Download Introduction: Biology Today Chapter 1

Immune System
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Lymphatic System, Innate Immunity
Much of the text material is from, “Principles of Anatomy and
Physiology, 14th edition” by Gerald J. Tortora and Bryan
Derrickson (2014). I don’t claim authorship. Other sources are
noted when they are used.
Mappings of the lecture slides to the 12th and 13th editions are
provided in the supplements.
2
Due to the complexity of the conceptual material and how it is
presented, most visual references are to the detailed
illustrations in the textbook.
Very few visuals are included in these lecture notes.
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Outline
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Introduction
Lymphatic system
Innate immunity—external defenses
Innate immunity—internal defenses
Inflammation and fever
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Introduction
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Immunity
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Most people remain healthy despite constant exposure to pathogens;
that is, disease-producing bacteria and viruses.
•
The body is also susceptible to abrasions and cuts, exposure to ultraviolet (UV) radiation from sunlight, exposure to chemical toxins, and
burns.
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Immunity—also known as resistance—involves the body’s defenses
that respond to diseases and other damage.
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The two general types of immunity are known as innate immunity and
adaptive immunity.
Chapter 22, page 831
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Immunity (continued)
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Innate Immunity
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Innate (or nonspecific) immunity involves defenses that are active
as early as birth.
•
The defenses respond rapidly to provide protection against many
diseases.
•
Innate immunity does not recognize specific microbes—its mechanisms respond to all microbes in the same manner and with similar actions.
Microbe = a very tiny form of life. Microbes include bacteria,
fungi, and protozoan parasites, They are best visualized under
a light microscope.
(www.emedicinehealth.com)
Chapter 22, page 831
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Innate Immunity (continued)
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The first line of defense includes physical and chemical barriers of
the skin and mucous membranes.
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The second line includes anti-microbial substances, natural killer
(NK) cells, phagocytes, inflammation, and fever.
•
Both lines of defense help prevent microbes from entering the body
and eliminate those that do gain access.
•
Second-line responses also serve as an “early-warning system” for
the body.
Natural killer cell = a type of lymphocyte (white blood cell) that
can kill microbial or tumor cells.
Phagocyte = macrophages and neutrophils (white blood cells)
that engulf and digest debris and invading microbes.
Chapter 22, page 831
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Adaptive Immunity
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Adaptive or specific immunity are defenses involving the recognition
of specific microbes when they breach the nonspecific defenses.
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Adaptive immunity is slower to respond than innate immunity, but it
has “memory” to facilitate the immune response if the microbe is ever
encountered again.
•
The responses involve B lymphocytes (B cells) and T lymphocytes (T
cells).
B and T lymphocytes = types of white blood cells.
Chapter 22, page 831
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Lymphatic System
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Lymphatic System
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The lymphatic system mediates adaptive immunity and aspects of
innate immunity.
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It also works with the cardiovascular system, and with the digestive
system in the absorption of lipids.
Chapter 22, page 831
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Lymphatic System (continued)
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The lymphatic system consists of:
Fluid known as lymph
- Lymphatic vessels that transport the lymph
- Structures and organs containing lymphatic tissue
- Red bone marrow where stem cells develop into blood cells
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The lymphatic system, like the cardiovascular system, circulates body
fluids.
Chapter 22, page 832
Figure 22.1
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Lymphatic System (continued)
http://www.clinic-clinic.com
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Lymph
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Some components of blood plasma filter through capillary walls to
form interstitial fluid.
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When interstitial fluid passes into lymphatic vessels, it is known as
lymph.
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The key difference between interstitial fluid and lymph is their locations.
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Interstitial fluid is found in the space surrounding cells, and lymph in
lymphatic vessels and lymphatic tissue.
Chapter 22, page 832
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Lymphatic Tissue and Lymphocytes
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Lymphatic tissue consists of reticular connective tissue containing
large numbers of B and T lymphocytes.
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Lymphocytes are agranular white blood cells, as discussed in the
lecture on blood.
Reticular connective tissue = a network of reticular fibers,
composed of type III collagen.
Agranular = lacking granules when properly stained and
viewed under a light microscope.
Chapter 22, page 832
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Lymphatic Functions
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The primary functions of the lymphatic system are to:
Drain excess fluid from the interstitial spaces and return it to the
blood.
- Transport lipid-soluble food molecules and lipid-soluble vitamins
(A, D, E, and K) absorbed by the gastrointestinal tract.
- Initiate immune responses against microbes and abnormal cells.
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These lymphatic functions are covered in subsequent slides and the
textbook.
Chapter 22, page 832
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Lymphatic Vessels
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Lymphatic vessels begin as lymphatic capillaries in the interstitial
space.
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Lymphatic capillaries are closed at the end terminating in the interstitial space.
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They converge to form larger lymphatic vessels, just as blood capillaries converge to form venules and then veins.
