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Chapter 22
The Lymphatic
System and
Immunity
Copyright © John Wiley & Sons, Inc. All rights reserved.
The Lymphatic System

A system consisting of lymphatic vessels through which a
clear fluid (lymph) passes

The major functions of the lymphatic system include:
• Draining interstitial fluid
• Transporting dietary lipids absorbed by the
gastrointestinal tract to the blood
• Facilitating the immune responses
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The Lymphatic System

Components of the lymphatic
system include:
• Lymphatic capillaries
• Lymphatic vessels
• Lymphatic trunks
• Lymphatic ducts
• Primary lymphatic organs
• Secondary lymphatic organs
and tissues
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Lymphatic Vessels and Fluid

Lymph is a clear to milky fluid
• Interstitial fluid – the clear fluid filtered through
capillary walls when it enters the “interstitium” (space
between cells, also called the intracellular space)
• Lymphatic fluid –interstitial fluid that enters the
lymphatic vessels. In the GI tract, lymphatic fluids also
include absorbed dietary lipids.
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Lymphatic Vessels and Fluid

The flow of lymph fluid is always from the periphery
towards the central vasculature.
• It starts as interstitial fluid.
• Then enters lymphatic
capillaries.
• It travels in lymphatic
vessels to the regional
lymph nodes…
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• Lymphatic trunks are formed by the union of the largest
lymphatic vessels

Major trunks include:
• Paired lumbar, bronchomediastinal, subclavian, and
jugular trunks
• A single intestinal trunk
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Drainage from lymph trunks thoracic
duct & right lymphatic duct
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Lymphatic Vessels and Fluid

The flow of lymph fluid continued…
• Lymph trunks drain into the Left or Right Lymphatic
Duct.
• Lymph fluid’s final destination is the bloodstream, as it
enters through the Subclavian veins.
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• Right lymphatic duct – drains
the right upper arm and the
right side of the head and thorax
• Thoracic duct – arises from the
cisterna chyli and drains the rest
of the body
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Lymphatic Vessels and Fluid

Lymphatic capillaries are slightly larger than blood
capillaries and have a unique one-way structure.
• The ends of endothelial cells overlap and permit
interstitial fluid to flow in, but not out.
• Anchoring filaments pull openings wider when
interstitial fluid accumulates.

There are specialized lymphatic capillaries called lacteals
that take up dietary lipids in the small intestine.

Chyle is the name of this “lymph with lipids”.
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Lymphatic capillaries showing blind ends and one way flow
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Lymphatic Vessels and Fluid

Lymphatic capillaries unite to form larger lymphatic
vessels which resemble veins in structure but have
thinner walls and more valves.

Lymphatic vessels pass
through lymph nodes –
encapsulated organs with
masses of B and T cells.
• Function as lymph filters
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Lymphatic Vessels and Fluid

Lymphatic fluid is moved by pressure in the interstitial
space and the milking action of skeletal muscle
contractions and respiratory movements.
• An obstruction or
malfunction of lymph
flow leads to edema
from fluid
accumulation in
interstitial spaces.
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Lymphatic Organs

Composed of a number of primary
and secondary organs and tissues
widely distributed throughout
the body - all with the purpose
of facilitating the immune
response.
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Lymphatic Organs

Facilitate the immune response

Primary lymph organs are the bone marrow and
thymus.
• Red bone marrow gives rise to B & T cells
.They become immunocompetent (capable of
mounting an immune response) in the bone
marow ( B cells) and in thymus ( T cells)

Secondary lymphatic organs are
sites where most immune responses
occur, including the spleen and
lymph nodes, lymphatic nodules, MALT
tonsils.
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Thymus
• The outer cortex is composed of a large number of
immature T cells which migrate from the bone marrow

They proliferate and begin to mature with the help of
dendritic cells (derived from monocytes) and
specialized epithelial cells ( form hormones)
• The inner medulla is composed of more mature T cells.
• T cells that leave the thymus via blood migrate to
lymph nodes, spleen, other lymphatic tissues and
populates them
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
The thymus is lcated in the
mediastinum behind the
sternum
• It is a palpable 70g
in infants, atrophies
by puberty, and is
scarcely distinguishable
from surrounding fatty
tissue by old age.
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Lymph Nodes

There are about 600 lymph nodes scattered along
lymphatic vessels (in superficial and deep groups) that
filter lymph to trap and destroy
foreign objects in lymph fluid.

