Lymphatic System

Functions of the Lymphatic System

1. Fluid Balance
The lymphatic vessels transport back to the blood fluids that have escaped from the blood vascular
system. About 30 liters (L) of fluid pass from the blood capillaries into the interstitial spaces each day,
whereas only 27 L pass from the interstitial spaces back into the blood capillaries. If the extra 3 L of
interstitial fluid remained in the interstitial spaces, edema would result, causing tissue damage and
eventually death. The remaining fluid enters the lymphatic capillaries, where the fluid is called lymph.

2. Fat absorption
The lymphatic system absorbs fats and other substances from the digestive tract. Lacteals are special
lymphatic vessels located in the lining of the small intestine. Fats enter the lacteals and pass through
the lymphatic vessels to the venous circulation.

3. House of the body’s defenses

The lymphoid tissues and organs house phagocytic cells and lymphocytes, which play essential roles in
body defense and resistance to disease.

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 Anatomy of the Lymphatic System
The lymphatic system actually consists of two semi-independent parts: (1) a meandering network of
lymphatic vessels and (2) various lymphoid tissues and organs scattered throughout the body.

Tonsil
Cervical lymph nodes
Subclavian vein
Thymus gland Red bone marrow
Axillary lymph nodes

Thoracic duct Spleen

Appendix Inguinal lymph nodes

Popliteal lymph nodes

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 Lymph Vessels
The function of the lymphatic vessels is to form an elaborate drainage system that picks up
excess tissue fluid, now called lymph.

Lymphatics

The lymphatic vessels, also called

lymphatics, form a one-way
system, and lymph flows only
toward the heart.

Lymph capillaries
The microscopic, blind-ended lymph
capillaries weave between the tissue
cells and blood capillaries in the
loose connective tissues of the body
and absorb the leaked fluid.

Minivalves
The edges of the endothelial cells forming their walls loosely overlap one another,
forming flaplike mini-valves that act as one-way swinging doors; the flaps, anchored by
fine collagen fibers to surrounding structures, gape open when the fluid pressure is
higher in the interstitial space, allowing fluid to enter the lymphatic capillary.
Lymphatic collecting vessels
Lymph is transported from the lymph capillaries through successively larger lymphatic
vessels referred to as lymphatic collecting vessels, until it is finally returned to the
venous system through one of the two large ducts in the thoracic region.
Right lymphatic duct
The right lymphatic duct drains the lymph from the right arm and the right side of the
head and thorax.

Thoracic duct
The large thoracic duct receives lymph from the rest of the body; both ducts empty
the lymph into the subclavian vein on their own side of the body.

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 Lymph Nodes
The lymph nodes in particular help protect the body by removing foreign material such as bacteria and
tumor cells from the lymphatic stream and by producing lymphocytes that function in the immune
response.
Lymphatic capillary
Lymph nodes
Macrophages Swollen lymph nodes

Within the lymph nodes are macrophages,

which engulf and destroy bacteria, viruses,
and other foreign substances in the lymph
before it is returned to the blood.

Artery Vein Normal

lymph
Lymphocytes nodes
Collections of lymphocytes (a type of white blood cell) are also strategically located in the lymph
nodes and respond to foreign substances in the lymphatic stream.

Size and shape

Lymph nodes vary in size and shape, but most are kidney-shaped, less than 1 inch (approximately 2.5 cm)
long, and “buried” in the connective tissue that surrounds them.
Trabeculae
Each node is surrounded by a fibrous capsule from which strands called trabeculae extend inward to
divide the node into a number of compartments.
Cortex
The outer part of the node, the cortex, contains collections of lymphocytes called follicles, many of
which have dark-staining centers called germinal centers.

Plasma cells
These centers enlarge when specific lymphocytes (the B cells) are generating daughter cells called
plasma cells, which release antibodies.

T cells
The rest of the cortical cells are lymphocytes “in transit”, the so-called T cells that circulate
continuously between the blood, lymph nodes and lymphatic stream, performing their surveillance role.

Medulla
Phagocytic macrophages are located in the central medulla of the lymph node.

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Afferent lymphatic vessels
Lymph enters the convex side of a lymph node through the afferent lymphatic vessels.
Efferent lymphatic vessels
It then flows through a number of sinuses that cut through the lymph node and finally exits from
the node at its indented region, the hilum, via the efferent lymphatic vessels.

Other Lymphoid Organs

Lymph nodes are just one of the many types of lymphoid organs in the body. Others are the spleen,
thymus gland, tonsils, and Peyer’s patches of the intestine, as well as bits of lymphoid tissue scattered
in the epithelial and connective tissues.

