Download Lymph Transport and Immunity

Lymph Transport and Immunity
Outline
• The Lymphatic System
– Lymph Vessels
– Lymphoid Organs
• Nonspecific Defenses
– Barriers
– Inflammatory Response
• Specific Defenses
– Antibodies
– T Cells
• Induced Immunity
– Active versus Passive Immunity
• Immunity Side Effects
– Allergies
– Blood Typing
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The Lymphatic System
• Consists of lymphatic vessels and the
lymphoid organs
– Three main homeostatic functions:
• Lymphatic capillaries take up and return excess
fluid to the bloodstream
• Lacteals receive lipoproteins and transport them to
the bloodstream
• Helps defend body against disease
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Lymphatic System
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The Lymphatic Organs
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Lymphatic System
• One-way system that begins with lymphatic
capillaries
– Take up fluid that has been diffused from, and
not reabsorbed by, blood capillaries
• Edema - Localized swelling due to accumulation of
tissue fluid
– Lymph flows one way
• From a capillary to ever-larger lymphatic vessels
• Finally to a lymphatic duct, which enters a subclavian
vein
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Lymphoid Organs
• Lymph Nodes - Capsule surrounding two
distinct regions, cortex and medulla
– Lymphocytes congregate in cortex when
fighting off a pathogen
– Macrophages concentrated in medulla cleanse lymph
– Lymph nodes named for their location
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Lymphoid Organs
• Tonsils
– Patches of lymphatic tissue located around
the pharynx
– First to encounter pathogens that enter via the
nose and mouth
• Spleen
– Located in upper left region of abdominal
cavity just beneath diaphragm
– Cleanses blood
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Lymphoid Organs
• Thymus Gland
– Located along trachea behind the sternum in
upper thoracic cavity
– Produces thymic hormones
• Red Bone Marrow
– Origin for all types of blood cells
– Area of maturation for most white blood cells
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Immune System
• Nonspecific Defenses
– Barriers to entry serve as mechanical barriers
• Skin
• Mucous membranes lining respiratory, digestive,
and urinary tracts
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Nonspecific Defenses
• Inflammatory Reaction
– Damaged cells and mast cells release
histamine and kinins
– Capillaries dilate and become more permeable
– Enlarged capillaries cause skin to redden
– Swollen area and kinins stimulate free nerve
endings causing pain
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Inflammatory Reaction
• Neutrophils and monocytes migrate to the
site of injury
– Neutrophils and mast cells phagocytize
pathogens
– Monocytes differentiate into macrophages
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Inflammatory Response
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Complement System
• A collection of plasma proteins
– Activated when pathogens enter the body
– Complements certain immune responses
• Interferon binds to receptors of noninfected cells
– Causes them to prepare for possible attack
– Produce substances that interfere with viral
replication
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Action of the Complement System
Against a bacterium
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Specific Defenses
• An antigen is any foreign substance that
stimulates the immune system to react
– Lymphocytes capable of recognizing antigens
– Have antigen receptors on plasma membrane
– Protein’s shape allow it to combine with a
specific antigen
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Specific Defenses
• Immunity primarily the result of
– B lymphocytes
• B cells give rise to plasma cells
• Produce antibodies
– T lymphocytes
• T cells directly attack cells that bear non-self
proteins
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T Cells
• Requirements for T cell antigen recognition:
– Antigen must be presented by an antigenpresenting cell
– Antigen is first linked to a major
histocompatibility complex (MHC) protein in
the plasma membrane
– Cytokines - signaling chemicals that stimulate
various immune cells
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Types of T Cells
• Cytotoxic T Cells
– Destroy antigen-bearing cells
– Contain Perforins
• Helper T Cells
– Regulate immunity by secreting cytokines
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Cell-mediated immune response
Humoral (antibody-mediated) immune response
Key
Antigen (1st exposure)
+
Engulfed by
Gives rise to
Antigenpresenting cell
+
Stimulates
+
+
B cell
Helper T cell
+
Cytotoxic T cell
+
Memory
Helper T cells
+
+
+
Antigen (2nd exposure)
Plasma cells
Memory B cells
+
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
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Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.