Important group of regional
lymph nodes include:
• Submandibular
• Mediastinal
• Cervical
• Inguinal
• Axillary
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Lymph Node
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Lymph Nodes

Lymph fluid enters the node through afferent vessels and
is directed towards the central
medullary sinuses.

Lymph is slowly filtered - allows lymphocytes and
macrophages time to carry out protective functions

Macrophages destroy foreign substances by phagocytosis

Lymphocytes mount an immune response

Efferent vessels convey lymph, antibodies and activated T
cells out of the node at an indentation called the hilum.
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Spleen

The spleen is the body’s largest mass of lymphatic tissue.

The parenchyma of the organ consists of:
• White pulp - lymphatic tissue where lymphocytes carry
out immune function, and macrophages destroy
pathogens
• Red pulp – blood-filled venous sinuses & splenic cords
•
here platelets are stored ( one third of total produced)
•
old red blood cells are destroyed
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Spleen
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Lymphatic Nodules
MALT – mucosa-associated lymphatic tissue includes:
Peyer’s patches in ileum, tonsils, and the appendix
(digestive tract)
Lymphoid nodules in the walls of the respiratory tract, &
mucosa of genitourinary tract
MALT protects these passages that open to the exterior
Tonsils- form a ring of lymphatic tissue around the pharynx
Palatine tonsils – either side of the posterior end of the
oral cavity
Lingual tonsils – lie at the base of the tongue
Pharyngeal tonsil – posterior wall of the nasopharynx
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Immunity

Immunity is resistance to disease

There are two types of immunity innate and adaptive immunity:
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Innate Immunity

The innate immune response is present at birth. It
is non-specific. It includes:

The first line of defense -the physical and chemical
barriers of the skin and mucous membranes

The second line of defense -antimicrobial
substances, phagocytes, inflammation, natural
killer cells and fever
natural killer cells ( NK cells): kill virus infected
and tumor cells ( bind to target cells & kill by
releasing perforins and granzymes)
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Innate Immunity- Barriers

Surface barriers-- skin, mucous membranes, & their secretions
are the physical barrier to microorganisms

Protective chemicals inhibit or destroy microorganisms
• Skin acidity, lipids in sebum and dermcidin in sweat
• HCl and protein-digesting enzymes of stomach mucosae
• Lysozyme of saliva and lacrimal fluid
• Mucus

Respiratory system--mucus-coated hairs in the nose
• Cilia of upper respiratory tract sweep dust- and bacterialaden mucus from lower respiratory passages
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Innate
Immunity
- barriers
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Innate Immunity

Necessary if microorganisms invade deeper tissues:
• Phagocytes
• Natural killer (NK) cells
• Inflammatory response (macrophages, mast cells,
WBCs, and inflammatory chemicals)
• Antimicrobial proteins (interferons and complement
proteins)
• Fever
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Innate
Immunity
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Innate Immunity-Antimicrobial
substances:

Complement system
• A group of inactive proteins in plasma- when activated
promote, phagocytosis, inflammation, cause cytolysis of
microbes and enhance certain immune responses

Interferons:

Are proteins produced
by lymphocytes &
macrophages- interfere with viral replication

Interferons gamma (), interferon alpha () interferon ()
interferon
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Innate Immunity

Phagocytosis is a non-specific
process wherein neutrophils
and macrophages (from
monocytes) migrate to an
infected area. There are 5
steps:
• Chemotaxis
• Adherence to phagocyte
• Ingestion by phagocyte
• Killing & Digestion
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Innate Immunity

Inflammation is defensive response of almost all body
tissues to damage of any kind (infection, burns, cuts, etc.).
• The four characteristic signs and symptoms of
inflammation are redness, heat, pain, and swelling.
• It is a non-specific attempt to dispose of microbes and
foreign materials, dilute toxins, and prepare for healing.
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Innate Immunity

Vasodilation allows more blood to flow to the damaged
area- causes redness and heat
• Increased permeability permits entrance of plasma with
defensive proteins (antibodies and clotting factors) to site
of injury – causes local edema & swelling
• Pain results from sensitization of nerve endings by the
chemical mediators ( baradykinin, some prostagalndins)
• Chemical mediators of inflammation: include
histamine, kinins, prostaglandins (PGs), leukotrienes
(LTs), and complement.
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Innate Immunity

Emigration (movement) of phagocytes from the
blood into the interstitial space and then to site
of damage (chemotaxis)
• Neutrophils predominate in early stages but die off
quickly.
• Monocytes transform into macrophages and become
more potent phagocytes than neutrophils.

