Saladin 5e Extended Outline
The Lymphatic and Immune Systems
I. The Lymphatic System (pp. 816–829)
A. The lymphatic system is composed of a network of vessels that penetrate nearly every tissue,
and a collection of tissues and organs that produce immune cells. (p. 816) (Fig. 21.1)
B. The lymphatic system has three functions. (p. 816)
1. Fluid recovery. Fluid continually filters from blood capillaries into tissue spaces, and
the lymphatic system reabsorbs any excess and return it to the blood.
a. The blood capillaries reabsorb about 85% of fluid, leaving 15% extra.
b. This amounts to 2 to 4 L of water and ¼ to ½ of the plasma protein; a person
would die within hours if this were not returned via the lymph system.
c. Even partial interference with lymphatic drainage can lead to severe edema.
2. Immunity. The lymphatic system also picks up foreign cells and chemicals from
a. The fluid passes through lymph nodes where immune cells stand guard.
b. These cells activate a protective immune response.
3. Lipid absorption. In the small intestine, special lymphatic vessels called lacteals absorb
dietary lipids not absorbed by blood capillaries.
C. The components of the lymphatic system are lymph, lymphatic vessels, lymphatic tissue, and
lymphatic organs. (p. 816)
D. Lymph is a clear, colorless fluid, similar to blood plasma but low in protein, that originates as
tissue fluid taken up by the lymphatic vessels. (pp. 818–820)
1. The composition of lymph varies from place to place and at different times.
2. Lymph leaving the lymph nodes contains a large number of lymphocytes and may also
contain macrophages, hormones, bacteria, viruses, cellular debris, or even cancer cells.
3. Lymphatic vessels are similar to blood vessels.
a. The vessels begin with microscopic lymphatic capillaries (terminal
lymphatics); these are present almost everywhere but are absent from the CNS,
cartilage, cornea, bone, and bone marrow.
b. They are closely associated with blood capillaries, but are closed at one end.
c. A lymphatic capillary consists of a sac of thin endothelial cells that overlap
like shingles of a roof.
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i. They are tethered to surrounding tissue by protein filaments that
prevent the sac from collapsing.
d. Lymphatic endothelial cells are not joined by tight junctions and do not have
a continuous basal lamina; thus cells and particles can enter with the fluid.
e. The overlapping edges of the endothelial cells act as valvelike flaps that can
open and close in response to tissue pressure.
f. Lymphatic vessels form in the embryo by budding from veins, and the larger
ones have a similar histology.
i. A tunica interna has an endothelium and valves. (Fig. 21.4)
ii. A tunica media has elastic fibers and smooth muscle.
iii. A tunica externa is the thin outermost layer.
g. The lymphatic vessels converge and become larger vessels with changing
names: lymphatic capillaries collecting vessels six lymphatic trunks
two collecting ducts subclavian veins. (Fig. 21.5)
h. The lymphatic capillaries converge to form collecting vessels.
i. These vessels often travel alongside veins and arteries and share a
common connective tissue sheath with them.
i. Collecting vessels empty into lymph nodes at irregular intervals; lymph leaves
the nodes through another collecting vessel and may continue through several
j. Eventually the collecting vessels converge to form larger lymphatic trunks,
each of which drains a major portion of the body.
i. The six lymphatic trunks are named by their locations and the parts of
the body they drain: jugular, subclavian, bronchomediastinal,
intercostal, intestinal, and lumbar.
k. The lymphatic trunks converge to form the two collecting ducts, the largest of
the lymphatic vessels. (Fig. 21.6)
i. The right lymphatic duct is formed by the convergence of the right
jugular, subclavian, and bronchomediastinal trunks in the right thoracic
cavity; it drains the right arm, right side of the thorax, and head, and it
empties into the right subclavian vein.
ii. the thoracic duct, on the left, is larger and longer, beginning just
below the diaphragm anterior to the vertebral column near L2.
iii. The two lumbar trunks and the intestinal trunk join to form a
prominent sac called the cisterna chyli, names for the large amount of
chyle (fatty lymph) that it collects after a meal.
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iv. The thoracic duct than passes upward through the diaphragm with
the aorta and ascend the mediastinum; as it passes through the thorax, it
connects with the left bronchomediastinal, left subclavian, and left
jugular trunks, then empties into the left subclavian vein.
4. Flow of lymph is governed by forces similar to those for venous return, except that the
lymphatic system has no pump like the heart, and lymph flows at an even lower pressure
and speed compared to venous blood.
a. The primary mechanism of flow is rhythmic contractions of the lymphatic
vessels themselves in response to distention.
b. The valves of lymphatic vessels prevent fluid from flowing backward.
c. Lymph flow is also produced by skeletal muscles squeezing the lymphatic
d. Because lymphatic vessels are often next to an artery inside a common sheath,
arterial pulsation may also contribute to lymph flow.
e. A thoracic (respiratory) pump promotes the flow of lymph from the
abdominal to the thoracic cavity as one inhales.
f. At the point where the ducts empty into the subclavian veins, the rapidly
flowing bloodstream draws the lymph into it.
g. Physical exercise significantly increases the rate of lymphatic return.
E. Lymphatic cells range from loosely scattered cells in different tracts to compact populations in
lymphatic organs; a variety of lymphocytes and other cells have roles in immunity. (pp. 820–822)
1. Natural killer (NK) cells are large lymphocytes that attack and destroy bacteria,
transplanted tissue cells, and host cells that are infected with virus or have turned
2. T lymphocytes (T cells) mature in the thymus and later depend on thymic hormones;
the T stands for thymus-dependent.
3. B lymphocytes (B cells) are lymphocytes that mature in the bone marrow and
differentiate into plasma cells that secrete the antibodies of the immune system.
4. Macrophages are very large, avidly phagocytotic cells of the connective tissues; they
develop from monocytes that have emigrated from the bloodstream and phagocytize
tissue debris, dead neutrophils, bacteria, and other foreign matter. (Fig. 21.7)
a. They also process foreign matter and display antigenic fragments of it on their
surface to alert certain T cells of a foreign presence; cells that do this are
collectively termed antigen-presenting cells (APCs).
5. Dendritic cells are branched, mobile APCs found in the epidermis, mucous
membranes, and lymphatic organs; in the skin they are often called Langerhans cells.
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a. They help alert the immune system to pathogens that have breached body
b. They engulf foreign matter by receptor-mediated endocytosis rather than
phagocytosis and are included in the macrophage system.
6. Reticular cells are branched stationary cells that contribute to the stroma of lymphatic
organs and act as APCs in the thymus; they should not be confused with reticular fibers.
F. Lymphatic (lymphoid) tissues are aggregations of lymphocytes in the connective tissues of
mucous membranes and various organs. (p. 822)
1. Diffuse lymphatic tissue has lymphocytes scattered rather than densely clustered and is
prevalent in body passages open to the exterior (respiratory, digestive, etc.) where it is
called mucosa-associated lymphatic tissue (MALT).
a. In the respiratory and digestive tracts is it sometimes called bronchus-
associated (BALT) and gut-associated (GALT) lymphatic tissue.
2. In some places, lymphocytes and macrophages congregate in dense masses called
lymphatic nodules (follicles). (Fig. 21.8)
a. These come and go as pathogens invade tissues and are dealt with.
b. Abundant lymphatic nodules are a relatively constant feature of the lymph
nodes, tonsils, and appendix.
c. In the ileum, they form clusters called Peyer patches.
