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Biology

Sylvia S. Mader
Michael Windelspecht

Topic 7 (Chp 33)


The Lymphatic and Immune
Systems

Copyright McGraw-Hill Education. Permission required for reproduction or display.

Outline

Learning Outcomes

https://www.youtube.com/watch?v=X4Wn0j3eJrA

Foods and Anaphylactic Shock


Seemingly harmless items or foods
may pose a threat to some people.
Upon contact with these items,
individuals may develop a lifethreatening condition known as
anaphylactic shock, which if not
treated, can result in loss of
consciousness and even death.
These strong allergic reactions
illustrate the power of the
immune system, harmful in
some, but not most cases.
Our immune system protects us
against viruses, bacteria, fungi,
parasites, and environmental toxins.

an extreme, often life-threatening


allergic reaction to an antigen to which
the body has become hypersensitive.

Battle of the Armies

Soldiers & Armies : WBC

Types of Immunity

Terms in Lymphatic System

Types of Immunity
Innate Immunity

Adaptive Immunity

Innate immunity
Recognizes microbial invaders quickly, but shows no signs of an
increased response upon repeated exposure
Adaptive immunity
Results in the production of receptors on surface of white blood
cells that bind to a foreign antigen
Stimulates lymphocytes to increase in number, resulting in
an increased response to specific antigens and
immunological memory
Originally developed in an ancestor that gave rise to the
jawed vertebrates
Precise mechanism causing adaptive immunity in
ancestor not known
Likely involved insertion of transposon or jumping gene
into a gene coding for an antigen receptor similar to
receptor for PAMPs
Gene rearrangement is involved
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Lymphatic System
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Tonsils: aggregates of lymphoid tissue that respond to pathogens


in the pharynx
Right lymphatic duct:
empties lymph into the
right subclavian vein
Right subclavian vein:
transports blood away from the
right arm and the right ventral
chest wall toward the h eart

Left subclavian vein: transports blood away from the left arm and
the left ventral chest wall toward the heart
Red bone marrow: site for the origin of all types of blood cells
Thymus: lymphoid organ where T cells mature

Axillary lymph nodes:


located in the underarm region
Thoracic duct: empties
lymph into the left
subclavian vein

Spleen: resident T cells and B cells respond to the presence of


antigen in blood

tissue
fluid
lymphatic
capillary
Inguinal lymph nodes:
located in the groin region

tissue cell
blood
capillary
valve
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Lymphatic System - Functions

The Lymphatic System


Lymphatic Vessels

Lymphatic Organs

Lymphatic Vessels
One-way system that begins with lymphatic capillaries
Tiny, closed-ended vessels found throughout the body
Take up excess tissue fluid (interstitial)
Lymph fluid located within lymphatic capillaries
Lymph flows one way
From a capillary to ever-larger lymphatic
vessels
Finally to a lymphatic duct, which returns
lymph to a subclavian vein
Backflow is prevented by one-way valves
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The Lymphatic Vessels

The (Lymphoid)Lymphatic Organs


Primary Lymphatic Organ
Red bone marrow

Thymus Gland

Red Bone Marrow


Site of origin for all types of blood cells
Site of maturation for B cells
Thymus Gland
Located between the trachea and the sternum in the upper thoracic
cavity
Site of maturation for T cells
T cells migrate to thymus from red bone marrow.
T cells learn to recognize combinations of self and foreign molecules.
Mature T cells in bloodstream encounter foreign molecules or cells
and proliferate and become activated.

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The (Lymphoid)Lymphatic Organs


Secondary Lymphatic Organ
Lymph Nodes

Spleen

Lymph Nodes
The capsule surrounds two distinct regions, cortex and
medulla.
Macrophages concentrated in medulla cleanse lymph.
Macrophages present debris or pathogens to T cells in
lymph node.
B and T cells in lymph nodes help destroy pathogens.
Lymph nodes are named for their location.
Spleen
It is located in upper left side of the abdominal cavity just
posterior to the stomach.
Macrophages remove old and defective blood cells.
Red pulp filters and cleanses blood.

