CHAPTER 22: LYMPHATIC SYSTEM
transport the lymph
Pathogens – disease-producing microbes such as
bacteria and virus.
Immunity or Resistance – ability to ward off
damage or disease through our defences.
Susceptibility – vulnerability or lack of resistance
2 General Types of Immunity
1. Innate Immunity
 Refers to defenses that are present
at birth.
 Does not involve specific
recognition of a microbe and acts
against all microbes in the same
way.
 Components are:
o First line of defense (physical
and chemical barriers)
o Second line of defense
(antimicrobial substances)
 Innate immune responses represent
immunity’s early warning system
 Designed to prevent microbes from
entering the body and help eliminate
those that do gain access.
2. Adaptive Immunity
 Defenses that involve specific
recognition of a microbe once it has
breached the innate immunity
defenses.
 Is based on a specific responses to
a specific microbe; it adapts or
adjusts to handle a specific microbe.
 Involves lymphocytes (T
lymphocytes and B lymphocytes)
LYMPHATIC SYSTEM STRUCTURE AND
FUNCTION
Lymphatic System
 Responsible for adaptive immunity
 Closely allied with the cardiovascular
system
 Functions with the digestive system in the
absorption of fatty foods.
 Assists in circulating body fluids and helps
defend the body against disease-causing
agents.
 Consists of a fluid called lymphs,
o vessels called lymphatic vessels that
Lymphatic Tissue – a specialized form of reticular
connective tissue that contains large numbers of
lymphocytes.
FUNCTIONS OF THE LYMPHATIC SYSTEM
3 Primary functions:
a. Drains excess interstitial fluid
b. Transports dietary lipids
c. Carries out immune responses
LYMPHATIC VESSELS AND LYMPH
CIRCULATION
 Lymphatic vessels begin as lymphatic
capillaries – located in the spaces between
cells, are closed at one end.
 Lymphatic capillaries unite to form larger
lymphatic vessels which resemble small
veins in structure but have thinner walls and
more valves.
Lymphatic Capillaries
 Have greater permeability than blood
capillaries and thus can absorb large
molecules such as proteins and lipids.
 Slightly larger in diameter than blood
capillaries and have a unique one-way
structure that permits interstitial fluid to flow
into them but not out.
 Attached to the lymphatic capillaries are
anchoring filaments – contains elastic fibers.
 In the small intestine, lymphatic capillaries
called lacteals carry dietary lipids into
lymphatic vessels and ultimately into the
blood.
Lymph Trunks and ducts
 As lymphatic vessels exit lymph nodes in a
particular region of the body, they unite to
form lymph trunks
 The principal trunks are the following:
o Lumbar trunks – drain lymph from
the lower limbs, the wall of viscera of
the pelvis, the kidney, the adrenal
glands and the abdominal wall.
o Intestinal trunks – drains lymph from
the stomach, intestines, pancreas,
spleen and part of the liver
 o Bronchomediastinal trunks- drains
lymph from the thoracic wall, lung
and heart.
o Subclavian trunk – drain the upper
limbs
o Jugular trunk – drain the head and
neck
 Lymph passes from lymph trunks into two
main channels:
o Thoracic duct - about 38-45 cm long
and begins as a dilation called
cisterna chyli anterior to the second
lumbar vertebra.
 Is main duct for the return of
the lymph to blood
o Right lymphatic duct – about 1.2 cm
long and receives lymph from the
right jugular, right subclavian and
right bronchomediastinal trunks.
Formation and flow of lymph
 The sequence of fluid flow is blood
capillaries (blood) to interstitial spaces
(interstitial fluid) to lymphatic capillaries
(lymph) to lymphatic vessels (lymph) to
lymphatic ducts (lymph) to the junction of
the internal jugular and subclavian veins
(blood).
The same 2 “pumps” that aid the return of venous
blood to the heart maintain the flow of lymph.
1. Skeletal muscle pump – milking action of
skeletal muscle contractions compresses
lymphatic vessels
2. Respiratory pump - lymph flow is also
maintained by pressure changes that occur
during inhalation
LYMPHATIC ORGANS AND TISSUES
 Primary lymphatic organs are the sites
where stem cells divide and become
immunocompetent that is capable of
mounting an immune response.
 The secondary lymphatic organs and
tissues are the sites where most immune
responses occur
Thymus
 a bilobed organ located in the mediastinum
between the sternum and the aorta.
 Thymic macrophages help clear out the
debris of dead and dying cells.
 Medulla is consists of widely scattered,
more mature T cells, epithelial cells,
dendritic cells and macrophages.
Lymph Nodes
 Located along lymphatic vessels that are
about 600 bean shaped
 1-25 mm long and like the thymus are
covered by a capsule of dense connective
tissue that extends into the node.
 The parenchyma of a lymph node is divided
into a superficial cortex and an inner cortex.
o Within the outer cortex are egg
shaped aggregates of B cells called
lymphatic nodules.
 A lymphatic nodule
consisting chiefly of B cells is
called primary lymphatic
nodule
 Most lymphatic nodules in
the outer cortex are
secondary lymphatic
nodules, which form in
response to an antigen.
 the center of a
secondary lymphatic
nodule contains a
region of light-staining
cells called germinal
center
o the inner cortex does not contain
lymphatic nodules
o the medulla of a lymph node
contains B cells
 lymph nodes function as a type of filter
Spleen
 Largest single mass of lymphatic tissues in
the body measuring about 12 cm in length.
 Located in the left hypochondriac region
between the stomach and diaphragm
 The superior surface of the spleen is
smooth and convex and conforms to the
concave surface of the diaphragm
 White pulp – is lymphatic tissue, consisting
mostly of lymphocytes and macrophages
arranged around branches of the splenic
artery called central arteries
  Red pulp- consists of blood-filled venous
sinuses and cords of splenic tissue called
splenic cords or Billroth’s cords
o Splenic cord – consists of RBC,
macrophages, lymphocytes, plasma
cells and granulocytes.
3 Functions related to Blood Cells
provided by the skin and mucous
membranes.
 It also includes various internal defenses,
such as antimicrobial substances, natural
killer cells, phagocytes, inflammation, and
fever.