G. Lymphatic (lymphoid) organs have well-defined anatomical sites and at least partial connective
tissue capsules that separate lymphatic tissue from neighboring tissue. (pp. 822–828)
1. These organs include the red bone marrow, thymus, lymph nodes, tonsils, and spleen.
2. Red bone marrow and thymus are regarded as primary lymphatic organs because they
are sites where B and T lymphocytes become immunocompetent.
3. Lymph nodes, tonsils, and spleen are called secondary lymphatic organs because they
are populated with immunocompetent lymphocytes only after the cells have matured in
the primary organs.
4. Red bone marrow is involved in hemopoiesis (blood formation) and immunity.
a. In children, red bone marrow occupies the medullary spaces of nearly the
entire skeleton, whereas in adults, it is limited to parts of the axial skeleton and
the proximal heads of the humerus and femur.
b. Red bone marrow is a soft, loosely organized, highly vascular material
separated from osseous tissue by the endosteum.
c. It produces all classes of formed elements of the blood, and its red color is
from the abundance of erythrocytes.
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d. Numerous arteries penetrate the bone via nutrient foramina and empty into
large sinusoids in the marrow. (Fig. 21.9)
e. The sinusoids drain into a central longitudinal vein that exits via the same
f. The sinusoids are lined by endothelial cells, like other blood vessels, and are
surrounded by reticular cells and reticular fibers.
i. The reticular cells secrete colony-stimulating factors that induce
formation of leukocytes.
ii. In the long bones, aging reticular cells accumulate fat and transform
into adipose cells, eventually replacing red bone marrow with yellow
g. The spaces between the sinusoids are occupied by islands (cords) of
hemopoietic cells—macrophages and blood cells in all stages of development.
i. The macrophages destroy malformed blood cells and nuclei discarded
by developing erythrocytes.
ii. As blood cells mature, they push their way through the reticular and
endothelial cells to enter the sinus and the bloodstream.
5. The thymus is a member of the endocrine, lymphatic, and immune systems.
a. It houses developing lymphocytes and secretes hormones that regulate their
b. It is a bilobed organ located between the sternum and aortic arch in the
superior mediastinum; it degenerates with age as described earlier. (Fig. 17.8)
c. The fibrous capsule of the thymus give off trabeculae (septa) that divide the
gland into several angular lobules.
i. Each lobule has a dense, dark-staining cortex and a lighter medulla
populated by T lymphocytes. (Fig. 21.10)
ii. Reticular epithelial cells seal off the cortex from the medulla and
surround blood vessels and lymphocyte clusters, forming the blood–
thymus barrier that isolates developing lymphocytes from blood-borne
d. After developing in the cortex, the T cells migrate to the medulla, where they
spend another 3 weeks.
i. There is no blood–thymus barrier in the medulla; mature T cells enter
blood or lymphatic vessels and leave the thymus.
ii. In the medulla, the reticular epithelial cells form whorls called
thymic (Hassall) corpuscles, useful for identifying the thymus
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e. Reticular epithelial cells also produce signaling molecules that promote
development and action of T cells, including thymosin, thymopoietin, thymulin,
interleukins, and interferon.
f. If the thymus is removed from newborn mammals, they waste away and never
g. Other lymphatic organs depend on thymosins or T cells and develop poorly in
6. Lymph nodes are the most numerous lymphatic organs, numbering about 450 in a
typical young adult. (Fig. 21.11)
a. They serve to functions: cleansing the lymph, and acting as a site of T and B
b. A lymph node is an elongated or bean-shaped structure, usually less than 3 cm
long, often with an indentation called the hilum on one side. (Fig. 21.12)
i. It is enclosed in a fibrous capsule with trabeculae that partially divide
the interior into compartments.
ii. Between the capsule and parenchyma is a narrow, relatively clear
space called the subcapsular sinus, which contains reticular fibers,
macrophages, and dendritic cells.
iii. Deep to this sinus the gland consists mainly of a stroma of reticular
connective tissue and a parenchyma of lymphocytes and APCs.
c. The parenchyma is divided into an outer C-shaped cortex that encircles about
4/5 of the organ and an inner medulla that extends to the surface at the hilum.
i. The cortex consists of lymphatic nodules that acquire germinal
centers for B cell multiplication when the lymph node is fighting a
ii. The medulla consists of a branching network of medullary cords
composed of lymphocytes, plasma cells, macrophages, reticular cells,
and reticular fibers.
iii. Both regions also contain lymph-filled sinuses continuous with the
d. Afferent lymphatic vessels lead into a node along its convex surface.
i. Lymph flows from these vessels into the subcapsular sinus and
percolates slowly through the sinuses of the cortex and medulla.
e. The lymph leaves the node through one to three efferent lymphatic vessels
that emerge from the hilum.
f. No other lymphatic organs have afferent lymphatic vessels, and lymph nodes
are the only organs that filter lymph.
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i. Macrophages and reticular cells of the sinuses remove about 99% of
the impurities before lymph leaves the node.
ii. Sequential passage through a number of nodes thoroughly cleanses
the lymph before it returns to the blood.
g. Blood vessels also penetrate the hilum of a lymph node.
i. Arteries follow the medullary cords and give rise to capillary beds in
the medulla and cortex.
ii. In the deep cortex, lymphocytes can emigrate from the bloodstream
into the parenchyma of the node; most are T cells.
h. Lymph nodes are widespread, but especially concentrated in seven locations.
i. Cervical lymph nodes occur in deep and superficial groups in the
neck, monitoring lymph coming from the head and neck.
ii. Axillary lymph nodes are concentrated in the armpit and receive
lymph from the upper limb and the female breast. (Fig. 21.6b)
iii. Thoracic lymph nodes occur in the thoracic cavity, especially
embedded in the mediastium.
iv. Abdominal lymph nodes occur in the posterior abdominopelvic wall
and monitor lymph from the urinary and reproductive system.
v. Intestinal and mesenteric lymph nodes are found in the mesenteries
and adjacent to the appendix and intestines. (Fig. 21.11a)
vi. Inguinal lymph nodes occur in the groin and receive lymph from the
entire lower limb. (Fig. 21.1b)
vii. Popliteal lymph nodes occur at the back of the knee and receive
lymph from the leg proper.
i. When a lymph node is challenged by a foreign antigen, it may become swollen
and painful, a condition called lymphadenitis.
j. The collective term for all lymph node diseases is lymphadenopathy.
k. Lymph nodes are common sites of metastatic cancer.
Insight 21.1 Lymph Nodes and Metastatic Cancer
7. Tonsils are patches of lymphatic tissue located at the entrance to the pharynx, where
they guard against ingested and inhales pathogens.
a. Each is covered by epithelium and has deep pits called tonsillar crypts lined
by lymphatic nodules. (Fig. 21.13)
b. Below the crypts, the tonsils are partially separated from underlying
connective tissue by an incomplete fibrous capsule.
c. There are three main sets of tonsils.
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i. A single medial pharyngeal tonsil (adenoids) is located on the wall of
the pharynx just behind the nasal cavity.
ii. A pair of palatine tonsils is at the posterior margin of the oral cavity.
iii. Numerous lingual tonsils, each with a single crypt, are concentrated
in a patch on each side of the root of the tongue. (Fig. 25.5a)
d. The palatine tonsils are largest and most often infected in tonsillitis, an acute
inflammation usually caused by a Streptococcus infection.
i. Surgical removal (tonsillectomy) used to be a common surgical
procedure in children but is done less often today.
ii. Tonsillitis is now usually treated with antibiotics.
