Download Ch15AdaptiveImmuneF13

Chapter 15: The Adaptive
Immune Response
General Characteristics of the
Adaptive Immune Response
• Involves specialized white blood cells
known as lymphocytes
• Response is highly specific (molecular
specificity)
• Response generates memory
• Can discriminate between self and non-self
(tolerance)
BodyImmune cells are born
circulatory in bone marrow and
system
thymus gland
Cells circulate
looking for the
invader labeled
with antibodies
NKcell
Antibody on
microbe
Cells sample the
environment of the
body
Migrate to
lymphoid tissue
In the secondary lymph organs, B-cells, T-cells, and Dendritic
cells exchange information.
T-cells activate B-cells into plasma cells that make antibodies.
T-cells also activate Dendritic cells and Macrophages to kill cells.
T-cells also inactivate cells that present antigens from self –
healthy body cells (prevents autoimmunity)
From Last week: Innate and Adaptive immune cells—how they relate
Hematopoietic stem cell
(in bone marrow)
Common
myeloid progenitor
Common
lymphoid progenitor
Selfrenewal
Monoblast
Erythroblast Megakaryoblast Putative
mast
cell
precursor
Lymphoblasts
Myeloblast
Megakaryocyte
Red blood cell
Platelets
(erythrocyte) (thrombocytes)
Basophil
Natural
Monocyte
T cell B cell
Eosinophil
Neutrophil
killer (NK) cell
Granulocytes
Lymphocytes
Macrophage
Mast cell
Dendritic cell
White blood cells (leukocytes)
The Cells of the Immune System
• Four types of leukocytes (white blood cells)
– Granulocytes contain cytoplasmic granules
• Neutrophils engulf and destroy
• Basophils involved in allergic reactions,
inflammation (Mast cells)
• Eosinophils fight
parasitic worms
– Also involved in
allergic reactions
Selfrenewal
Common
myeloid progenitor
Erythroblast
Megakaryoblast
Putative mast
cell precursor
Myeloblast
Common
lymphoid progenitor
Monoblast
Lymphoblasts
Megakaryocyte
Eosinophil
Red blood cell
(erythrocyte)
Platelets
(thrombocytes)
Basophil
Neutrophil
Monocyte
Natural
killer (NK) cell
Lymphocytes
Granulocytes
Mast cell
T cell
Macrophage
White blood cells (leukocytes)
Dendritic cell
B cell
The Cells of the Immune System
• Four types of leukocytes (cont…)
– Mononuclear Phagocytes
Selfrenewal
• monocytes (circulate in
Common
blood) and develop
myeloid progenitor
into Macrophages and Dendritic
cells
– Dendritic Cells
• Sentinel cells, function as “scouts”
• Engulf material in tissues, bring it
to cells of adaptive immune
system for “inspection”
Monoblast
Monocyte
Macrophage Dendritic cell
Four types of leukocytes (cont…)
Lymphocytes
Responsible for adaptive
immunity
B cells, T cells highly specific
in recognition of antigen
Generally reside in lymph
nodes, lymphatic tissues
Natural killer (NK) cells lack
specificity
Common
lymphoid progenitor
Lymphoblasts
Natural
T cell
killer (NK) cell
B cell
Lymphocytes
Lymphocytes are responsible for the
adaptive immune response
Anatomy of the Lymphoid System
• Primary Lymphoid Organs
– where the cells are made
– Bone marrow and thymus
• Lymphatic Vessels—transport
cells, and receive fluid from tissue—
lymph
• Secondary lymphoid Organswhere cells get together and exchange
antigen information
– Lymph nodes, spleen, tonsils,
peyer’s patches, MALT and SALT
SALT (skin associated lymph
tissue) MALT (mucosal
associated lymph tissue) and
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Peyer’s Patch is
example of secondary
lymphoid organ
Antigens
Lumen of
intestine
M cell
Absorptive
epithelial cell
Dendritic
cell
Macrophage
Peyer’s
patch
Area where
T cells gather
Area where
B cells gather
Lymphatic vessels
that drain to local
lymph nodes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Lymphatic
vessel
Excess tissue fluid
becomes lymph
Tissue
fluid
Blood
flow
Capillary
Filtration
Absorption
Venule
Arteriole
Lympth nodes—where the cells
communicate
Lymph vessels take in fluid
from tissue
What promotes an immune response?
