Chapter 15

Adaptive Immunity:
Specific Defenses of the Host

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Q&A

 Why doesn’t the

adaptive immune
system normally
attack your own
body tissues?
Antibodies and Specific Immunity

faculty.ccri.edu
SEM Human Macrophage, Streptococcus
pyogenes, Antibody secreting Lymphocyte
Host Defenses

•Innate immunity: Defenses against any pathogen

•Adaptive immunity: Induced resistance to a
specific pathogen
Figure 16.1
Specific Defenses of the Host:
The Immune Response
 Immunity: Specific antibody and lymphocyte
response to an antigen

 Antigen (Ag): A substance that causes the body to

produce specific antibodies or sensitized T cells

 Antibody (Ab): Proteins made in response to an

antigen
Historical Development

 Pasteur observed immunity in chickens injected

with weakened pathogens
 Von Behring received the Nobel Prize for
development of antitoxin
 Ehrlich’s work led to the identification of antibodies
in serum
Active and Passive Immunity
Adaptive Immunity

 Naturally acquired active immunity

 Resulting from infection
 Naturally acquired passive immunity
 Transplacental or via colostrum
 Artificially acquired active immunity
 Injection of Ag (vaccination)
 Artificially acquired passive immunity
 Injection of Ab
 The Immune Response
 Humoral immunity (antibody mediated immunity)
Involves Antibodies produced by B cells
Defends primarily against bacteria, bacterial
toxins, and freely circulating viruses
 Cell-mediated immunity
Involves T-lymphocytes that act directly against
foreign organisms
Activates other immune cells like macrophages
Effective against bacteria/viruses within host
cells, also against eukaryotic infections
 Dual Nature of Adaptive Immunity
 T and B cells develop from stem cells in red bone marrow
 Humoral immunity
 B cells mature in the bone marrow
 Chickens: Bursa of Fabricius
 Due to antibodies
 Cellular immunity
 Due to T cells
 T cells mature in the thymus

Figure 17.8
15.1. Strategy of the Adaptive Immune
Response Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Dendritic cell Innate immunity

Activates T cells that

Activation bind antigens
representing “danger”

Naive B cell Naive cytotoxic T cell

Naive helper T cell

Proliferation
and differentiation
Plasma cells TH cells Tc cells

Produce Deliver Deliver “death

antibodies cytokines packages”

Effector action
and consequence

Antibodies Antibodies bind Macrophage that Macrophage with Infected Infected “self”
antigen has engulfed increased killing power “self” cell cell undergoes
invaders apoptosis
Adaptive immunity Adaptive immunity
(humoral) (cell-mediated)
 Antigenic Determinants
Antibodies recognize and react with specific antigenic
determinants.

Figure 17.3
15.3. The Nature of Antigens
Response to antigens varies depending on type
Proteins generally elicit strong response; lipids weak
Small molecules usually not antigenic
Terms antigenic and immunogenic used interchangeably
to describe ability of antigen to elicit immune response
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Epitopes trigger response

Called antigenic determinants Antibodies

Regions of macromolecules Epitopes

(antigenic
E.g., 10 or so amino acids; determinants)

three-dimensional shapes
Bacterial cell

Bacterial cell has multitude

of different epitopes Epitopes
(antigenic
determinants)
Nature of Antibodies

 Antibodies –proteins produced by B cells

 Structure of Antibodies
 Classes of Antibodies
 Specific reactions of Antibodies
 Antibody Structure
Proteins that are specific for an antigen

Figure 17.5a-c
IgG Antibodies

 Monomer
 80% of serum Abs
 Fix complement
 In blood, lymph, and intestine
 Cross placenta
 Enhance phagocytosis; neutralize toxins and
viruses; protects fetus and newborn
 Half-life = 23 days
15.4. The Nature of Antibodies
 IgG
 Maternal IgG protects fetus and newborn
 Degrade gradually over 6 month period
 Infant begins producing
 IgG found in colostrum (first breastmilk); absorbed by
newborn’s intestinal tract
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100
Percent of normal average
adult level of IgG

Total IgG

Infant IgG
Maternal IgG

0
4 6 8 2 4 6 8
Before birth Birth Infant age

Months
IgM Antibodies

 Pentamer
 5–13% of serum Abs
 Fix complement
 In blood, in lymph, and on B cells
 Agglutinates microbes; first Ab
produced in response to infection
 Half-life = 5 days
IgA Antibodies