8. The spleen is the largest lymphatic organ, up to 12 cm long and 160 g; it is located in
the left hypochondriac region inferior to the diaphragm and posterolateral to the stomach.
a. The spleen has indentations called the gastric area and the renal area where it
presses against these organs, and a medial hilum penetrated by the splenic
artery, splenic vein, and lymphatic vessels.
b. The parenchyma exhibits two types of tissue reflecting its functions.
i. Red pulp consists of sinuses containing erythrocytes.
ii. White pulp consists of lymphocytes and macrophages aggregated
along small branches of the splenic artery; it appears in sections as an
ovoid mass of lymphocytes with an arteriole passing through.
c. The spleen produces blood cells in the fetus and may resume this role in
adults in the event of severe anemia.
d. Lymphocytes and macrophages of the white pulp monitor the blood for
foreign antigens, much like the lymph nodes do for the lymph.
e. Splenic capillaries are permeable and allow RBCs to leave the bloodstream,
accumulate in the sinuses of red pulp, and reeneter the bloodstream later.
i. Old, fragile RBCs rupture as they squeeze through into the sinuses
and are phatocytized by macrophages; thus the spleen is an
ii. The spleen also helps to stabilize blood volume by transferring
excess plasma to the lymphatic system.
f. The spleen is highly vascular and vulnerable to trauma and infection.
i. A ruptured spleen can hemorrhage fatally, but is difficult to repair.
ii. Splenectomy is a common procedure in such cases; a person can live
without a spleen but is somewhat more vulnerable to infections.
II. Nonspecific Resistance (pp. 829–837)
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A. Pathogens are environmental agents capable of producing disease; this includes infectious
organisms, toxic chemicals, and radiation. (p. 829)
B. The human body has three lines of defense against pathogens. (p. 829)
1. The first line of defense consists of external barriers, such as the skin and mucous
2. The second line of defense consists of nonspecific mechanisms to deal with pathogens
that break through the skin or mucous membranes.
a. These include leukocytes and macrophages, antimicrobial proteins, immune
surveillance, inflammation, and fever.
b. These mechanisms are present from birth and are broadly effective against
many pathogens; they even work against pathogens to which the body has never
3. The third line of defense is the immune system, which defeats and pathogen and
retains a ―memory‖ of it to guard against future encounters.
4. The first two are called nonspecific resistance; immunity is called a specific defense.
C. The first line of defense is the external barrier presented by the skin and mucous membranes.
1. The surface of skin is composed mainly of keratin, a tough protein.
a. With some exceptions the skin is dry and poor in nutrients and is therefore
hostile to microbial reproduction.
b. It is also coated with antimicrobial chemicals such as defensins and lactic
i. Defensins are peptides that kill microbes by creating holes in their
ii. Lactic acid makes up the acid mantle, which is generated by sweat
and inhibits bacterial growth.
2. The digestive, respiratory, urinary, and reproductive tracts are open to the exterior, and
are protected by mucous membranes.
a. Mucus physically ensnares microbes.
i. In the respiratory tract, cilia move the mucus to the pharynx to be
ii. Microbes are flushed from the upper digestive tract by saliva.
iii. Urine flushes microbes from the lower urinary tract.
b. Mucus, tears, and saliva contain lysozyme, and enzyme that dissolved
bacterial cell walls.
3. Beneath the epithelia of the skin and mucous membranes is a layer of areolar tissue.
Saladin Outline Ch.21 Page 10
a. The ground substance of this tissue contains a giant glycosaminoglycan called
hyaluronic acid, a gel-like substance through which it is difficult for microbes to
i. Some organisms produce hyaluronidase that breaks down the
ii. Hyaluronidase occurs in some snake venoms and bacterial toxins as
well as some parasitic protozoans.
D. Leukocytes and macrophages attack microbes that get past the physical barriers. (pp. 764–766)
1. Five types of leukocytes (Table 18.7) make individual contributions to resistance and
a. Neutrophils wander in connective tissues killing bacteria.
i. They engulf and digest bacteria and also release bactericidal
ii. When bacteria are detected, neutrophils’ lysosomes migrate to the
surface and degranulate, or discharge enzymes into the tissue fluid.
iii. One enzyme catalyzes the respiratory burst, in which oxygen is
reduced to superoxide anions (O2•–) that react with H+ to form
hydrogen peroxide (H2O2).
iv. Another enzyme produces hypochlorite (HClO).
v. These toxic chemicals form a killing zone around the neutrophil,
which kills the neutrophil as well as the microbes.
b. Eosinophils are found especially in mucous membranes where they guard
against parasites, allergens, and other pathogens.
i. They become concentrated at sites of allergy, inflammation, or
ii. They help to kill tapeworms and roundworms by producing
superoxide, hydrogen peroxide, and toxic proteins.
iii. They promote the action of basophils and mast cells.
iv. They phagocytize and degrade antigen–antibody complexes.
v. They secrete enzymes that limit the action of histamine and other
c. Basophils secrete chemicals that aid the mobility and action of other
i. Leukotrienes activate and attract neutrophils and eosinophils.
ii. Histamine, a vasodilator, increases blood flow and delivery of
iii. Heparin inhibits clotting.
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iv. Mast cells, a type of connective tissue cell very similar to basophils,
also produce these substances.
d. Lymphocytes appear similar, but several different functional types are
i. Three basic categories are NK cells (5% of lymphocytes), T cells
(80% of lymphocytes), and B cells (15% of lymphocytes).
ii. These have roles in immune surveillance and specific immunity.
e. Monocytes are leukocytes that emigrate from blood into connective tissues
and transform into macrophages.
i. All avidly phagocytotic cells except leukocytes are called the
ii. Dendritic cells are included in this system even though they come
from different stem cells than macrophages and employ receptor-
iii. Macrophages are widely distributed in loose connective tissues
iv. Microglia are specialized macrophages of the CNS.
v. Alveolar macrophages are specific to the lungs.
vi. Hepatic macrophages are specific to the liver.
E. Many types of proteins play a role in nonspecific resistance; two families of antimicrobial
proteins described here are interferons and the complement system. (pp. 831–832)
1. Interferons are secreted by certain cells, especially leukocytes, that are infected with
a. Interferons alert neighboring cells and protect them from becoming infected.
b. Interferons bind to surface receptors and activate second-messenger systems
that lead to synthesis of proteins that defend against virus infection.
c. They also activate NK cells and macrophages that destroy infected cells.
d. They may confer resistance to cancer cells as well.
2. The complement system is a group of 30 or more globulins that contribute to both
nonspecific resistance and specific immunity.
a. Complement proteins are synthesized mainly by the liver and circulate in the
blood in inactive form; they are activated in the presence of pathogens.
b. In their inactive form, the proteins are named with the letter C and a number
(C3); activation splits them into fragments, which are identified by lowercase
letters (C3a, C3b)
c. Activated complement brings about four methods of pathogen destruction:
inflammation, immune clearance, phagocytosis, and cytoloysis.