 Removal by macrophages of ruptured, worn

out or defective blood cells and platelets
 Storage of platelets, up to 1/3 of the body’s
supply
 Production of blood cells during fetal life
Lymphatic Nodules

 Are egg shaped masses of lymphatic tissue

that are not surrounded by a capsule
 Lymphatic nodules in these areas are also
referred to as mucosa-associated lymphatic
tissue (MALT)
 Usually there are 5 tonsils which form ring
at the junction of the oral cavity and
oropharynx and at the junction of the nasal
cavity and nasopharynx.
o The single pharyngeal tonsil or
adenoid is embedded in the
posterior wall of the nasopharynx
o The 2 palatine tonsils lie at the
posterior region the oral cavity
o The paired lingual tonsils located at
the base of the tongue
DEVELOPMENT OF LYMPHATIC TISSUES

 Lymphatic tissues begin to develop by the

end of the 5th week of embryonic life.
 Lymphatic vessels develop from lymph sacs
that arise from developing veins which are
derived from mesoderm
 The first lymph sacs to appear are the
paired jugular lymph sacs at the junction of
the internal jugular and subclavian veins
 At about the time the retroperitoneal lymph
sac is developing, another lymph sac, the
cisterna chyli, develops inferior to the
diaphragm on the posterior abdominal wall.
 The last of the lymph sacs, the paired
posterior lymph sacs, develop from the iliac
veins.
INNATE IMMUNITY
 Innate (nonspecific) immunity includes the PHAGOCYTOCIS OCCURS IN 5 PHASES
external physical and chemical barriers
  Chemotaxis –chemically stimulated
movement of phagocytes to a site of
damage
 Adherence – attachment of the phagocyte
to the microbe or other foreign material
 Ingestion – process of engulfing the microbe
 Digestion
 Killing
ADAPTIVE (SPECIFIC) IMMUNITY
 The ability of the body to defend itself
against specific invading agents such as
bacteria, toxins, viruses, and foreign tissues
 Antigens (Ags; antibody generators) -
substances that are recognized as foreign
and provoke immune responses
2 properties that distinguish Adaptive Immunity
from Innate Immunity:
1. Specificity for particular foreign molecules
(antigens), which also involves
distinguishing itself from nonself molecules
2. Memory for most previously encountered
antigens so that a second encounter
prompts an even more rapid and vigorous
response
 Immunology – the branch of science that
deals with the responses of the body when
challenged by antigens
 Immune System – includes the cells and
tissues that carry out immune responses
Maturation of T cells and B cells
 B Cells and T Cells – lymphocytes involved
in adaptive immunity
o Develop in primary lymphatic organs
(red bone marrow and the thymus)
from pluripotent stem cells that
originate in red bone marrow
o B Cells complete their development
in red bone marrow, a process that
continues throughout life
o T Cells develop from pre-T cells that
migrate from red bone marrow into
the thymus, where they mature
 Bursa Equivalent – the red bone marrow
where B cells mature
 Thymus Gland – where T cells mature
 Immunocompetence – the ability to carry
out adaptive immune responses
 Antigen Receptors – molecules capable of
recognizing specific antigens
2 Major Types of Mature T Cells that exit the
thymus:
1. Helper T Cells or CD4 T Cells – in addition
to antigen receptors, their plasma
membranes include a protein called CD4
2. Cytotoxic T Cells or CD8 T Cells – their
plasma membranes contain not only antigen
receptors but also a protein known as CD8
Types of Adaptive Immunity
1. Cell-Mediated Immunity – cytotoxic T cells
directly attack invading antigens
o Always involves cells attacking cells
Particularly effective against:
a. Intracellular pathogens, which include
any viruses, bacteria, or fungi that are
inside cells
b. Some cancer cells
c. Foreign tissue transplants
2. Antibody-Mediated Immunity/Humoral
Immunity – B cells transform into plasma
cells, which synthesize and secrete specific
proteins called antibodies (Abs) or
immunoglobulins (Igs)
o works mainly against extracellular
pathogens, which include any
viruses, bacteria, or fungi that are in
body fluids outside cells
Clonal Selection: The Principle
- the process by which a lymphocyte
proliferates (divides) and differentiates
(forms more highly specialized cells) in
response to a specific antigen
 Clone – population of identical cells that can
recognize the same specific antigen as the
original lymphocyte
2 Major Types of Cells in the Clone:
1. Effector Cells – carry out immune
responses that ultimately result in the
destruction or inactivation of the antigen
 Most effector cells eventually
die after the immune
response has been
completed
a. Active Helper T Cells – part of a
helper T cell clone
b. Active Cytotoxic T Cells – part of
a cytotoxic T cell clone
 c. Plasma Cells – part of a B cell
clone