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Although lymphatic vessels resemble veins, they have thinner walls
and a greater number of valves to assure one-way flow of lymphatic
fluid.
Chapter 22, page 832
Figure 22.2
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Lymphatic Vessels (continued)
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Once absorbed from the interstitial fluid, lymph passes through the
lymph nodes found at intervals along the lymphatic vessels.
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Lymph nodes are encapsulated, bean-shaped organs that contain
masses of B cells and T cells.
Chapter 22, page 832
Figure 22.2
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Lymphatic Vessels (continued)
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Lymphatic vessels in the subcutaneous tissue often follow the
same routes as veins.
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Lymphatic vessels in the viscera typically follow arteries and form
plexuses (networks).
Viscera = the internal organs in the main cavities
of the body.
Chapter 22, page 832
Figure 22.2
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Lymphatic Vessels (continued)
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Some tissues do not have lymphatic capillaries—they include:
Avascular tissues including cartilage, epidermis, and cornea
of the eye
- Central nervous system (brain and spinal cord)
- Portions of the spleen
- Red bone marrow
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Avascular = without blood vessels.
Chapter 22, page 832
Figure 22.2
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Lymphatic Capillaries
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Lymphatic capillaries are of slightly larger diameter than blood capillaries.
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Their walls have a one-way structure to enable interstitial fluid to flow
into, but not out of, the lumen.
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The endothelial cells of the lymphatic capillary wall overlap to enable
this one-way flow.
Chapter 22, page 832
Figure 22.2
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Lymphatic Capillaries (continued)
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Lymphatic Capillaries (continued)
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When the hydrostatic pressure is higher in the interstitial fluid than
in the lymphatic capillary, the endothelial cells open slightly, as in a
one-way swinging door.
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Interstitial fluid enters the lymphatic capillary through the openings.
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When the hydrostatic pressure is higher in the lymphatic capillary
than in the interstitial fluid, the endothelial cells adhere more closely
to close the openings.
•
Lymph cannot re-enter the interstitial fluid since the openings are
now closed.
Chapter 22, page 832
Figure 22.2
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Lymphatic Capillaries (continued)
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Further inflow of interstitial fluid occurs when the pressure in the
lumen is reduced as lymph flows down the lymphatic capillary.
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Lymphatic capillaries are attached to elastic anchoring filaments
that connect the lymphatic endothelial cells to surrounding tissues.
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The filaments are pulled when excess interstitial fluid accumulates,
which causes tissue swelling.
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The openings widen between endothelial cells to permit more interstitial fluid to flow into the lymphatic capillary.
Chapter 22, page 832
Figure 22.2
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Lacteals
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Lacteals—specialized lymphatic capillaries in the small intestine—
transport dietary lipids into lymphatic vessels and into the blood.
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The lipids make the lymphatic fluid, known as chyle juice, appear
creamy-white.
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Lymph is a clear, pale-yellow fluid in the other tissues of the body.
Chapter 22, page 832
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Digestive Tract
Note the centrally-located lacteal in the enlarged villus
to the right.
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Lymph Production
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Many components of the blood plasma can filter through the walls
of blood capillaries to produce interstitial fluid.
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The formed elements (RBCs, WBCs, and platelets) usually cannot
pass.
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More fluid filters out of blood capillaries than is reabsorbed into the
capillaries.
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The excess fluid—about 3 liters per day—drains into the lymphatic
vessels to produce lymph.
Chapter 22, page 834
Figure 21.7
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Lymph Production (continued)
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Interstitial fluid contains only a small amount of proteins since most
protein molecules are too large to pass through blood capillary walls.
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The small amount of proteins in interstitial fluid is not reabsorbed
through the blood capillary walls because of the opposing concentration gradient.
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These proteins pass into the more readily-permeable lymphatic capillaries.
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The proteins are returned to the blood through the lymphatic system.
Chapter 22, page 834
Figure 22.4
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Lymphatic Flow
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Lymph flows from lymphatic capillaries, into afferent lymphatic vessels,
and then into the lymph nodes.
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Efferent lymphatic vessels exit the lymph nodes and converge to form
lymph trunks.
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Lymph then drains into the thoracic and right lymphatic ducts, and then
into venous blood.
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The anatomical relationships between the lymphatic system and cardiovascular system are shown in Figure 22.4 in the textbook.
Chapter 22, page 834
Figure 22.4
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Skeletal Muscle Pump
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Lymphatic vessels, like veins in the cardiovascular system, have
valves that permit one-way flow.
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Skeletal muscle and respiratory pumps assist in the flow of lymph,
just as they aid in the return of venous blood to the right atrium of
the heart.
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Skeletal muscle contractions compress the lymphatic vessel walls.
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The compressions force lymph toward the junction of the internal
jugular and subclavian veins where it empties into venous blood.