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d. There are three routes to complement activation: The classical, alternative,
and lectin pathways. (Fig. 21.15)
e. The classical pathway requires an antibody molecule to get started and thus is
a part of specific immunity.
i. The antibody binds to an antigen on the surface of a pathogenic
organism, forming and antigen–antibody (Ag–Ab) complex.
ii. This binding changes the antibody’s shape, exposing two
complement-binding sites. (Fig. 21.27a)
iii. Binding of the first complement (C1) to these sites sets off a
reaction cascade in an amplifying process; this is called complement
f. The alternative and lectin pathways require no antibodies and thus belong to
g. Complement C3 slowly and spontaneously breaks down in the blood into C3a
h. In the alternative pathway, C3b binds directly to targets such as human tumor
cells, viruses, bacteria, and yeasts, triggering a reaction cascade.
i. In this case the cascade has an autocatalytic effect.
ii. C3b eventually leads to the accelerated splitting of more C3 and
production of more C3b.
i. Lectins are plasma proteins that bind to carbohydrates; in the lectin pathway, a
lectin binds to certain sugars of a microbial cell surface and sets off a reaction
cascade leading to C3b production.
3. The splitting of C3 into C3a and C3b is where all activation pathways of the
complement system converge; the end results produced by these fragments are as
follows. (Fig. 21.15)
i. C3a stimulates mast cells and basophils to secrete histamine and
other inflammatory chemicals.
ii. It also activates and attracts neutrophils and macrophages.
b. Immune clearance.
i. C3b binds Ag–Ab complexes to RBCs.
ii. As these RBCs circulate through the liver and spleen, macrophages
strip of and destroy the complexes, leaving the RBCs unharmed.
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i. Bacteria, viruses, and other pathogens are phagocytized and digested
by neutrophils and macrophages, but they cannot internalize ―naked‖
ii. C3b coats microbial cells and serves as binding sites for phagocyte
attachment, a process called opsonization.
i. C3b splits another complement protein, C5, into C5a and C5b.
ii. C5a joins C3a in its proinflammatory actions.
iii. C5b binds to an enemy cell and attracts complements C6, C7, and
iv. This conglomeration (C5b678) binds up to 17 molecules of C9,
forming a ring called the membrane attack complex. (Fig. 21.16)
v. This complex forms a hole in the target cell, leading to cell rupture.
F. Immune surveillance is a phenomenon in which NK cells patrol the body looking for pathogens
or diseased cells to attack. (pp. 832–833)
1. Upon recognition of an enemy cell, the NK cell binds to it and releases proteins called
a. The perforins polymerize in a ring and create a hole in the enemy cell’s
plasma membrane. (Fig. 21.17)
b. This hole allows water and salts to flow into the cell, possibly killing it.
2. The NK cell also secretes protein-degrading enzymes called granzymes, which enter
the pore made by the perforins; these destroy cellular enzymes and induce apoptosis.
G. Fever is an abnormal elevation of body temperature also known as pyrexia; febrile means
pertaining to fever. (pp. 833–834)
1. Fever can result from trauma, infections, drug reactions, brain tumors, and other
causes; natural variations in body temperature make defining a fever an individual matter.
2. Fever was long considered an undesirable side effect, but it is now recognized as an
adaptive defense that can do more good than harm.
3. Antipyretic (fever-reducing) medications such as aspirin can sometime prolong illness,
as in colds.
4. Fever is beneficial in that it (1) promotes interferon activity, (2) elevates metabolic rate
and accelerates tissue repair, (3) inhibits reproduction of bacteria and viruses.
5. Fever is typically initiated by exogenous pyrogens (fever-producing agents) such as the
surface glycolipids of bacteria and viruses.
a. As neutrophils and macrophages attack pathogens, they secrete endogenous
pyrogens—interleukins, interferons, and other chemicals.
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b. These chemicals stimulate neurons in the anterior hypothalamus to secrete
prostaglandin E2 (PGE2).
c. PGE2 in turn raises the hypothalamic set point for body temperature. (Fig.
d. Aspirin and ibuprofen reduce fever by inhibiting prostaglandin synthesis, but
using aspirin for this purpose may have deadly consequences.
Insight 21.2 Reye Syndrome
e. When the set point rises, a person shivers to generate heat and the cutaneous
blood vessels constrict to reduce heat loss.
i. In fever onset, one has chills, feels cold and clammy, and has a rising
ii. In the next stage, stadium, the body temperature oscillates around the
new set point; the liver and spleen hoard zinc and iron, depriving
bacteria of minerals needed for reproduction.
iii. When the infection is defeated, the hypothalamic setpoint is
returned to normal, and temperature drops in the phase called
defervescence, crisis (if abrupt), or lysis (if falling slowly).
6. Excessively high temperature can be dangerous because of metabolic discoordination
and cellular dysfunction.
a. Fevers above 40.5°C (105°F) can make a person delirious.
b. Convulsions and coma ensue at higher temperatures, and death or irreversible
brain damage can result from fevers of 44° to 46°C (111° to 115°F).
H. Inflammation is a local defensive response to tissue injury of any kind. (pp. 834–837)
1. It has three general purposes:
a. To limit the spread of pathogens and ultimately destroy them.
b. To remove the debris of damaged tissue.
c. To initiate tissue repair.
2. Inflammation is characterized by four cardinal signs: redness, swelling, heat, and pain.
3. Words ending in the suffix -itis denote inflammation of specific organs and tissues, as
in arthritis, peritonitis, etc.
4. Inflammation is most common and observable in the skin, because it is subject to more
trauma than any other organ.
5. Inflammatory process are mediated by several types of cells and chemicals,
summarized in Table 21.1.
6. Many of the chemicals are in the class called cytokines—small proteins secreted by
leukocytes that alter physiology or behavior of receptor cells.
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a. Cytokines usually act at short range, on neighboring cells (paracrine effects)
or on the same cell that secretes them (autocrine effects).
b. cytokines include interferons, interleukins, tumor necrosis factor, chemotactic
factors, and others.
7. Inflammation involved three major processes: mobilization of defenses, containment
and destruction of pathogens, and tissue cleanup and repair.
8. Mobilization of defenses is the most immediate requirement.
a. Local hyperemia, increasing blood flow beyond its normal rate, is a quick way
to get defensive leukocytes to the scene.
b. Certain cells secrete vasoactive chemicals, among them histamine,
leukotrienes, and other cytokines.
i. These are secreted by basophils of the blood, mast cells of connective
tissue, and cells damaged by the trauma, toxins, or organisms.
ii. Hyperemia also helps flush toxins and wastes from the tissues.
c. Vasoactive chemicals also stimulate endothelial cells of the blood capillaries
to separate slightly, increasing capillary permeability to fluid, leukocytes, and
i. These protein include complement, antibodies, and clotting proteins.
d. Endothelial cells of the blood vessels actively recruit leukoctyes.
i. In the area of injury, they produce cell-adhesion molecules called
selectins, which make their membranes sticky and snag leukocytes, a
process called margination.
ii. The leukocytes adhere loosely, sometimes coating the endothelium
so thickly that they obstruct blood flow.
iii. The leukocytes then crawl through the gaps between endothelial
cells, an action called diapedesis or emigration—and thus enter the
tissue fluid. (Fig. 21.19)
iv. Cells and chemicals that have left the bloodstream are said to be
e. The basis of the four cardinal signs of inflammation occurs in these events.
i. The heat results from the hyperemia.
ii. Redness is also due to hyperemia, and in cases such as sunburn, to
extravasated erythrocytes in the tissue.
iii. Swelling is due to increased fluid filtration from the capillaries.
iv. Pain results from direct injury to nerves, pressure on the nerves from
edema, and stimulation of pain receptors by prostaglandins, toxins of
some bacteria, and bradykinin, an eicosanoid.