 Dimer
 10–15% of serum Abs
 In secretions
 Mucosal protection
 Half-life = 6 days
IgD Antibodies

 Monomer
 0.2% of serum Abs
 In blood, in lymph, and on B cells
 On B cells, initiate immune response
 Half-life = 3 days
IgE Antibodies

 Monomer
 0.002% of serum Abs
 On mast cells, on basophils, and in
blood
 Allergic reactions; lysis of parasitic
worms
 Half-life = 2 days
 Antibody-Antigen Interactions
 Binding of antibody to antigen does not destroy the antigen
 Instead, the antibody tags foreign cells and molecules for
destruction by phagocytes and complement
Activation of B Cells

 Major histocompatibility complex (MHC)

expressed on mammalian cells
 T-dependent antigens
 Ag presented with (self) MHC to TH cell
 TH cell produces cytokines that activate the B cell
 T-independent antigens
 Stimulate the B cell to make Abs
Activation of B Cells

Figure 17.6
Activation of B Cells

A mature B cell recognizes antigen receptors

using IgM and IgD antibodies
Figure 17.4
Clonal Selection
15.5. Clonal Selection and Expansion of
Lymphocytes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

 Clonal Selection
 Billions of different B
and T cells present Development
Immature B cells: As
these develop, a
functionally limitless
Hematopoietic stem cell

 Each interacts with

assortment of B-cell
receptors is randomly
generated. Antigen X

Naive B cells: Each

only a single epitope

cell is programmed to
recognize a specific
epitope on an antigen;
Bcell W B cell X B cell Y B cell Z
B-cell receptors guide
recognizing antigen X
that recognition.

 Pathogen has multiple

Selected B cell receives confirmation from a
Activation specific T H cell that are sponseis warranted
(not shown here; process is illustrated
Activated B cells: in figure 15.11)
These cell scan

epitopes
proliferate because
their B-cell receptors
are bound to antigen X
and the cells have
received required
signals from T H cells.

 Lymphocytes that Proliferation and

recognize epitope
differentiation

respond; progeny
Plasma cells
(effector B cells):
These descendants of
activated B cells
secrete large quantities

leave lymphoid organs

of antibody molecules
that bind to antigen X.

Memory B cells:

 Plasma cells produce

These long-lived
descendants of
activated B cells
recognize antigen X
when it is encountered

antibodies
again.

Effector action
Antibodies:
These neutralize the
invader and tag it for
destruction.
15.5. Clonal Selection and Expansion of
Lymphocytes
 Lymphocytes change as they encounter antigen
 Immature lymphocytes lack fully developed antigen-
specific receptors
 Naive lymphocytes have receptors; have not yet
encountered appropriate antigen
 Activated lymphocytes have bound antigen and received
confirmation, are able to proliferate
 Effector lymphocytes are descendants of activated
lymphocytes: plasma cells, TC cells, TH cells
 Memory lymphocytes are long-lived descendants of
activated lymphocytes; responsible for rapid secondary
response if antigen encountered again
The Results of Ag-Ab Binding

Figure 17.7
15.6. B Lymphocytes and the Antibody Response

 Characteristics of Primary Response

 Takes 10–14 days for substantial antibody accumulation
 Person may be sick, possibly seriously so, although
immune system is actively responding
 Some activated B cells
continue dividing, others Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display

differentiate to form Primary

response
Secondary
response

antibody-secreting

Concentration of antibody
plasma cells
IgG

 Affinity Maturation
 occur in multiplying B cells
IgG

 Additional exposure to IgM

antigen yields much Ag

Days Months

Ag
Days Months

faster secondary response Time after antigen (Ag) injection

15.6. B Lymphocytes and the Antibody Response

 Characteristics of Secondary Response

 Significantly faster, more effective than primary
 Pathogens usually eliminated before causing harm
 Vaccination exploits this natural phenomenon
 Memory B cells responsible: greater numbers present
 Receptors already fine-tuned through affinity maturation
 Antibodies coded by these cells bind antigen effectively
 When activated, some quickly become plasma cells,
produce antibodies
 Often IgG or IgA due to class switching
 Proliferating B cells again undergo affinity maturation,
generating even more effective antibodies; future
exposures elicit an even stronger response
Immunological Memory

