outwards
so different parts of the bone are at different stages of development
and calcium deposition. Eventually we are left with a hollow center
to the bone which is colonized by blood capillaries and marrow cells.
At first the marrow cells are primarily given over to a supportive
role in forming bone which it continues to do throughout life. Gradually
though the marrow develops the ability to produce blood cells in
the fashion we described in chapter 3.
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