Saladin Outline Ch.21 Page 16
9. Containment and destruction of pathogens protects the rest of the body.
a. Fibrinogen that filters into the tissue fluid clots in areas adjacent to the injury,
sequestering bacteria and other microbes.
b. Heparin prevents clotting in the area of the injury itself, so bacteria and other
pathogens are essentially trapped in a fluid pocket surrounded by a capsule of
c. The trapped pathogens are attacked by phagocytes, antibodies, and other
d. Neutrophils are the chief enemies of bacteria; they accumulate within an hour
i. After emigrating from the bloodstream, they exhibit chemotaxis—
attraction to chemicals such as bradykinin and leukotrienes that guide
them to the injury or infection site.
ii. Upon encountering bacteria, the neutrophils avidly phagocytize and
digest them, and destroy many by means of the respiratory burst.
iii. Neutrophils also recruit macrophages and additional neutrophiles by
secreting cytokines themselves.
e. Activated macrophages and T cells in the inflames tissue secrete cytokines
called colony-stimulating factors, which promote production of more leukocytes
(leukopoiesis) by the red bone marrow.
i. Within a few hours, the neutrophil count can raise from 4,000–5,000
cells/μL to as high as 25,000 cells/μL, a condition called neutrophilia.
ii. In the case of an allergy or parasitic infection, and elevated
eosinophil count, or eosinophilia, may also occur.
10. Tissue cleanup and repair is largely undertaken by monocytes.
a. Monocytes arrive within 8 to 12 hours of an injury, emigrate from the
bloodstream, and turn into macrophages.
i. Macrophages engulf and destroy bacteria, damaged host cells, and
dead and dying neutrophils.
ii. They also act as antigen-presenting cells (APCs), activating specific
b. Edema also contributes to tissue cleanup.
i. Swelling compresses veins and reduces venous drainage, but forces
open the valves of lymphatic capillaries and promotes lymphatic
ii. Lymphatics collect and remove bacteria, dead cells, and other tissue
debris better than do blood capillaries.
Saladin Outline Ch.21 Page 17
c. Neutrophils and most macrophages die, and these dead cells and other tissue
debris and fluid form a yellowish fluid called pus, which accumulates in a tissue
cavity called an abscess.
i. Pus is usually absorbed, but sometimes it forms a blister between the
epidermis and dermis and may be released by its rupture.
d. Blood platelets and endothelial cells in an area of injury secrete platelet-
derived growth factor, which stimulates fibroblasts to multiply and synthesize
e. Hyperemia delivers oxygen and nutrients to the area, while the heat of the
inflamed tissue increases metabolic rate and mitosis speed.
f. The fibrin clot may provide a scaffold for tissue reconstruction.
g. Pain contributes to recovery in that it limits the use of a body part, giving it a
chance to rest and heal.
III. General Aspects of Specific Immunity (pp. 837–841)
A. The third line of defense, the immune system, is composed of a large population of widely
distributed cells that recognize foreign substances and act to neutralize or destroy them. (p. 837)
B. Two characteristics distinguish immunity from nonspecific resistance. (p. 838)
1. Specificity. Immunity is directed against a particular pathogen.
2. Memory. When reexposed to the same pathogen, the body reacts so quickly that no
noticeable illness occurs.
C. Two forms of immunity are recognized, called cellular immunity and humoral immunity; these
two forms interact, and they often respond to the same pathogen. (p. 838)
1. Cellular (cell-mediated) immunity employs lymphocytes that directly attack and
destroy foreign or diseased cells.
a. Cellular immunity is a way of fighting pathogens that reside inside human
cells, such as viruses, some bacteria and yeasts, and protozoans.
b. It also fights parasitic worms, cancer cells, and cells of transplanted tissues
2. Humoral (antibody-mediated) immunity involves antibodies that do not directly
destroy a pathogen, but tag them for destruction.
a. The antibodies, not the immune cells that produce them, attack the pathogen.
b. ―Humoral‖ comes from the old term for body fluids, ―humors.‖
c. Humoral immunity is effective against extracellular viruses, bacterial, yeasts,
and protozoans, as well as toxins, venoms, and allergens.
d. Humoral immunity can work only against the extracellular stages of
infectious organisms; when these invade host cells, however, they may still be
vulnerable to attack by cellular immunity.
Saladin Outline Ch.21 Page 18
3. Cellular and humoral immunity are summarized and compared in Table 21.5.
4. Immunity can also be classified as active versus passive and natural versus artificial;
thus four classes of immunity can be recognized.
a. In natural active immunity, one produces one’s own antibodies and/or T cells
as a result of natural exposure to an antigen.
b. In artificial active immunity, one produces one’s own antibodies or T cells as
a result of vaccination against a disease.
i. A vaccine consists of dead or attenuated pathogens that can stimulate
an immune response but normally cause little or no disease.
ii. In some cases periodic booster shots are given to restimulate
iii. A number of diseases, including smallpox, have been eliminated
c. In natural passive immunity, one acquires antibodies produced by another
person, which confer temporary immunity.
i. This normally occurs when a fetus acquires antibodies from the
mother before birth, or an infant acquires them from her during breast
d. In artificial passive immunity, temporary immunity results from injection of
an immune serum from another person or animal that has produced antibodies.
i. Immune serum is used for emergency treatment of snakebite,
botulism, tetanus, rabies, and other diseases.
5. Only the two forms of active immunity involve immune memory; passive immunity
typically lasts for only 2 or 3 weeks. Here we discuss the process of natural active
D. An antigen (Ag) is any molecule that triggers an immune response. (p. 839)
1. Some are free molecules such as venoms and toxins; others are components of plasma
membranes and bacterial cells.
2. Small, universal molecules are not antigenic; most antigens have molecular weights
over 10,000 amu and are complex molecules.
3. The immune system ―learns‖ to distinguish self from nonself prior to birth, and
thereafter normally attacks only nonself antigens.
4. Only regions of an antigen molecule called epitopes (antigenic determinants) stimulate
immune responses; one molecule typically has several different epitopes.
5. Haptens are molecules too small to be antigenic, but that can stimulate an immune
response by binding to a host molecule to create a unique complex.
Saladin Outline Ch.21 Page 19
a. Haptens cause allergic responses to cosmetics, detergents, industrial
chemicals, poison ivy, and animal dander.
b. The most common drug allergy is to penicillin and its derivatives; penicillin is
a hapten, and allergic reaction to it can cause death from anaphylactic shock.
E. Lymphocytes are one of the major cells of the immune system, the others being macrophages
and dendritic cells. (pp. 839–840)
1. Lymphocytes fall into three classes: natural killer (NK) cells described earlier, T
lymphocytes, and B lymphocytes.
2. T lymphocytes (T cells) have a three-stage life history of ―birth, training, and
deployment,‖ and three anatomical stations where these stages occur.
a. T cells are ―born‖ in the red bone marrow as descendants of pluripotent stem
i. They are released into the blood as still-undifferentiated stem cells
that colonize the thymus. (Fig. 21.20)
b. The thymus is where the cells mature into fully functional T cells, their
i. In the thymic cortex, reticular epithelial (RE) cells secrete thymic
hormones that stimulate T cells to produce surface antigen receptors.
ii. With receptors, T cells are immunocompetent, capable of
recognizing antigens presented to them by APCs.
iii. The RE cells test the T cells by presenting self-antigens to them/
iv. Failure to recognize MHC antigens on the RE cells means
elimination, as does reacting to self-antigens.
v. T cells that fail are eliminated by negative selection, either by clonal
deletion in which they die and are phagocytized, or by anergy in which
they remain alive but unresponsive.
vi. Negative selection leaves the body in a state of self-tolerance.
c. T cells that pass the test ―graduate‖—only 2% of T cells pass—and move to
the medulla of the thymus.
i. In the medulla they undergo positive selection in which they form
clones of identical T cells programmed to respond to a particular
ii. These cells, which are immunocompetent but have not yet
encountered the foreign antigens, constitute the naïve lymphocyte pool.
d. The naïve T cells leave the thymus and colonize lymphatic tissues and organs
throughout the body.