Pus is a mass of dead phagocytes and damaged tissue.
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Inflammation
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Innate Immunity

Fever is an abnormally high body temperature due to
resetting of the hypothalamic thermostat.
• Non-specific response:

speeds up body reactions

increases the effects of endogenous antimicrobials
• Inhibits growth of microbes
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Adaptive Immunity

Substances recognized as foreign that provoke
an immune response are called antigens (Ag).

Adaptive immunity describes the ability of the
body to adapt defenses against the antigens of
specific bacteria,
viruses, foreign tissues…
even toxins

Two separate overlapping arms
1.
Humoral (antibody-mediated) immunity
2.
Cellular (cell-mediated) immunity
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Adaptive Immunity

Two properties distinguish between adaptive immunity
and innate immunity:
1. Specificity for foreign molecules which act as Ag

this involves distinguishing self-molecules
(normal, not antigenic) from nonself molecules
2. Memory for previously
encountered Ag
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Cells of the Adaptive Immune System

Two types of lymphocytes
• B lymphocytes (B cells)—humoral immunity
• T lymphocytes (T cells)—cell-mediated immunity

Antigen-presenting cells (APCs)
• Engulf antigens, process them and present to T cells
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Lymphocytes

Originate in red bone marrow
• B cells mature in the red bone marrow
• T cells mature in the thymus


CD4 Tcells (helper T cells ) and CD8 Tcells ( cytotoxic T cells)
When mature, they have
• immunocompetence; they are able to recognize and bind to a
specific antigen
• self-tolerance – unresponsive to self antigens

Naive (unexposed to antigen) B and T cells are exported to lymph
nodes, spleen, and other lymphoid organs

Lymphocytes have up to a billion different types of antigen receptors
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Antigen-Presenting Cells (APCs)

Engulf antigens- present fragments of antigens to be recognized
by T cells- which get activated- release cytokines that activate
macrophages

Major types

Macrophages in connective tissues and
lymphoid organs

Dendritic cells in connective tissues and epidermis
(in tissues in contact with the external environment)
Dendritic cell
Dendritic cells internalize pathogens and enter lymphatics to
present the antigens to T cells in lymphoid organs

B lymphocytes also act as APCs
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Types of Adaptive Immunity

Cell Mediated Immunity:

T cells provide defense against processed antigens displayed on
cells ( APCs & others)

CD4 cells become helper T cells when activated
• Participate in cell mediated immune responses
• Activate CD8 cells
• helper T cells also aid antibody-mediated immunity

CD8 cells become cytotoxic T cells
• cytotoxic T cells directly attack target cells harboring foreign
antigens – (those containing intracellular pathogens and some
cancer cells).
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Types of Adaptive Immunity

Antibody-mediated immunity involves B cells that
transform into antibody making plasma cells.

Antibodies (Ab) circulate in extracellular fluids.

Works mainly against extracellular pathogens that are in
body fluids- viruses, bacteria, other foriegn antigens
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Clonal Selection

Clonal selection is the process by which a lymphocyte proliferates
and differentiates in response to a specific antigen.
• A clone is a population of identical cells, all recognizing the same
antigen as the original cell.

Lymphocytes undergo clonal selection to produce:
• Effector cells (the active helper T cells, active cytotoxic T cells, and
plasma cells)
•
participate in the initial immune response & die after the
immune response.
• Memory cells that do not participate in the initial immune
response but are able to respond to a subsequent exposure proliferating and differentiating into more effector and memory
cells.
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Antigens

Antigens are substances that can provoke an immune
response

Molecules, or parts of molecules tend to be antigenic
if they are:
• Foreign – not ourselves
• Structurally complex (proteins are usually complex
and form many of the most potent antigens)
• Large (high molecular weight)
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Antigens

Antigens can have multiple antigenic determinants called
epitopes.
• Each epitope is capable of producing
an immune response.

