Chapter 16

Adaptive Immunity

Third Line of Defense

Is called specific or acquired immunity
The bodys ability to recognize and defend
itself against distinct invaders and their
products
A smart system whose memory allows
it to respond rapidly to a second encounter
with a pathogen

Elements of Adaptive Immunity

Is acquired over time
Antigens trigger specific immune
responses
Various cells, tissues, and organs are
part of specific immunity
Includes B and T lymphocytes

Lymphatic System
Screens the tissues of the body for
foreign antigens
Composed of lymphatic fluid,
vessels and lymphatic cells

Lymphatic Vessels
Form a one-way system that
conducts lymph from local tissues
and returns it to the circulatory
system
Lymph is a liquid with similar
composition to blood plasma that arises
from fluid leaked from blood vessels
into surrounding tissues

Figure 16.2 The lymphatic system.

Blood
capillary

From heart

Tonsils

Tissue cell

Cervical lymph node

Lymphatic ducts
Intercellular
fluid

Thymus gland

Lymph
to heart
via lymphatic
vessels

Axillary lymph
node
Heart
Breast lymphatics
Spleen

Gap in wall
Valve

Abdominal
lymph node

To heart

Intestines

Lymphatic capillary

Peyers patches in
intestinal wall
Appendix

Red bone
marrow

Afferent
lymphatic vessel

Inguinal lymph
node
Medulla

Lymphatic
vessel

Cortex
Vein
Valve
(prevents backflow)

Artery

Efferent
lymphatic
vessel

Lymphatic nodule

Capsule
Primary follicle

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Part of mucosaassociated lymphoid

tissue (MALT)

Lymph Nodes
House leukocytes that recognize and
attack foreign antigens present in the
lymph
Concentrated in the cervical (neck),
inguinal (groin), axillary (armpit), and
abdominal regions
Receives lymph from afferent
lymphatic vessels and drains lymph
into efferent lymphatic vessels

Other Lymphoid Tissues and

Organs
Spleen
Similar in structure and function to the lymph nodes
Filters bacteria, viruses, toxins, and other foreign matter
from the blood
Tonsils and mucosa-associated lymphoid tissue (MALT)
Physically trap foreign particles and microbes that are
ingested or inhaled
MALT includes the appendix, lymphoid tissue of the
respiratory tract, and Peyers patches in the wall of the
small intestine

Antigens
Molecules that trigger a specific immune
response
Include components of bacterial cell walls,
capsules, pili, and flagella, as well as
proteins of viruses, fungi, and protozoa
Food and dust can also contain antigenic
particles
Enter the body by various methods:
Through breaks in the skin and mucous
membranes
Direct injection, as with a bite or needle
Through ingestion or inhalation

The Nature of Antigens

Figure 16.1

Why are B cells called B cells?

Figure 16.3a

The
production,
maturation,
and
deployment
of lymphocytes

Figure 16.3b

B Lymphocytes
Arise and mature in the bone marrow
Found primarily in the Secondary
lymphoid tissue: spleen, lymph nodes,
bone marrow, and Peyers patches
Small percentage of B cells circulate in
the blood
Major function is the differentiation into
plasma cells which secrete antibodies

Antibodies
Also called immunoglobulins (Ig)
Soluble, glycoprotein molecules that
bind antigen
Secreted by plasma cells, which are
activated and differentiated B cells
Considered part of the humoral
immune response since bodily fluids
such as lymph and blood were once
called humors

Basic structure
of an antibody

Figure 16.5

Figure 16.5b Basic antibody structure.

Arm (Fab)

Hinge

Stem (Fc)

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Antibody Functions
Antigen-binding sites are complementary to
antigenic determinants (epitopes)
Due to the close fit, can form strong,
noncovalent interactions
Hydrogen bonds, ionic attractions, and
hydrophobic interactions are involved
Neutralization (both viruses and toxins)
Opsonization
Agglutination
Activation of complement

Figure 16.6 Five functions of antibodies.