2. Memory Cells – do not actively
participate in the initial immune
response to the antigen
 Most memory cells do not die
at the end of an immune
response; have long life
spans
a. Memory Helper T Cells – part of
a helper T cell clone
b. Memory Cytotoxic T Cells – part
of a cytotoxic T cell clone
c. Memory B Cells – part of a B cell
clone
Antigens and Antigen Receptors
2 important characteristics of Antigens:
1. Immunogenicity – the ability to provoke
an immune response by stimulating the
production of specific antibodies, the
proliferation of specific T cells, or both
o Antigen – derived from its function
as an antibody generator
2. Reactivity – the ability of the antigen to
react specifically with the antibodies or
cells it provoked
 Complete Antigens – substances with both
immunogenicity and reactivity
 Epitopes/Antigenic Determinants – small
parts of a large antigen molecule that act as
the triggers for immune responses
Antigens that get past the innate defenses
follow one of these three routes into lymphatic
tissue:
1. Most antigens that enter the
bloodstream are trapped as they flow
through the spleen
2. Antigens that penetrate the skin enter
lymphatic vessels and lodge in lymph
nodes
3. Antigens that penetrate mucous
membranes are entrapped by mucosa-
associated lymphatic tissue (MALT)
Chemical Nature of Antigens
- Antigens are large, complex, molecules.
Most often, they are proteins.
- Complete antigens usually have large
molecular weights of 10,000 Daltons or
more, but large molecules that have simple,
repeating subunits are not usually antigenic.
 Hapten – smaller substance that has
reactivity but lacks immunogenicity
o Can stimulate an immune response
only if it is attached to a larger
carrier molecule
Diversity of Antigen Receptors
- An amazing feature of the human immune
system is its ability to recognize and bind to
at least a billion (109) different epitopes.
 Genetic Recombination – shuffling and
rearranging a few hundred versions of
several small gene segments
o Gene segments are put together in
different combinations as the
lymphocytes are developing from
stem cells in red bone marrow and
the thymus
Major Histocompatibility Complex Antigens
- Located in the plasma membrane of body
cells
- “self-antigens”
- Also called Human Leukocyte Antigens
(HLA) because they were first identified on
white blood cells
- Their normal function is to help T cells
recognize that an antigen is foreign, not self
2 Types of Major Histocompatibility Complex
Antigens:
1. Class I MHC (MHC-I) – built into the
plasma membranes of all body cells
except red blood cells
2. Class II MHC (MHC-II) – appear on the
surface of antigen-presenting cells
Pathways of Antigen Processing
- B cells can recognize and bind to antigens
in lymph, interstitial fluid, or blood plasma
- T cells only recognize fragments of
antigenic proteins that are processed and
presented in a certain way
 Antigen Processing – antigenic proteins are
broken down into peptide fragments that
then associate with MHC molecules
 Antigen Presentation – the insertion of the
complex into the plasma membrane
- When a peptide fragment comes from a
self-protein, T cells ignore the antigen-MHC
complex
- If the peptide fragment comes from a
foreign protein, T cells recognize the
 antigen-MHC complex as an intruder, and 5. Insertion of antigen-MHC-I
an immune response takes place. complexes into the plasma
membrane
Processing of Exogenous Antigens
 Exogenous Antigens – foreign antigens that Cytokines
are present in fluids outside body cells - Small protein hormones that stimulate or
o Include intruders such as bacteria inhibit many normal cell functions, such as
and bacterial toxins, parasitic cell growth and differentiation
worms, inhaled pollen and dust,
and viruses that have not yet
infected a body cell
 Antigen-Presenting Cells (APCs) –
special class of cells that process and
present exogenous antigens
o Include dendritic cells,
macrophages, and B cells
o Strategically located in places
where antigens are likely to
penetrate the innate defenses
CELL-MEDIATED IMMUNITY
and enter the body (epidermis and
- Begins with activation of a small number of
dermis of the skin; mucous
T cells by a specific antigen
membranes that line the respiratory,
- T cell undergoes clonal selection, once it
gastrointestinal, urinary, and
has been activated
reproductive tracts; and lymph
- The result of clonal selection is the
nodes)
formation of a clone of cells that can
recognize the same antigen as the original
Steps in the processing and presenting of
lymphocyte
an exogenous antigen by an antigen-
- Some of the cells of a T cell clone become
presenting cell:
effector cells, while others become memory
1. Ingestion of the antigen
cells
2. Digestion of antigen into peptide
- The effector cells of a T cell clone carry out
