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LESSON 3: LYMPHATIC SYSTEM AND BODY DEFENSES

3rd QUARTER | ANATOMY AND PHYSIOLOGY 2


• Lymphatic Vessels (lymphatics)
OUTLINE
§ Form a one-way system
I. Lymphatic System § Lymph flows only toward the heart.
II. Body Defenses
III. Developmental Aspect of Lymphatic System
and Body Defenses
IV. Interrelation among other organ systems

LYMPHATIC SYSTEM Figure 11.1 shows the


one way system of
• Consists of two semi-independent parts: lymphatic vessels where
1. Lymphatic Vessels lymph flows only towards
2. Lymphoid Tissues and Organs the heart (see pink arrow)
• Lymphatic System Functions
§ Transports escaped fluids from the
cardiovascular system back to the blood
§ Plays essential roles in body defense and
resistance to disease
LYMPHATIC VESSELS • Lymphatic Capillaries
§ Weave between tissue cells and blood
• Lymph consists of excess tissue fluid and plasma capillaries
proteins carried by lymphatic vessels § Walls overlap to form flaplike minivalves
• If fluids are not picked up, edema occurs as fluid § Fluid leaks into lymph capillaries
accumulates in tissues § Capillaries are anchored to connective tissue by
• Lymphatic vessels (lymphatics) pick up excess fluid filaments
(lymph) and return it to the blood § Higher pressure on the inside closes minivalves
§ Fluid is forced along the vessel

Figure 11.1 shows the


relationship between the
blood vessels and
lymphatic vessels. As
pointed by the pink arrow,
the tissue fluid that goes
out of the capillaries will
become lymph and will
enter the lymph
capillaries Figure 11.3a shows how the lymphatic capillaries (green vessels in the
photo above) weaves itself to the blood capillaries. Figure 11.3b shows
the flaplike minivalve of the lymphatic capillary as well as the filaments
that it uses to anchor to connective tissues.
Figure 11.2 shows how • Lymphatic collecting vessels
edema looks like which is § Collect lymph from lymph capillaries
a consequence of failure § Carry lymph to and away from lymph nodes
to pick up fluids that § Return fluid to circulatory veins near the heart
accumulates in tissues. o Right lymphatic duct drains the lymph
Edema can also be a from the right arm and the right side of the
consequence of high head and thorax
blood pressure o Thoracic duct drains lymph from rest of
body.

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LYMPHATIC NODES
• Lymph nodes filter lymph before it is returned to the
blood
• Harmful materials that are filtered:
§ Bacteria
§ Viruses
§ Cancer cells
§ Cell debris
Figure 11.1 highlights the
• Defense cells within lymph nodes
location of the lymphatic
§ Macrophages – engulf and destroy bacteria,
collecting vessels.
viruses, and other foreign substances in lymph
§ Lymphocytes – respond to foreign substances
in lymph
• Most lymph nodes are kidney-shaped, less than 1
inch long, and buried in connective tissue
§ Surrounded by a capsule
§ Divided into compartments by trabeculae
• Cortex (outer part)
§ Contains follicles - collections of lymphocytes
§ Germinal centers enlarge when antibodies are
released by plasma cells
• Medulla (inner part)
§ Contains phagocytic macrophages

Figure 11.4 highlights the different regions of the body that is drained
by the right lymphatic and thoracic duct.
LYMPHATIC VESSELS (continuation)
• Lymphatic vessels are similar to veins of the
cardiovascular system Figure 11.5 shows the parts of the lymphatic nodes. Highlighted are the
§ Thin-walled cortex and the follicle cells and germinal center in it and the medulla.
§ Larger vessels have valves
§ Low-pressure, pumpless system • Flow of lymph through nodes
• Lymph transport is aided by: 1. Lymph enters the convex side through afferent
§ Milking action of skeletal muscles (similar to lymphatic vessels.
how skeletal muscles can open valves of veins 2. Lymph flows through a number of sinuses inside
when it is “squeezed” by the muscles) the node
§ Pressure changes in thorax during breathing 3. Lymph exits through efferent lymphatic vessels.
§ Smooth muscle in walls of lymphatics Because there are fewer efferent than afferent
vessels, flow is slowed.