Saladin Outline Ch.21 Page 20
3. B lymphocytes (B cells) differentiate from another group of fetal stem cells in the bone
a. Those that respond to self-antigens undergo either anergy or clonal deletion.
b. Self-tolerant B cells go on to produce surface receptors for antigens, divide,
and produce immunocompetent B cell clones.
c. These cells disperse throughout the body to the same organs as T cells.
F. Antigen-presenting cells (APCs) are critical to assisting T cells to recognize foreign antigens.
1. Dendritic cells, macrophages, reticular cells, and B cells function as APCs.
2. APC function depends on a family of genes on chromosome 6 called the major
histocompatibility complex (MHC), which code for MHC proteins.
a. The MHC proteins on the APC surface are shaped a bit like hotdog buns with
a groove for holding the foreign antigen.
b. MHC proteins are structurally unique to every person except for identical
3. When an APC encounters an antigen, it performs antigen processing: it internalizes the
antigen by endocytosis, digests it into fragments, and displays its epitopes in the grooves
of the MCH proteins. (Fig. 21.21a)
4. Wandering T cells regularly inspect APCs for displayed antigens. (Fig. 21.21b)
a. If an APC presents a self-antigen, the T cells disregard it.
b. If it displays a nonself-antigen, the T cells initiate an immune attack.
5. The many cell types involved in immunity require chemical messengers to coordinate
activities; lymphocytes and APCs communicate via the cytokines called interleukins.
6. Agents of specific immunity and their actions are summarized in Table 21.4.
IV. Cellular Immunity (pp. 841–844)
A. Cellular (cell-mediated) immunity is a form of specific defense in which T lymphcytes directly
attack and destroy diseased or foreign cells; the immune system then remembers the antigens of
the invaders. (p. 841)
B. Cellular immunity employs four classes of T cells. (pp. 841–842)
1. Cytotoxic T (TC) cells are the ―effectors‖ of cellular immunity that carry out attack;
they are also called killer T cells, but are not the same as NK cells.
2. Helper T (TH) cells promote the action of TC cells as well as playing key roles in other
forms of immunity; all other T cells are involved only in cellular immunity.
3. Regulatory T (TR) cells, or T-regs, inhibit multiplication and cytokine secretion by
other T cells and limit immune responses; they may play a role in preventing autoimmune
Saladin Outline Ch.21 Page 21
4. Memory T (TM) Cells are descended from cytotoxic T cells and are responsible for
5. TR and TM are not widely used abbreviations, but TC and TH are.
6. TC cells are also known as T8, CD8, or CD8+ cells because they have a surface
glycoprotein called CD8.
7. TH and TR cells are also known as T4, CD4, or CD4+ cells because they carry CD4.
8. CD stands for cluster of differentiation.
9. The CD glycoproteins are cell-adhesion molecules.
10. The three stages of both cellular and humoral immunity are recognition, attack, and
memory (three Rs: recognize, react, and remember).
C. The recognition phase has two aspects: antigen presentation and T cell activation. (p. 842)
1. When an antigen-presenting cell (APC) encounters and processes an antigen, it
migrates to the nearest lymph node and displays it to T cells.
a. When TC and TH cells encounter a displayed antigen on an MHC protein
(MHCP) they initiate an immune response.
b. T cells respond to two classes of MHCPs.
i. MHC-I proteins occur on every nucleated cell and display small
peptides from the cytoplasm; if they are normal self-antigens, no T cell
response occurs, but if they are viral proteins or abnormal cancer-cell
antigens, they do elicit a response.
ii. MHC-II proteins (human leukocyte antigens, HLAs) occur only on
APCs and display only foreign antigens.
c. TC cells respond only to MHC-I proteins, and TH cells respond only to MHC-
II. (Table 21.2)
2. T cell activation occurs in several steps. (p. 842) (Fig. 21.22)
a. It begins when a TC or TH binds to an MHCP displaying an epitope that the T
cell is programmed to recognize.
b. The T cell must then bind to another APC protein, related to interleukins.
c. This process, called costimulation, helps ensure that the immune system does
not launch an attack in the absence of an enemy.
d. Successful costimulation triggers clonal selection, in which the activated T
cell divides to give rise to a clone of programmed T cells.
D. During the attack phase, TH and TC cells play different roles. (pp. 842–843)
1. Helper T cells are necessary for most immune responses.
a. They play a coordinating role in both humoral and cellular immunity. (Fig.
Saladin Outline Ch.21 Page 22
b. When a TH cell recognizes an Ag–MHCP complex, it secretes interleukins
that have three effects.
i. They attract neutrophils and NK cells.
ii. They attract and stimulate macrophages, and inhibit them from
iii. They stimulate T and B cell mitosis and maturation.
2. Cytotoxic T cells are the only T lymphocytes that directly attack and kill other cells.
a. When a TC cell recognizes a complex of antigen and MHC-I protein on a
diseased or foreign cell, it docks on it.
b. It then delivers a lethal hit of cytotoxic chemicals.
c. The TC cell then goes off in search of other enemy cells
d. The lethal hit includes three types of chemical agents.
i. Perforin and granzymes, which kill in the same manner as for NK
ii. Interferons, which inhibit viral replication and recruit and activate
iii. Tumor necrosis factor (TNF), which aids in macrophage activation
and kills cancer cells.
e. As more cells are recruited by helper T cells, the immune response exerts an
overwhelming force again the pathogen, which peaks in about a week and then
E. Immune memory follows the primary response. (pp. 843–844)
1. After clonal selection, some T C and TH cells become memory cells, which are long-
lived and much more numerous than naïve T cells.
2. Memory cells require fewer steps for them to become activated.
3. Upon reexposure to the same pathogen later in life, memory cells mount a quick attack
called the T cell recall response.
a. Often this response destroys a pathogen so quickly that no noticeable illness
V. Humoral Immunity (pp. 844–850)
A. In humoral immunity, B lymphocytes produce antibodies that bind to antigens and tag them for
destruction by other means; the same three stages of response occur.. (p. 844)
B. In the recognition phase, an antigen binds to several of the thousands of surface receptors on an
immunocompetent B cell.
1. The antigen links these receptors together and is then taken into the cell by receptor-
Saladin Outline Ch.21 Page 23
2. After endocytosis, the B cell processes the antigen, links some epitopes to its MHC-II
proteins, and displays these.