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Humoral (antibody-mediated) immune response
Key
+
Antigen (1st exposure)
Stimulates
Gives rise to
Engulfed by
Antigenpresenting cell
+
+
B cell
Helper T cell
+
Memory
Helper T cells
+
+
Antigen (2nd exposure)
Memory
B cells
Plasma cells
+
Secreted
antibodies
Defend against extracellular pathogens
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Cell-mediated immune response
Key
+
Antigen (1st exposure)
Engulfed by
Antigenpresenting cell
Stimulates
Gives rise to
+
+
Helper T cell
Cytotoxic T cell
+
Memory
Helper T cells
+
+
Antigen (2nd exposure)
+
Active
Cytotoxic T cells
Memory
Cytotoxic T cells
Defend against intracellular pathogens
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Helper T Cells: A Response to Nearly All Antigens
• A surface protein called CD4 binds the class II
MHC molecule
• This binding keeps the helper T cell joined to the
antigen-presenting cell while activation occurs
• Activated helper T cells secrete cytokines that
stimulate other lymphocytes
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Antigenpresenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytokines
+
B cell
+
+
+
Cytotoxic T cell
Cell-mediated
immunity
(attack on
infected cells)
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Cytotoxic T Cells: A Response to Infected Cells
• Cytotoxic T cells are the effector cells in cellmediated immune response
• Cytotoxic T cells make CD8, a surface protein that
greatly enhances interaction between a target cell
and a cytotoxic T cell
• Binding to a class I MHC complex on an infected
cell activates a cytotoxic T cell and makes it an
active killer
• The activated cytotoxic T cell secretes proteins
that destroy the infected target cell
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Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Peptide
antigen
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Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Pore
Peptide
antigen
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Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Dying target cell
Pore
Peptide
antigen
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Cell-mediated Immunity
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B Cells: A Response to Extracellular Pathogens
• The humoral response is characterized by
secretion of antibodies by B cells
• Activation of B cells is aided by cytokines
and antigen binding to helper T cells
• Clonal selection of B cells generates
antibody-secreting plasma cells, the effector
cells of humoral immunity
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Bacterium
Antigen-presenting cell
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
+
CD4
Cytokines
Secreted
antibody
molecules
Endoplasmic
reticulum of
plasma cell
Helper T cell
Activated
helper T cell
Clone of memory
B cells
2 µm
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Antigen-presenting cell
Bacterium
Peptide
antigen
Class II MHC
molecule
TCR
CD4
Helper T cell
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Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
+
CD4
Helper T cell
Cytokines
Activated
helper T cell
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Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
+
CD4
Helper T cell
Cytokines
Activated
helper T cell
Secreted
antibody
molecules
Clone of memory
B cells
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Fig. 43-14
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells
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Endoplasmic
reticulum of
plasma cell
2 µm
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How many antibody classes do have we?
Antibody Classes
• The five major classes of antibodies, or
immunoglobulins, differ in distribution and function
• Polyclonal antibodies are the products of many
different clones of B cells following exposure to a
microbial antigen
• Monoclonal antibodies are prepared from a single
clone of B cells grown in culture
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Immunoglobins
• IgG - Main antibody type in circulation
• IgM - Found in circulation Largest antibody
• IgA - Found in secretions
• IgD - Found on surface of immature B cells
• IgE - Found as antigen receptors on
basophils in blood and on mast cells in tissue
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Fig. 43-20
Class of Immunoglobulin (Antibody)
IgM
(pentamer)
Distribution
Function
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Promotes neutralization and crosslinking of antigens;
very effective in
complement system
activation
Most abundant Ig
class in blood;
also present in
tissue fluids
Promotes opsonization, neutralization,
and cross-linking of
antigens; less effective in activation of
complement system
than IgM
J chain
IgG
(monomer)
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
IgA
(dimer)
J chain
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
Presence in breast
milk confers
passive immunity
on nursing infant
Secretory
component
IgE
(monomer)
Present in blood
at low concentrations
Triggers release from
mast cells and
basophils of histamine and other
chemicals that cause
allergic reactions
IgD
(monomer)
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
Transmembrane
region