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The (Lymphoid)Lymphatic Organs


Patches of lymphoid tissue in the
body encounter pathogens and
antigens that enter the body by
way of mouth
Tonsils
Patches of lymphatic tissue
are located in the pharynx.
They prevent entry of
pathogens through the nose
and mouth
Peyer patches
Located in intestinal wall
Vermiform appendix
Attached to cecum
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The Lymphatic Organs

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Types of Immunity

Innate Immune Defenses

Immunity
The capability of removing or killing foreign substances,
pathogens, and cancer cells from the body.

Innate Defenses
Do not distinguish one type of threat from another
Are fully functional without previous exposure to invaders
Occur immediately or shortly after infection occurs
No immunological memory
Types of innate immune defenses:

Physical and chemical barriers to entry


Inflammatory response
Phagocytes and natural killer cells
Protective proteins such as complement and interferons
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Overview of Innate Immune Defenses


Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Innate defenses

Barriers
to entry

skin and
mucous
membranes

Protective
proteins

Phagocytes and
natural killer cells

Inflammatory
response

dendritic
cell

pathogens
antimicrobial
molecules

macrophage

cytokines
neutrophil

monocyte

complement proteins
and interferons
in plasma

natural
killer cells

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Innate Immune Defenses


1. Physical and Chemical Barriers
Skin and mucous membranes
lining the respiratory, digestive,
and urinary tracts
Cilia lining the respiratory tract
sweep mucus and particles into
the throat
Antimicrobial molecules in
secretions of oil glands, mucous
membranes, and the stomach
Lysozyme, in mucus, an
enzyme that lyses bacteria
Acidic pH of stomach kills
microbes

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Innate Immune Defenses


2. Inflammatory Response
Localized tissue response to injury
Damaged cells and mast cells release histamine which causes
capillaries to dilate and become more permeable.
Enlarged capillaries, increased blood flow cause skin to redden.
Swelling stimulates free nerve endings, causing pain.
Neutrophils and monocytes migrate to the site of injury.
Monocytes differentiate into macrophages.
Macrophages release colony-stimulating factors, stimulating
production and release of white blood cells.
Neutrophils, dendritic cells, and macrophages phagocytose
pathogens.
Acute-phase proteins, released by the liver in response to
inflammatory mediators, make it easier for phagocytes to engulf
invaders.
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Inflammatory Response
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Skin

2. Resident macrophages and dendritic


cells phagocytize pathogens and
release cytokines, which stimulate
the inflammatory response.

Tissue
mast cell

macrophage

neutrophil

cytokines

monocyte

histamine

1. Injured tissue cells and mast cells


release histamine and other chemical
mediators, which cause capillaries
to dilate and increase blood flow.

injured tissue
pathogen
dendritic
cell

blood clot
Capillary

4. Blood clotting walls off


capillary and prevents
blood loss.

3. Neutrophils and monocytes (become


macrophages) squeeze through the
capillary wall and phagocytize
pathogens.

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Macrophage Engulfing Bacteria


Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.

Resident macrophages and


dendritic cells phagocytize
pathogens and release
cytokines, which stimulate
the inflammatory response.

cytoplasmic
extension from
macrophage

Signals send to neutrophils

bacteria
SEM 1,075
Dennis Kunkel/Phototake

Neutrophils and monocytes


(become macrophages) squeeze
through the capillary wall and
phagocytize pathogens.
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Innate Immune Defenses

Symptom: Fever
Maintenance of an elevated body temperature
In some instances, a fever may be beneficial.
Its the bodys way of informing us that something is
wrong.
Certain bacteria or viruses may not survive as well at
higher temperatures.
Some immune mechanisms work better at higher body
temperatures.