3. Most B cells require binding by a helper T cell to this Ag–MHCP complex for
activation, although some are directly activated.
a. When a TH cell binds, it secretes interleukins that activate the B cell.
b. Clonal selection is triggered, giving rise to a battalion of identical B cells
programmed against the antigen. (Fig. 21.25)
4. Most cells of the clone differentiate into plasma cells, which are larger than B cells and
contain an abundance of rough ER. (Fig. 21.26)
a. Plasma cells develop mainly in the terminal centers of the lymphatic nodules
of the lymph nodes.
b. About 10% of them remain in the nodes, but the rest take up residence in the
bone marrow and elsewhere, where they produce antibodies until they die after 4
or 5 days.
c. During this time a plasma cell secretes antibodies at the rate of 2,000
molecules per second, which circulate throughout the body.
d. The first time a person is exposed to an antigen, the plasma cells produce
IgM; upon later exposures they produce IgG.
C. In the attack phase, highly specific antibodies are produced (pp. 846–848)
1. An antibody, also called an immunoglobulin (Ig), is a defensive gamma globulin found
in blood plasma, tissue fluids, body secretions, and some leukocyte membranes.
2. The basic structural unit of an antibody, an antibody monomer, is composed of four
polypeptides linked by disulfide (–S–S–) bonds. (Fig. 21.27)
a. The two larger heavy chains are about 400 amino acids long.
b. The two light chains are about half that long.
c. Each heavy chain has a hinge regions where the antibody is bent, giving the
monomer a T or Y shape.
3. All four chains have a variable (V) region that gives an antibody its uniqueness.
a. The V regions of a heavy chain and a light chain combine to form an antigen-
binding site on each arm.
b. This site attaches to the epitope of an antigen molecule.
4. The rest of each chain is a constant (C) region, which has the same amino acid
sequence as all antibodies of a given class within an individual.
a. The C region determines the mechanism of an antibody’s action.
5. The five classes of antibodies are IgA, IgD, IgE, IgG, and IgM, named for the
structures of their C regions. (Table 21.3)
a. IgD, IgE, and IgG are monomers.
Saladin Outline Ch.21 Page 24
b. IgA has a monomeric and a dimeric form.
c. IgM is a pentamer—composed of five monomers.
6. IgD and IgM are surface antigen receptors synthesized by a developing B cell.
7. IgG is important in the immunity of the newborn.
a. It crosses the placenta and transfers immunity from the mother to the fetus.
8. A newborn also acquires some material IgA through breast milk and colostrum.
9. The human immune system is believed capable of producing at least 10 billion and
perhaps 1 trillion different antibodies.
a. Any one individual does not have the entire set of possibilities, but still an
enormous potential for dealing with diverse antigens.
b. A different gene does not exist for every antibody; somatic recombination
allows shuffling and combination of genes in nonreproductive (somatic) cells.
c. B cells in the germinal centers of lymphatic nodules also undergo somatic
hypermutation, by which a large number of mutations create entirely new
10. Once released by a plasma cell, antibodies use four mechanisms to render antigens
harmless; note that antibodies do not directly destroy an antigen.
a. Neutralization. Only certain regions of an antigen are pathogenic, and an
antibody can neutralize an antigen by masking these active regions.
b. Complement fixation. When antibodies IgM and IgG bind to enemy cells,
they change shape and expose their complement-binding sites. (Fig. 21.27a)
i. Binding of complement leads to inflammation, phagocytosis, immune
clearance, and cytolysis. (Fig. 21.15)
ii. Complement fixation is the primary mechanism of defense against
foreign cells such as bacteria and mismatched erythrocytes.
c. Agglutination occurs when an antibody molecule, with 2 to 10 binding sites,
binds to antigens on two or more enemy cells, sticking them together and
preventing their spread. (Fig. 21.28)
d. Precipitation is similar to agglutination, but it links antigen molecules and not
whole cells, creating Ag–Ab complexes that are removed by immune clearance
or phagocytized by eosinophils.
D. The memory phase occurs as part of the primary response to first exposure to an antigen. (pp.
1. In the primary response, appearance of antibodies is delayed 3 to 6 days while naïve B
cells multiply and differentiate.
2. As plasma cell begin secreting antibody, the antibody titer rises. (Fig. 21.29)
a. IgM appears first, peaks in about 10 days, and soon declines.
Saladin Outline Ch.21 Page 25
b. IgG levels rise as IgM declines, but even IgG titer drops within a month.
3. During clonal selection, some members of the clone become memory B cells rather
than plasma cells. (Fig. 21.25)
a. These cells, found mainly in germinal centers of lymph nodes, mount a very
quick secondary (anamnestic) response if reexposed to the same antigen.
i. Plasma cells form within hours, so the IgG titer rises sharply; the
antigen may have no chance to create illness.
ii. A low level of IgM is also secreted and quickly declines.
b. IgG remains elevated for weeks to years, but does not last as long as humoral
4. Table 21.4 summarizes cellular and chemical agents involved in humoral and cellular
5. Table 21.5 compares the main features of the two types of immunity.
VI. Immune System Disorders (p. 850–856)
A. Hypersensitivity is an excessive, harmful immune reaction to antigens that most people
tolerate. (p. 850–852)
1. It includes reactions to transplanted tissues (alloimmunity), abnormal reactions to
one’s own tissues (autoimmunity), and allergies, which are reactions to environmental
antigens called allergens (Fig. 22.9)
a. Allergens occur in mold, dust, pollen, vaccines, insect venoms, animal dander,
poison ivy toxins, etc. as well as in food such as nuts, milk, eggs, and shellfish.
b. Drugs such as penicillin, tetracycline, and insulin are allergenic to some
2. One classification system recognizes four kinds of hypersensitivity distinguished on
the basis of immune agents and their attack.
a. Type I, or acute (immediate) hypersensitivity, includes the most common
i. Some use the word allergy for type I reactions only, others for all
ii. Type I is an IgE-mediated reaction that begins within second of
exposure; it usually subsides usually within 30 minutes, although it can
be severe and even fatal.
iii. Allergens bind to IgE on the membranes of basophils and mast
cells, stimulating them to secrete histamine and other inflammatory and
Saladin Outline Ch.21 Page 26
iv. Clinical signs include local edema, mucus hypersecretion and
congestion, watery eyes, runny nose, hives, and sometimes cramps,
diarrhea, and vomiting.
v. Some examples of type I hypersensitivity are food allergies and
asthma, a local reaction to inhaled allergens.
Insight 21.3 Asthma
b. Anaphylaxis is an immediate and severe type I reaction.
i. Local anaphylaxis can be relieved with antihistamines.
ii. Anaphylactic shock is a severe, widespread, acute hypersensitivity
that occurs when an allergen is introduced into the bloodstream.
iii. It is characterized by bronchoconstriction, dyspnea, vasodilation,
circulatory shock, and sometimes sudden death.
iv. Antihistamines are inadequate by themselves, but epinephrine can
relieve the symptoms; fluid therapy and respiratory support are
c. Type II (antibody-dependent cytotoxic) hypersensitivity occurs when IgG or
IgM attacks antigens bound to cell surfaces.
i. The reaction leads to complement activation and lysis or opsonization
of the target cell.
ii. Examples of cell destruction by type II reactions are blood
transfusion reaction, pemphigus vulgaris, and some drug reactions.
iii. In some other type II responses, an antibody binds to cell surface
receptors and either interferes with function (myasthenia gravis) or
overstimulates function (toxic goiter).
d. Type III (immune complex) hypersensitivity occurs when IgG or IgM forms
Ag–Ab complexes that precipitate beneath the endothelium of blood vessels or
in other tissues.
i. At the sites of deposition, these complexes activate complement and
trigger inflammation, causing tissue destruction.
ii. Two example of type III hypersensitivity are acute
glomerluonephritis and systemic lupus erythematosus. (Table 21.6)
e. Type IV (delayed) hypersensitivity is a cell-mediated reaction in which signs
appear 12 to 72 hours after exposure.
i. APCs in the lymph nodes display antigens to helper T cells, and these
secrete interferon and other cytokines to activate cytotoxic T cells and
ii. The result is a mixture of nonspecific and immune responses.