Chapter 22, page 834
Figure 21.9
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Respiratory Pump
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During inhalation, lymph flows from the abdominal region where the
pressure is higher to the thoracic region where the pressure is lower.
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When a lymphatic vessel is distended by lymph, the smooth muscle
in its wall contracts in response, propelling the lymph from one segment of the vessel to the next.
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Valves prevent the backflow of lymph when the pressure differential is
reversed during exhalation.
Chapter 22, page 834
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Primary Lymphatic Organs and Tissues
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Lymphatic organs and tissues are called primary or secondary based
on their functions.
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Primary lymphatic organs are sites where stem cells can divide and
become immunocompetent—that is, capable of an immune response.
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The primary lymphatic organs are the red bone marrow and thymus.
Chapter 22, page 834
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Red Bone Marrow
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Pluripotent stem cells in red bone marrow form mature, immunocompetent B cells and pre-T cells.
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Pre-T cells migrate to the thymus where they mature into immunocompetent T cells.
Chapter 22, page 834
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Red Bone Marrow (continued)
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Secondary Lymphatic Organs and Tissues
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Most immune responses occur in the secondary lymphatic organs
and tissues.
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They include the spleen, lymph nodes, and lymphatic nodules (or
follicles).
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They also include the thymus, spleen, and lymph nodes which are
organs since each one is surrounded by a capsule of connective
tissue.
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Lymphatic nodules lack this capsule, and are not considered to be
organs.
Chapter 22, page 836
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Thymus
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The thymus is a bilobed organ located in the mediastinum between
the sternum and aorta.
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A layer of connective tissue holds the two lobes closely together.
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Each lobe is further divided by extensions of the connective tissue
capsule to form smaller lobules.
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A lobule has a darker-staining outer cortex and lighter-staining central medulla.
Bilobed = divided into two lobes.
Chapter 22, page 836
Figure 22.5
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Thymus (continued)
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Thymus—Cortex
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The cortex is composed of large numbers of T cells, and dendritic
cells, epithelial cells, and macrophages.
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Immature pre-T cells migrate from red bone marrow to the cortex
where they proliferate and begin to mature.
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Dendritic cells, derived from monocytes, assist in the maturation
process.
Proliferate = to increase in number or spread rapidly.
Monocyte = a large phagocytic white blood cell which, when
it enters tissue, develops into a macrophage.
(http://thyroid.about.com)
Chapter 22, page 836
Figure 22.5
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Thymus—Cortex (continued)
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Each epithelial cell has long processes that surround and form a
framework for as many as 50 T cells.
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They also produce thymic hormones for the maturation of T cells.
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About 2 percent of the T cells survive in the cortex—the others die
by apoptosis.
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Surviving T cells enter the medulla of the thymus—macrophages
dispose of the dead and dying T cells in the thymic cortex.
Process = a natural prolongation or projection from a part of
an organism.
(http://wordnetweb.princeton.edu)
Apoptosis = normal cellular process involving a genetically
programmed series of events leading to the death of a cell.
(http://science.education.nih.gov)
Chapter 22, page 836
Figure 22.5
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Thymus—Medulla
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The medulla contains mature T cells, epithelial cells, dendritic cells,
and macrophages.
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Epithelial cells form concentric layers of flat cells that serve as sites
for T cell death.
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The surviving T cells eventually exit the medulla via the blood, and
migrate to the lymph nodes, spleen, and other lymphatic tissues to
colonize them.
Concentric = circles sharing the same center.
Chapter 22, page 837
Figure 22.5
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Thymus—Age Progression
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The thymus is large in infants and young children, weighing about
70 grams.
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Adipose and areolar connective tissues begin replacing the thymic
tissue at puberty.
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The thymus atrophies substantially by adulthood.
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It may weigh as little as 3 grams later in life—a 96 percent decrease
from infancy.
Atrophy = wasting away of tissue or an organ due to the
degeneration of cells.
(http://medclinic.bli.uci.edu)
Chapter 22, page 837
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Thymus—Age Progression (continued)
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The thymus populates the secondary lymphatic organs and tissues
with T cells before it atrophies.
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Small numbers of T cells continue to proliferate in the thymus during
an individual’s lifetime.
Chapter 22, page 837
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Lymph Nodes
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About 600 lymph nodes are located among the lymphatic vessels.
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Lymph nodes are found in superficial and deep tissues of the body.
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The nodes are often grouped, including near the mammary glands
and in the groin and axillae.
Axillae = plural for axilla; the armpits.
Chapter 22, page 837
Figure 22.1
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Lymph Nodes (continued)
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Lymph Nodes—Structure
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Lymph nodes are 1 to 25 mm in length and are enclosed in
capsules of dense connective tissue that extends into the nodes.
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These trabeculae divide each node into compartments to provide
structural support and a path for blood vessels into the node.