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Innate Immune Defenses


3. Phagocytes and Natural Killer (NK) Cells
Neutrophils
Leave the bloodstream and phagocytize bacteria
Release antimicrobial peptides and bacteria-digesting enzymes
Generate free radicals which kill engulfed bacteria
Eosinophils
Phagocytic cells
Also mount an attack against parasites that are too large to be
consumed via phagocytosis
Macrophages and dendritic cells
Engulf and destroy pathogens
Stimulate T cells in lymph nodes, which initiate adaptive immune
responses
Natural killer (NK) cells
Large, granular lymphocytes
Kill virus-infected cells and cancer cells by cell-to-cell contact
Virus-infected cells, lacking a self molecule (MHC-1) may be
recognized and killed.
Numbers dont increase after stimulation, like lymphocytes.
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Innate Immune Defenses


4. Protective Proteins
Complement
A collection of plasma proteins that complement certain
immune responses
Must be activated by pathogens
Helps to destroy pathogens in three ways
Enhanced inflammation
Bind to pathogens coated with antibodies to ensure
phagocytosis
Form a membrane attack complex that produces holes
in the surface of some bacteria and viruses
Fluids entering bacterial cell or virus cause
bursting.

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Innate Immune Defenses


4. Protective Proteins
Interferons
Cytokines that affect the behavior of other cells
Produced by virus-infected cells
Bind to receptors of non-infected cells
Causes them to produce substances that interfere with
viral replication
Used to treat certain cancers and viral infections, such as
hepatitis C

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Action of the Complement System


Against a Bacterium
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

complement proteins

membrane
attack complex

Complement proteins
form a donutlike ring,
called a membrane
attack complex, in the
plasma membrane.

Fluid and salts enter


susceptible cells
through the membrane
attack complex.
fluids
and
salts

Lysis of the cell results


in its destruction.

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Types of Immunity

Adaptive Immune Defenses

Also known as acquired immunity


Because adaptive defenses are not inborn
Take 57 days to become activated but last for years

Involve three steps

What is ANTIGEN?
An antigen is any substance that stimulates the immune
system to react/immune system recognizes at foreign
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Adaptive Immune Defenses

Adaptive Immune Defenses

Lymphocytes
Are capable of recognizing and binding to specific antigens
Have antigen receptors on their plasma membrane
The receptor proteins shape allows it to combine with a
specific antigen.
Pathogens, cancer cells, and transplanted tissues and organs
bear antigens the immune system recognizes as nonself.

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Adaptive Immune Defenses

Adaptive immunity is primarily the result of


B cells
B-cell receptors bind directly to antigens.
B cells give rise to plasma cells.
Plasma cells produce and secrete antibodies.

T cells
T-cell receptors bind to antigens presented by antigenpresenting cells.
Helper T cells regulate specific immunity.
Cytotoxic T cells kill virus-infected cells and cancer cells.

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Adaptive Immune Defenses


Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

memory
B cell
B cell

antibody
Antibodymediated
immunity

plasma
cell

BCR
APC

antigen

TCR
memory
TH cell

Adaptive
defenses
activated
TH cell

TH cell

activated
TC cell

Cellmediated
immunity
antigen

memory
TC cell
virus-infected
cell

TC cell

TCR

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B-cell & Antibody-Mediated


Immunity
Clonal selection theory :
Lymphocytes (B cell or T cell recognizes and binds to
specific antigen)
The antigen selects which lymphocyte will
Undergo clonal expansion
Produce more lymphocytes

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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Clonal Selection
Theory as It
Applies to B Cells

B-cell
receptor
(BCR)

B cell
antigens

cytokines from T cells

Activation
1

Most of the cloned


lymphocytes become plasma
cells that produce specific
antibodies.
Some of the cloned
lymphocytes become
memory B cells.
If the same antigen
enters the system again,
memory B cells quickly
divide and give rise to
more lymphocytes
capable of quickly
producing antibodies.

