White Blood Cells & Macrophages
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A "macrophage" is NOT one of the types of "white blood cells." But, they
derive FROM a white blood cell and inter-relate often, as described below.
The macrophage is the "eating" cell that engulfs bacteria (and dead cancer).
The Macrophage is derived from one of the types of white blood cells.
Blood is a liquid tissue. Suspended in the watery
plasma are seven types of cells and cell fragments.
Blood performs two major functions:
|If one takes a sample of blood, treats it with an agent to prevent
clotting, and spins it in a centrifuge,
The fraction occupied by the red cells is called the hematocrit.
Normally it is approximately 45%. Values much lower than this are a sign of
- the red cells settle to the bottom
- the white cells settle on top of them forming the "buffy coat".
- transport through the body of
- oxygen and carbon dioxide
- food molecules (glucose, lipids, amino acids)
- ions (e.g., Na+, Ca2+, HCO3−)
- wastes (e.g., urea)
- defense of the body against infections and other foreign materials. All
the WBCs participate in these defenses.
The formation of blood cells (cell types and acronyms are defined below)
All the various types of blood cells
These stem cells
- are produced in the bone marrow (some 1011 of them each
day in an adult human!).
- arise from a single type of cell called a pluripotent stem cell.
Which path is taken is regulated by
- are very rare (only about one in 10,000 bone marrow cells);
- are attached (probably by
adherens junctions) to
osteoblasts lining the inner surface of bone cavities;
- express a surface protein designated CD34;
- produce, by mitosis, two kinds of progeny:
- more stem cells
- cells that begin to differentiate along the paths leading to the various
kinds of blood cells.
- the need for more of that type of blood cell which is, in turn, controlled
cytokines and/or hormones.
- Interleukin-7 (IL-7) is the major cytokine in stimulating
bone marrow stem cells to start down the path leading to the various
B cells and
Erythropoietin (EPO), produced by the kidneys, enhances the
production of red blood cells (RBCs).
Thrombopoietin (TPO), assisted by Interleukin-11 (IL-11),
stimulates the production of megakaryocytes. Their fragmentation
- Granulocyte-monocyte colony-stimulating factor (GM-CSF), as
its name suggests, sends cells down the path leading to both those cell types.
In due course, one path or the other is taken.
- Under the influence of granulocyte colony-stimulating factor (G-CSF),
they differentiate into neutrophils.
- Further stimulated by interleukin-5 (IL-5) they develop into
- Interleukin-3 (IL-3) participates in the differentiation of most
of the white blood cells but plays a particularly prominent role in the
formation of basophils (responsible for some
- Stimulated by macrophage colony-stimulating factor (M-CSF)
the granulocyte/macrophage progenitor cells differentiate into
monocytes, the precursors of macrophages.
Red Blood Cells (erythrocytes)
The most numerous type in the blood.
As RBC precursors mature in the bone marrow,
- Women average about 4.8 million of these cells per cubic millimeter (mm3;
which is the same as a microliter [µl]) of blood).
- Men average about 5.4 x 106 per µl.
- These values can vary over quite a range depending on such factors as
health, and altitude. (Peruvians living at 18,000 feet may have as many as 8.3
x 106 RBCs per µl.)
- they manufacture hemoglobin until it accounts for some 90% of the dry
weight of the cell.
- The nucleus is squeezed out of the cell. Nearby macrophages ingest the
extruded nuclei and break down their DNA.
This scanning electron micrograph (courtesy of Dr. Marion J. Barnhart) shows
the characteristic biconcave shape of red blood cells.
Thus RBCs are terminally differentiated; that is, they can never
divide. They live about 120 days and then are ingested by phagocytic cells in
the liver and spleen. Most of the iron in their hemoglobin is reclaimed for
reuse. The remainder of the heme portion of the molecule is degraded into bile
pigments and excreted by the liver. Some 3 million RBCs die and are scavenged by
the liver each second.
Red blood cells are responsible for the transport of oxygen and carbon
The hemoglobin (Hb) molecule
The reaction is reversible.
- consists of four polypeptides.
- Each of these is attached the
prosthetic group heme.