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The capsule, trabeculae, reticular fibers, and fibroblasts form the
supporting connective tissue, known as stroma, of a lymph node.
Chapter 22, page 837
Figure 22.6
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Lymph Nodes—Structure (continued)
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Lymph Nodes—Outer Cortex
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The functioning part of a lymph node is known as the parenchyma.
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The parenchyma consist of an outer and inner cortex and a deeper
medulla.
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The outer cortex contains aggregates of B cells known as lymphatic
nodules or follicles.
Chapter 22, page 839
Figure 22.6
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Nodules
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A nodule consisting mostly of B cells is called a primary lymphatic
nodule.
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Secondary lymphatic nodules—the more common type—form in
response to antigens.
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These nodules are sites of plasma cell and memory B cell formation.
Antigen = any substance such as a toxin or enzyme that
stimulates an immune response in the body, especially the
production of antibodies.
(http://wordnetweb.princeton.edu)
Chapter 22, page 839
Figure 22.6
49
Medulla and Germinal Center
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The central, medullary region of a secondary lymphatic nodule has
cells that form the germinal center.
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The germinal center contains B cells, follicular dendritic cells, and
macrophages.
Chapter 22, page 839
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B Cell Responses
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B cells proliferate into antibody-producing plasma cells or memory B
cells when follicular dendritic cells present an antigen.
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Memory B cells persist after the immune response ends to serve as
memory of a specific antigen if it is ever encountered again by the
body.
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B cells that fail to develop properly undergo apoptosis and destruction
by macrophages.
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The region surrounding the germinal center has dense accumulations
of B cells that migrated from their site of origin within the nodules.
Antibody = any of a large variety of proteins normally present
in the body or produced in response to an antigen which it
neutralizes, thus producing an immune response.
(http://wordnetweb.princeton.edu)
Chapter 22, page 839
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Inner Cortex
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The inner cortex of a lymph node does not contain lymphatic
nodules, but it does have T cells and dendritic cells that migrated
from other tissues.
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Dendritic cells present antigens to T cells, triggering a proliferation
of T cells.
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Newly-formed T cells migrate from the lymph node to sites of antigen activity in the body.
Chapter 22, page 839
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Medulla
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The medulla of a lymph node contains B cells—antibody-producing
plasma cells that migrated from the cortex—and macrophages.
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The cells are embedded in a network of reticular fibers and reticular
cells.
Chapter 22, page 839
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Lymph Nodes and Lymph
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Lymph enters the lymph nodes though afferent lymphatic vessels.
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The vessels have valves that direct lymphatic flow into the nodes.
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The textbook describes the flow of lymph through the sinuses within a lymph node.
Chapter 22, page 839
Figure 22.6
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Filtration
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The lymph nodes filter lymph—foreign substances entering a node are
trapped by the reticular fibers within the sinuses.
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Macrophages destroy some of the foreign substances through phagocytosis, while lymphocytes destroy others through immune responses.
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The filtered lymph exits the lymph node into efferent lymphatic vessels.
Lymphocyte = a type of white blood cell or leukocyte that occurs
in two forms; B-lymphocytes, which produce antibodies in the
humoral immune response, and T-lymphocytes, which participates
in the cell-mediated immune response.
(http://en.wiktionary.org)
Chapter 22, page 839
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Efferent Lymphatic Vessels
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The sinuses in the medulla of a lymph node drain into 1 or 2 efferent lymphatic vessels.
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The efferent vessels have one-way valves to convey lymph away
from the lymph node.
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The lymph exiting a lymph node contains activated T cells and antibodies from plasma cells.
Chapter 22, page 839
Figure 22.6
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Spleen
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Spleen
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The spleen is the largest single mass of lymphatic tissue—it is oval
in shape and measures about 12 cm in length.
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The organ is located in the left hypochondriac region (hypochondrium) between the stomach and diaphragm.
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The stomach, left kidney, and large intestine make impressions on
the surface of the spleen due to their close proximity.
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Anatomical details of the spleen are described in Chapter 22 of the
textbook.
Chapter 22, page 840
Figure 22.7
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Spleen—White Pulp
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The functioning part of the spleen—its parenchyma—has two types
of tissue known as white pulp and red pulp.
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White pulp is lymphatic tissue arranged around the central arteries
of the spleen.
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Blood flowing into the spleen through the central arteries enters the
white pulp.
Chapter 22, page 841
Figure 22.7
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Functions
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White pulp is composed mostly of lymphocytes and macrophages.••
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The B cells and T cells perform immune functions similar to those in
lymph nodes.
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Macrophages in the white pulp destroy pathogens by phagocytosis.
Chapter 22, page 841
60
Spleen—Red Pulp
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Red pulp consists of blood-filled venous sinuses and cords of splenic
(spleen) tissue known as splenic cords.
•
The cords contain red blood cells, macrophages, lymphocytes, plasma
cells, and granulocytes.