fragments
immune responses that ultimately result in
3. Synthesis of MHC-II molecules
elimination of the intruder
4. Packaging of MHC-II molecules
5. Fusion of vesicles
Activation of T Cells
6. Binding of peptide fragments to
 T-cell receptors (TCRs) – antigen receptors
MHC-II molecules
on the surface of T cells that recognize and
7. Insertion of antigen-MHC-II
bind to specific foreign antigen fragments
complexes into the plasma
that are presented in antigen-MHC
membrane
complexes
Processing of Endogenous Antigens  Costimulation – a T cell becomes activated
only if it binds to the foreign antigen and at
 Endogenous Antigens – foreign antigens
the same time receives a second signal
that are present inside body cells
 Anergy – prolonged state of inactivity
Steps in the processing and presenting of
an endogenous antigen by an infected body Activation and Clonal Selection of Helper T
cell: Cells
1. Digestion of antigen into peptide  Helper T cells/CD4 T cells – most T cells
fragments that display CD4
2. Synthesis of MHC-I molecules  Active Helper T cells – start secreting a
3. Binding of peptide fragments to variety of cytokines hours after
MHC-I molecules costimulation
4. Packaging of antigen-MHC-I  Memory Helper T cell – not active cells
molecules
 Activation and Clonal Selection of Cytotoxic
T Cells
 Cytotoxic T cells/CD8 T cells – most T cells
that display CD8
 Active Cytotoxic T cells – attack other body
cells that have been infected with the
antigen
 Memory Cytotoxic T cells – do not attack
infected body cells
Elimination of Invaders
 Cytotoxic T cells are the soldiers that march
forth to do battle with foreign invaders in
cell-mediated immune responses
o Recognize and attach to target cells
o Deliver a “lethal hit” that kills the
target cells
 Cytotoxic T cells have receptors specific for
a particular microbe and thus kill only target
body cells infected with one particular type
of microbe; natural killer cells can destroy a
wide variety of microbe-infected body cells
2 Principal Mechanisms of Cytotoxic T cells for
killing infected target cells:
1. Cytotoxic T cells recognize and bind to
infected target cells that have microbial
antigens displayed on their surface
o Granzymes – protein-digesting
enzymes that trigger apoptosis
2. Cytotoxic T cells bind to infected body
cells and release two proteins from their
granules: perforin and granulysin
o Perforin – inserts into the plasma
membrane of the target cell and
creates channels in the membrane
o Granulysin – enters through the
channels and destroys the microbes
by creating holes in their plasma
membranes
o Lymphotoxin – a toxic molecule that
may destroy target cells; activates
enzyme in the target cell
Immunological Surveillance
 Tumor Antigens – novel cell surface
components displayed in a cancerous cell
 Immunological Surveillance – carried out
by cytotoxic T cells, macrophages, and
natural killer cells
o Most effective in eliminating tumor
cells due to cancer-causing
viruses
ANTIBODY-MEDIATED IMMUNITY
Activation and Clonal Selection of B Cells
 B-cell receptors (BCRs) – where antigen
binds during activation of a B cell
o Chemically similar to the antibodies
that eventually are secreted by
plasma cells
 Plasma cells – secrete antibodies
o A few days after exposure to an
antigen, a plasma cell secretes
hundreds of millions of antibodies
each day for about 4 or 5 days, until
the plasma cell dies
 Memory B cells – do not secrete antibodies
o They can quickly proliferate and
differentiate into more plasma cells
and more memory B cells should the
same antigen reappear at a future
time
Antibodies
 Antibody (Ab) – can combine specifically
with the epitope on the antigen that
triggered its production
Antibody Structure
 Immunoglobulins (Igs) – antibodies belong
to a group of glycoproteins called globulins;
another term for antibodies
 Heavy (H) chains – two of the chains that
are identical to each other; each consists of
about 450 amino acids
 Light (L) chains – the other two polypeptide
chains, also identical to each other; each
consists of about 220 amino acids
 Hinge region – a part of the antibody that
displays considerable flexibility
 Stem region – formed by the parts of the
two heavy chains, beyond the hinge region
 Variable (V) regions – the tips of the H and
L chains, constitute the antigen-binding site
 o Part of the antibody that recognizes
and attaches specifically to a
particular antigen
 Constant (C) region – the remainder of each
H and L chain, nearly the same in all
antibodies of the same class and is
responsible for the type of antigen-antibody
reaction that occurs
C3 can be activated in three ways:
1. Classical Pathway – starts when
antibodies bind to antigens
(microbes)
2. Alternative Pathway – does not
involve antibodies; initiated by an
interaction between lipid-

