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Chapter 3
Introduction
Antigen: any agent capable of binding specifically to
components of the immune system (eg. BCR on B cells)
Substances that can mobilize adaptive defenses and provoke an
immune response
Targets of all adaptive immune responses
Immunogen: any agent capable of inducing an immune
response immunogenic
All immunogens are antigens but not all antigens are
immunogens (eg. low molecular weight compounds such
as many antibiotics and drugs)
By themselves, these compounds (low MW hapten) are incapable
of inducing an immune response but when coupled with a larger
entity (carrier protein), the conjugate induces a response
Complete Antigens
Important functional properties
Immunogenicity: ability to stimulate
proliferation of specific lymphocytes
Reactivity: ability to react with activated
lymphocytes and antibodies released by
immunogenic reactions
Examples: foreign protein,
polysaccharides, lipids, and nucleic
acids
Requirements for Immunogenicity
Foreignness vs. self
we will not make antibody to human albumin but
will make antibody to rabbit albumin; the more
foreign the compound, the more immunogenic; autoimmunity is an
exception!!!
High molecular weight: small substances have immunogenicity
while large substances have immunogenicity
Immature
lymphocyte
Red bone marrow
T cell T cell
receptor receptor
Maturation
Activation Activation
APC
(dendritic cell) Memory APC
cells (dendritic cell)
CD4 CD8
Effector
cells
Blood plasma
Primary and Secondary
Responses
First exposure to antigen is the primary
immunization
The first measurable response is the
primary response
The second exposure results in a stronger
secondary response
quick onset and higher magnitude
also called memory (anamnestic) response by
memory B & T cells
Memory T cells: central memory Tcm & effector memory Tem expressing for
different chemokine receptors
More on memory T cells
Recent studies suggest that Tcm are mostly
found in lymph nodes and have limited
effector function but can become effector
cells with subsequent stimulation
Intended for long term protection?
By contrast, Tem subpopulation has a strong
presence in peripheral tissues which can
rapidly produce cytokines (IFN) with antigenic
encounter but are limited in proliferative
capacity
Short term or immediate protection?
Antigenic Determinants
Only certain parts (antigenic
determinants) of entire antigen are
immunogenic
Antibodies and lymphocyte receptors
bind to them as enzyme binds substrate
Antigenic Determinants
Most naturally occurring antigens have
numerous antigenic determinants that
Mobilize several different lymphocyte
populations
Form different kinds of antibodies against
them
Large, chemically simple molecules
(e.g., plastics) have little or no
immunogenicity
Figure 21.7 Most antigens have several different antigenic determinants.
Antigen
Antibody B
Antibody C
Major Classes of Antigens
Carbohydrates (polysaccharides)
may be part of cell-surface polysaccharides
Lipids (may be regarded as haptens)
are rarely immunogenic unless conjugated to
carrier proteins
Nucleic acids
poor immunogens by themselves but are very
good when bound to carrier proteins
Proteins (due to size and complexity)
best immunogens, multideterminant antigens
Summary of Antigens
Self-antigens: MHC Proteins
Protein molecules (self-antigens) on
surface of cells not antigenic to self but
antigenic to others in transfusions or
grafts
Example: MHC glycoproteins
Coded by genes of major histocompatibility
complex (MHC) and unique to individual
Have groove holding self- or foreign
antigen
T lymphocytes can only recognize antigens that
are presented on MHC proteins
MHC Proteins and Antigen
Presentation
T cells respond only to processed
fragments of antigens displayed on
surfaces of cells
Antigen presentation vital for activation
of naive T cells and normal functioning
of effector T cells
MHC Proteins
Two types of MHC proteins important to
T cell activation
Class I MHC proteins displayed by all
cells except RBCs
Class II MHC proteins displayed by APCs
(dendritic cells, macrophages, and B cells)
Both types are synthesized at ER and
bind to peptide fragments
Class I MHC Proteins
Bind with fragment of protein synthesized in
the cell (endogenous antigen)
Endogenous antigen is self-antigen in normal
cell; a nonself antigen in infected or abnormal
cell
Crucial for CD8 cell activation
Inform cytotoxic T cells of microorganisms
hiding in cells (cytotoxic T cells ignore
displayed self-antigens)
Act as antigen holders; form "self" part that T
cells recognize
Class II MHC Proteins
Bind with fragments of exogenous
antigens that have been engulfed and
broken down in a phagolysosome
Recognized by helper T cells
Signal CD4 cells that help is required
What do T and B Cells See in
an Antigen?
T cells, unlike B cells, are not able to
bind soluble antigen
TCRs require processing of antigen and
association with MHC I (Tc) or MHC II (Th)
Generally T cells recognize internal,
denatured protein segments
Polysaccharides do not yield internal
epitopes and therefore do not activate T
cells
What do T Cells See in an
Antigen?
