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The Lymphatic System & Body Defenses
Chapter 12
1
Outline
•
Functions of the Lymphatic System
–
•
•
Primary & Secondary Lymphatic Organs
First Line of Defense- Innate Immunity
–
•
Barriers to Entry
Second Line of Defense- Innate Immunity
–
•
Definitions
Nonspecific Defenses
Third Line of Defense- Adaptive Immunity
–
Specific Defenses: The Immune Response


•
B-lymphocytes: Antibody-Mediated Immunity
T-lymphocytes: Cell-Mediated Immunity
Active vs. Passive Immunity
2
Functions of The Lymphatic System
Drains excess interstitial fluid (lymph) and puts it
back into the blood
1.
–
Formation of lymph

–
Flow of lymph


Skeletal muscle pump
Respiratory pump
Transports dietary lipids
2.
–
3.
Refer back to capillary exchange in Chap. 21
Lacteals in GI tract
Carries out immune responses
3
Lymphatic System
4
Figure 12.3 Distribution of lymphatic vessels and lymph nodes.
Regional
lymph nodes:
Entrance of right
lymphatic duct into right
subclavian vein
Cervical
nodes
Axillary
nodes
Internal jugular vein
Thoracic duct
entry into left
subclavian vein
Thoracic duct
Aorta
Spleen
Inguinal
nodes
Cisterna chyli (receives
lymph drainage from
digestive organs)
Lymphatics
KEY:
Drained by the right lymphatic duct
Drained by the thoracic duct
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Figure 12.2a Special structural features of lymphatic capillaries.
Tissue fluid
Tissue cell
Lymphatic
capillary
Blood
capillaries
(a)
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Arteriole
Venule
Figure 12.2b Special structural features of lymphatic capillaries.
Fibroblast in loose
connective tissue
Endothelial
cell
(b)
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Flaplike
minivalve
Filaments
anchored to
connective
tissue
Figure 12.4 Structure of a lymph node.
Lymph Node
Afferent
lymphatic
vessels
Germinal
center in
follicle
Capsule
Subcapsular
sinus
Trabecula
Afferent
lymphatic
vessels
Cortex
Follicle
Efferent
lymphatic
vessels
Hilum
Medullary sinus
Medullary cord
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Functions of The Lymphatic System (Cont.)
3.
Carries out immune responses
– function to defend the body against all attackers
including bacteria, viruses, and cancer cells.
– protects “self” from “non-self”
– Immunity is the ability to react to antigens so
that the body remains free of disease
– Disease is a state of homeostatic imbalance
– Disease can be due to infection, failure of the
immune system, genetic defects, or
autoimmune issues
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Functions of The Immune System (Cont.)
•
Definitions
– Antigen: Piece or part of a foreign attacker
such as a piece of protein or cell
membrane.
– Antibody: Special protein produced by the
immune system to bind specifically to
antigens. Antibody shape fits like a glove
to the surface shape of the antigen.
Helps to remove attacker from the body.
10
Primary Lymphatic Organs
•
•
•
•
Lymphatic system is network of organs, tissues,
cells, and cell products.
Principal cells are the lymphocytes, aided and
assisted by neutrophils, macrophages.
Two types: B lymphocytes and T lymphocytes
Primary Lymphatic organs contain large numbers
of lymphocytes.
– Red Bone Marrow: Source of B & T
lymphocytes; B lymphocytes mature here; move
to lymph nodes
– Thymus Gland: T lymphocytes move here from
bone marrow; mature here; move to lymph
nodes.
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12
Lymphatic Organs
13
Thyroid gland
Trachea
Right common
carotid artery
Brachiocephalic veins
Superior vena cava
Right lung
Thymus
Left lung
Fibrous
pericardium
Diaphragm
(a) Thymus of adolescent
Secondary Lymphatic Organs
•
Secondary Lymphatic Organs: Secondary
lymphatic organs are places where lymphocytes
encounter and bind with antigens.
– Spleen- largest single mass of lymphatic tissuefor immune monitoring of the blood
– Lymph nodes
– Lymphatic Nodules- not surround by capsule
MALT: Mucosa-associated lymphatic tissue
 Tonsils: Lymphatic tissue at back of mouth
 Adenoids: Lymphatic tissue at back of nasal
passages
 Peyer’s patches: Lymphatic tissue in intestines