• Antigens
– Any molecule that reacts with antibody, B cell
receptor or T cell receptor
– Composition is usually proteins or
polysaccharides
– Foreign substance with MW of 10,000 daltons
– Examples of antigens: bacterial capsules, cell
walls, flagella, toxins of bacteria
Small molecules are not recognized as
antigens until bound to another
Players of the Adaptive Immune Response
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Innate immunity
Dendritic cell
Naive B cell
Activates T cells that
bind antigens
representing “danger”
Activation
activated
Naive helper T cell
Naive cytotoxic T cell
activated
Proliferation
and differentiation
Plasma cells
Produce
antibodies
TH cells
Tc cells
Deliver
cytokines
Deliver “death
packages”
Effector action
and consequence
Antibodies
Antibodies bind
antigen
Adaptive immunity
(humoral)
Macrophage that
has engulfed
invaders
Infected
Macrophage with
increased killing power “self” cell
Adaptive immunity
(cell-mediated)
Infected “self”
cell undergoes
apoptosis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Antibodies bind
antigens
Antibodies
Epitopes
(antigens)
Bacterial cell
Epitopes
(antigens)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
B cell
Plasma
membrane
Antigen-binding
site
T cell
Antigen-binding
site
CD marker
Antigen
B-cell
receptor (BCR)
Antigen
T-cell receptor
(TCR)
Structure of an antibody
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Antigenbinding site
Variable
region
Fab region
Light
chain
Fc region
Constant
region
Heavy
chain
(a)
(b)
(c)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
How are B cells
activated?
Development
Hematopoietic stem cell
Immature B cells: As
these develop, a
functionally limitless
assortment of B-cell
receptors is randomly
generated.
Naive B cells: Each
cell is programmed to
recognize a specific
epitope on an antigen;
B-cell receptors guide
that recognition.
Activation
Activated B cells:
These cell scan
proliferate because
their B-cell receptors
are bound to antigen X
and the cells have
received required
signals from T H cells.
Proliferation and
differentiation
Plasma cells
(effector B cells):
These descendants of
activated B cells
secrete large quantities
of antibody molecules
that bind to antigen X.
Memory B cells:
These long-lived
descendants of
activated B cells
recognize antigen X
when it is encountered
again.
Effector action
Antibodies:
These neutralize the
invader and tag it for
destruction.
Antigen X
B cell W
B cell X
recognizing antigen X
B cell Y
B cell Z
Selected B cell receives confirmation from a
specific T H cell that a response is warranted
(not shown here; process is illustrated
in figure 15.11)
That’s great. But, how do the cells know
what is foreign and what is self?
(self vs. non-self recognition)
• Self markers also known as MHC markers
• MHC (major histocompatibility complex)
• MHC Class I-produced by all body cells (signal
SELF—material from inside the cell)
• MHC Class II-produced by dendritic cells, B cells,
and macrophages (PRESENT NON-SELF—
potential invader—material outside the cell)
– These cells are also called antigen presenting
cells (APCs)
B cell activation by Helper T cell
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
B-cell receptor
1
Antigen
4
Antigen
fragment
MHC class II
molecule
Peptide fragments are
presented on MHC class II
molecules.
B cell internalizes antigen.
B cell degrades antigen into
peptide fragments.
T-cell receptor
TH cell recognizes
antigen fragment
and activates B cell.
Microbial
antigen
presented.
Harmless
antigen
presented.
3
Endosome
B-cell receptor binds
to antigen.
5a
2
Cytokine delivery
5b
No TH cell recognizes
antigen fragment;
B cell becomes
anergic.
Anergic cells undergo cell deathelliminated
T-independent antigens activate
B-cells without T cells
What can happen when antibody binds antigen.
Opsonization
Bacterium
Complement System Activation
Neutralization
Phagocyte
Complement
system protein
Virus
Toxin
Bacterium
Opsonization by C3b
Inflammatory response
Lysis of foreign cells
Antibody-Dependent Cellular
Cytotoxicity (ADCC)
Infected
“self” cell
Immobilization and Prevention
of Adherence
Natural
killer cell
Cross-Linking
Bacterium
Bacterium
Kills cell
Flagellum
There are 5 classes of antibodies
•
•
•
•
•
IgM
IgG
IgA
IgE
IgD
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
100
Percent of normal average
adult level of IgG
Fig. 15.9
Total IgG
Infant IgG
Maternal IgG
0
4
6
Before birth
8
2
Birth
Months
4
6
Infant age
8
Naïve B cells produce IgM, then
IgG antibodies
Primary and secondary response to antigen
Concentration of antibody
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Primary
response
Secondary
response
IgG
IgG
IgM
Days
Ag
Months
Days
Months
Ag
Time after antigen (Ag) injection
More about T cells
—distinguish self from non-self
• Have own T cell receptor (TCR)
• Do not make antibodies
• Must recognize MHC markers which
“present” antigen
T cells differ from B cells
• Must use MHC markers on host cells to
recognize antigens
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
CD8
T-cell receptor
MHC class I
molecule
Endogenous
antigen
TC cells recognize
All nucleated cells present endogenous
antigens presented on antigens on MHC class I molecules.