Antibody Actions
 Neutralizing antigen – reaction of antibody
with antigen blocks or neutralizes some
bacterial toxins and prevents attachment of
some viruses to body cells
 Immobilizing bacteria – the antigen-antibody
reaction may cause the bacteria to lose their
motility
 Agglutinating and precipitating antigen – the
antigen-antibody reaction may cross-link
pathogens to one another, causing carbohydrate complexes on the
agglutination (clumping together) surface of microbes and
 Activating complement – antigen-antibody complement protein factors B, D,
complexes initiate the classical pathway of and P
the complement system 3. Lectin Pathway – macrophages
 Enhancing phagocytosis – stem region of
an antibody acts as a flag that attracts
phagocytes once antigens have bound to
the
 antibody’s variable region

Role of the Complement System in

Immunity
 Complement System – defensive system
made up of over 30 proteins produced by
the liver and found circulating in blood
plasma and within tissues throughout the
body
 Most complement proteins are designated
that digest microbes release
by an uppercase letter C, numbered C1
chemicals that cause the liver to
through C9, named for the order in which
produce proteins called lectins
they were discovered
 The C1-C9 complement proteins are
Immunological Memory
inactive and become activated only when
- Due to the presence of long-lasting
split by enzymes into active fragments,
antibodies and very long-lived lymphocytes
which are indicated by lowercase letters a
that arise during clonal selection of antigen-
and b
stimulated B cells and T cells
 Opsonization – C3b enhances phagocytosis
 Antibody Titer – the amount of antibody in
by coating a microbe
serum
 Membrane Attack Complex – cylinder-
 Primary Response – a slow rise in the
shaped, which inserts into the plasma
antibody titer occurs, first IgM and then IgG,
membrane
followed by a gradual decline in antibody
 Cytolysis – bursting of the microbial cells titer
due to the inflow of extracellular fluid
 Secondary Response – accelerated, more
through the channels
intense response
SELF-RECOGNITION AND SELF-TOLERANCE

2 Traits that T cells must have to function properly:

1. Self-Recognition – they must be able to
recognize your own major histocompatibility
complex (MHC) proteins
2. Self-Tolerance – they must lack reactivity to
peptide fragments from your own proteins

 Positive Selection – pre-T cells in the

thymus develop the capability for self-
recognition
 Negative Selection – weeding-out process
in which the T cells interact with dendritic
cells located at the junction of the cortex
and medulla in the thymus
 Deletion – self-reactive T cells undergo
apoptosis and die
 Anergy – they remain alive but are
unresponsive to antigenic stimulation