Saladin Outline Ch.21 Page 27
iii. Type IV reaction include allergies to haptens in cosmetics and
poison ivy, graft rejection, the tuberculosis skin test, and beta cell
destruction that causes type 1 diabetes mellitus.
B. Autoimmune diseases are failure of self-tolerance in which the immune system produces
autoantibodies. (p. 852)
1. Self-tolerance may fail for at least three reasons.
a. Cross-reactivity. Some antibodies against foreign antigens react to similar
self-antigens, such as in rheumatic fever.
i. A streptococcus infection stimulates production of antibodies that
also react against heart tissue.
ii. Scarring and stenosis (narrowing) of mitral and aortic valves can
b. Abnormal exposure of self-antigens to the blood. Some native antigens are
not normally exposed, and when they are, a response may occur.
i. The blood–testis barrier (BTB) normally isolates sperm cells form the
ii. Breakdown of this barrier can cause sterility when sperm first form
and active the production of autoantibodies.
c. Changes in the structure of self-antigens. Viruses and drugs may change the
structure of self-antigens so that they appear foreign.
i. One theory of type 1 diabetes mellitus is that a viral infection alters
antigens of the beta cells.
ii. An autoimmune attack is then mounted against these cells.
2. Evidence indicates that not all self-reactive T cells are eliminated by clonal detection
in the thymus.
a. Regulatory T cells, whose existence was confirmed only in 1995, keep these
in check and normally prevent autoimmune diseases.
C. Immunodeficiency diseases are those in which the immune system fails to respond vigorously
enough. (pp. 852–855)
1. Severe combined immunodeficiency disease (SCID) is a group of disorders caused by
recessive alleles that result in scarcity or absence of both T and B cells.
a. Children with SCID are highly vulnerable to opportunistic infections and must
live in protective enclosures. (Fig. 21.30)
b. These children are sometimes helped by transplants of bone marrow or fetal
thymus, but in some cases the transplanted cells fail to survive, or they attack the
recipient’s tissues (graft-versus-host response).
2. Acquired immunodeficiency diseases are nonhereditary diseases contracted after birth.
Saladin Outline Ch.21 Page 28
a. The best-known example is acquired immunodeficiency syndrome (AIDS), a
group of conditions that involved a severely depressed immune response.
b. AIDS is caused by infection with the human immunodeficiency virus (HIV).
c. Structurally, the inner core of HIV consists of a protein capsid enclosing two
RNA molecules, two reverse transcriptase molecules, and a few other enzymes.
d. The capsid is enclosed in another layer of viral protein, the matrix.
e. External to this is a viral envelope of phospholipids and glycoproteins derived
from the host cell.
f. HIV can replicate only inside a living host cell; it invades helper T (CD4)
cells, dendritic cells, and macrophages.
i. It adheres to a target cell by means of an envelope glycoprotein and
tricks the cell into internalizing it by receptor-mediated endocytosis.
ii. Within the host cell, reverse transcriptase uses the viral RNA as a
template to synthesize DNA (viruses capable of this are termed
iii. The new DNA is inserted into the host cell’s DNA, where it may lie
dormant for months to years.
iv. When activated, it induces the host cell to replicate the virus
components; as they emerge, they are coated with bits of the cell’s
plasma membrane. (Fig. 21.31b)
g. By destroying helper T cells, HIV strikes the coordinating agent of
nonspecific defense, humoral immunity, and cellular immunity. (Fig. 21.23)
h. After the incubation period ends, the patient begins to experience flulike
episodes of chills and fever as HIV attacks the T H cells.
i. At first, antibodies against HIV are produced and the T H count returns
nearly to normal.
ii. As the virus destroys more and more cells, however, the symptoms
become more pronounced and include night sweats, fatigue, headache,
extreme weight loss, and lympadenitis.
i. A normal TH count is 600 to 1,200 cells/μL, but a criterion of AIDS is a count
less than 200/μL.
j. With such a severe depletion of T H cells, a person succumbs to opportunistic
infections with such pathogens as Toxoplasma, Pneumocystis, herpes simplex
virus, cytomegalovirus, or tuberculosis bacteria.
i. White patches (leukoplakia) may appear in the mouth cause by
Candida (thrush) or Epstein-Barr virus.
Saladin Outline Ch.21 Page 29
ii. A cancer, Kaposi sarcoma, is common in AIDS patients, and affects
endothelial cells of the blood vessels. (Fig. 21.32)
k. Death from cancer or infection is inevitable, usually within a few months but
sometimes as long as 8 years.
l. Some HIV-positive people have survived for 10 years or longer without
m. HIV is transmitted through blood, semen, vaginal secretions, and breast milk,
and can also be transmitted from mother to fetus through the placenta.
i. HIV occurs in saliva and tears, but is apparently not transmitted by
ii. The most common means of transmission are unprotected sexual
intercourse, contaminated blood products, and injections with
iii. Worldwide, about 75% of HIV infections are acquired through
heterosexual, vaginal intercourse.
iv. In the U.S., most cases occur in men who have sex with other men,
but adolescents are the fastest rising group because of the exchange of
unprotected sexual intercourse for drugs.
v. Sharing of needles for drug use remains the chief means of
transmission in urban ghettos.
vi. Since 1984, all blood donated for transfusion has been tested for
HIV, and the risk of infection from this means is less than 1%.
vii. AIDS is not known to be transmitted through casual contact, or by
kissing, or from mosquitoes or other blood sucking arthropods.
n. HIV survives poorly outside the human body and is destroyed by laundering,
dishwashing, exposure to heat of 50°C (135°F) for 10 minutes, chlorination of
swimming pools, and disinfectants such as bleach, Lysol, hydrogen peroxide,
rubbing alcohol, and germicidal skin cleansers.
o. A properly used, undamaged latex condom is an effective barrier to HIV, but
not animal membrane condoms.
p. Many efforts have been launched to find a vaccine or cure for AIDS.
q. About 1% of HIV’s genes mutate every year.
i. This mutation rate is a barrier to both natural immunity and vaccine
ii. The virus soon evolves new surface antigens that escape recognition
by any immune cells that have become sensitized to it.
Saladin Outline Ch.21 Page 30
iii. The high mutation rate means that a vaccine that works today may
be ineffective against future strains.
r. The first anti-HIV drugs include azidothymidine (AZT, Retrovir), which
inhibits reverse transcriptase, and protease inhibitors; HIV has developed
resistance to these drugs.
s. Today at least 24 anti-HIV drugs are on the market, but none totally
eliminates the virus and all have serious side effects.
t. A number of unanswered questions exist about HIV, such as its patterns of
transmission in different countries, and why some people succumb quickly
while others do not develop the disease.
3. Table 21.6 describes additional lymphatic and immune system disorders.
Insight 21.4 Neuroimmunology—The Mind-Body Connection
Connective Issues: Lymphatic and Immune System Interactions
Additional information on topics mentioned in Chapter 21 can be found in the chapters listed below.
Chapter 7: The two types of bone marrow, red and yellow.
Chapter 17: Eicosanoid synthesis
Chapter 18: The types of leukocytes
Chapter 18: Pluripotent stem cells