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Chapter 9
WHITE BLOOD CELLS
Any nucleated cell normally found in blood is a white blood
cell. White blood cells are also known as WBCs or leukocytes.
When white blood cells accumulate in one place, they grossly
appear white or cream-colored. For example, pus is an accumulation of white blood cells. Mature white blood cells are
larger than mature red blood cells.
There are five types of white blood cells. They are neutrophils, eosinophils, basophils, monocytes and lymphocytes
(Table 9-2).
White blood cells can be classified in three different ways:
1. Type of defense function
• Phagocytosis: neutrophils, eosinophils, basophils, monocytes
• Antibody production and cellular immunity: lymphocytes
2. Shape of nucleus
• Polymorphonuclear
(multilobed, segmented nucleus):
neutrophils, eosinophils, basophils (Figure 9-4)
• Mononuclear (single, rounded nucleus): lymphocytes
• Pleomorphic (varying shapes, nonsegmented nucleus):
monocytes
3. Presence or absence of specific staining cytoplasmic
granules
Granulocytes (presence of granules): neutrophils,
eosinophils, basophils
• Agranuloctyes (absence of granules): lymphocytes,
monocytes
Blood, Lymph, and Immunity
231
All white blood cells develop in the bone marrow except
for some lymphocytes (they start out in bone marrow but
develop elsewhere). At the beginning of leukopoiesis all the
immature white blood cells look alike even though they're
already committed to a specific cell line. It's not until the
cells start developing some of their unique characteristics
that we can tell them apart.
Function
The function of all white blood cells is to provide a defense
for the body against foreign invaders. Each type of white
blood cell has its own unique role in this defense. If all the
white blood cells are functioning properly, an animal has a
good chance of remaining healthy. Individual white blood
cell functions will be discussed with each cell type (see
Table 9-2).
In providing defense against foreign invaders, the white
blood cells do their jobs primarily out in the tissues. The
white blood cells use the peripheral blood to travel from
their site of production (bone marrow) to their site of activity (tissue). There is a constant flow of white blood cells out
of marrow and into tissues in an attempt to control the millions of foreign invaders that attack a body every day. It's
happening in us too. And as long as they do their job, we
don't even realize what's going on and we remain healthy.
Formation
The general term for the formation of white blood cells is
. leukopoiesis. All white blood cell production starts out in
the red bone marrow from the same pluripotent stem cell
(PPSC) population that produced red blood cells and megakaryocytes. It is the stimuli that act upon the PPSCs that
determine which cell type will be produced. Each type of
white blood cell has its own stimulus for production.
TABLE 9-2
~
TEST YOURSELF
1. List the five white blood cells and indicate if each one is
a granulocyte or an agranulocyte.
2. What is the common function of all white blood cells?
3. Which cell is the only white blood cell not capable of
phagocytosis?
White Blood Cells
Name
Cytoplasmic Granules
Nuclear Shape
Function
Site of Action
Neutrophil
Polymorphonuclear
Phagocytosis
Body tissues
Eosinophil
Don't stain (usually
invisible)
Stain red
Polymorphonuclear
Body tissues
Basophil
Stain blue
Polymorphonuclear
Allergic reactions, anaphylaxis,
phagocytosis
Initiation of immune and allergic
Body tissues
None
Pleomorphic
reactions
Phagocytosis and process antigens
Body tissues or blood
None
Mononuclear
None
Mononuclear
Monocyte
(macrophage)
B cell
(lymphocyte)
T cell
(lymphocyte)
Antibody production and
humoral immunity
Cytokine production and
cell-mediated immunity
Lymphoid tissue
Lymphoid tissue and
other body tissues
232
Chapter 9
Blood, Lymph, and Immunity
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he total white blood cell count and differential count are
used to evaluate a patient for the diagnosis or prognosis
of an abnormal condition. For example,. if an infection is'
present in the body, there will be an increased need for neutrophils to killthe invading microorganisms. The bone marrow
responds to this need by releasing more neutrophils into the
bloodstream that willtravel to the infected tissue.