 Antibody titer is the amount of Ab in serum

 Primary response occurs after initial contact
with Ag
 Secondary (memory or anamnestic)
response occurs after second exposure
Immune Responses to an Antigen

Figure 17.16
15.7. T Lymphocytes: Antigen Recognition and
Response
 T cells play different role than B cells
 Never produce antibodies
 Effector T cells directly interact with target cells
 Cause distinct changes in target cells
 Cells involved in Cellular Immunity
• Four main types of T-cells
1. Helper T Cells (TH)
 TH1 Activate cells related to cell-mediated
immunity
 TH2 Activate B cells to produce eosinophils,
IgM, and IgE

2. Cytotoxic T Cells (TC)

3. Delayed Hypersensitivity T Cells (TD)

4. Suppressor T Cells (Treg)

 Turn off immune response when Ag no longer present
15.7. T Lymphocytes: Antigen Recognition and
Response
 General Characteristics of T Cells
 Multiple copies of T-cell receptor (TCR)
 Two polypeptide chains: alpha plus beta or gamma plus
delta; each has a variable and constant region
 Structurally comparable to one “arm” of B-cell receptor
 T-cell receptor does not interact with free antigen
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display

 Only antigen presented by Antigen:

MHC-binding site
Alpha Beta
chain chain

another cell
 Held in major histo- Variable
region

compatibility complex
(MHC) molecules on Constant
region

surface of cell

(a) (b)
15.7. T Lymphocytes: Antigen Recognition and
Response
 General Characteristics of T Cells (continued…)
 Two types of MHC molecules
 MHC class I present endogenous antigens
 Produced by all nucleated cells
 MHC class II present exogenous antigens
 Produced by antigen-
presenting cells (dendritic Peptide-binding groove
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Peptide-binding groove

cells, B cells, macrophages)

 T cell recognizes peptide:
MHC complex

(a) MHC Class I Molecule (b) MHC Class II Molecule

T Cells and Cellular Immunity
 T cells mature in the thymus
 Thymic selection eliminates many immature T cells
 T cells respond to Ag by T-cell receptors (TCRs)
 T cells require antigen-presenting cells (APCs)
 Important in the cell mediated immune response
 Pathogens entering the gastrointestinal or
respiratory tracts pass through
 M (microfold) cells over
 Peyer’s patches, which
contain APCs
15.7. T Lymphocytes: Antigen Recognition and
Response
 General Characteristics of T Cells (continued…)
 Cytotoxic T cells recognize antigen presented on MHC class I
molecules
 TC cells respond to endogenous antigens
 Helper T cells recognize antigen presented on MHC class II
molecules Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display

 TH cells respond to exogenous

MHC class I
CD8 T-cell receptor
molecule

antigens Endogenous
antigen

 Cluster of differentiation (CD) T cells recognize

antigens presented on
All nucleated cells present endogenous
antigens on MHC class I molecules.

markers
MHC class I molecules.

(a)

 TC cells usually CD8 CD4 T-cell receptor

MHC class II
molecule
Exogenous

 TH cells usually CD4

antigen

 CD4 is receptor for HIV TH cells recognize

antigens presented on
MHC class II molecules.
B cells and macrophages present
exogenous Antigens on MHC class II
Molecules.

(b)
T Helper Cells

 CD4+ or TH cells
 TCRs recognize Ags and MHC II on APC
 TLRs are a costimulatory signal on APC and TH
 TH cells produce cytokines and differentiate into
 TH1
 TH2
 Memory cells

 TH1 produces IFN-which activates cells related to cell-mediated

immunity, macrophages, and Abs
 TH2 activate eosinophils and B cells to produce IgE
Activation of CD4+ T Helper Cells

Figure 17.10
T Cytotoxic Cells

 CD8+ or TC cells
 Target cells are self carrying endogenous
antigens
 Activated into cytotoxic T lymphocytes (CTLs)
 CTLs recognize Ag + MHC I
 Induce apoptosis in target cell
 CTL releases perforin and granzymes
15.7. T Lymphocytes: Antigen Recognition and
Response
 Effector Functions of TC (CD8) Cells
 Cells present internal proteins on MHC class I; binding by
TC indicates recognition of pathogen or cancer
 TC induces apoptosis: proteases, cytotoxins (perforin)
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Normal CD8 T-cell receptor

cytoplasmic MHC class I
proteins molecule

All nucleated cells present peptides from

cytoplasmic proteins on MHC class I molecules.