Figure 11.1 shows the


relationship of the lymph
nodes to the lymphatic
vessels in terms of
location.

Figure 11.5 shows the flow of lymph from the afferent lymphatic vessels
to the efferent lymphatic vessels.
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OTHER LYMPHOID ORGANS BODY DEFENSES
• Several other lymphoid organs contribute to Innate (nonspecific) defense system
lymphatic function (in addition to the lymph nodes) • Mechanisms protect against a variety of invaders
§ Spleen • Responds immediately to protect body from foreign
§ Thymus materials
§ Tonsils Adaptive (specific) defense system
§ Peyer’s patches • Fights invaders that get past the innate system
§ Appendix • Specific defense is required for each type of
invader
• The highly specific resistance to disease is
immunity
INNATE (NONSPECIFIC) BODY DEFENSES
• Innate body defenses are mechanical barriers to
pathogens (harmful or disease-causing
microorganisms) and include:
§ Body surface coverings
o Intact skin
o Mucous membranes
§ Specialized human cells
§ Chemicals produced by the body
Figure 11.6 shows the location of other lymphoid organs in the body. • Table 12.1 provides a more detailed summary
Spleen
• Located on the left side of the abdomen
• Filters and cleans blood of bacteria, viruses, debris
• Provides a site for lymphocyte proliferation and
immune surveillance
• Destroys worn-out blood cells
• Forms blood cells in the fetus (this function will later
on be passed to the bone marrow)
• Acts as a blood reservoir.
Thymus
• Found overlying the heart
• Functions at peak levels only during youth
• Produces T-lymphocytes
Tonsils
• Small masses of lymphoid tissue deep to the
mucosa surrounding the pharynx (throat)
• Trap and remove bacteria and other foreign
pathogens
• Tonsillitis results when the tonsils become
congested with bacteria
Peyer’s Patches
• Found in the wall of the small intestine
• Similar lymphoid follicles are found in the appendix
• Macrophages capture and destroy bacteria in the
intestine
Mucosa-associated lymphoid tissue (MALT)
• Includes:
§ Peyer’s patches
§ Tonsils
§ Appendix
• Acts as a sentinel (indicator of the presence of a
disease) to protect respiratory and digestive tracts

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Surface membrane barriers • Process of the inflammatory response
• Surface membrane barriers, such as the skin and 1. Neutrophils migrate to the area of
mucous membranes, provide the first line of inflammation by rolling along the vessel wall
defense against the invasion of microorganisms. (following the scent of chemicals from
o Protective secretions produced by these inflammation)
membranes. 2. Neutrophils squeeze through the capillary
§ Acidic skin secretions inhibit bacterial walls by diapedesis (passage of blood
growth vessels through the intact walls of the
§ Sebum is toxic to bacteria capillaries) to sites of inflammation
§ Mucus traps microorganisms 3. Neutrophils gather in the precise site of
§ Gastric juices are acidic and kill tissue injury (positive chemotaxis) and
pathogens consume any foreign material present
§ Saliva and tears contain lysozyme
(enzyme that destroys bacteria).
Cells and chemicals: Internal defenses
• Cells and chemicals provide a second line of
defense.
§ Natural killer cells and phagocytes Figure 11.8 shows the process
§ Inflammatory response of inflammatory response
§ Chemicals that kill pathogens through phagocytes such as
§ Fever neutrophils