The increased number of neutrophils in the blood will
increase the total white blood cell count. The total white blood
cell count is equal to the sum of each of the individual white
blood cell counts. If one cell type increases or decreases, the
total white blood cell count will increase or decrease accordingly. Sounds simple, doesn't it? Unfortunately, it's not always
that simple. If one cell type increases and another cell type
decreases, the net effect could be a normal total white blood
cell count. That's the tricky part, so the total white blood cell
count is only one of a series of tests performed to evaluate
the white blood cells.
To find out which white blood cells are affecting the total
white blood cell count, we have to look at a stained smear of
the blood. The usual method for evaluating the blood smear
is to count the first 100 white blood cells and keep track of the
number of each white blood cell type you see. This is called a
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characteristics.
differential count, commonly referred to as "the diff." Because
you're counting 100 cells, the number of each cell type you see
can be expressed as a percentage. For example, if you count
100 cells and find that 20 of the cells are neutrophils and 80
of the cells are lymphocytes, you would report you saw 20%
neutrophils and 80% lymphocytes.
There are automated hematology analyzers that will
provide these numbers, but they won't pick up all cellular
abnormalities. For this reason, you should always look at a
stained blood smear even if you're using an automated analyzer. You don't have to complete a differential count; just
look for physical abnormalities.
For every species of common domestic animal, there is a
value range that represents a normal white blood cell count.
There is also a normal range for individual white blood cell
types. For example, a dog willnormally have between 6 billion
and 17 billion white blood cells per liter of blood, and 60%
to 70% of these cells should be neutrophils. Cattle will have
between 4 billion and 12 billion white blood cells per liter and
only 15% to 45% of the cells should be neutrophils.
Taken together, the total white blood cell count and the
differential count can provide a lot of information about an
animal's state of health.
Granulocytes
CLINICAL APPLICATION
The granulocytes are the neutrophils, eosinophils, and basophils. They are named for the color of the granules in their
cytoplasm when viewed on a stained blood smear (see an
earlier discussion of stains in this chapter). Eosinophil granules pick up the acidic stain and appear red, basophil granules pick up the basic stain and appear blue, and neutrophils
don't pick up either stain very well, so for the most part, the
neutrophil granules appear colorless or faintly violet on a
stained blood smear.
:/.ld.r~~h!J!i!~~ti~2·;Z~'.!~;~.~i&z1~;i"~l0C~~;t~,.::.;;]
he word leukemia means "white blood." It is caused by
an abnormal proliferation of one of the white blood cell
types. In response to some unknown stimulus, the stem cells
in the bone marrow start producing abnormal cells in one
cell line at an increased rate. These abnormal cells show up
in peripheral blood in large numbers, many times before
they are mature, and cause the total white blood cell numbers
to increase dramatically aeukocytosis}. Leukemias are considered a form of malignancy or cancer and can be acute
or chronic. They are classified by the type of cell involved
(e.g., lymphocytic leukemia, monocytic leukemia, eosinophilic leukemia).
T
Formation. The production of all granulocytes is called
granulopoiesis. In the bone marrow, early granulocytes are
impossible to distinguish from one another. They are all
large cells with lots of cytoplasm and large round nuclei.
Initially there are no cytoplasmic granules. As the granulocytes mature, a first set of granules is formed.
Chapter 9
These granules are the same in all three granulocytes and
are called nonspecific granules. Gradually, the nonspecific
granules are replaced by a new set of granules that is unique
to each granulocyte type. These are called specific granules.
The Golgi apparatus produces both nonspecific and specific
granules.
The substances found in its granules determine the function of a granuloctye. For example, neutrophil granules
contain chemicals called lysosomal enzymes, which aid in
killing microorganisms that have been engulfed by the neutrophil. Neutrophils have therefore become a major factor
in preventing invading microorganisms from causing disease.
An early granulocyte has blue cytoplasm indicating that
it is a metabolically active cell. As it matures, the cytoplasm
becomes less active and therefore doesn't stain as blue.
Mature granulocytes in circulation contain almost colorless
cytoplasm containing the specific granules. In fact, if it
weren't for the granules, the limits of the cell membrane
would be difficult to see, making it look like the nucleus was
pretty much floating around alone. This sometimes is just
how neutrophils appear because of their colorless or faintly
stained granules.
As a granulocyte matures, its nucleus transforms from a
round structure to a segmented structure that takes on many
shapes (polymorphonuclear). Thin filaments connect these
segments. The chromatin pattern of the nucleus starts out
quite loose. As the nucleus squeezes itself down into segments, the chromatin becomes more condensed. As the cell
ages and approaches death, the segments break apart and
lose all evidence of any chromatin pattern. This process is
called pyknosis, and it is an indication of a dead cell.