(a)

Virus
Viral Cytokines
proteins

Targeted delivery
of a “death package”

Virally infected “self” cells TC Cell recognizes viral peptides Target cell undergoes apoptosis.
present viral peptides on presented by an infected “self” cell
MHC class I molecules. and initiates apoptosis in that target.
it also releases cytokines that alert
neighboring cells.

(b)
T Cytotoxic Cells

Figure 17.11
Apoptosis
15.7. T Lymphocytes: Antigen Recognition and
Response
 Effector Functions of TH (CD4) Cells
 Recognize antigen presented on MHC class II from antigen-presenting
cells (APCs)
 Activates with cytokines; may recognize different epitope
 E.g., B cell likely recognized epitope on pathogen’s surface; TH
could recognize peptide from within
 Can make conjugate vaccine against T-independent antigen (e.g.,
capsule of Haemophilus influenzae)
 Converts to T-dependent antigen by covalently attaching
protein; B cell responds to capsule, TH responds to protein
component, activates B cell
 Hapten is a molecule that binds a B-cell receptor, does not elicit
response unless binds a protein, acts like a conjugate vaccine
(e.g., penicillin causing allergic reaction)
Antigen Presenting Cells -APC

 Associated with Cellular Immunity

 Recognition of antigens by T cells requires they be
processed by APC’s
 Digest antigen
 Efficient in internalizing antigen and then displaying a
fragment of the antigen on their membrane with Major
Histocompatibility Complex (MHC)

 Dendritic Cells
 Macrophages
 B cells also present antigens to which their antibody is
directed
 Antigen Presenting Cell APC
Dendritic Cell
 Long extensions
 Poorly phagocytic
 Abundant in skin, inner
lining of nose, lungs,
stomach, intestines
 Important role as APC’s
 Antigenic fragments are
presented on APC surface
along with MHC
 Activate helper T cells with
specific antigen
 Considered the most
powerful APC
Macrophages -APC

 Phagocytosis in non-specific
defenses and also important in
cell mediated immunity
 stimulated by cytokines in
specific immunity
 When activated, macrophages
ingest antigenic materials and
become effective phagocytes
and APC’s
 Control cancer, intracellular
pathogens, virus infected cells
 Appearance is large and ruffled
 Important in its ability to migrate
to T cells
Major Histocompatibility Complex
MHC
 Sign post for immune system
 Protein- presented as pieces of
antigens on host cell surface
 Play a major role in antigen
recognition by T cells
 Bind fragments of microbes and
present these at the cell surface
for inspection of T cell antigen
receptors
 Illicit a specific immune
response; T and B cells
 Immune response is to kill
malfunctioning or infected cells
Natural Killer Cells -NK

 Component of innate immune  A natural killer cell (NK cell, yellow) of the immune cell

system  attacking a cancer cell (red). (Photo: Prof. Dr. Rupert

 Can also destroy virus infected Handgretinger, Clinic for Children’s and Youth Medicine

cells and tumor cells

 Attack parasites
 No need to be stimulated by an
antigen
 Recognizes low levels of MHC
which is an early sign of viral
infection
 NK form pores in cell –lyse and
apoptosis (destroy cell)
 Activated by cytokines
 Contain viral infections while the
adaptive immunity generates
cytotoxic T cells
Extracellular Killing
 ADCC= Antibody-
dependent cell-
mediated cytotoxicity.
 Natural killer cells
destroy cells which
don’t express MHC I.

Figure 17.14b
Cytokines

 Chemical messengers
 Interleukin-1 (IL-1)
 Interleukin-2 (IL-2)
 Chemokines
 TNF
 Interferons

 Overproduction leads to cytokine storm

15.9. Lymphocyte Development
 Negative Selection of Self-Reactive B Cells
 B cells are exposed to “self” in bone marrow; if bind,
induced to undergo apoptosis
 This negative selection removes most B cells; critical
for preventing immune system from attacking body
 Positive and Negative Selection of T Cells
 Positive selection: T cells must recognize MHC
 Eliminated if unable to recognize
 Negative selection: T cells also eliminated if recognize
“self” peptides presented on MHC molecules
 Process is so stringent that over 95% of developing T
cells undergo apoptosis in thymus
Q&A

 Why doesn’t the

adaptive immune
system normally
attack your own
body tissues?