- There is one atom of iron at the center of each heme.
- One molecule of oxygen can bind to each heme.
- Under the conditions of lower temperature, higher pH, and increased oxygen
pressure in the capillaries of the lungs, the reaction proceeds to the right.
The purple-red deoxygenated hemoglobin of the venous blood becomes the
bright-red oxyhemoglobin of the arterial blood.
- Under the conditions of higher temperature, lower pH, and lower oxygen
pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin
gives up its oxygen.
Carbon Dioxide Transport
Carbon dioxide (CO2) combines with water forming carbonic acid, which
dissociates into a hydrogen ion (H+) and a
CO2 + H2O ↔ H2CO3 ↔ H+
95% of the CO2 generated in the tissues is carried in the red
- About one-half of this is directly bound to hemoglobin (at a site
different from the one that binds oxygen).
- The rest is converted — following the equation above — by the enzyme
carbonic anhydrase into
- bicarbonate ions that diffuse back out into the plasma and
- hydrogen ions (H+) that bind to the protein portion of the
hemoglobin (thus having no effect on pH).
Only about 5% of the CO2 generated in the tissues dissolves
directly in the plasma. (A good thing, too: if all the CO2 we make
were carried this way, the pH of the blood would drop from its normal 7.4 to an
When the red cells reach the lungs, these reactions are reversed and CO2
is released to the air of the alveoli.
Anemia is a shortage of
Anemia has many causes. One of the most common is an inadequate intake of
iron in the diet.
Red blood cells have surface antigens that differ between people and that create
the so-called blood groups such as the ABO system.
- RBCs and/or
- the amount of hemoglobin in them.
White Blood Cells (leukocytes)
White blood cells
There are several kinds of lymphocytes (although they all look alike under the
microscope), each with different functions to perform . The most common types of
- are much less numerous than red (the ratio between the two is around
- have nuclei,
- participate in protecting the body from infection,
- consist of lymphocytes and monocytes with relatively clear
cytoplasm, and three types of granulocytes, whose cytoplasm is filled
B lymphocytes ("B cells"). These are responsible for making
- T lymphocytes ("T cells"). There are several subsets of these:
Although bone marrow is the ultimate source of lymphocytes, the lymphocytes
that will become T cells migrate from the bone marrow to the thymus [View]
where they mature. Both B cells and T cells also take up residence in lymph
nodes, the spleen and other tissues where they
Monocytes leave the blood and become macrophages.
- encounter antigens;
- continue to divide by mitosis;
- mature into fully functional cells.
This scanning electron micrograph (courtesy of Drs. Jan M. Orenstein and Emma
Shelton) shows a single macrophage surrounded by several lymphocytes.
Macrophages are large, phagocytic cells that engulf
- foreign material (antigens) that enter the body
- dead and dying cells of the body.
The most abundant of the WBCs. This photomicrograph shows a single neutrophil
surrounded by red blood cells.
Neutrophils squeeze through the capillary walls and into infected tissue
where they kill the invaders (e.g., bacteria) and then engulf the remnants by
This is a never-ending task, even in healthy people: Our throat, nasal
passages, and colon harbor vast numbers of bacteria. Most of these are
commensals, and do us no harm. But that is because neutrophils keep them in
can reduce the numbers of neutrophils so that formerly harmless bacteria begin
to proliferate. The resulting opportunistic infection can be
The number of eosinophils in the blood is normally quite low (0–450/µl).
However, their numbers increase sharply in certain diseases, especially
infections by parasitic worms. Eosinophils are cytotoxic, releasing the contents
of their granules on the invader.
- heavy doses of radiation
- and many other forms of stress
The number of basophils also increases during infection. Basophils leave the
blood and accumulate at the site of infection or other inflammation. There they
discharge the contents of their granules, releasing a variety of mediators such
which increase the blood flow to the area and in other ways add to the
inflammatory process. The mediators released by basophils also play an important
part in some allergic responses such as
Platelets are cell fragments produced from megakaryocytes.
Blood normally contains 140,000 to 440,000 per microliter (µl) or cubic
millimeter (mm3). This number is normally maintained by a homeostatic
(negative-feedback) mechanism [Link].