15
Figure 12.4 Structure of a lymph node.
Lymph Node
Afferent
lymphatic
vessels
Germinal
center in
follicle
Capsule
Subcapsular
sinus
Trabecula
Afferent
lymphatic
vessels
Cortex
Follicle
Efferent
lymphatic
vessels
Hilum
Medullary sinus
Medullary cord
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Lymphatic System
17
Figure 12.6 An overview of the body’s defenses.
The Immune System
Innate (nonspecific) defense mechanisms
Adaptive (specific) defense
mechanisms
First line of defense
Second line of defense
Third line of defense
• Skin
• Mucous membranes
• Secretions of skin
and mucous
membranes
• Phagocytic cells
• Natural killer cells
• Antimicrobial proteins
• The inflammatory
response
• Lymphocytes
• Antibodies
• Macrophages and other
antigen-presenting cells
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•
The First Line of Defense
Barriers to Entry
–
Skin



–
Tears, Saliva, Earwax


–
Tears, saliva contain lysozyme
Earwax; very sticky traps microbes
Mucous Membranes

–
Layers of dead keratinized cells
Constant sloughing of cells
Sweat glands; low pH, dermicidin
Mucus moved by ciliated cells, e.g. respiratory tract
Stomach

Acid in stomach; pH 1-2.
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•
The First Line of Defense (Cont.)
Barriers to Entry (Cont.)
–
Vaginal Acids

–
Vomiting, Urination, Defecation



–
Vaginal secretions are acidic, prevent growth
Remove bacteria & toxins from stomach
Constant flushing of urinary tract
Diarrhea-increase outflow of pathogen
Resident Bacteria (vagina, intestinal tract)


Out compete pathogens for nutrients
Secrete compounds to inhibit growth of pathogens
20
The Second Line of Defense: Nonspecific Defenses
•
Phagocytes Engulf Foreign Cells
–
Phagocytic cells: white blood cells that surround
& engulf invading bacteria
 Neutrophils, monocytes, eosinophils