Neutrophils. Neutrophils are also known as polymorphonuclear cells (because their nuclei have many shapes), PMNs
(PolyMorphoNuclear leukocytes), and segs (because their
nuclei are segmented). Even though eosinophil, basophil,
and monocyte nuclei can be polymorphonuclear, the neutrophil is the only cell that is commonly called a PMN. The
neutrophil is the most numerous white blood cell in circulation in the dog, horse, and cat.
Formation.
Neutrophils are produced in the bone marrow
and released into blood as needed, when neutrophils already
in circulation leave the bloodstream and enter tissue to kill
microorganisms or simply die of old age. It takes 3 to 6 days
to produce a mature neutrophil under normal conditions,
depending on the species of animal. If the body has a sudden
need for more neutrophils, this time can be shortened.
Blood, Lymph, and Immunity
f a neutrophil nucleus in peripheral blood has more than
segments, it is called a hypersegmented nucleus (see
figure). This indicates that the neutrophil has stayed in peripheral blood longer than normal, because hypersegmenting
usually takes place in tissue as part of the normal aging
process. The presence of hypersegmented neutrophils on
a stained blood smear can be indicative of a pathological
condition that prevented neutrophils from leaving circulation,
or it can mean the smear was made from old blood. Remember, blood is still living when it is removed from the animal,
and it will continue the aging process as long as it can. So
hypersegmented neutrophils may be just aging normally in
the tube.
Hypersegmented neutrophils are seen within a day after
.dhe blood sample was drawn. For this reason, it is important
that a smear be made as soon as possible after the blood
sample is drawn.
Ifive
Nucleus
Cytoplasm
Hypersegmented nucleus. Can indicate an older cell than is
normally found in peripheral blood.
pieces of nucleus but are joined by a thin strand of chromatin. Sometimes this strand of chromatin is difficult to see,
so it looks like the segments are separated. If the neutrophil
is released from the bone marrow before it is mature, it
will have a horseshoe nucleus without any segmentation.
This is called a band neutrophil. When band neutrophils are
seen in peripheral blood, it is an indication that there is an
increased demand for neutrophils beyond what the bone
marrow can supply in mature neutrophils. If the bone
marrow runs out of band neutrophils and still hasn't met
the body's demand, it will start releasing progressively more
immature cells.
function. Neutrophils
Characteristics:
Neutrophil granules don't stain with
either the blue alkaline stain or the red acid stain, so they are
said to be neutral. This means they are difficult to see on a
stained smear; so identification of neutrophils is commonly
based on nuclear morphology, rather than granule staining
characteristics.
A mature neutrophil in peripheral blood will have from
two to five nuclear segments. The segments aren't separate
233
are phagocytes. That means they
engulf (phagocytize) microorganisms and other microscopic
debris in tissues. Neutrophils are part of the second line of
defense, after the skin and/or mucous membranes, when
invading microorganisms enter the body.
Neutrophils can respond very quickly. Their granules
contain digestive enzymes that are capable of destroying bacteria and viruses that have been engulfed. The neutrophil
granules are organelles called lysosomes.
;------~
234
. Chapter 9
Blood, Lymph, and Immunity
Tissue
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Neutrophils use blood as a transportation medium to
take them to their site of action in tissue. Normally a neutrophil will spend an average of 10 hours in circulation
before it enters the tissue. This circulation time is shorter
when there is an increased demand for neutrophils in the
tissue. Once a neutrophil enters tissue it doesn't return to
blood, so all circulating neutrophils need to be replaced
about two and a halftimes a day. Under normal conditions,
they are replaced by mature neutrophils held in reservein
the bone marrow.
Neutrophils leave the blood vessel by squeezing between
the cells of the endothelium in a process called diapedesis
(Figure 9-5). Neutrophils are normally found in tissues that
are constantly exposed to microorganism invasion (e.g.,
the lungs and intestinal tract). Other neutrophils wander
through tissue to the sites where they are needed.
Neutrophils stay in tissue until they die of old age or are
destroyed by the microorganisms they are trying to destroy.