MHC class I molecules.
(a)
CD4
T-cell receptor
MHC class II
molecule
Exogenous
antigen
TH cells recognize
antigens presented on
MHC class II molecules.
(b)
B cells and macrophages present
exogenous antigens on MHC class II
molecules.
Effector function of Helper-T cells
B-cell receptor
1
Antigen
B-cell receptor binds
to antigen.
5a
4
Antigen
fragment
MHC class II
molecule
Peptide fragments are
presented on MHC class II
molecules.
3
Endosome
B cell internalizes antigen.
T-cell receptor
TH cell recognizes
antigen fragment
and activates B cell.
Microbial
antigen
presented.
Harmless
antigen
presented.
2
Cytokine delivery
5b
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
No TH cell recognizes
antigen fragment;
B cell becomes
anergic.
B cell degrades antigen into
peptide fragments.
Effector function of Helper-T cells
Effector functions of Cytotoxic T cells
Natural Killer
Cells…lymphocyte but not a T
cell
Activation of T Cells
Dendritic cells in the tissue collect
particulate and soluble antigen and then
travel to the secondary lymphoid tissues.
Lymphoid organ
MHC class I molecule
Co-stimulatory molecule
Dendritic cells presenting
microbial peptides produce
co-stimulatory molecules.
MHC class II molecule
T-cell receptor
CD4
T-cell receptor
CD8
Naive T cells that recognize antigen presented
by dendritic cells expressing co-stimulatory molecules
can become activated.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Figure 15.20
Activation of T Cells
Dendritic cells in the tissue collect
particulate and soluble antigen and then
travel to the secondary lymphoid tissues.
Lymphoid organ
MHC class I molecule
Co-stimulatory molecule
Dendritic cells presenting
microbial peptides produce
co-stimulatory molecules.
Dendritic cells presenting “self”
peptides or other harmless
material do not produce
co-stimulatory molecules.
MHC class II molecule
T-cell receptor
T-cell receptor
CD4
CD8
Naive T cells that recognize antigen presented
by dendritic cells expressing co-stimulatory molecules
can become activated.
Naïve T cells that recognize antigen presented
By dendritic cells not expressing co-stimulatory
molecules become anergic.
Activated T cells proliferate and differentiate.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Figure 15.20
Activation of T Cells
Dendritic cells in the tissue collect
particulate and soluble antigen and then
travel to the secondary lymphoid tissues.
Lymphoid organ
MHC class I molecule
Co-stimulatory molecule
Dendritic cells presenting
microbial peptides produce
co-stimulatory molecules.
Dendritic cells presenting “self”
peptides or other harmless
material do not produce
co-stimulatory molecules.
MHC class II molecule
T-cell receptor
T-cell receptor
CD4
CD8
Naive T cells that recognize antigen presented
by dendritic cells expressing co-stimulatory molecules
can become activated.
Activated T cells proliferate and differentiate.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Naïve T cells that recognize antigen presented
By dendritic cells not expressing co-stimulatory
molecules become anergic.
Anergic T cells cannot respond and eventually undergo apoptosis.
Figure 15.20
Antibody dependent cell
mediated cytotoxicity
Primary lymphoid organs
Immature B cells
(bone marrow)
Immature T cells
(thymus)
Peripheral tissues
Dendritic cells that have gathered
antigen in the periphery present it
to naïve T cells; co-stimulatory
molecules are expressed if the
material collected represents
“danger.”
Secondary lymphoid
organs
Naïve cytotoxic Naïve helper T
Naïve B cells
cells(CD4)
T cells (CD8)
TH cells activate
B cells that present
specific antigen
Dendritic cell
(gathers antigen
for presentation
to naive T cells)
TC cells
Infected “self” cell
(harbors antigen
within the cell)
TC cells induce apoptosis
in infected “self” cells; also
produce cytokines that
alert neighboring cells.
Memory
helper
T cells
Memory
cytotoxic
T cells
TH cells activate macrophages
that present antigen via MHC
class II molecules; also produce
cytokines that determine other
responses.
Macrophage (engulfs and
destroys invaders; limited
killing powers)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
TH cells
Memory
B cells
Plasma cells
secrete antibodies.
Antibodies
(tag extracellular
antigen for removal)
Activated macrophage (engulfs
and destroys invaders; enhanced
killing powers)
Extracellular
antigen
Figure 15.24