Clonal expansion
3
2
antibody

Memory B cells
Plasma cells

Apoptosis
Apoptosis

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B-cell Activation

Structure of Antibodies

Antibodies (immunoglobulins)
Consist of two heavy and two light polypeptide chains in a Y
shape
Both types of chains have variable and constant regions.
Neutralize pathogens by coating their antigens, preventing
them from binding to receptors on cells
Attract white blood cells that move in for the kill
Immune complexes may be engulfed by neutrophils or
macrophages or may activate the complement system.
Class is determined by the structure of the antibodys constant
region.
IgG Main type of antibody in circulation
IgA Main type secreted in milk, tears, and saliva
IgM The first antibodies produced; also indicate infection
IgE Bound to receptors on eosinophils and mast cells in
tissues
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Structure of Antibodies
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

antigen-binding
sites

antigen
V

antigen binds
to binding site
V

V
C

light
chain

C
heavy
chain
C = constant
V = variable

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Monoclonal Antibodies
Antibodies against a specific antigen
All of the same type
In vitro (outside the body in the laboratory) production of
monoclonal antibodies
B cells are removed from an animal and exposed to a
particular antigen.
The resulting plasma cells are fused with myeloma cells
(malignant plasma cells that live and divide indefinitely).
The fused cells (hybridomas) secrete the monoclonal
antibody.

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Adaptive Immune Defenses

Medical Uses for Monoclonal Antibodies


To make quick and certain diagnoses of various conditions
Used to signify pregnancy by detecting a particular hormone (hCG) in
the urine of a pregnant woman
Promise as potential drugs to help fight disease
RSV, a common virus that causes serious respiratory tract
infections in very young children, is being treated with a
monoclonal antibody drug.
Since the first therapeutic monoclonal antibody was approved by
the FDA in 1986, over 20 are now available and hundreds more are
being tested.
Adalimumab (Humira) binds to and inhibits tumor necrosis
factor and is used to treat several autoimmune diseases.

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T-Cells and Cell-Mediated


Immunity

Types of T Cells
Cytotoxic T Cells
Destroy antigen-bearing cells
Contain storage vacuoles containing perforins and
granzymes
Helper T Cells
Activate other T cells and B cells
Regulate immunity by secreting cytokines (signaling
molecules)
Memory T cells
Persist after a successful immune response
Provide protection if the same antigen is encountered again

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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Clonal Selection
Theory as It
Applies to T Cells

T-cells receptor (TCR)


recognizes antigens displayed by
antigen-presenting cells
(APCs).
Antigen is first linked to a
major histocompatibility
complex (MHC) protein in
the plasma membrane of the
APC.
After the TCR binds to the
antigen, the T cell undergoes
clonal expansion.
After the immune response has
been successful, most of the T
cells undergo apoptosis.
Some T cells remain as memory T
cells.

T-cell receptor (TCR)


TC
cell

Binding to
MHC-I + antigen
1
cytokines

Dendritic
cell

MHC-I

viral
antigen

Cytotoxic
T cell

virus-infected
cell

Activation and
clonal expansion
2

Death by
apoptosis

3
Apoptosis
4

Memory
T cell

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Cell-Mediated Immunity
cytotoxic T cell
antigen fragment
MHC-I
target cell
(virus-infected
or cancer cell)

cytotoxic
T cell

Cytotoxic T cell
vesicle

granzyme

perforin

Perforin
forms hole
in target cell.

Target cell
a.

target cell

Granzymes
enter through the
hole and cause
target cell to
undergo apoptosis.
b.

SEM 1,250X

(b): Steve Gschmeissner/Photo Researchers, Inc.


Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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Adaptive Immunity HIV Infection


The primary host for HIV is a helper T cell.
The host (helper T cell) produces viruses that go on to
destroy more helper T cells.
At first an individual is able to stay ahead of the virus by
producing enough helper T cells.
Gradually, the HIV count rises and the helper T-cell count
drops.
Affected patients become susceptible to opportunistic
infections.
Characteristic of an AIDS diagnosis

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AIDS and Opportunistic Infections

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Progression of HIV Infection


During Its Three Stages
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

107
Category A: Acute Phase

Category B: Chronic Phase

Category C: AIDS

HIV count in
blood peaks.