•
Veins are found in the red pulp.
Chapter 22, page 841
Figure 22.7
61
Functions
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Red pulp has three functions:
Removal of ruptured, worn-out, and defective blood cells and
platelets by macrophages.
- Storage of up to one-third of the body’s supply of platelets.
- Production of blood cells through hemopoiesis during the
fetal period.
-
Chapter 22, page 841
62
Lymphatic Nodules
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Lymphatic nodules are small, egg-shaped masses of lymphatic tis-sue,
but without a surrounding capsule.
•
They are also called mucosa-associated lymphatic tissue, or MALT.
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The nodules are located in connective tissue of mucous membranes
lining the respiratory airways, and in the digestive, urinary, and reproductive tracts.
Chapter 22, page 841
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Lymphatic Nodules (continued)
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While some lymphatic nodules are single, many form large aggregations.
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Aggregations are found in the tonsils located in the throat’s pharyngeal region, the ileum of the small intestine, and the appendix.
•
The five tonsils—two adenoid, two lingual, and one palatine—are
involved in immune responses to inhaled and ingested foreign substances.
Chapter 22, page 841
Figure 23.2
64
Innate Immunity, External Defenses
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External Defenses
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Innate immunity involves external barriers to provide a first line of
defense against pathogens.
•
The barriers include the skin, mucous membranes, body fluids, and
chemicals.
Chapter 22, page 842
66
Skin
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The epidermis—the outer, epithelial layer of the skin—has layers
of closely-packed, keratinized cells.
•
The epidermis is a barrier to microbes and other pathogens for
example, bacteria rarely penetrate an intact skin surface.
•
Pathogens, however, can enter to invade tissues and circulate in
the blood when the skin is cut, punctured, or burned.
•
The periodic shedding of epidermal cells helps remove microbes
at the skin surface.
Chapter 22, page 842
Figure 5.1
67
Mucous Membranes
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The epithelial layer of the mucous membranes secretes mucus,
a fluid that lubricates and moistens the surface of the cavity.
•
Mucous also traps microbes and other foreign substances since
it is slightly viscous.
•
The mucous membrane of the nose has mucous-coated hairs to
trap and filter microbes, dust, and pollutants in inhaled air.
Viscous = having a high resistance to flow.
Chapter 22, page 842
68
Mucous Membranes (continued)
•
The mucous membranes of the upper respiratory tract contain many
cilia.
•
Cilia are microscopic, hair-like projections composed of protein molecules on the surface of epithelial cells.
•
The coordinated waving motion helps move microbes and dust trapped
in mucus toward the throat.
Chapter 22, page 842
69
Coughing, Sneezing, and Swallowing
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Coughing and sneezing accelerate the movement of mucus with
entrapped microbes and dust out of the body.
•
Swallowing mucus transports microbes to the stomach where many
are destroyed by gastric acid.
Chapter 22, page 842
70
Tears and Lysozyme
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The lacrimal glands of the eyes produce tears in response to environmental irritants and some emotional states.
•
Blinking spreads the tears over the surface of the eye to help dilute
microbes and keep them from settling on the cornea.
•
Tears contain lysozyme, an enzyme that breaks-down the cell walls
of some bacteria.
•
Lysozyme is also found in saliva, perspiration, nasal secretions, and
tissue fluids.
Chapter 22, page 842
Figure 17.6
71
Saliva
•
Saliva, secreted by the salivary glands, washes microbes from the
teeth and mucous membrane of the oral cavity (mouth).
•
Saliva helps reduce the over-colonization of microbes in the mouth.
Colonization = proliferation of microorganisms on or within
body sites without detectable host immune response, cellular
damage, or clinical expression.
(http://www.cdc.gov)
Chapter 22, page 842
72
Other Mechanisms
•
Cleansing of the urethra by urine inhibits microbial colonization of
the urinary system.
•
Vaginal secretions sweep microbes out of the female reproductive
tract.
•
Defecation and vomiting can expel many microbes from the body.
•
The smooth muscle of the lower gastrointestinal tract contracts
vigorously in response to some microbes—diarrhea expels many
of them through defecation.
Chapter 22, page 842
73
Chemicals
•
Sebaceous glands secrete sebum, an oily substance, to form a
protective film on the surface of the skin.
•
Unsaturated fatty acids in sebum inhibit the growth of some pathogenic types of bacteria and fungi.
•
The high acidity of the skin (pH 3 - 5)—which is inhospitable to
some pathogens—results from fatty acids and lactic acid secretions.
•
Perspiration can help flush microbes from the surface of the skin.
Pathogenic = a disease-producing agent.
Chapter 22, page 842
74
Chemicals (continued)
•
Gastric juice—secreted by exocrine glands in the stomach wall—
contains hydrochloric acid, enzymes, and mucus.