Spleen The spleen is a soft, blood-rich organ that filters blood.

The spleen is located on the left side of the abdominal cavity, just beneath the diaphragm, and curls
around the anterior aspect of the stomach.
Instead of filtering lymph, the spleen filters and cleanses the blood of bacteria, viruses, and other debris;
it provides a site for lymphocyte proliferation and immune surveillance, but its most important function
is to destroy worn-out red blood cells and return some of their breakdown products to the liver.
Fetal spleen
In the fetus, the spleen is an important hematopoietic (blood cell-forming) site, but as a rule only
lymphocytes are produced by the adult spleen.

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Thymus Gland The thymus gland functions at peak levels only during youth.

The thymus gland is a lymphoid mass found low

in the throat overlying the heart.
The thymus gland produces thymosin and others,
that function in the programming of certain
lymphocytes so they can carry out their
protective roles in the body.

Tonsils
Their job is to trap and remove any bacteria or other
foreign pathogens entering the throat.

Tonsilitis
They carry out this function so efficiently that
sometimes they become congested with bacteria
and become red, swollen, and sore, a condition
called tonsilitis.

Peyer’s Patches

Peyer’s patches are found in the wall of the small

intestine.
The macrophages of Peyer’s patches are in an ideal
position to capture and destroy bacteria (always
present in tremendous numbers in the intestine), thereby
preventing them from penetrating the intestinal wall.

Mucosa-associated lymphatic tissue

Peyer’s patches and the tonsils are part of the collection of small lymphoid tissues referred to as
mucosa-associated lymphatic tissue (MALT); MALT acts as a sentinel to protect the upper respiratory
and digestive tracts from the never-ending attacks of foreign matter entering those cavities.

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 Physiology of the Lymphatic System
Every second of the day, an army of hostile bacteria, viruses, and fungi swarms on our skin and
invades our inner passageways- yet we stay amazingly healthy most of the time, thanks to our body
defense, the lymphatic system.

Blood Flow

Body Defenses
The body’s defenders against these tiny but mighty enemies are two systems, simply called the innate
and the adaptive defense systems; together, they make up the immune system.

Innate Defense System

The innate defense system, also called the non-specific defense system, responds immediately to protect
the body from all foreign substances, whatever they are.
The term innate or nonspecific body defense refers to the mechanical barriers that cover body surfaces
and to the cells and chemicals that act on the initial battlefronts to protect the body from invading
pathogens.

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Surface Membrane Barriers
The body’s first line of defense against the invasion of disease-causing microorganisms is the skin and
mucous membranes.

Skin
As long as the skin is unbroken, its keratinized epidermis is a strong physical barrier to most
microorganisms that swarm on the skin.
Mucous membranes
Intact mucous membranes provide similar mechanical barriers within the body; recall that mucous
membranes line all body cavities open to the exterior: the digestive, respiratory, urinary, and
reproductive tracts.

Protective secretions
Besides serving as physical barriers, these membranes produce a variety of protective secretion: (1)
the acidic pH of skin secretions (pH of 3-5) inhibits bacterial growth, and sebum contains chemicals
that are toxic to bacteria; vaginal secretions of adult females are also very acidic; (2) the stomach
mucosa secretes hydrochloric acid and protein-digesting enzymes, both kill pathogens; (3) Saliva and
lacrimal fluid contain lysozyme, an enzyme that destroys bacteria; and (4) sticky mucus traps many
microorganisms that enter digestive and respiratory passageways.
Structural modifications
Mucus-coated hairs inside the nasal cavity trap inhaled particles, and the respiratory tract mucosa is
ciliated; the cilia sweep dust- and bacteria-laden mucus superiorly toward the mouth, preventing it from
entering the lungs.

Damage
Although surface barriers are quite effective, they are broken from time to time by small nicks and
cuts resulting, for example from brushing the teeth or shaving, so microorganisms invade deeper
tissues, and then the internal innate mechanisms come into play.

Internal Defenses: Cells and Chemicals

For its second line of defense, the body uses an enormous number of cells and chemicals to protect itself.

Phagocytes

Pathogens that make it through the mechanical barriers are confronted by phagocytes, such as a
macrophage or neutrophil, engulfs a foreign particle much the way an amoeba ingests a food particle;
flowing cytoplasmic extensions bind to the particle and then pull it inside, enclosing it in a vacuole; the
vacuole is then fused with the enzymatic contents of a lysosome, and its contents are broken down, or
digested.