Dead or abnormal neutrophils are picked up and destroyed
by tissue macrophages. (See the discussion of tissue macrophages in the section on monocytes.) Think of neutrophils
as garbage cans and tissue macrophages as garbage trucks.
Neutrophils are attracted to a site of infection by chemotaxis, a process by which neutrophils and other cells
are attracted by inflammatory chemicals produced by the
interaction between microorganisms and the tissues they
are invading. Having arrived at the site invaded by the
microorganisms,
the neutrophil
must recognize what
to ingest.
Detecting some microorganisms is not a problem for the
neutrophils. Other microorganisms try to "hide" inside capsules that make them difficult for neutrophils to recognize.
To help make the microorganism more recognizable to the
neutrophil, the encapsulated microorganism is coated with
a plasma protein, usually a specific antibody. (See the discussion of antibody production in the immunity section.) These
plasma proteins are called opsonins. Coating the microorganism enables the neutrophil to recognize it as foreign
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Figure 9-5
Diapedesis. 1, Neutrophil lying against vessel wall
begins to squeeze through the space between endothelial cells by
flowing into pseudopod (false foot). 2, Pseudopod continues to push
its way between cells. Rest of the cell cytoplasm flows along with it.
3, Pseudopod and the rest of the cell emerge on tissue side of blood
vessel. 4, Neutrophil is off in search of foreign invaders to
phagocytize.
Neutrophil
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Figure 9-6
Phagocytosis and destruction of microorganisms.
1, Neutrophil membrane engulfs microorganisms. 2, Phagocytic
vacuole is formed. 3, Cytoplasmic granules (lysosomes) line up
around phagocytic vacuole and empty their digestive enzymes into
vacuole. 4, Microorganisms are destroyed.
and to begin phagocytosis. The coating process is called
opsonization.
When the neutrophil recognizes a foreign microorganism, its outer membrane flows around the invader and
encases it within a membrane-bound
phagocytic vacuole
(Figure 9-6). If you've seen the 1950s sci-fi movie The Blob,
then you've seen how a neutrophil operates: it flows around
anything in its way. (If you haven't seen the movie you
should. It's a hoot.) The microorganism is surrounded by
the neutrophil membrane, but isn't really inside the neutrophil. Think of it as a hug. When you put your arms around
something, you're encasing it but not taking it inside your
body.
At this point, the neutrophil's cytoplasmic granules (lysosomes) move to the edge of the vacuole that contains the
microorganism, fuse with the membrane, and secrete their
digestive contents into the vacuole.
Neutrophils increase their metabolism of oxygen during
ingestion of microorganisms to produce substances that are
toxic to ingested bacteria. Hydrogen peroxide is the product of
oxygen metabolism that is the most important for the killing
activity of neutrophils. Hydrogen peroxide is capable of
killing bacteria (bactericidal effect) all by itself, but its action
is enhanced by the enzyme myeloperoxidase, which is released
from neutrophil granules. Lysozyme from the granules also
enhances the bactericidal action of hydrogen peroxide and is
capable of destroying the cell walls of microorganisms.
Count in Peripheral Blood. The neutrophil count in peripheral blood is kept within a specific range
in a healthy animal. This number is controlled by three
factors:
l. Release of mature neutrophils from the storage pool in the
bone marrow into the peripheral blood. In the bone marrow
storage pool, there is usually a 5-day supply of mature
neutrophils. They are ready for immediate release if there
Neutrophil
Chapter 9
~~~
Blood, Lymph, and Immunity
235
~
fthere is an increased demand for neutrophils in tissue,
bone marrow willrelease its reserve stores of mature-and,
if necessary, immature-neutrophils into blood, so they can
be transported to the site where neutrophils are needed. If a
blood sample is drawn while these neutrophils are in transit,
there will be a higher than normal number of neutrophils in
the sample. This is called neutrophilia, and it is usually
detected during a differential cell count.
The increased number of neutrophils will also increase
the total number of white blood cells in the sample. This is
called leukocytosis and usually is detected using an automated blood analyzer or by looking at the thickness of the
buffy coat in a hematocrit tube. Leukocytosis with accompanying neutrophilia can indicate an infection somewhere
in the body.