Natural Killers (NK) Cells


• Lyse (burst) and kill cancer cells, virus-infected
cells
• Release chemicals called perforin and granzymes
to degrade target cell contents Phagocytes
Inflammatory Response • Cells such as neutrophils and macrophages engulf
• Triggered when body tissues are injured foreign material by phagocytosis
• Four most common indicators (cardinal signs) of • The phagocytic vesicle is fused with a lysosome,
acute inflammation. and enzymes digest the cell’s contents
1. Redness
2. Heat
Figure 11.9 shows a
3. Pain
scanning electron micrograph
4. Swelling (edema) of phagocytosis by a
• Damaged cells release inflammatory chemicals macrophage as it ingests a
§ Histamine bacillus-shaped bacteria
§ Kinin (encircled)
• These chemicals cause:
§ Blood vessels to dilate
§ Capillaries to become leaky
§ Phagocytes and white blood cells to move into
the area (called positive chemotaxis)
Figure 11.7 is a flowchart that
shows the cascade of
inflammatory events after an
injury.
Release of kinins, histamines Figure 11.10 shows the
and other chemicals cause steps involved in
blood vessels to dilate, phagocytosis by a
capillaries to become leaky and microphage.
WBC’s to enter the area.
Dilation of blood vessels can
lead to increase blood flow,
capillaries becoming leaky can
lead to edema and clotting
proteins in the area while WBC’s
are for removal and damaged
tissues and pathogens. This will
all eventually cause healing.

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Antimicrobial Proteins ADAPTIVE DEFENSE SYSTEM
• Enhance innate defenses by: • Adaptive Body Defenses
§ Attacking microorganisms directly Three aspects of Adaptive Defense
§ Hindering reproduction of microorganisms § Antigen specific – the adaptive defense
• Most important types: system recognizes and acts against particular
§ Complement proteins foreign substances
§ Interferon § Systemic—immunity is not restricted to the
initial infection site
• Antimicrobial proteins: complement proteins § Memory – the adaptive defense system
§ Complement refers to a group of at least 20 recognizes and mounts a stronger attack on
plasma proteins that circulate in the plasma previously encountered pathogens
§ Complement is activated when these plasma o Two arms of the Adaptive Defense System
proteins encounter and attach to cells (known § Humoral immunity = antibody-mediated
as complement fixation) immunity
§ Membrane attack complexes (MACs), one ² Provided by antibodies present in body fluids
result of complement fixation, produce holes § Cellular immunity = cell-mediated immunity
or pores in cells. ² Targets virus-infected cells, cancer cells,
o Pores allow water to rush into the cell and cells of foreign grafts
o Cell bursts (lyses) 1. Antigen
§ Activated complement enhances the o Antigens are any substance capable of exciting the
inflammatory response immune system and provoking an immune
response for using words and different patterns of
development
o Examples of common nonself antigens (those
that are not found in the cells of your body; “Self”
antigens include the antigens A and B in our RBCs
that are used to determine blood type)
§ Nominalization – act of transforming verbs to
nouns as much as possible; instead of suggest
refuse, employ, you use suggestion, arrival,
employment
§ Foreign proteins provoke the strongest
response
Figure 11.13 shows activated complement proteins forming a § Nucleic acids
membrane attack complex after complement fixation. This causes § Large carbohydrates
formation of pores that allow water to rush into the cell causing cell § Some lipids
lysis § Pollen grains
§ Microorganisms (bacteria, fungi, viruses)
• Antimicrobial proteins: interferons
o Self-Antigens
§ Interferons are small proteins secreted by
§ Human cells have many protein and
virus-infected cells. carbohydrate molecules
§ Interferons bind to membrane receptors on § Self-antigens do not trigger an immune
healthy cell surfaces to interfere with the ability response in us
of viruses to multiply. § The presence of our cells in another person’s
Fever body can trigger an immune response because
• Abnormally high body temperature is a systemic they are foreign
response to invasion by microorganisms ² Restricts donors for transplants
o Haptens, or incomplete antigens, are not
• Hypothalamus regulates body temperature at
37oC (98.6oF) antigenic by themselves
§ Humoral immunity = antibody-mediated
• The hypothalamus thermostat can be reset higher
immunity
by pyrogens (secreted by white blood cells) § When they link up with our own proteins, the
• High temperatures inhibit the release of iron and immune system may recognize the combination
zinc (needed by bacteria) from the liver and spleen as foreign and respond with an attack
• Fever also increases the speed of repair processes § Found in poison ivy, animal dander, detergents,
hair dyes, cosmetics
2. Cells of the Adaptive System
o Crucial Cells of the Adaptive System
§ Lymphocytes – respond to specific antigens
² B lymphocytes (B cells) produce
antibodies and oversee humoral immunity
² T lymphocytes (T cells) constitute the cell-
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mediated arm of the adaptive defenses; do
not make antibodies
§ Antigen-presenting cells (APCs) — help the
lymphocytes but do not respond to specific
antigens
o Lymphocytes
§ Arise from hemocytoblasts of bone marrow
§ Whether a lymphocyte matures into a B cell or
T cell depends on where it becomes
immunocompetent (capability to respond to a
specific antigen by binding to it with antigen-
specific receptors that appear on the
lymphocyte’s surface)
§ T cells develop immunocompetence in the
thymus and oversee cell-mediated immunity
² Identify foreign antigens
² Those that bind self-antigens are destroyed. o Active Immunity
Self-tolerance is important part of § Occurs when B cells encounter antigens and
lymphocyte “education” produce antibodies
§ B cells develop immunocompetence in bone § Active immunity can be:
marrow and provide humoral immunity ² Naturally acquired during bacterial and viral
§ Immunocompetent T and B lymphocytes infections
migrate to the lymph nodes and spleen, where ² Artificially acquired from vaccines
encounters with antigens occur o Passive Immunity
§ Differentiation from naïve cells into mature § Occurs when antibodies are obtained from
lymphocytes is complete when they bind with someone else
recognized antigens ² Naturally acquired from a mother to her
§ Mature lymphocytes (especially T cells) fetus or in the breast milk
circulate continuously throughout the body ² Artificially acquired from immune serum or
o Antigen-presenting Cells (APCs) gamma globulin (donated antibodies)
§ Lymphocytes – respond to specific antigens § Immunological memory does not occur
§ Engulf antigens and then present fragments of § Protection is short-lived (2–3 weeks)
them on their own surfaces, where they can be § Monoclonal Antibodies
recognized by T cells ² B lymphocytes (B cells) produce
§ Major types of cells behaving as APCs antibodies and oversee humoral immunity
² Dendritic Cells ² Antibodies prepared for clinical testing for
² Macrophages diagnostic services
² B lymphocytes ² Produced from descendants of a single cell
§ When they present antigens, dendritic cells and line
macrophages activate T cells, which release ² Exhibit specificity for only one antigen
chemicals ² Examples of uses for monoclonal antibodies
3. Humoral (antibody-mediated) immune response Ä Cancer Treatment
o B lymphocytes with specific receptors bind to a Ä Diagnosis of Pregnancy
specific antigen Ä Treatment after exposure to hepatitis and
o The binding event sensitizes, or activates, the rabies
lymphocyte to undergo clonal selection
o A large number of clones is produced (primary
humoral response)
o Most of the B cell clone members (descendants)
become plasma cells
§ Produce antibodies to destroy antigens
§ Activity lasts for 4 or 5 days
§ Plasma cells begin to die
o Some B cells become long-lived memory cells
capable of mounting a rapid attack against the
same antigen in subsequent meetings (secondary
humoral response)
§ These cells provide immunological memory