Entire microbes may act as an
antigen, but typically just
certain small parts (epitopes) of
a large antigen complex triggers
a response.
Antigens can have multiple
antigenic determinants called
epitopes. Each epitope is capable
of producing an immune response.
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Antigens

Complete Antigens- are immunogenic, & can
stimulate proliferation of specific lymphocytes and
antibodies

Examples: foreign protein, polysaccharides, lipids, and
nucleic acids



Incomplete Antigens or Haptens- are small molecules
not immunogenic by themselves
Become immunogenic when attached to body
proteins & then cause the immune system to mount a
harmful attack
Examples: drugs, poison ivy, detergents and cosmetics
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MHC Molecules

MHC molecules are proteins on the plasma membrane of
body cells - are coded by a group of genes called the major
histocompatibility complex (MHC).

These are the 'self antigens'- they are used as cell-markers
to “flag” self from non-self

MHC genes are diverse, and vary greatly from individual
to individual – making MHC molecules unique to an
individual

MHC molecules are antigenic to others in transfusions or
grafts
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MHC Molecules

There are two general classes:

Class I molecules (MHC-I)
• Class I MHC proteins display peptides from within
the cell (usually self-antigens), but in infected cells
fragments of foreign antigens are displayed
• Display antigen to cytotoxic T cells.

Class II molecules (MHC-II) are only found only on APCs
• Class II MHC proteins display peptides taken from
outside the cell by endocytosis (bacteria, toxins)

Display antigen to helper T cells.
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MHC Molecules

T cells only recognize antigens that are presented by the
antigen presenting cells

Antigen processing- antigens are broken down in cells into
peptide fragments and then associate with MHC molecules

Antigen presentation- antigen- MHC complex is inserted on
the plasma membrane of the body cell

If the peptide fragments is a self protein- Tcells ignore the
complex

If the peptide fragments is a foreign protein- Tcells recognize
the antigen and an immune response takes place
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MHC Molecules

Processing & presentation of endogenous Ag by an infected
body cell using MHC-1 molecules
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Processing & presentation of exogenous Ag by an
APC using MHC-1I molecules
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Cytokines

Cytokines are chemical signals from one cell that
influences another cell

They are produced by activated Tcells, antigen presenting
cells & others
• cytokines are small protein hormones that control cell
growth and differentiation:

Interferons

Interleukins

Tumor necrosis factor
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Cell- Mediated Immunity- Activation of T cells
APCs (most often a dendritic cell) migrate to lymph nodes &

other lymphoid tissues- present their antigens to T cells
T cell activation is a two-step process:

1. Antigen presented with MHC I or II proteins binds to T cell
receptor (TCR)

CD4 cells bind to antigen linked to class II MHC of APCs

CD8 cells activated by antigen linked to class I MHC on cells
2.
Co-stimulation- mostly by cytokines
•
On antigen recognition & binding clonal selection occurs- T
cells activated
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Cell- Mediated Immunity- activation of
Helper T cells

CD4 Tcells ( helper T cells) play
a central role in the adaptive
immune response

As an antigen-presenting cell
engulfs and destroys a foreign
invader, it“displays”the antigen

Processed Ag
is presented
The APC then presents the
foreign Ag to the inactive helper
T cell (CD4 cell) .
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


Cell- Mediated Immunity- activation of Helper
T cells
Once stimulated by antigen presentation,
helper T cells become activated.
Activated helper T cells produce various
cytokines by which:
• They can activate T cytotoxic cells (CD8 cells)
which directly kill foreign invaders or
• Activate macrophages or
• B cells (which make antibodies that help kill
foreign invaders).
Memory helper T cells produced
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Cell- Mediated Immunity- activation of
Cytotoxic T cells

CD8 T cells (Cytotoxic T cells) recognize foriegn antigen
bound to MHC 1 on the surface of :
• Virus-infected cells, cells with intracellular bacteria or
parasites, cancer cells (immunological surveillance),
transplanted tissue cells