I
fan infection is out of control, all the reserves of neutrophiIs can be used up faster than the bone marrow can
replace them. If this happens, the number of neutrophils in
circulation decreases, because the neutrophils are leaving
the bloodstream and entering tissue, and there are no cells
in the bone marrow to replace them. This condition is called
neutropenia. The total white blood cell count will also
decrease. This is leukocytopenia. The prognosis is poor for
an animal that is clinicallyillwith accompanying neutropenia
and leukocytopenia. It means the body is losing the war
against the invading microorganisms.
I
is a sudden drop in circulating numbers of neutrophils
caused by increased movement of neutrophils into tissue.
2. Rate of escape from peripheral blood into tissue. This rate
depends on the need for neutrophils in the tissue. With
a massive acute infection (e.g., coliform mastitis in
cattle), the total neutrophil population of the peripheral
blood can enter the tissue in a matter of hours.
3. The entrance of increased numbers of pluripotent stem cells
into the neutrophil production line. This is a slow method
of control because it takes 3 to 6 days for the neutrophils
to mature and be ready to be released.
Intravascular Pools of Neutrophils. In peripheral
blood there are two pools of mature neutrophils:
1. The circulating pool is contained in the blood as it
flows through the blood vessels. It is found toward the
center of the lumen of the vessel. Blood samples
obtained for laboratory analysis contain the neutro-
eutrophils can move freely between the circulating and
marginal pools. At any given time in dogs, cattle, and
horses, there is about a 50:50 ratio between the number of
neutrophils in the circulating pool and the marginal pool. In
cats, the ratio is about a 30:70.
Cells can detach from the marginal pool and enter the
circulating pool when an animal is experiencing some sort
of physical or mental stress. Trauma, fear, and exercise are
a few of the stresses that may lead to a temporary transfer
of neutrophils from the marginal pool to the circulating
pool. This predictable neutrophil response is part of a larger
physiological reaction called the stress response.
Splenic contraction also plays an important role in this
,•. movement of cells out of the marginal pool. The temporary
movement of neutrophils into the circulating pool can artificially elevate the total neutrophil count (neutrophilia) and
the total white blood cell count (leukocytosis) because the
normal values are based only on the number of cells normally found in the circulating pool. These artificiallyelevated
results can lead to a possible misdiagnosis. Remember this
when you have to chase a horse around a pasture or wrestle
with a cat to get a blood sample.
The administration of corticosteroid drugs, which are
similar to glucocorticoid hormones (see Chapter 15) will
cause the same response. This is one good reason
for drawing a blood sample before medications are
administered.
N
t
phils from this pool. The normal range of neutrophil
numbers in peripheral blood is based on the neutrophils contained in this pool.
2. The marginal pool is composed of neutrophils that
line the walls of small blood vessels mainly in the
spleen, lungs, and abdominal organs. These neutrophils are not circulating and are not contained in
blood samples obtained for laboratory analysis.
Eosinophils. Eosinophils are named for the red granules
in the cytoplasm of mature cells. The granules stain with the
red eosin component of the blood stain. They make up 0%
to 5% of the total white blood cell count.
fonnation
and Characteristics. Eosinophils are produced in the bone marrow from the same pluripotent stem
cells that give rise to all other blood cells. It takes 2 to 6 days
to produce an eosinophil from a PPSc. The cytoplasmic
granules take up the acidic stain eosin and appear red when
seen on a blood smear. Frequently the segmented nucleus
has only two lobes.
The granules are shaped differently in various species:
• Dogs: Granules are round. Their size varies from small
to large within the same cell, and they stain very lightly.
236
Chapter 9
Blood, Lymph, and Immunity
Cats: Granules are small, rod-shaped, and numerous.
They stain darker than canine eosinophil granules.
• Horses: Granules are very large, round or oval, and
stain very intensely.
• Cattle, sheep, and pigs: Granules are round and much
smaller than equine granules. They stain pink to red.
There is a good bone marrow reserve of eosinophils.