Monocytes become macrophages in tissues
21
Figure 12.9b Phagocytosis by a macrophage.
1 Phagocyte
adheres to
pathogens.
Phagocytosis
2 Phagocyte
Phagosome engulfs the
(phagocytic particles, forming
a phagosome.
vesicle)
Lysosome
Acid
hydrolase
enzymes
(b) Events of phagocytosis
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3 Lysosome
fuses with the
phagocytic
vesicle, forming a
phagolysosome.
4 Lysosomal
enzymes digest
the pathogens or
debris, leaving a
residual body.
5 Exocytosis
of the vesicle
removes
indigestible and
residual material.
The Second Line of Defense: Nonspecific Defenses
•
Natural Killer Cells
–
A type of lymphocyte that attacks tumor cells &
virus-infected cells
23
The Second Line of Defense: Nonspecific Defenses
•
Inflammatory Reaction.
– Tissue damage causes tissue cells and
mast cells to release chemical mediators.
 Histamine and kinins.
 Capillaries dilate and become more
permeable.
 Skin reddens and becomes warm.
 Proteins and fluids escape from
capillaries.
 Swelling.
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25
The Second Line of Defense: Nonspecific Defenses
•
Inflammatory Reaction.
 Swelling stimulates free nerve
endings, causing the sensation of
pain.
– Neutrophils and monocytes migrate to site
of injury; engulf pathogens.
– Monocytes become macrophages; engulf
pathogens; spit out antigens.
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27
The Second Line of Defense: Nonspecific Defenses
•
Inflammatory Reaction Movies
1. Rolling Leukocytes
2. Lymphocyte Homing
3. Chemotaxis of Neutrophils
4. Neutrophil Chase
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The Second Line of Defense: Nonspecific Defenses
•
Complement system: Group of proteins in
blood that help to destroy pathogens.
– Complement proteins are activated when
antibodies coat pathogens in the body.
– They form membrane attack complex that
knocks holes in the membrane of
pathogen.
– Complement coated pathogens also
attract neutrophils and macrophages.
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1
2
Activated complement
proteins form complexes of
proteins that create holes
in the bacterial cell wall.
3
Water and salts diffuse
into the bacterium
through the holes.
The bacterium swells
and eventually bursts.
Water
and
salts
Complement
proteins
Bacterium
Cell wall of
bacteria
Photomicrograph of
an intact bacterium
A bacterium after lysis by activated
complement proteins
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Figure 9.8
The Second Line of Defense: Nonspecific Defenses
•
Interferons
–
–
Viral infected cells secrete proteins called
interferons
Interferons stimulate neighboring non-infected
cells to produce proteins that interfere with
synthesis of viral proteins
31
The actions of alpha and beta interferons
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Figure 15.7
The Second Line of Defense: Nonspecific Defenses
•
Fever Response
–
–
–
Pyrogens released (from macrophages)
increase basal temperature
May aid in preventing some bacterial growth
Stimulates phagocytosis & repair
33
Table 9.1
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The Third Line of Defense: Specific Defenses-The
Immune Response
•
Specific defenses respond to antigens.
– Lymphocytes recognize an antigen due to
antigen receptors whose shape allows
them to combine with a specific antigen.
 Immunity is primarily the result of the
action of B lymphocytes and T
lymphocytes.
35
The Third Line of Defense: Specific Defenses-The
Immune Response (Cont.)
–
B-lymphocytes and antibody-mediated
immunity.
 Main end products: Antibodies and
memory B-lymphocytes.
 Antibodies bind to pathogens; they help
complement to work; help neutrophils
and macrophages find and engulf them.
36
37
Figure 12.12 Clonal selection of a B cell.
Primary response
(initial encounter
with antigen)
Activated B
cells
Proliferation
to form a
clone
Plasma
cells
Antigen
Antigen binding
to a receptor on a
specific B cell
(B cells with
non-complementary
receptors remain
inactive)
Memory
B cell
Secreted
antibody
molecules
Secondary response
(can be years later)
Clone of cells
identical to
ancestral cells
Subsequent
challenge
by same
antigen results
in more rapid
response
Plasma
cells
Secreted
antibody
molecules
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Memory
B cells
Structure of most common antibody: IgG
39
Six functions of antibodies
(f) Complement Activation
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Figure 16.6