Once activated- Cytotoxic T cells undergo clonal selection

Clones of active cytotoxic T cells formed

Memory cytotoxic T cells formed
Lethal hit
• Cytotoxic T cells release perforins and granzymes by
exocytosis
• target cells killed

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Activation of Cytotoxic T cells

Cytotoxic T cell recognize
antigen presented with MHC-I

Cytotoxic T cell destruction of
an infected cell by release of
perforins that cause cytolysis

Memory cytotoxic T cell
remain
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Antibody- Mediated Immunity

B-cell Activation

First encounter between B lymphocyte & an antigen -usually
occurs in the spleen or a lymph node

B-cells can be activated by direct recognition of antigen
through B-cell receptors (BCRs)

Response more intense through T-helper cell help by
cytokines

Activated B-cells undergo clonal selection to become antibody
producing plasma cells

Clone cells that do not become plasma cells become memory
cells- mount an immediate response to future exposures of the
same antigen
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Antibody- Mediated Immunity- Activation of B
cells
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Antibody structure
•Antibodies (also called
immunoglobulins or Igs) are
produced by plasma cells
•Made of 4 polypeptide chains
•The variable region (antigenbinding region) gives an antibody
its specificity.
•The stem is similar for each class
of antibody.
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Antibodies

Some of the ways antibodies are effective include:
• Neutralizing a bacterial or viral antigen or a toxin by
covering the binding sites and causing agglutination and
precipitation (making what was soluble, insoluble)
• Activating the classical
complement pathway
• Enhancing phagocytosis a process called
opsonization
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Role of the complement system in
Immunity

The complement system is a series of blood proteins (C1C9) that often work in conjunction with antibodies –

It can be activated by antibodies binding to antigens- in a
step-wise or cascading fashion.

It encourages inflammation, antigen opsonization (coating
target cell),
and target cell destruction.
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Complement system & Immunity

A membrane attack complex (MAC) forms as a result of
activation of
the complement
cascade.
• The MAC
results in
lysis of the target cell.
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Classes of Antibodies

There are 5 classes of antibodies:
• IgG

Comprises 80% of total antibody in plasma

Only class able to cross the placenta

Provides long-term immunity

Activates complement cascade
• IgM

It is a great activator of complement, but
has a short-lived response.

It is the first antibody to appear in an
immune response
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Classes of Antibodies
• IgA (secretory IgA)

prevalent in body secretions like sweat, tears, saliva,
breast milk and gastrointestinal fluids
• IgE

Active in some allergies and parasitic infections

Binds to mast cells and basophils & causes them to
release histamine
• IgD
•
Attached to the surface of B cells, functions as a B cell
receptor
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Immunologic Memory

Thousands of memory cells exist after initial encounter with an
antigen - this is called Immunological Memory.

With the next exposure to the same antigen, memory cells ( T
cells, B cells) can proliferate and differentiate within hours.

Production of antibodies after first antigen exposure ( primary
response) and after a subsequent antigen exposure ( secondary
response) can be measured by antibody titers
• serum antibody titers are much higher and much faster on
the second response
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Immunologic Memory

Primary immune response- occurs on the first exposure to
a specific antigen
• Lag period: three to six days
• Peak levels reached in 10 days

Secondary immune response- occurs on
re-exposure to the same antigen
• Sensitized memory cells respond within hours
• Antibody levels peak in two to three days at much
higher levels
• Antibody level can remain high for weeks to months
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Ways to Acquire Immunity
• Active Immunity follows antigen recognition by B cells & T
cells
•
Active immunity gives long-term protection because
immunological memory occurs
•
E.g. -body’s response to make antibody after exposure to a
pathogen (antigen).
• In Passive Immunity, the body simply receives antibodies
that have been preformed.

Because immunological memory does not occur protection is immediate but for short period
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Ways to Acquire Immunity
• Natural active – contracting hepatitis A and production of antihepatitis A antibodies
• Natural passive - a baby receives antibodies from its mother
through the placenta and breast milk.
• Artificial active - a person receives a vaccine of an attenuated
(changed/weakened) pathogen that stimulates the body to form
an antibody
• examples: vaccines for measles, mumps, rubella, tetanus,
hepatitis B
• Artificial passive – an injection of prepared antibody- examples:
anti snake venom, anti tetanus toxin
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