8.

ANATOMY AND PHYSIOLOGY

The Immune Sysytem
The immune system is
composed of an integrated collection
of various cell types, each with a
designated functional role in
defending against infection and
invasion by other organisms. The
major components of the immune
system include the bone marrow, the
white blood cells (WBCs) produced
by the bone marrow, and the
lymphoid tissues, including the
thymus gland, the spleen, the lymph
nodes, the tonsils and adenoids, and
similar tissues in the gastrointestinal,
respiratory, and reproductive
systems.
Bone marrow
The bone marrow is the site of hematopoiesis, or blood cell formation. n a
child all s!eletal bones are involved, but as the child ages marrow activity
decreases. By adulthood, marrow activity is usually limited to the pelvis, ribs,
vertebrae, and sternum.
"arrow is one of the largest organs of the body, ma!ing up #$ to %$ of total
body weight. t consists of islands of cellular components (red marrow) separated by
fat (yellow marrow). &s the adult ages, the proportion of active marrow is gradually
replaced by fat' however, in the healthy person, the fat can again be replaced by
active marrow when more blood cell production is re(uired. n adults with disease
that causes marrow destruction, fibrosis, or scarring, the liver and spleen can also
resume production of blood cells by a process !nown as e)tramedullary
hematopoiesis.
The marrow is highly vascular. Within it
are primitive cells called stem cells. The stem
cells have the ability to self*replicate, thereby
ensuring a continuous supply of stem cells
throughout the life cycle. When stimulated to do
so, stem cells can begin a process of
differentiation into either myeloid or lymphoid
stem cells. These stem cells are committed to
produce specific types of blood cells. +ymphoid
stem cells produce either T or B lymphocytes.
"yeloid stem cells differentiate into three broad cell types, -BCs, WBCs, and
platelets. Thus, with the e)ception of lymphocytes, all blood cells are derived from
the myeloid stem cell. & defect in the myeloid stem cell can cause problems not only
with WBC production but also with -BC and platelet production. The entire process
of hematopoiesis is highly comple). -esearch has identified many of the comple)
mechanisms involved, often at the molecular level.
Blood
The cellular component of blood consists of three primary cell types, -BCs
(red blood cells or erythrocytes), WBCs (white blood cells or leu!ocytes), and
platelets (thrombocytes). These cellular components of blood normally ma!e up
#.$ to #%$ of the blood volume. Because most blood cells have a short life span,
the need for the body to replenish its supply of cells is continuous' this process is
termed hematopoiesis. The primary site for hematopoiesis is the bone marrow.
/uring embryonic development and in other conditions, the liver and spleen may
also be involved.
0nder normal conditions, the adult bone marrow produces about 12% billion
-BCs, 2. billion neutrophils (mature form of a WBC), and 12% billion platelets each
day. When the body needs more blood cells, as in infection (when WBCs are
needed to fight the invading pathogen) or in bleeding (when more -BCs are
re(uired), the marrow increases its production of the cells re(uired. Thus, under
normal conditions, the marrow responds to increased demand and releases
ade(uate numbers of cells into the circulation.
The volume of blood in humans is appro)imately 2$ to 1.$ of the normal
body weight and amounts to % to 3 +. Circulating through the vascular system and
serving as a lin! between body organs, the blood carries o)ygen absorbed from the
lungs and nutrients absorbed from the gastrointestinal tract to the body cells for
cellular metabolism. Blood also carries waste products produced by cellular
metabolism to the lungs, s!in, liver, and !idneys, where they are transformed and
eliminated from the body. Blood also carries hormones, antibodies, and other
substances to their sites of action or use.
To function, blood must remain in its normally fluid state. Because blood is
fluid, the danger always e)ists that trauma can lead to loss of blood from the
vascular system. To prevent this, an intricate clotting mechanism is activated when
necessary to seal any lea! in the blood vessels. 4)cessive clotting is e(ually
dangerous, because it can obstruct blood flow to vital tissues. To prevent this, the
body has a fibrinolytic mechanism that eventually dissolves clots (thrombi) formed
within blood vessels. The balance between these two systems, clot (thrombus)
formation and clot (thrombus) dissolution or fibrinolysis, is called hemostasis.
BLOOD !LLS
Red Blood Cells (RBCs)
The normal -BC is a biconcave dis! that resembles a soft ball compressed
between two fingers. t has a diameter of about 5 6m and is so fle)ible that it can
pass easily through capillaries that may be as small as 7.5 6m in diameter. The
-BC membrane is so thin that gases, such as o)ygen and carbon dio)ide, can
easily diffuse across it' the dis! shape provides a large surface area that facilitates
the absorption and release of o)ygen molecules.