•
The high acidity (pH 1.2 - 3.5) destroys many bacteria and the
toxins they release.
•
Vaginal secretions are slightly acidic, and hinder bacterial growth.
Chapter 22, page 842
75
Innate Immunity, Internal Defenses
76
Internal Defenses
•
Innate immunity includes internal defenses that respond when the
external defenses are breached.
•
The defenses include antimicrobial substances, natural killer cells,
phagocytes, inflammation, and fever.
Chapter 22, page 843
77
Antimicrobial Substances
•
Antimicrobial substances that hinder microbial growth include:
-
Interferons
Complement system
Iron-binding proteins
Antimicrobial proteins
Chapter 22, page 843
78
Interferons
•
Lymphocytes, macrophages, and fibroblasts infected with viruses
produce proteins known as interferons.
•
When released, interferons diffuse to uninfected cells where they
induce the synthesis of antiviral proteins to inhibit virus replication.
•
Interferons are a important defense mechanism because viruses
are only effective when they can replicate and spread to other cells.
Chapter 22, page 843
79
Complement System
•
The complement system consists of a group of normally-inactive
proteins found in blood plasma and on the plasma membranes of
cells.
•
The proteins complement, or enhance, some types of immune reactions.
•
The complement system initiates cytolysis, promotes phagocytosis,
and contributes to inflammation.
Cytolysis = breakdown of a cell by the destruction of its
plasma membrane.
Chapter 22, page 843
80
Iron-Binding Proteins
•
Iron-binding proteins inhibit the growth of some types of bacteria
by reducing the amount of available iron.
•
The proteins include:
Hemoglobin in red blood cells
- Transferrin in blood and tissue fluids
- Ferritin in the liver, spleen, and red bone marrow
- Lactoferrin in saliva, mucus, and a nursing mother’s milk
-
Chapter 22, page 843
81
Antimicrobial Proteins
•
Antimicrobial proteins (AMPs) are short peptide chains that exert a
broad spectrum, or range, of antimicrobial activity.
•
AMPs destroy many microbes, and attract dendritic cells and mast
cells for participation in immune responses.
•
Antimicrobial proteins include:
Dermicidin secreted by sweat glands
- Thrombocidin from platelets
- Defensins and cathelicidins from neutrophils, macrophages,
and epithelium
-
Chapter 22, page 843
82
Natural Killer Cells
•
Natural killer (NK) cells and phagocytes can destroy microbes that
penetrate the skin or mucous membrane and by-pass antimicrobial
substances in the blood.
•
About 5 - 10 percent of the lymphocytes in blood circulation are NK
cells.
•
NK cells are also found in the spleen, lymph nodes, and red bone
marrow.
•
NK cells lack the membrane molecules that identify other lymphocytes (B and T cells).
Chapter 22, page 843
83
Natural Killer Cells (continued)
•
NK cells can destroy a wide variety of infected body cells and some
tumor cells.
•
They can also attack cells that display abnormal or unusual proteins
on their plasma membranes.
Chapter 22, page 843
84
http://www.biotechnologie.de
Natural Killer Cells (continued)
NK cell, in yellow, attacking a cancer cell. Both cells are shown
in false color.
85
Perforin
•
The binding of NK cells to an infected cell triggers the release of
granules of toxic substances, including perforin and granzymes.
•
Perforin is a protein that inserts itself into the plasma membrane of
infected cells to create channels or perforations.
•
Extracellular fluid flows into the cells, causing them to burst (known
as cytolysis).
Chapter 22, page 843
86
Granzymes
•
Granzymes released by NK cells are protein-digesting enzymes that
induce the infected cell to undergo self-destruction known as apoptosis.
•
Apoptosis kills infected cells, but not the microbes contained within
them.
•
The microbes released upon the death of the cell are destroyed by
phagocytes.
Chapter 22, page 843
87
Phagocytes
•
Phagocytes ingest microbes and cellular debris.
•
While phagocytes are an innate defense mechanism, they also have
roles in active immunity, as will be discussed in part 2 of this material.
•
The two main types of phagocytes are neutrophils and macrophages.
Chapter 22, page 843
Figure 3.13
88
http://www.itb.cnr.it
Macrophage
False color, electron micrograph.
89
Wandering and Fixed Macrophages
•
During their migration, monocytes enlarge and develop into active
phagocytes called wandering macrophages.•
•
Wandering macrophages•
•
Fixed macrophages “stand guard” in tissues—examples include:
-
Histiocytes in connective tissues
Stellate reticuloendothelial cells (also called Kuppfer cells) in the
liver
Alveolar macrophages in the lungs
Microglia in the nervous system
Tissue macrophages in the spleen, lymph nodes, and red bone
marrow
Chapter 22, page 843
90
Phases of Phagocytosis
•
Chemotaxis
•
Adherence
•
Ingestion
•
Digestion
•
Destruction
Chapter 22, page 844
Figure 22.9
91
Phagocytosis
92
Chemotaxis
•
Chemotaxis is the chemically-stimulated movement of phagocytes to
the site of infection or other tissue damage.