There are also circulating and marginal pools of eosinophils
in peripheral blood, like the neutrophil pools. Eosinophils
don't stay in peripheral blood very long but migrate into
tissue in a few hours, where they spend the rest of their
lives. In tissue they undergo the same aging process as
neutrophils.
function. The functions of eosinophils are not yet entirely
understood, but like neutrophils, the functions are determined by the contents of their granules. Chemotaxis regulates their entry into tissue. They don't re-enter circulation
once they leave blood vessels. Large numbers of eosinophils-,
are normally found in certain tissues in the body (e.g., skin,
lung, small intestines). Three key functions are most often
associated with eosinophils:
• Anti-inflammatory response. Eosinophils are attracted to
and inhibit local allergic and anaphylactic reactions. Their
granules contain anti-inflammatory substances that are
released at the site of the allergic reaction.
• Immunity. Eosinophils can ingest substances associated
with the humoral immune response (e.g., antigenantibody reaction complexes).
• Phagocytosis. Eosinophils have minimal phagocytotic and
bactericidal functions, but they are especially effective in
the phagocytosis of large, pathogenic organisms, such as
protozoa and some parasitic worms but are not protective
against most bacterial infections.
Basophils. Basophils are named for the blue granules
in the cytoplasm of mature cells. The granules stain with
the basic component of the blood stain. They are the
white blood cell least often seen in circulation, and for
this reason they are also the least understood white blood
cell.
Formation.
Basophils are produced in the bone marrow
from the same pluripotent stem cell as the other blood cells.
Not much is known about the production and function of
basophils.
Characteristics.
The basophil granules are water soluble
and are frequently washed out during the staining procedure, so they are not always readily visible on a stained
smear. When they are seen, the basophil granules stain blue
and fill the cytoplasm. A dog has fewer granules than the
other common domestic species. Basophils most often have
a two- to three-lobed nucleus.
Basophils and Tissue Mast Cells. Basophils share some
characteristics with tissue mast cells, but some controversy
exists over the relationship between these two cells. Mast
cells are normally found in tissue and don't migrate there
from blood. Basophils are not commonly seen in tissue.
Mast cells are larger than basophils and have more cytoplasmic granules that are not water-soluble. Mast cells have a
round nucleus that doesn't segment.
Two theories currently exist regarding this relationship:
1. Mast cells and basophils are two different cell types
with similar characteristics. They are produced in two
different areas of the body and don't give rise to one
another.
2. Mast cells are tissue basophils. This theory is not as
popular as the first theory.
Eosinophilia and Leukocytosis.
Increased numbers of
eosinophils in peripheral blood (eosinophilia) can be seen
during allergic reactions and certain parasitic infections. The
increased numbers are a response to a demand created by a
pathological condition in the animal. An accompanying leukocytosis may also occur, but because there are normally few
eosinophils in circulation, the increased number may not be
enough to elevate the white blood cell count beyond the
normal range.
Eosinophilia can result from any of the following:
• Increased release of mature eosinophils from the storage
pool in the bone marrow
• Migration of eosinophils from the marginal pool to the
circulating pool
• Increased production in the bone marrow
• Increased time spent in peripheral blood before entering the tissue
Eosinopenia.
Decreased numbers of eosinophils in peripheral blood (eosinopenia) are difficult to detect and evaluate,
because their numbers are normally low.
function. Not much is known about the function of basophils. They are the least phagocytic of the granulocytes.
Basophil granules contain histamine and heparin, which are
responsible for at least part of basophil function in the following ways:
• Histamine helps initiate inflammation and acute allergic reactions.
Eosinophils are attracted to the site of an allergic reaction by eosinophilic chemotactic factor released from the
basophil granules.
• Heparin acts as a localized anticoagulant to keep blood
flowing to an injured or damaged area.
Basophilia
and Basopenia. Increased numbers of
basophils in peripheral blood (basophilia) can be associated
with an allergic or hypersensitivity reaction in tissue. Sometimes basophilia and eosinophilia are seen at the same
time.
Decreased numbers of basophils in peripheral blood
(basopenia) are difficult to evaluate because basophils are so
Chapter 9
Agranulocytes
Agranulocytes are white blood cells that don't have specific
staining granules in their cytoplasm. They include monocytes and lymphocytes.
Monocytes.
Monocytes make up 5% to 6% of the cirwhite blood cells in all common domestic
Formation and Characteristics.
Monocytes are formed
in the bone marrow from pluripotent stem cells. They
mature much faster than neutrophils (total monocyte
development time is 24 to 36 hours) and stay in the blood
longer (24 to 36 hours) than neutrophils. From peripheral
blood, monocytes enter the tissue, where they do their
work.