Bacterium

Adhesin
proteins

Virus

Toxin

Agglutination

Neutralization

NK lymphocyte
Pseudopod
of phagocyte

Fc receptor protein
Perforin allows granzyme
to enter, triggers apoptosis
and lysis

Fc receptor protein
Antibody-dependent cellular
cytotoxicity (ADCC)

Opsonization

Bacteria die

Oxidation

Classes of Antibodies
A single type of antibody is not
sufficient for the multiple types of
invaders to the body
The class involved in the immune
response depends on the type of
foreign antigen, the portal of entry,
and the antibody function needed
5 different classes of antibodies

Table 16.1 Characteristics of the Five Classes of Antibodies

B Cell Receptor (BCR)

Is an antibody that remains associated
with the cytoplasmic membrane
Each B lymphocyte has multiple copies
of a single type of BCR (either IgM or
IgD)
Antigen binding site is identical to that
of the secreted antibody for that
particular cell
The randomly chosen V, D, and J
regions and how they are put together
determines the BCR specificity

B Cell Receptor (BCR)

Each BCR on an
individual cell is
complementary
to only one
antigenic
determinant
The BCRs on all of
an individuals B
cells are capable of
recognizing millions
of different
antigenic
determinants

T Lymphocytes
Produced in the red bone marrow and mature
in the thymus (unique TCR made)
Circulate in the lymph and blood and migrate
to secondary lymphoid tissue: lymph nodes,
spleen, and Peyers patches
Part of the cell-mediated immune response
because they act directly against various
antigens
Endogenous invaders
Many of the bodys cells that harbor
intracellular pathogens
Abnormal body cells such as cancer cells
that produce abnormal cell surface proteins

Figure 16.7 A T cell receptor (TCR).

Antigen-binding
site
Carbohydrate

Variable
regions
Constant
regions

Cytoplasmic
membrane
of T cell
T cell receptor
(TCR)
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Cytoplasm

T Lymphocytes
Account for 70-85% of all lymphocytes in the
blood
Immunologists recognize types of T cells
based on surface glycoproteins and
characteristic functions
3 types:
Cytotoxic T cells
Helper T cells
Regulatory T cells

Cytotoxic T cells (TC Cells)

Distinguished by the CD8 cell-surface
glycoprotein
Directly kill certain cells
Cells infected with viruses and other
intracellular pathogens
Abnormal cells, such as cancer cells

Helper T Cells (TH Cells)

Distinguished by the CD4 cell-surface glycoprotein
Function to help regulate the activities of B cells
and cytotoxic T cells during an immune response
Secrete various soluble protein messengers, called
cytokines, that determine which immune response
will be activated
Type 1 helper T cells (Th1 cells): assist Tc cells,
and stimulate and regulate innate immunity
Type 2 helper T cells (Th2 cells): assist B cells
Conductors of your immunological orchestra

Regulatory T Cells
Previously known as suppressor T cells
Repress adaptive immune responses and prevent
autoimmune diseases
Distinguished by CD4 and CD25 cell-surface
glycoproteins
Activated by contact with other immune cells and
secrete cytokines

Lymphocyte Editing by Clonal

Deletion
Vital that immune responses not be
directed against self (autoantigens)
Body edits lymphocytes (via
apoptosis) to eliminate any selfreactive cells
Occurs in the thymus for T cells
Occurs in the bone marrow for B cells
End result: surviving lymphocytes
respond only to foreign antigens

Fig. 16-08

T cell Clonal
Deletion

Stem cell
(in red bone marrow)

T cells
TCRs
MHC I

Epitope
Recognize
MHC I?

Thymus

Thymus
cells

cells

No

Yes
Receive survival
signal
Recognize
MHC-autoantigen?