•
Chemicals that attract phagocytes are released from microbes, white
blood cells, activated complement proteins, and damaged tissue cells.
Chapter 22, page 844
Figure 22.9
93
Adherence
•
Adherence is the physical attachment of the phagocyte to a microbe
or other foreign substance.
•
The binding of complement proteins to the microbe enhances adherence.
Chapter 22, page 844
Figure 22.9
94
Ingestion
•
The plasma membrane of a phagocyte extends projections known as
pseudopods to engulf the microbe in a process known as ingestion.
•
The pseudopod fuses to surround the microbe to form a phagosome.
Chapter 22, page 844
Figure 22.9
95
Digestion
•
The phagosomes enter the cytoplasm of the phagocyte and merge with
lysosomes to form a large, single phagolysome.
•
Lysozyme destroys the cell walls of the engulfed microbe, and digestive
enzymes breakdown the microbe’s carbohydrates, proteins, lipids, and
nucleic acids.
•
The phagocyte also forms lethal oxidants—including superoxide anion
(O2-), hypochlorite anion (OCl-), and hydrogen peroxide (H2O2)—in an
oxidative burst.
Oxidative or respiratory burst = the rapid release of reactive
oxygen (superoxide radical and hydrogen peroxide) from
different types of cells.
(http://en.wikipedia.org)
Chapter 22, page 844
Figure 22.9
96
Destruction
•
Lysozyme, digestive enzymes, and oxidants destroy many types of
microbes.
•
Remaining materials that cannot be completely digested stay in the
phagocyte to form residual bodies.
Chapter 22, page 844
Figure 22.9
97
Microbial Evasion
•
Some microbes, such as bacteria that cause pneumonia, have extracellular structures known as capsules.
•
The capsules make if difficult for phagocytes to engulf the microbes.
•
Some toxin-producing microbes, such as those that cause some types
of food poisoning, produce leukocidins.
•
Leukocidins destroy phagocytes by causing the release of the phagocyte’s own destructive enzymes into its cytoplasm.
Evasion = elude or escape.
Chapter 22, page 843
98
Microbial Evasion (continued)
•
Other microbes, such as the bacteria that cause tuberculosis, inhibit
the fusion of phagosomes and lysosomes, and prevent the exposure
of microbes to lysosomal enzymes.
•
The bacteria within the phagosomes multiplies, which can destroy the
phagocyte.
•
Some bacteria contain chemicals in their cell walls that can counteract
the effects of lethal oxidants produced by phagocytes.
Phagosome = membrane-bound vacuole within a cell
containing foreign material captured by phagocytosis.
(http://en.wiktionary.org)
Oxidant = compound that donate electrons to other
compounds.
(http://www.hepatitis-central.com)
Chapter 22, page 843
99
Inflammation and Fever
100
Inflammation
•
Inflammation is a non-specific, defensive response to tissue damage
and infection.
•
Inflammation can result from microbes, abrasions, chemical irritation,
various disturbances of cells, and extreme temperatures.
•
Inflammation is an attempt by the body to dispose of microbes, toxins,
or foreign materials at an injury site.
•
It also helps prevent spread to other tissues, and prepares the site for
tissue repair.
•
The four signs of inflammation are: redness, pain, heat, and swelling.
Chapter 22, page 844
101
Inflammation (continued)
•
Inflammation can cause loss of function in the injured area depending on the location and extent of the injury.
•
The response is similar to burns, radiation, and bacterial or viral infection.
•
The inflammatory response has three stages:
Vasodilation and increased permeability of blood capillaries
- Emigration of phagocytes from the blood into the interstitial fluid
- Tissue repair
-
Chapter 22, page 844
102
Vascular Responses
•
Increased diameter of the arterioles (vasodilation) and increased
permeability of blood capillaries occur in the vicinity of the tissue
injury.
•
Blood flow increases through the damaged area.
•
The increase in blood flow also helps remove microbes, their toxins,
and dead tissue cells.
•
Increased permeability enables substances, including antibodies
and clotting factors, to pass from the blood into the interstitial fluid.
•
A number of chemicals contribute to vasodilation and permeability.
Chapter 22, page 844
Figure 22.10
103
Chemical Contributors
•
Histamine is released by mast cells in connective tissue and basophils and platelets in the blood.
•
This chemical promotes vasodilation and increased permeability of
blood capillaries.
•
Kinins, including bradykinin, are polypeptides formed in blood from
inactive precursors known as kininogens.
•
These chemicals promote vasodilation, increase capillary membrane
permeability, and serve as chemotaxic agents for migration of phagocytes to the site of infection or injury.