Monocytes are the largest white blood cells in circulation.
They have abundant cytoplasm that stains gray-blue and
may contain vacuoles of varying sizes. Sometimes the cytoplasm takes on a fine granular appearance that is commonly
referred to as a "ground glass" appearance. The nucleus can
be round or any number of shapes (pleomorphic), but it
doesn't split up into distinct segments like a mature granulocyte nucleus.
function. Monocytes are major phagocytic cells. When
they enter tissue, they become known as tissue macrophages.
Monocytes in the bloodstream are less effective phagocytes
than tissue macrophages. In fact, monocytes are considered
immature tissue macrophages. Tissue macrophages are
larger than monocytes and can be found in any tissue, but
are most prevalent in "filter" organs such as the liver, spleen,
lung, and lymph nodes. These filter organs are responsible
for removing or containing foreign invaders, damaged and
old blood cells, and cellular debris.
Some tissue macrophages wander through tissue freely,
while others become fixed in specific tissues and remain
there for the rest of their life span. Collectively the tissue
macro phages and monocytes are known as the mononuclear
phagocyte system (MPS).
Monocytes and tissue macrophages perform several
specific functions:
They clean up cellular debris that remains after an inflammation or infection clears up.
• They process certain antigens, making them more antigenic. Monocytes and tissue macrophages can ingest antigens and present them on their cell membranes to the
lymphocytes that will then destroy them. This important
role in the immune response will be discussed in the
immune system section of this chapter
237
• They ingest foreign substances. They have the same phagocytic capabilities as neutrophils and then some. They are
larger than neutrophils, so they can engulf structures
beyond the phagocytic capacity of neutrophils (e.g., fungi,
protozoa, viruses, and dead neutrophils).
Monocytes follow neutrophils into tissue by the process
of chemotaxis in response to tissue damage caused by trauma
or invading microorganisms. Neutrophils respond more
quickly to the tissue damage, but monocytes stay around
longer once they get to the damaged site and become tissue
macrophages. Tissue macrophages have a longer life span
than neutrophils, so they are often associated with chronic
infections.
Monocytes can also function in circulating blood to
phagocytize damaged blood cells or microorganisms found
in the blood, such as in the case of septicemia.
rarely seen in peripheral blood. In all of the common domestic species, basophils make up less than one percent of all
white blood cells in peripheral blood. They are not seen at
all on many blood smears.
culating
species.
Blood, Lymph, and Immunity
Monocytosis. An increased number of monocytes in
.,~peripheral blood is called monocytosis. It is often associated with a chronic inflammatory condition, such as an
infection.
Monocytopenia.
A decreased number of monocytes in
peripheral blood is called monocytopenia. It can be difficult
to evaluate because of the low numbers of monocytes normally found in circulation.
-
Lymphocytes. Lymphocytes are normally the predominant white blood cell in circulation in ruminants and pigs.
They are the only white blood cell that has no phagocytic
capabilities. Most of the lymphocytes in the body actually
live in what are called lymphoid tissues and constantly recirculate between these tissues and blood.
Formation and function. Some controversy still exists as
to the origin and development of lymphocytes. It is most
popularly believed that they arise from the same pluripotent
stem cells in the bone marrow as other blood cells. Before
they begin to mature, some of the cells leave the bone marrow
to develop in other central lymphoid organs located throughout the body before settling in their permanent home in
peripheral lymphoid tissue.
Types of Lymphocytes. There are three different types
of lymphocytes: T lymphocytes, B lymphocytes, and natural
killer cells.
T lymphocytes (T cells). T lymphocytes are processed in the
thymus before going to peripheral lymphoid tissue. The preT cells in the thymus are thymocytes. Thymocytes multiply
rapidly, leave the thymus, and travel to specific T -dependent
zones in lymph nodes and the spleen. After they leave the
thymus, thymocytes are known as T cells or T lymphocytes.
T cells are responsible for cell-mediated immunity and for
activating B cells. Most of the lymphocytes in peripheral
blood are T cells.
238
Chapter 9
Blood, Lymph, and Immunity
found in any tissue in the body, but are most numerous
in tissues engaged in antibody formation (e.g., lymph
nodes, spleen). Plasma cells are rarely found in peripheral
blood.