41
The Third Line of Defense: Specific Defenses-The
Immune Response (Cont.)
•
B-lymphocyte Review
– Provide antibody-mediated immunity against
bacteria
– Produced and mature in bone marrow.
– Reside in spleen and lymph nodes
– Directly recognize antigen and then undergo
clonal selection
– Clonal expansion produces antibody-secreting
plasma cells and memory B cells
– Antibodies circulate in blood and lymph
42
The Third Line of Defense: Specific Defenses-The
Immune Response (Cont.)
–
T-lymphocytes and cell-mediated
immunity.
 Two Types of T-cells:
 CD4 T-cells
 become Helper T-cells & Memory
T-cells
 CD8 T-cells
 become Cytotoxic T-cells
43
T Cells: Cell-Mediated Immunity
• Helper T-cells
– Secrete cytokines, which stimulate other
immune system cells
– Play a key role in directing the immune
response
– Are target of HIV infection
• Cytotoxic T-cells
– Directly attack and destroy abnormal (tumor
or viral-infected) cells and foreign cells
• Memory T-cells
– Reactivate during later exposures
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T Cells: Cell-Mediated Immunity
• T-cells must be presented with antigen
in conjunction with Major
Histocompatibility Complex (MHC)
protein by antigen-presenting cells
(APCs)
• APCs include
– Macrophages
– B cells
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AntigenPresenting
Cell (APC):
Macrophage
Major
histocompatibility Antigen
complex protein
Pathogen
(MHC)
1
The macrophage engulfs
a pathogen.
Lysosome
Vesicle with
MHC molecules
2
Lysosomes partially digest
the pathogen.
3
A vesicle containing MHC
molecules binds to the
digestive vesicle.
4
The MHC molecules and a
fragment of the antigen form
an antigen-MHC complex.
5
Antigen-MHC
complex
The antigen-MHC complex
is displayed on the surface
of the cell when the vesicle
fuses with the cell membrane
and releases its digestive
products.
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Figure 9.12
Figure 12.17 T cell activation and interactions with other cells of the immune response.
“Presented”
antigen
Antigen
T cell antigen
receptor
Cytotoxic
(killer)
T cell
Cell-mediated
immunity
(attack on
infected cells)
Helper
T cell
Dendritic
cell
Cytokines
Antigen
processing
Selfprotein
Cytokines
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B cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
MHC molecule
Antigen-presenting cell (APC)
CD4 T-cell:
Activation to
Helper T-cell
Antigen
fragment
CD4 receptor
Inactive
helper-T cell
Activation
Memory
T cells
Clonal
expansion
These Helper
T-cells help
both B-cell &
T-cell
responses
Cytokine
production
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Figure 9.13
MHC molecule
Antigen-presenting cell (APC)
CD8 T-cell:
Activation to
Cytotoxic T-cell
Antigen
fragment
Virus infected
CD8 receptor
Inactive
cytotoxic T cell
Activation
Memory
T cells
Clonal
expansion
Attack on
target cell
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Figure 9.14
Cytotoxic T-cell
killing a target
cell
Cytotoxic T cell
Target cell
a) Cytotoxic T cells (blue) attaching
to a target cell (pink).
Cytotoxic T cell
Vesicle
Perforin
Granzyme
Cytotoxic T
cell membrane
Intercellular
space
3
2
1
Intact target
cell membrane
Perforin pore
partially assembled
Completed pore;
granzyme passing
through
Target cell
b) How cytotoxic T cells kill a target cell.
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Figure 9.15
The Third Line of Defense: Specific Defenses-The
Immune Response (Cont.)
•
T-lymphocyte Review
–
–
–
–
–
Provide cell-mediated immunity
Produced in bone marrow, mature in thymus
Antigen must be presented in groove of MHC
molecule by an APC
Cytotoxic T cells destroy virus infected or
cancer cells- circulate in blood and lymph-roam
throughout the body
Helper T cells secrete cytokines that control the
immune response
51
Figure 12.19 A summary of the adaptive immune responses.
HUMORAL (ANTIBODY-MEDIATED) ADAPTIVE
IMMUNE RESPONSE
CELLULAR (CELL-MEDIATED) ADAPTIVE
IMMUNE RESPONSE
Antigen (1st exposure)
Engulfed by
Macrophage
Free antigens
directly activate
Antigens displayed by
infected cells activate
Becomes
Antigenpresenting
cell
Stimulates
Helper Stimulates
Stimulates
B cell
Cytotoxic
T cell
T cell
Memory
T cell
Gives rise to
Stimulates
Stimulates
Stimulates
Antigen (2nd exposure)
Stimulates
Gives rise to
Active
cytotoxic
T cells
Plasma
cells
Secrete
Memory
B cells
Memory
T cells
Antibodies
Defend against extracellular pathogens by