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Fig. 43-20a
Class of Immunoglobulin (Antibody)
IgM
(pentamer)
Distribution
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Function
Promotes neutralization and crosslinking of antigens;
very effective in
complement system
activation
J chain
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Fig. 43-20b
Class of Immunoglobulin (Antibody)
IgG
(monomer)
Distribution
Most abundant Ig
class in blood;
also present in
tissue fluids
Function
Promotes opsonization, neutralization,
and cross-linking of
antigens; less effective in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
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The Role of Antibodies in Immunity
• Neutralization occurs when a pathogen can no
longer infect a host because it is bound to an
antibody
• Opsonization occurs when antibodies bound to
antigens increase phagocytosis
• Antibodies together with proteins of the
complement system generate a membrane attack
complex and cell lysis
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Viral neutralization
Opsonization
Activation of complement system and pore formation
Bacterium
Complement proteins
Virus
Formation of
membrane
attack complex
Flow of water
and ions
Macrophage
Pore
Foreign
cell
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Fig. 43-20c
Class of Immunoglobulin (Antibody)
IgA
(dimer)
J chain
Secretory
component
Distribution
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Function
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
Presence in breast
milk confers
passive immunity
on nursing infant
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Fig. 43-20d
Class of Immunoglobulin (Antibody)
IgE
(monomer)
Distribution
Present in blood
at low concentrations
Function
Triggers release from
mast cells and
basophils of histamine and other
chemicals that cause
allergic reactions
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Fig. 43-20e
Class of Immunoglobulin (Antibody)
IgD
(monomer)
Transmembrane
region
Distribution
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Function
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
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Antibody-Mediated Immunity
• Clonal selection theory:
– The antigen selects which lymphocyte will
• Undergo clonal expansion, and
• Produce more lymphocytes
– If the same antigen enters the system again
• Memory B cells quickly divide
• Give rise to more lymphocytes capable of quickly
producing antibodies
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Structure of an Antibody
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Structure of an Antibody
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Overview of
Nonspecific and Specific Defenses
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Induced Immunity
• Active Immunity
– Immunization
• Pathogens or pathogen products treated to remove
virulence
• Dependent upon memory B cells & memory T cells
capable of responding to lower doses of antigen
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Active Immunity Due to Immunizations
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Passive Immunity
• Passive immunity
– Occurs when an individual is given prepared
antibodies (immunoglobins) to combat a
disease
• Short-lived
• Newborns are often passively immune due to
mother’s blood
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Passive Immunity
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Cytokines and Immunity
• Cytokines
– Signaling molecules produced by
lymphocytes, monocytes, or other cells
– Both interferon and interleukins have been
used as immunotherapeutic drugs
– Enhance the ability of the individual’s T cells
(and B cells) to fight cancer
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Production of Monoclonal Antibodies
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Immunity Side Effects
• Allergies
– Hypersensitivities to substances that
ordinarily would not harm the body
• Immediate Response
– IgE antibodies
• Delayed Response
– Memory T cells
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Immunity Side Effects
• Blood Type Reactions
– ABO blood typing
• Two self antigens - A and B
• If same antigen and its antibody are present in the
blood, agglutination occurs
– Rh blood typing
• People that are Rh+ have Rh factor
• People that are Rh- do not have Rh factor
• Rh- individuals may produce antibodies to Rh
factor if exposed
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Blood Transfusions
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Hemolytic Disease of the Newborn
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Immunity Side Effects
• Tissue Rejection
– Antibodies and cytotoxic T cells bring about
destruction of foreign tissues in the body
– Immune system is correctly distinguishing
between self and nonself
• Autoimmune Diseases
– Cytotoxic T cells or antibodies mistakenly
attack the body’s own cells
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Review
• The Lymphatic System
– Lymph Vessels
– Lymphoid Organs
• Nonspecific Defenses
– Barriers
– Inflammatory Response
• Specific Defenses
– Antibodies
– T Cells
• Induced Immunity
– Active versus Passive Immunity
• Immunity Side Effects
– Allergies
– Blood Typing
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