1000

106

900
Helper T-cell
count crashes and
then gradually
declines.

800
700

105

Person now
has AIDS.

600
500

104
HIV count in blood
rises dramatically.

400

HIV per ml Plasma

Helper T-cell Count in Blood (cells/mm3)

1100

300
103

HIV count crashes


due to immune
system activity.

200
100

helper T cell
HIV
102

1 2 months

10

11

Years Since Infection

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Cytokines as Therapeutic Agents


Cytokine
Soluble protein that acts as a signaling molecule
Cytokines called interleukins are produced by white blood cells.
Stimulate other white blood cells
Interleukins might awaken the immune system and lead to
the destruction of the cancer.
IL-2 is being used to treat some forms of melanoma
and kidney cancer.
Tumor necrosis factor (TNF) is a cytokine produced by
macrophages.
Promotes the inflammatory response
Causes the death of cancer cells
Anti-TNF monoclonal antibodies are being developed as
potential treatments for inflammatory diseases.

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Active Immunity
It occurs when an individual
produces his/her own immune
response against an antigen.
Immunization
It involves use of vaccines,
substances that contain an
antigen to which the immune
system responds.
Pathogens or pathogen products
treated to remove virulence are
introduced to the patient via a
vaccine.
It is dependent upon memory B
cells and memory T cells capable
of responding to lower doses of
antigen.
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Passive Immunity
Occurs when an individual receives another persons
antibodies (immunoglobulins) or immune cells to
combat a disease
Short-lived
Newborns are often passively immune since
antibodies have crossed the placenta from the
mothers blood.
Breast-feeding prolongs natural, passive
immunity.
May be used to prevent illness in a patient who
has
been exposed to certain infectious agents or
toxins.
Examples: Rabies, tetanus, botulism, snake
bites
Cells of the immune system may be transferred
to a patient in the case of a bone marrow
transplant.

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Immune System Disorders and


Adverse Reactions

Allergies
Hypersensitivities to substances that ordinarily would not harm the
body
Immediate allergic response
IgE antibodies
Causes release of histamine, which brings about the
symptoms of the allergy
Individuals with asthma have difficulty breathing and
wheezing.
Anaphylactic shock occurs after the allergen has entered
the bloodstream.
Life-threatening
Delayed allergic response
Memory T cells regulated by influence of cytokines
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An Allergic Reaction
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reproduction or display.

allergen

B cell
IgE
antibodies

plasma cell

histamine and other


chemicals
IgE receptor

mast cell

Damien Lovegrove/SPL/Photo Researchers, Inc.

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Autoimmune Disease
Cytotoxic T cells or antibodies mistakenly attack the bodys own cells
or molecules.
There appears to be a genetic tendency to develop autoimmune
diseases.
Immune system fails to distinguish between self and nonself
antigens.
Certain antigens of microbial pathogens can resemble host antigens
(molecular mimicry).
Examples of autoimmune diseases:
Rheumatoid arthritis (inflammation in synovial joints)
Myasthenia gravis
Systemic lupus erythematosus (lupus)

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Immune System Disorders and


Adverse Reactions

Rheumatoid Arthritis

Systemic Lupus
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Immune System Disorders and


Adverse Reactions

Transplant Rejection
Antibodies and cytotoxic T cells cause destruction of transplanted
foreign tissues in the body.
Immune system is correctly distinguishing between self and
nonself antigens.
Xenotransplantation
It is the transplantation of animal tissues and organs into
humans.
Potential way to solve human donor organ shortage
Genetic engineering makes animal organs less antigenic by
removing MHC antigens.
Tissue Engineering
Production of human organs from stem cells may eliminate
rejection problem.

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