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 Natural killer cells

Natural killer cells, which “police” the body in blood and lymph, are a unique group of lymphocytes
that can lyse and kill cancer cells and virus-infected body cells well before the adaptive arm of the
immune system is enlisted to fight; they act spontaneously against any such target by recognizing
certain sugars on the “intruder’s” surface as well as their lack of certain “self” cell surface
molecules; they attack the target cell’s membrane and release a lytic chemical called perforins.

Inflammatory response

The inflammatory response is a nonspecific response that is triggered whenever body tissues are
injured; the four most common indicators of an acute inflammation are redness, heat, swelling, and
pain.

Antimicrobial proteins

A variety of antimicrobial proteins enhances the innate defenses: (1) Complement is a group of plasma
proteins that lyses microorganisms, enhances phagocytosis by opsonization, and intensifies
inflammatory response; (2) Interferons are proteins released by virus-infected cells that protect
uninfected tissue cells from viral takeover and mobilize immune system; (3) Urine has a normally acidic
pH that inhibits bacterial growth, and cleanses the lower urinary tract as it flushes from the body.

Fever

Fever, or abnormally high body temperature, is a systemic response to invading microorganisms;

normally the body’s “thermostat” is set at approximately 37 degrees Celsius, but it can be reset
upward in response to pyrogens, chemicals secreted by white blood cells and macrophages exposed to
foreign cells or substances in the body.

The Inflammatory Process

Chemical alarm
When cells are injured, they release inflammatory chemicals, including histamine and kinins.

Body’s reaction
The release of histamine, kinins, and other chemicals cause blood vessels in the involved area to dilate
and capillaries to become leaky, activate pain receptors, and attract phagocytes and white blood cells
to the area (chemotaxis).

Redness and heat

Dilatation of the blood vessels increases the blood flow to the area, accounting for the redness and
heat observed.

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Edema and pain
Increased permeability of the capillaries allows plasma to leak from the blood into the tissue spaces,
causing local edema (swelling) that also activates pain receptors in the area.

Limitation of joint movement

If the swollen, painful area is a joint, its function may be impaired temporarily, which forces the injured
part to rest, which aids healing.

Adaptive Body Defenses

Sometimes referred to as the body’s third line of defense, the specific defense system is a functional
system that recognizes foreign molecules (antigens) and acts to inactivate or destroy them.

Important aspects
There are three important aspects of the adaptive defense: (1) It is antigen-specific, it recognizes and
acts against particular pathogens or foreign substances; (2) It is systemic, immunity is not restricted
to the initial infection site; (3)It has “memory“, it recognizes and mounts even stronger attacks on
previously encountered pathogens.

Classifications
Humoral immunity, also called antibody-mediated immunity, is provided by antibodies present in the
body’s “humors”, or fluids. while cellular immunity or cell-mediated immunity involves lymphocytes
that defend the body, as the protective factor is living cells.

Antigens
An antigen (Ag) is any substance capable of mobilizing our immune system and provoking an immune
response.

Foreign intruders
An almost limitless variety of substances can act as antigens, including virtually all foreign proteins,
nucleic acids, many large carbohydrates, and some lipids; proteins are the strongest antigens.
Self-antigens
Our own cells are richly studded with a variety of protein molecules or self-antigens; although these
self-antigens do not trigger an immune response in us, they are strongly antigenic to other people.
Hapten
As a rule, small molecules are not antigenic, but when they link up with our own proteins, the immune
system may recognize the combination as foreign and mount an attack that is harmful rather than
protective; in such cases, the troublesome small molecule is called a hapten or incomplete antigen.

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Cells of the Adaptive Defense System: An Overview
The crucial cells of the adaptive system are lymphocytes and macrophages.

Lymphocytes
Lymphocytes exist in two major “flavors”: the B lymphocytes, or B cells, and the T lymphocytes,
or T cells.
Hematopoiesis

B lymphocytes
The B lymphocytes, or B cells, produce antibodies and oversee humoral immunity.

T lymphocytes
The T lymphocytes, or T cells, are non-antibody-producing lymphocytes that constitute the
cell-mediated arm of the adaptive defense system.

Origin
Like all blood cells, lymphocytes originate from hemocytoblasts in red bone marrow.

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Immunocompetent
Whether a given lymphocyte matures into a B cell or T cell depends on where in the body it becomes
immunocompetent, that is, capable of responding to a specific antigen by binding to it.

Maturation of T cells
T cells arise from lymphocytes that migrate to the thymus, where they undergo a maturation
process of 2 to 3 days, directed by thymic hormones; only those maturing T cells with the sharpest
ability to identify foreign antigens survive.