If this value should drop much below 50,000/µl, there is a danger of
uncontrolled bleeding because of the essential role that platelets have in blood
- certain drugs and herbal remedies;
- autoimmunity. [Link]
When blood vessels are cut or damaged, the loss of blood from the system must
be stopped before
shock and possible death occur. This is accomplished by solidification of
the blood, a process called coagulation or clotting.
A blood clot consists of
- a plug of platelets enmeshed in a
- network of insoluble fibrin molecules.
|Details of the clotting process are in a separate page.
Link to it.
Plasma is the straw-colored liquid in which the blood cells are
Composition of blood plasma
|Glucose (blood sugar)
Plasma transports materials needed by cells and materials that must be
removed from cells:
Most of these materials are in transit from a place where they are added to the
blood (a "source")
- various ions (Na+, Ca2+, HCO3−,
- glucose and traces of other sugars
- amino acids
- other organic acids
- cholesterol and other lipids
- urea and other wastes
to places ("sinks") where they will be removed from the blood.
- exchange organs like the intestine
- depots of materials like the liver
- every cell
- exchange organs like the kidney, and skin.
Proteins make up 6–8% of the blood. They are about equally divided between
serum albumin and a great variety of serum globulins.
After blood is withdrawn from a vein and allowed to clot, the clot slowly
shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:
Serum is blood plasma without fibrinogen and other clotting factors.
The serum proteins can be separated by electrophoresis.
- A drop of serum is applied in a band to a thin sheet of supporting
material, like paper, that has been soaked in a slightly-alkaline salt
- At pH 8.6, which is commonly used, all the proteins are negatively
charged, but some more strongly than others.
- A direct current can flow through the paper because of the conductivity of
the buffer with which it is moistened.
- As the current flows, the serum proteins move toward the positive
- The stronger the negative charge on a protein, the faster it migrates.
- After a time (typically 20 min), the current is turned off and the
proteins stained to make them visible (most are otherwise colorless).
- The separated proteins appear as distinct bands.
- The most prominent of these and the one that moves closest to the positive
electrode is serum albumin.
- Serum albumin
- is made in the liver
- binds many small molecules for transport through the blood
- helps maintain the
osmotic pressure of the blood
- The other proteins are the various serum globulins.
- They migrate in the order
- alpha globulins (e.g., the proteins that transport
retinol [vitamin A])
- beta globulins (e.g., the iron-transporting protein
- gamma globulins.
- Gamma globulins are the least negatively-charged serum proteins. (They
are so weakly charged, in fact, that some are swept in the flow of buffer
back toward the negative electrode.)
- Most antibodies are gamma globulins.
- Therefore gamma globulins become more abundant following infections or
If an antibody-secreting cell — called a
plasma cell — becomes cancerous, it grows into a
clone secreting a single kind of antibody molecule. The image
(courtesy of Beckman Instruments, Inc.) shows — from left to right — the
electrophoretic separation of:
- normal human serum with its diffuse band of gamma globulins;
- serum from a patient with multiple myeloma producing an
- serum from a patient with Waldenström's macroglobulinemia where the
cancerous clone secretes an IgM antibody;
- serum with an IgA myeloma protein.
- Gamma globulins can be harvested from donated blood (usually pooled
from several thousand donors) and injected into persons exposed to certain
diseases such as chicken pox and hepatitis. Because such preparations of
immune globulin contain antibodies against most common infectious
diseases, the patient gains temporary protection against the disease. [More]
Because of their relationship to cardiovascular disease, the analysis of
serum lipids has become an important health measure.
The table shows the range of typical values as well as the values above (or
below) which the subject may be at increased risk of developing
||Typical values (mg/dl)
- Total cholesterol is the sum of
- HDL cholesterol
- LDL cholesterol and
- 20% of the triglyceride value
- Note that
- high LDL values are bad, but
- high HDL values are good.
- Using the various values, one can calculate a
cardiac risk ratio = total cholesterol divided by HDL
- A cardiac risk ratio greater than 7 is considered a warning.
18 March 2004
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