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o
Antigen
o
Epitope
o
Antibody
Figure 9-7
Antigens and antibodies. Every antigen has a uniquely
shaped epitope on its cell membrane that will fit into a combining
shape on an antibody. (Modified from the National Cancer Institute,
NIH Publication No, 03-5423, September 2003.)
Natural killer cells. Natural killer (NK) lymphocytes are
neither T cells nor B cells. They don't have to be activated
by a specific antigen, and they have the ability to kill some
types of tumor cells and cells infected with various viruses.
NK cells must come in direct contact with these cells before
they can destroy them.
Every lymphocyte has surface markers that differentiate
B cells from T cells and subsets of each type of lymphocyte.
These markers are not visible under light microscopy. We'll
discuss the function of lymphocytes in more detail in the
immunity section of this chapter.
Characteristics. The lymphocytes we see in circulation are
'(., classified as either large or small. Large lymphocytes have
more cytoplasm and are thought to be younger than small
lymphocytes, They gradually develop into small lymphocytes that have very little cytoplasm.
B lymphocytes (B cells). The B means "bursa equivalent"
Lymphocytes contain no granules in their cytoplasm. The
and refers to bone marrow and other lymphoid tissue
nucleus is round or oval and does not segment. Large lymthought to be the equivalent of a bird organ called the bursa
phocytes have abundant sky-blue cytoplasm. Small lymphoof Fabricius. Inactive B cells travel through lymph nodes, the
cytes have such a scant amount of cytoplasm that it is
spleen, and other lymphoid structures but rarely circulate
, sometimes difficult to see. Small lymphocytes frequently
in peripheral blood. B cells are ultimately responsible for
look like nuclei without cytoplasm. Or there may be just a
antibody production.
small amount of sky-blue cytoplasm visible on one side of
Each B cell is preprogrammed to produce only one spe-the nucleus.
cific antibody type against one specific antigen (foreign
protein). On its cell surface, it has thousands of receptors
Memory Cells. Both T cells and B cells can become
shaped to fit only one antigen shape. Every antigen has a
memory cells. These cells are clones of an originallymphounique shape on its cell surface made up of amino acids. This
cyte. They don't participate in an initial immune response
area is called the epitope. The sequence of amino acids
to a specific antigen but survive in lymphoid tissue waiting
determines the shape of the epitope. And there is a B cell
for a second exposure to that same antigen. When the animal
that has a complementary combining site or receptor that
is exposed to the antigen for a second time, the memory
fits the shape of the epitope (Figure 9-7).
cells are ready to respond. This response is much quicker
When the B cell and antigen are joined, an antigenantibody complex is formed. For example, there are certain
and mounts a greater response than the initial immune
B cells that are preprogrammed to receive only the canine
response.
distemper virus. If a dog is exposed to the distemper virus,
Lymphocytosis and Leukocytosis. Lymphocytosis is an
only the B cells that are preprogrammed to recognize the
virus will respond by eventually making antibodies against
increased number oflymphocytes in peripheral blood. It can
the virus. All the other B cells will be unaffected. The amazing
be the result of leukemia (a form of cancer of the lymphocytes), chronic infections, or epinephrine release (as part of
thing is that the B cells are preprogrammed to produce antibodies against antigens to which they have never been
the fight-or-flight response). Lymphocytosis can be signifiexposed. When B cells recognize an antigen, they transform
cant enough to cause leukocytosis.
into plasma cells that release antibodies. The human body
can produce over 100 trillion (102°) antibodies, and there is
Lymphopenia and Leukopenia. Lymphopenia is a
no reason to think an animal can't do the same. This is called
decreased number oflymphocytes in peripheral blood. It can
humoral immunity.
be the result of many factors, including decreased producPlasma cells are derived from B cells in response to an
tion of lymphocytes, the presence of corticosteroids (drugs
antigenic stimulus. The B cells that are activated by their
similar to glucocorticoid hormones from the adrenal cortex),
antigen multiply by mitosis in a process called blastic transimmune deficiency diseases, and acute viral diseases. In
formation to become plasma cells.
some animals, especially ruminants, in which lymphocytes
Plasma cells produce, store, and release antibodies that
are the primary white blood cell in circulation, lymphocytoare also known as immunoglobins.
Plasma cells can be
penia can result in leukocytopenia.