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2. IgA—found mainly in secretions, such as
mucus or tears
3. IgD—important in activation of B cell
4. IgG—can cross the placental barrier and
fix complement; most abundant antibody in
plasma
5. IgE—involved in allergies

o Antibodies (immunoglobulins, lgs)


§ Occurs when antibodies are obtained from
someone else
§ Constitute gamma globulin part of blood
proteins
§ Soluble proteins secreted by activated B cells o Antibody Function
(plasma cells) § Antibodies inactivate antigens in a number
§ Formed in response to a huge number of of ways
antigens ² Complement fixation: chief antibody
o Antibody Structure ammunition used against cellular antigens
§ Four polypeptide chains, two heavy and two ² Neutralization: antibodies bind to specific
light, linked by disulfide bonds to form a T- or Y- sites on bacterial exotoxins or on viruses that
shaped molecule can cause cell injury
§ Each polypeptide chain has a variable (V) ² Agglutination: antibody-antigen reaction
region and a constant (C) region that causes clumping of cells
² Variable regions form antigen-binding sites, ² Precipitation: cross-linking reaction in
one on each arm of the T or Y which antigen-antibody complex settles out
² Constant regions determine the type of of solution
antibody formed (antibody class)

o Antibody Classes
§ Antibodies of each class have slightly different
roles and differ structurally and functionally 4. Cellular (cell-mediated) Immune Response
§ Five major immunoglobulin classes
o Main difference between 2 arms of the adaptive
(MADGE)
1. IgM—can fix complement (refers to a grp response
of at least 20 plasma proteins that circulate § B cells secrete antibodies
in the plasma) § T cells fight antigens directly