Apoptosis

Yes

No
Few

Most

Apoptosis
Repertoire of
immature Tc cells

Regulatory
T cell (Tr)

Fig. 16-09

B cell Clonal
Deletion

Stem cell
(in red bone marrow)

B cells

BCRs
Cell with
autoantigens

Cell with
autoantigens

Apoptosis

Blood vessel

To spleen

Cytokines
Soluble regulatory proteins (over 200
total) that act as intercellular signals
when released from certain body cells
Immune system cytokines signal
among various leukocytes
The complex web of signals among all
the cell types of the immune system is
referred to as the cytokine network

Cytokines of the Immune System

Interleukins (ILs)- signal among leukocytes
Interferons (IFNs)- antiviral proteins that
may act as cytokines
Growth factors- proteins that stimulate stem
cells to divide, maintaining an adequate
supply of leukocytes
Tumor necrosis factors (TNFs)- Secreted by
macrophages and T cells to kill tumor cells
and regulate immune responses and
inflammation
Chemokines- signal leukocytes to go to a
site of inflammation or infection and
stimulate other leukocytes

Major Histocompatibility Complex

(MHC)
Important in determining the compatibility of
tissues in successful grafts
MHC class I antigens are glycoproteins found in
the membranes of most all nucleated cells of
vertebrate animals
Function to hold a peptide fragment from an
intracellular protein (endogenous antigen)
for presentation to T cells
MHC class II antigens found only on B cells and
APCs
Function to hold a peptide fragment from an
extracellular protein (exogenous antigen) for
presentation to T cells

Figure 16.10 The two classes of major histocompatibility complex (MHC) proteins.

Antigen-binding
sites (grooves)

Cytoplasmic
membrane

Class I MHC
on every
nucleated
cell

Class II MHC
on B cell or other
antigen-presenting
cell (APC)

Cytoplasm

Fig. 16-11

Dendritic Cells:

Professional APCs

Dendrites

Antigen Processing
T-independent antigen
Large antigen molecules with readily
accessible, repeating antigenic
determinants
B cells can bind and respond to these
directly without T cell cytokine help
Stimulates B cells to differentiate into a
plasma cell and produce antibodies
Antibodies produced are often IgM only

Relatively uncommon

Antigen Processing
T-dependent antigens
Smaller antigens with less accessible
antigenic determinants
B cells require involvement from helper T
cells to respond to these antigens
Helper T cells are assisted by antigen
presenting cells that process the antigen
and make the antigenic determinants
accessible to T cells
Processing is different based on whether the
antigen is exogenous or endogenous

Processing of Endogenous
Antigens
Intracellular proteins are broken down
into smaller peptide fragments by the
proteosome; fragments transported
into endoplasmic reticulum (ER)
Each fragment binds to a class I MHC
molecule located in the ER
The membrane is packaged into a
vesicle by a Golgi body which is
inserted into the cytoplasmic
membrane so the antigen is displayed
on the cells surface

Fig. 16-12

Processing and
Presentation of
Endogenous Antigen
Polypeptide
Epitopes
MHC I protein
in membrane
of endoplasmic
reticulum

Lumen of
endoplasmic
reticulum

The polypeptide is catabolized to yield epitopes,

which are loaded onto complementary MHC I
proteins in the ER.

MHC I protein
epitope complex

MHC I proteinepitope
complexes are packaged in vesicle.

Vesicle fuses with cytoplasmic membrane.

MHC I protein
epitope
complexes on
cell surface
Cytoplasmic
membrane
MHC I proteinepitope complexes displayed on
cytoplasmic membranes of all nucleated cells

Processing of Exogenous
Antigens
APC internalizes the invading pathogen and
enzymatically digests it into smaller
antigenic fragments which are contained
within an endosome
Endosome fuses with a vesicle containing
class II MHC molecules
Each fragment binds to the antigen-binding
groove of a complementary MHCII molecule
The fused vesicle then inserts the MHCIIantigen complex into the cytoplasmic
membrane so the antigen is presented on
the outside of the cell

Fig. 16-13
Phagocytosis
by APC
Exogenous
pathogen
with antigens

Processing and
Presentation of
Exogenous Antigen
MHC II protein
epitope complex

MHC II protein in
membrane of vesicle

Epitopes in
phagolysosome

Vesicles fuse and epitopes bind to

complementary MHC II molecules.