Self-tolerance
Lymphocytes capable of binding strongly with self-antigens (and of acting against body cells) are
vigorously weeded out and destroyed; thus, the development of self-tolerance for the body’s own
cells is an essential part of a lymphocyte’s “education”.

Maturation of B cell
B cells develop immunocompetence in bone marrow, but less is known about the factors that regulate
B cell maturation.

Migration
After they become immunocompetent, both T cells and B cells migrate to the lymph nodes and
spleen (and loose connective tissues), where their encounters with antigens will occur.

Full maturation
Then, when the lymphocytes bind with recognized antigens, they complete their differentiation
into fully mature T cells and B cells.

Macrophages
Macrophages, which also become largely distributed throughout the lymphoid organs and connective
tissues, arise from monocytes, formed in the bone marrow.
A major role of macrophages in the innate defense system is to engulf foreign particles and rid them
from the area; they also present fragments of those antigens, like signal flags, on their own surfaces,
where they can be recognized by immunocompetent T cells.
Macrophages also secrete cytokines proteins that are important in the immune response.
Activated T cells, in turn, release chemicals that causes macrophages to become insatiable phagocytes,
or killer macrophages.
Macrophages tend to remain fixed in the lymphoid organs, but lymphocytes, especially T cells circulate
continuously through the body.

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Humoral (Antibody Mediated) Immune Response
An immunocompetent but as yet immature B lymphocyte is stimulated to complete its development,
when antigens bind to its surface receptors.
Clonal selection
An immunocompetent but as yet immature B lymphocyte is stimulated to complete its development (into
a fully mature B cell) when antigens bind to its surface receptors; this binding event sensitizes, or
activates, the lymphocyte to “switch on”, and undergo clonal selection.
Primary humoral response
The resulting family of identical cells descended from the same ancestor cell is called a clone, and
clone formation is the primary humoral response to that antigen.
Plasma cells
Most of the B cell clone members, or descendants, become plasma cells.
Antibody production
After an initial lag period, these antibody-producing “factories” swing into action, producing the
same highly specific antibodies at an unbelievable rate of about 2000 antibody molecules per second.
Life span
This flurry of activity lasts only 4 to 5 days, then the plasma cells begin to die; antibody levels in
the blood during this primary response peak about 10 days after the response begins and then slowly
decline.
Memory cells
B cell clone members that do not become plasma cells become long-lived memory cells capable of
responding to the same antigen at later meetings with it; memory cells are responsible for the
immunological memory, and these later immune responses, called secondary humoral responses, are
produced much faster, are more prolonged, and are more effective than the events of the primary
response because all the preparations for this attack have already been made.

Active and Passive Humoral Immunity

There are two kinds of humoral immunity: active and passive humoral immunity.

Active immunity
When your B cells encounter antigen and produce antibodies against them, you are exhibiting active
immunity; active immunity is (1) naturally acquired during bacterial and viral infections, and (2)
artificially acquired when we receive vaccines.

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Vaccines
We receive two benefits from vaccines: (1) they spare us most of the signs and symptoms of the
disease that would otherwise occur during the primary response and (2) the weakened antigens are
still able to stimulate antibody production and promote immunological memory.

Booster shots
So-called booster shots, which may intensify the immune response at later meetings with the same
antigen, are also available.

Passive immunity
In passive immunity, the antibodies are obtained from the serum of an immune human or animal
donor; as a result, the B cells are not challenged by the antigen, immunological memory does not
occur, and the temporary protection provided by the “borrowed antibodies” ends when they naturally
degrade in the body.

Natural passive immunity

Passive immunity is conferred naturally on a fetus when the mother’s antibodies cross the placenta
and enter fetal circulation, and after birth during breastfeeding.

Artificial passive immunity

Passive immunity is artificially conferred when one receives immune serum or gamma globulin.

Monoclonal antibodies
Monoclonal antibodies prepared commercially for use in research are produced by descendants of a
single cell and are pure antibody preparations that exhibit specificity for one, and only one, antigen.

Antibodies
Antibodies, also referred to as immunoglobulins, or Igs, constitute the gamma globulin part of
blood proteins.
Antibodies are soluble proteins secreted by activated B cells or by their plasma-cell offspring in
response to an antigen and they are capable of binding specifically with that antigen.

Basic antibody structure

Regardless of its class, every antibody has a basic structure consisting of four amino acid
(polypeptide) chains linked together by disulfide (sulfur-to-sulfur) bonds.

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Heavy chains
Two of the four chains are identical and contain approximately 400 amino acids each.