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o Like B cells, immunocompetent T cells are FUNCTION OF CELLS INVOLVED IN IMMUNITY
activated to form a clone by binding with a FUNCTION IN THE IMMUNE
ELEMENT
recognized antigen RESPONSE
o Unlike B cells, T cells are unable to bind to free Lymphocyte that resides in the
antigens lymph nodes, spleen, or other
§ Antigens must be presented by a macrophage, lymphoid tissues where it is induced
and double recognition must occur B Cell to replicate by antigen-binding and
§ APC (Antigen presenting cells) engulfs and helper T cell interactions; its
presents the processed antigen in combination progeny (clone members) form
with a protein from the APC plasma cells and memory cells.
o Different classes of effector T cells Antibody-producing “machine” ;
§ Helper T cells produces huge numbers of the
² Recruit other cells to fight invaders Plasma Cell
same antibody (immunoglobulin);
² Interact directly with B cells bound to an specialized B cell clone descendant
antigen, prodding the B cells into clone A T cell that binds w a specific
production antigen presented by an APC; it
² Release cytokines, chemicals that act
stimulates the production of other
directly to rid the body of antigens
Helper T cell immune cells (cytotoxic T cells and
§ Regulatory T cells
² Release chemicals to suppress the activity of B cells) to help fight the invader;
T and B cells acts both directly and indirectly by
² Stop the immune response to prevent releasing cytokines
uncontrolled activity Activity enhanced by Helper t Cells;
² A few members of each clone are memory its specialty is killing virus-invaded
Cytotoxic T
cells body cells, as well as body cells that
Cell
§ Cytoxic (killer) T Cells have become cancerous; involved
² Specialize in killing infected cells in graft rejection
² Insert a toxic chemical (perforin or Slows or stops the activity of B and
granzyme) T cells once the infection (or attack
² The perforin enters the foreign cell’s plasma Regulatory T
by foreign cells) has been
membrane Cell
conquered. Thought to be important
² Pores now appear in the target cell’s in preventing autoimmune diseases
membrane Descendant of an activated B cell or
² Granzymes (protein-digesting enzymes) T cell; generated during both
enter and kill the foreign cell primary and secondary immune
² Cytotoxic T cell detaches and seeks other responses; may exist in the body for
targets Memory Cell
years thereafter, enabling it to
respond quickly and efficiently to
subsequent infections or meetings
w the same antigen
Any of several cell types
(macrophage, dendritic cell, B cell)
that engulfs and digests antigens
that it encounters and presents
parts of them on its plasma
membrane for recognition by T cells
Antigen-
bearing receptors for the same
presenting Cell
antigen; this function, antigen
(APC)
presentation, is essential for normal
cell-mediated responses.
Macrophages and dentritic cells
also release chemicals (cytokines)
that activate many other immune
cells.

o T cells must recognize nonself and self through the FUNCTION OF CELLS INVOLVED IN IMMUNITY
process of antigen presentation FUNCTION IN THE IMMUNE
ELEMENT
§ Nonself—the antigen fragment presented by RESPONSE
APC Protein produced by a B cell or its
Antibody
§ Self—coupling with a specific glycoprotein on plasma-cell offspring and
(immunoglobulin)
the APC’s surface at the same time released into body fluids (blood,