"ature -BCs consist primarily of hemoglobin, which contains iron and
ma!es up 8%$ of the cell mass. -BCs have no nuclei, and they have many fewer
metabolic en9ymes than do most other cells. The presence of a large amount of
hemoglobin enables the -BC to perform its principal function, the transport of
o)ygen between the lungs and tissues. :ccasionally the marrow releases slightly
immature forms of -BCs, called reticulocytes, into the circulation. This occurs as a
normal response to an increased demand for -BCs (as in bleeding) or in some
disease states. The o)ygen*carrying hemoglobin molecule is made up of four
subunits, each containing a heme portion attached to a globin chain. ron is present
in the heme component of the molecule. &n important property of heme is its ability
to bind to o)ygen loosely and reversibly. :)ygen readily binds to hemoglobin in the
lungs and is carried as o)yhemoglobin in arterial blood. :)yhemoglobin is a brighter
red than hemoglobin that does not contain o)ygen (reduced hemoglobin), which is
why arterial blood is a brighter red than venous blood. The o)ygen readily
dissociates (detaches) from hemoglobin in the tissues, where the o)ygen is needed
for cellular metabolism. n venous blood, hemoglobin combines with hydrogen ions
produced by cellular metabolism and thus buffers e)cessive acid. Whole blood
normally contains about 1%g of hemoglobin per 1.. m+ of blood.
White Blood Cells (WBCs)
+eu!ocytes are divided into two general categories, granulocytes and
lymphocytes. n normal blood, the total leu!ocyte count is %... to 1.,... cells per
cubic millimeter. :f these, appro)imately 3.$ to 2.$ are granulocytes and ;.$ to
#.$ are lymphocytes. <rimarily, WBCs protect the body against infection and tissue
injury.
WBCs protect the body from invasion by bacteria and other foreign entities.
The major function of neutrophils is phagocytosis. =eutrophils arrive at the site
within 1 hour after the onset of an inflammatory reaction and initiate phagocytosis,
but they are short*lived. &n influ) of monocytes follows' these cells continue their
phagocytic activities for long periods as macrophages. This process constitutes a
second line of defense for the body against inflammation and infection. &lthough
neutrophils can often wor! ade(uately against bacteria without the need for
e)cessive involvement with macrophages, macrophages are particularly effective
against fungi and viruses. "acrophages also digest senescent (aging or aged)
blood cells, such as -BCs, primarily within the spleen. The primary function of
lymphocytes is to produce substances that aid in attac!ing foreign material. :ne
group of lymphocytes (T*lymphocytes) !ills foreign cells directly or releases a variety
of +ympho!ines, substances that enhance the activity of phagocytic cells. T
lymphocytes are responsible for delayed allergic reactions, rejection of foreign
tissue (eg, transplanted organs), and destruction of tumor cells. This process is
!nown as cellular immunity. The other group of lymphocytes (B*lymphocytes) is
capable of differentiating into plasma cells. <lasma cells, in turn, produce
immunoglobulin (g), or antibodies, which are protein molecules that destroy foreign
material by several mechanisms. This process is !nown as humoral immunity.
4osinophils and basophils function in hypersensitivity reactions. 4osinophils
are important in the phagocytosis of parasites. The increase in eosinophil levels in
allergic states indicates that these cells are involved in the hypersensitivity reaction'
their function there is to neutrali9e histamine. Basophils produce and store
histamine as well as other substances involved in hypersensitivity reactions. The
release of these substances provo!es allergic reactions.
Platelets (Thrombocytes)
<latelets, or thrombocytes, are not actually cells. -ather, they are granular
fragments of giant cells in the bone marrow called mega!aryocytes. <latelet
production in the marrow is regulated in part by the hormone thrombopoietin, which
stimulates the production and differentiation of mega!aryocytes from the myeloid
stem cell. <latelets play an essential role in the control of bleeding. They circulate
freely in the blood in an inactive state, where they nurture the endothelium of the
blood vessels, maintaining the integrity of the vessel. When vascular injury does
occur, platelets collect at the site and are activated. They adhere to the site of injury
and to each other, forming a platelet plug that temporarily stops bleeding.
>ubstances released from platelet granules activate coagulation factors in the blood
plasma and initiate the formation of a stable clot composed of fibrin, a filamentous
protein. <latelets have a normal life span of 2 to 1. days.