Light chains
The two other chains, the light chains, are also identical to each other but are only about
half as long as the heavy chains.

Antibody classes:
IgD
IgD is virtually always attached to B cell and is believed to be the cell surface receptor of
immunocompetent B cell; and it is also important in activation of B cell.
IgM
IgM is attached to B cell and free in plasma; when it is bound to the B cell membrane, it serves as
an antigen receptor; first Ig class released to plasma by plasma cells during primary response; it is
also a potent agglutinating agent and fixes complement.
IgG
IgG is the most abundant antibody in plasma, representing 75% to 85% of circulating antibodies; it
is the main antibody of both primary and secondary responses; crosses the placenta and provides
passive immunity to fetus; fixes complement.
IgA
Some are found in plasma; dimer in secretions such as saliva, tears, intestinal juice, and milk; it
bathes and protects mucosal surfaces from attachment of pathogens.
IgE
It is secreted by plasma cells in skin, mucosae of gastrointestinal and respiratory tracts, and
tonsils; it binds to mast cells and basophils and triggers release of histamine and other chemicals
that mediate inflammation and certain allergic responses.

Antibody function
Antibodies inactivate antigens in a number of ways- by complement fixation, neutralization,
agglutination, and precipitation.

Complement fixation
Complement is the chief antibody ammunition used against cellular antigens, and it is fixed (activated)
during innate defenses; it is also activated very efficiently when it binds to antibodies attached to
cellular targets.

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 Neutralization
Neutralization occurs when antibodies bind to specific sites on bacterial exotoxins (toxic chemicals
secreted by bacteria) or on viruses that can cause cellular injury; in this way they block the
harmful effects of the exotoxin or virus.

Agglutination
When the cross-linking involves cell-bound antigens, the process causes clumping of the foreign cells,
a process called agglutination; this type of antigen-antibody reaction occurs when mismatched
blood is transfused and is the basis of tests used for blood typing.

Precipitation
When the cross-linking involves soluble antigenic molecules, the resulting antigen-antibody complexes
are so large that they become insoluble and settle out of solution; this cross-linking reaction is
more precisely called precipitation.

Cellular (Cell-Mediated) Immune Response

Like B cells, immunocompetent T cells are activated to form a clone by binding with a “recognized”
antigen; however, T cells are not able to bind with free antigens.

Antigen presentation
Apparently, T cell must recognize “nonself”, the antigen fragment presented by the macrophage, and
also “self” by coupling with a specific glycoprotein on the macrophage’s surface at the same time;
antigen binding alone is not enough to sensitize T cells; they must be “spoon-fed” the antigens by
macrophages, and something like a “double handshake” must occur; this is called antigen presentation
and is essential for activation and clonal selection of the T cells.
Cytotoxic (killer) T cells
Some T cells are cytotoxic ,or killer, T cells that specialize in killing virus-infected, cancer, or foreign
graft cells; one way a cytotoxic T cell accomplishes this is by binding tightly to a foreign cell and
releasing toxic chemicals called perforins and granzymes from its granules.
Helper T cells
Helper T cells are the T cells that act as the “directors” or “managers” of the immune system; once
activated, they circulate through the body, recruiting other cells to fight the invaders; the helper T
cells also release a variety of cytokine chemicals that act indirectly to rid the body of antigens by
(1) stimulating cytotoxic T cells and B cells to grow and divide; (2) attracting other types of
protective white blood cells, such as neutrophils, into the area; and (3) enhancing the ability of
macrophages to engulf and destroy microorganisms.

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Regulatory T cells
Another t cell population, the regulatory T cells, formerly called suppressor T cells, releases
chemicals that suppress the activity of both T and B cells; regulatory T cells are vital for winding
down and finally stopping the immune response after an antigen has been successfully inactivated
or destroyed.
Memory cells
Most of the T cells enlisted to fight in a particular immune response are dead within a few days;
however, a few members of each clone are long-lived memory cells that remain behind to provide
immunological memory for each antigen encountered and enable the body to respond quickly to
subsequent invasions.

Lymphocyte Differentiation and Activation

The process of differentiation and activation of lymphocytes include the following:

Immunocompetence
Lymphocytes destined to become T cells migrate from bone marrow to the thymus and develop
immunocompetence there; B cells develop immunocompetence in the bone marrow.

Activation
After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes “seed” the
infected connective tissues, where the antigen challenge occurs and the lymphocytes become fully
activated.

Circulation
Activated (mature) lymphocytes circulate continuously in the bloodstream and lymph, and
throughout the lymphoid organs of the body.

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