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lymph, saliva, mucus, etc.), o Isografts—tissue grafts from a genetically identical
where it attaches to antigens, person (identical twin)
causing neutralization, o Allografts—tissue taken from a person other than
opsonization, precipitation, or an identical twin (most common type of graft)
agglutination, which "marks" the o Xenografts—tissue taken from a different animal
antigens for destruction by species (never successful)
phagocytes or complement. • Blood group and tissue matching is done to ensure
Chemicals released by the best match possible
sensitized T cells, macrophages, o 75% match is needed to attempt a graft
and certain other cells • Organ Transplant is followed by immunosuppressive
• Migration inhibiting factor therapy to prevent rejection
(MIF)—" inhibits" macrophage
migration and keeps them in DISORDERS OF IMMUNITY
the local area.
• Interleukin 2—stimulates T • The most important disorders of the immune
cells and B cells to proliferate; system
activates NK cells. o Allergies
• Helper factors—enhance § Types of Allergies
antibody formation by plasma ² Immediate (acute) Hypersensitivity
Ä Seen in hives and anaphylaxis (allergic
cells.
reaction)
• Suppressor factors— Ä Due to IgE antibodies and histamine
suppress antibody formation Ä Anaphylactic shock is systemic, acute
Cytokines
or T cell-mediated immune allergic response and is rare
responses (interleukin-10 ² Delayed Hypersensitivity
transforming growth factor and Ä Reflects activity of T cells, macrophages,
others). and cytokines
• Chemotactic factors—attract Ä Symptoms usually appear 1–3 days after
leukocytes (neutrophils, contact with antigen
eosinophils, and basophils) Ä Allergic contact dermatitis (poison ivy,
into inflamed area. cosmetics)
• Gamma interferon—
secreted by lymphocytes;
helps make tissue cells
resistant to viral infection;
activates macrophages and
NK cells; enhances maturation
of cytotoxic T cells.
Like perforin, causes cell killing;
Tumor necrosis
attracts granulocytes; activates T
factor (TNF)
cells and macrophages.
Group of bloodborne proteins
activated after binding to
antibody-covered antigens; when
Complement activated, complement causes
lysis of the microorganism and
enhances inflammatory
response.
Substance capable of provoking
an immune response; typically a
Regulatory T Cell
large, complex molecule not o Autoimmune diseases
normally present in the body. § Occurs when the body’s self-tolerance breaks
Perforin, granzymes—cell toxins down
Cytotoxins released by cytotoxic T cells and § The body produces auto-antibodies and
NK cells sensitized T lymphocytes that attack its own
tissues
§ Most forms of autoimmune disease result
ORGAN TRANSPLANT AND REJECTIONS from the:
• Major Types of Transplants, or Grafts ² appearance of formerly hidden self-antigens
o Autografts—tissue transplanted from one site to ² changes in the structure of self-antigens, and
another on the same person ² antibodies formed against foreign antigens

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that resemble self-antigens INTERRELATION AMONG OTHER ORGAN
§ Examples of autoimmune diseases
² Rheumatoid arthritis—destroys joints
SYSTEM
² Myasthenia gravis—impairs
communication between nerves and skeletal
muscles
² Multiple sclerosis—white matter of brain
and spinal cord is destroyed
² Graves’ disease—thyroid gland produces
excess thyroxine
² Type I diabetes mellitus—destroys
pancreatic beta cells, resulting in deficient
insulin production
² Systemic lupus erythematosus (SLE)—
affects kidney, heart, lung, and skin
² Glomerulonephritis—severe impairment of
kidney function due to acute inflammation
§ Immunodeficiencies
² May be congenital or acquired
Ä Severe combined immunodeficiency
disease (SCID) is a congenital disease
Ä AIDS (acquired immune deficiency
syndrome) is caused by a virus that
attacks and cripples the helper T cells
² Result from abnormalities in any immune
element
² Production or function of immune cells or
complement is abnormal

DEVELOPMENTAL ASPECT OF LYMPHATIC


SYSTEM AND BODY DEFENSES
• Lymphatic vessels form by budding off from veins
• Lymph nodes present by fifth week of development
• The thymus and the spleen are the first lymphoid
organs to appear in the embryo
• Other lymphoid organs are poorly developed before
birth
• The immune response develops around the time of
birth
• The ability of immunocompetent cells to recognize
foreign antigens is genetically determined
• Stress appears to interfere with normal immune
response
• Efficiency of immune response wanes in old age,
and infections, cancer, immunodeficiencies, and
autoimmune diseases become more prevalent

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