Chapter 22, page 845
104
Chemical and Other Contributors
•
Prostaglandins are lipid molecules released by damaged cells.
•
They intensify the effects of histamine and kinins, and stimulate the
emigration of phagocytes through the membranes of blood capillaries.
•
Leukotrienes are produced by basophils and mast cells to increase
membrane permeability, promote adherence of phagocytes to pathogens, and serve as chemotaxic agents for phagocytes.
•
The complement system stimulates histamine release, attracts neutrophils via chemotaxis, promotes phagocytosis, and destroys bacteria.
Chapter 22, page 845
105
Symptoms of Inflammation
•
Arteriole dilation and increased permeability of capillaries produce
some of the symptoms of inflammation—heat, redness (erythema),
and swelling (edema).
•
Heat and redness result from blood accumulating in the damaged
area.
•
As the local temperature rises, metabolic reactions are more rapid
and release even more heat.
•
Edema results from the increased permeability of blood capillaries,
enabling more fluid to move from blood circulation into the interstitial
space.
Chapter 22, page 845
106
Inflammation and Pain
•
Pain is a prime symptom of inflammation—it results from injury to nerve
fibers and release of microbial toxins.
•
Kinins can affect nerve endings, and can intensify the pain associated
with inflammation.
•
Prostaglandins intensify and prolong the pain associated with an inflammation.
•
Pain can also result from the increased mechanical pressure on tissues
due to edema.
Chapter 22, page 845
107
Clotting Factors
•
An increase in capillary permeability enables blood-clotting factors,
including fibrinogen, to emigrate into tissues.
•
Fibrinogen is converted to an insoluble, thick mesh of fibrin threads
that localizes and trap microbes and hinders their spread to other
tissues.
•
The clotting sequence is described in Chapter 19 of the textbook.
Emigrate = to leave and usually not return.
Chapter 22, page 845
108
Emigration of Phagocytes
•
Phagocytes, including neutrophils, emigrate to the site of a tissue
injury within about an hour of the start of the inflammation process.
•
Emigration depends on chemotaxis.
•
Neutrophils stick to the endothelium or lining of blood vessels as
blood accumulates in the injured area.
•
They squeeze through the blood vessel wall to reach the damaged
area.
Chapter 22, page 845
Figure 22.10
109
Emigration of Phagocytes (continued)
•
Neutrophils destroy microbes in the damaged tissue by phagocytosis.
•
A steady stream of neutrophils is assured through the production
and release of additional neutrophils from the red bone marrow.
•
The increase in the production of neutrophils is known as leukocytosis.
Chapter 22, page 845
Figure 22.10
110
Monocytes and Macrophages
•
Neutrophils rapidly die-off after predominating in the early stages of
an infection.
•
Monocytes move into damaged tissue to prolong the inflammatory
response.
•
Upon entering the tissue, monocytes are transformed into wandering macrophages to supplement the activity of fixed macrophages.
•
Macrophages are much more potent phagocytes than neutrophils—
they are large enough to engulf damaged tissue, dead neutrophils,
and microbes.
Chapter 22, page 845
111
Pus
•
Macrophages eventually die-off as the inflammatory response progresses.
•
A pocket of dead macrophages and damaged tissue forms within a
few days—the collection of dead cells and fluids is known as pus.
•
Pus forms in many inflammatory responses, and usually continues
until the infection subsides.
Chapter 22, page 845
112
Abcesses and Ulcers
•
Pus may reach the surface of the body, drain into an internal cavity,
or remain in the tissue to be gradually absorbed.
•
An abscess can form if pus cannot drain out of the inflamed region.
•
Pimples and boils are examples of abcesses.
•
An open sore, called an ulcer, results when inflamed tissue sloughs
off the surface of the tissue.
Chapter 22, page 846
113
Ulcerations in Diabetic Individuals
•
Individuals with poor blood circulation, such as diabetics who have
advanced atherosclerosis, are susceptible to ulcers in the tissues of
their legs.
•
These are known as statis ulcers, which are due to diminished oxygen and nutrient supply to tissues.
•
The tissues become even more susceptible to mild injury or infection.
Atherosclerosis = a type of arteriosclerosis in which the
vessels that supply oxygen-rich blood to the heart become
clogged with plaque (a fatty substance) and calcium,
depriving the heart muscle of the oxygen it needs for normal
functioning.
(http://www.cardiogenesis.com)
Chapter 22, page 846
114
Fever
•
Fever is an abnormally-high body temperature that occurs due to
changes in the thermoregulatory mechanism in the hypothalamus.
•
Fever can occur during infection and inflammation.
•
Many bacterial toxins can elevate body temperature by triggering the
release of fever-causing cytokines, such as interleukin-1, from macrophages.
•
An elevated body temperature accelerates the effects of interferons,
inhibits the growth of some microbes, and speeds-up cellular actions
for tissue repair.
Chapter 22, page 846
115