binding to antigens and making them easier
targets for phagocytes and complement.
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Defend against intracellular pathogens and
cancer by binding to and lysing the infected
cells or cancer cells.
Immune Memory Creates Immunity
• Primary immune response
– Occurs on first exposure to antigen
– Characteristics
• Lag time of 3–6 days for antibody production
• Peak at 10–12 days
• Secondary immune response
– Occurs on second and subsequent exposure
to antigen
– Characteristics
• Lag time in hours
• Peak in days
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Antibody concentration (units/ml)
Primary immune
response
Secondary immune
response
100
10
1
0.1
0
7
14
1st exposure
21
28
0
7
14
21
28
35
42
2nd exposure
Time (days after exposure)
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Figure 9.16
Active Immunity
•
Active Immunity
– Immunization involves use of vaccines
 Contain an antigen to which the
immune system responds
 Primary response
– Secondary response
 Dependent upon the presence of
memory B and T cells capable of
responding to lower antigen doses
55
Passive Immunity
•
Passive immunity occurs when an individual
is given prepared antibodies
– Temporary
 Could be life savings
 But no memory cells
56
Inappropriate Immune System Activity
Causes Problems: Allergies
• Allergies are hypersensitivity reactions
– Inappropriate response to an allergen
– Allergen: any substance (antigen) that
causes an allergic reaction (not a pathogen,
but the body reacts as though it is a
pathogen)
– Examples of allergens
•
•
•
•
Pollen
Bee venom
Foods (nuts, seafood)
Oil from poison ivy plant
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Allergen
B cell
1
Exposure to an allergen
causes B cells to produce
specific IgE antibodies.
IgE antibodies
Binding sites
for IgE
Mast
cell or
basophil
2
The IgE antibodies bind to
mast cells and basophils,
sensitizing them to future
exposures to the same
allergen.
Vesicles
containing
histamine
Allergens
specific
for IgE
3
The next exposure to
the allergen causes
mast cells and basophils
to release histamine.
4
Histamine causes a
localized or systemic
inflammatory response.
Histamine
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Figure 9.18
Inappropriate Immune System Activity
Causes Problems: Allergies
• Excessive inflammatory response
mediated by
– IgE
– Basophils and mast cells
– Histamine
• Reactions may be localized or systemic
– Localized: affect only the area exposed
– Systemic: affect several organ systems
• Anaphylactic shock: severe life-threatening
systemic reaction (difficulty breathing, circulatory
collapse, drop in blood pressure)
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Inappropriate Immune System Activity
Causes Problems: Allergies
• Treatment of allergies
– Antihistamines – treatment of mild to
moderate reactions
– Epinephrine injection – treatment of
anaphylactic shock
– Allergy shots
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Need to Know
1.
Functions of Immune System
A.
Defense against “non-self”.
1.
Bacteria
2.
Viruses
3.
Cancer Cells
B.
Generate Immunity
1.
To remain free of disease.
C.
Definitions
1.
Antigen: Part or piece of foreign attacker,
usually a piece of protein or cell membrane
2.
Antibody: Special protein made to fit
antigen like a glove
61
Need to Know (Cont.)
First Line of Defense
2.
A.
B.
C.
D.
E.
F.
G.
Skin
Tears- Lysozyme
Mucus
Stomach acid
Vaginal acids
Vomiting, urination, defecation
Resident bacteria
Second Line of Defense
3.
A.
B.
C.
D.
E.
F.
Phagocytes
Natural killer cells
Inflammation
Complement
Interferons
Fever
62
Need to Know (Cont.)
4.
Third Line of Defense: Specific Defenses
B-cells- Antibody Mediated Immunity
A.
Six functions of antibodies
1.
T-cells- Cell Mediated Immunity
B.
CD4 T-cell
1.


CD8 T-cell
2.

3.
5.
Helper T-cell
Memory T-cell
Cytotoxic T-cell
T-cells need antigen presented by APC in MHC protein
to get response
Immune Memory
A.
Primary vs. Secondary Response
63
Need to Know (Cont.)
6.
Immunization
A.
7.
Active vs. Passive Immunity
Primary & Secondary Immune Organs
A.
B.
Primary
1.
Red Bone Marrow: both B & T-lymphocytes
2.
Thymus Gland: T-lymphocytes mature here
Secondary: Lymphatic tissue throughout the body
1.
Spleen
2.
Lymph nodes
3.
Tonsils, Adenoids
4.
Peyer’s Patches
64
Need to Know (Cont.)
8.
Allergy Response
A.
Inappropriate immune system activity
1.
Mediated by IgE
2.
Involves mast and basophil cells and
histamine
65