Vesicle fuses with cytoplasmic membrane.

MHC II protein
epitope
complexes on
cell surface
Cytoplasmic
membrane
MHC II proteinepitope complexes displayed on
cytoplasmic membranes of antigen-presenting cell

Cell-Mediated Immune Response

Responds to intracellular pathogens and
abnormal body cells
The most common intracellular pathogens
are viruses but the response is also effective
against intracellular bacteria
Triggered when antigenic determinants of
the pathogen are displayed on the host cells
surface

Fig. 16-14

Activating
a Clone of
Cytotoxic
T cells

Dendritic cell

Antigen presentation
MHC I
CD8

DC

MHC II protein
Epitope
TCR

TCR

Th
cell

IL-12

Inactive
Tc cell
IL-2 receptor
(IL-2R)

Th differentiation

Tc cell
Immunological synapse

IL-2
Th1 cell

Clonal expansion

IL-2R

IL-2

IL-2R

Epitope

Memory
T cell

Active
Tc cells

IL-2

Self-stimulation

Active Tc cells

IL-2

Fig. 16-15

Tc cell
Granzyme

Perforin
Active
cytotoxic T
(Tc) cell
TCR

Perforin
complex (pore)

CD8

Viral epitope
MHC I
protein

Inactive
apoptotic
enzymes

Granzymes activate
apoptotic enzymes
Active apoptotic
enzymes induce
apoptosis

Virally
Infected cell

Virally infected cell

Intracellular
virus

Tc cell
CD95L
CD95

Killing Mechanisms of
Active Cytotoxic T cells

Inactive
apoptotic
enzymes
Virally infected cell

Enzymatic
portion of CD95
becomes active
Active apoptotic
enzymes induce
apoptosis

Humoral Immune Response

Body mounts humoral immune
responses against exogenous
pathogens
Components of a humoral immune
response
B cell activation and clonal selection
Antibodies
Memory B cells and the establishment of
immunological memory

Fig. 16-18

Events in
a Humoral
Immune
Response

Repertoire of Th cells (CD4 cells)

Th cell
CD4

TCR
CD4

CD28

Epitope

TCRs

CD80
(or
CD86)

MHC II
APC

Antigen
presentation
for Th activation
and cloning

APC

Differentiation of
Th into Th2 cell
Th cell clones

MHC II
proteins

IL-4

CCR3
CCR4
Th2 cell

Clonal
selection
of B cell

Th2 cell
Th2 cell

TCR

CD40L

Epitope
MHC II

CD40

IL-4

B cell

Repertoire of B cells

Activation of
B cell

BCR

Clone of
plasma
cells

Antibodies

Memory B cells

Plasma Cells
Make up the majority of cells produced
during B cell proliferation
Each plasma cell secretes antibody
molecules complementary to one specific
antigenic determinant.
The class of antibody produced is
determined by signals from T-helper cells
Many are short-lived cells that produce
massive amounts of antibody (2,000 per
sec) and then die within a few days. Others
are longer-lived.

Fig. 16-17

Golgi body

A Plasma
Cell

Nucleus

Rough endoplasmic
reticulum

Memory B Cells
Cells produced by B cell proliferation that do
not secrete antibodies
Cells that have BCRs complementary to the
specific antigenic determinant that triggered
their production
Long-lived cells that divide only a few times
and then persist in the lymphoid tissue
Are available to initiate antibody production
more rapidly if the same antigen is
encountered again

The Humoral Immune Response

Acquired Immunity
Specific immunity acquired during an
individuals life
2 types:
Naturally acquired- immune response
against antigens encountered in daily life
Artificially acquired- response to antigens
introduced via medical intervention
Further distinguished as either active or
passive
Active- products made by the individual
(humoral or cell-mediated responses)
Passive- passively receive antibodies
made by another individual

Table 16.4 A Comparison of the Types of Acquired Immunity

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