What do T and B Cells See in an Antigen?
B cells recognize 5-7 amino acids, the size that
binds to the IgD antibody
Th and Tc cells recognize 8-15 amino acids that
binds to the TCR
a few more amino acids are needed to bind with the
MHC II (Th) or MHC I (Tc) on APC
B cells have membrane-bound antibody that
binds free antigen in solution
the antigen will be on the outside of the molecule and
accessible (for interaction with B cell receptor)
antigen may be sequential or nonsequential amino
acids
Protein
Structure
Sequential Epitopes
Sperm whale
myoglobin
showing
location of five
sequential
epitopes
Nonsequential Epitopes
Chicken egg
lysozyme showing
location of
nonsequential
epitopes
residues in red contact
antibody heavy chain
3 Clone
formation Activated
CD4 T cells proliferate
(clone), and become
memory and effector
cells.
Memory
CD4 T cell Helper
T cells
T cell Activation: Proliferation
and Differentiation
Primary T cell response peaks within a week
T cell apoptosis occurs between days 7 and
30
Benefit of apoptosis: activated T cells are a hazard
produce large amount inflammatory cytokines
hyperplasia, cancer
Effector activity wanes as amount of antigen
declines
Memory T cells remain and mediate
secondary responses
Roles of Helper T (TH) cells
Play central role in adaptive immune
response
Activate both humoral and cellular arms
Once primed by APC presentation of
antigen, they
Help activate T and B cells
Induce T and B cell proliferation
Their cytokines recruit other immune cells
Without TH, there is no immune
response
Helper T cells: Activation of
B cells
Interact directly with B cells displaying antigen
fragments bound to MHC II receptors
Stimulate B cells to divide more rapidly and
begin antibody formation
B cells may be activated without TH cells by
binding to T cellindependent antigens
Response weak and short-lived
Most antigens require TH co-stimulation to
activate B cells: T celldependent antigens
Figure 21.18a The central role of helper T cells in mobilizing both humoral and cellular immunity. Slide 1
Helper T cell
1 TH cell binds
T cell receptor (TCR) with the self-nonself
complexes of a B cell
that has encountered
Helper T cell
its antigen and is
CD4 protein displaying it on
MHC II on its surface.
MHC II protein
of B cell displaying
processed antigen 2 TH cell releases
interleukins as co-
IL-4 and other stimulatory signals to
cytokines complete B cell
activation.
3 Dendritic cell
can now activate
Class I CD8 CD8 cell with the
MHC protein protein help of interleukin 2
CD8 T cell secreted by TH cell.
(becomes TC cell
after activation)
Helper T cells: Amplification of
Innate Defenses
Granule
Perforin
TC cell
membrane Cytotoxic
T cell
Target
cell
membrane
Target Cancer cell
cell Perforin
pore
Granzymes
Inhibits Inhibits
Triggers
Surface Internal
barriers defenses
Free Ags
may directly
activate B cell
Ag-infected
body cell engulfed
by dendritic cell Antigen-
activated
Becomes B cells
Clone and
Secrete
Cytotoxic Helper
T cells T cells
Cytokines stimulate
Nonspecific killers
(macrophages and Antibodies (Igs)
Together the nonspecific killers
and cytotoxic T cells mount a NK cells of innate Circulating lgs along with complement
physical attack on the Ag immunity) mount a chemical attack on the Ag
Cross-Reactivity
A toxoid cross-reacts with its toxin
10-12 grams tetanus toxin kills a mouse while
10-6 grams required for immunization
Toxoid that is modified still acts as an
immunogen that cross-reacts with toxin
Toxoid still shares epitopes with toxin
Human blood group A reacts with antiserum
raised against Streptococcus capsule or
influenza virus
Human blood group B reacts to serum raised
to E. coli
Immunologic Adjuvants
To enhance the immune response to a
given immunogen, additives are added
Adjuvant (Latin, to help) enhances the
immune response
aluminum potassium sulfate (alum) is
the only adjuvant used in the United
States
causes immunogen to precipitate resulting
in time-release (released more slowly) & increased
precipitated antigen size is more likely to be phagocytized
Immunologic Adjuvants
In Europe, they use BCG adjuvant (bacille
Calmette-Guerin): most widely used vaccination in the world
composed of attenuated Mycobacterium bovis,
Corynebacterium, and Bordetella pertussis
also acts as TB vaccine
very good at activating macrophages to
phagocytize and present to T cells
In animals, use Freunds complete adjuvant
that contains killed Mycobacterium
tuberculosis