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ANTIBODY STRUCTURE AND FUNCTION
Asilmi 06 - B CELLS AND ANTIBODIES
Antigens are detected by specialized T cell receptors (TCR)
or B cell receptors (BCR).
APC
T cell
T cells require antigen
presentation by dedicated
antigen presenting cells
(APC)
B cell
The BCR directly
recongnizes its
cognate antigen
Asilmi 06 - B CELLS AND ANTIBODIES
LYMPHOCYTE ACTIVATION IS TRIGGERED BY ANTIGEN RECOGNITION
Antigen recognition is mediated
by structurally related cell
surface molecules: membranebound antibodies on B
lymphocytes and T cell receptors
on T lymphocytes.
MICROBE
B CELL
Antigen receptors distinguish many, and often chemically related,
structures.
Antigen receptors are clonally distributed: Each clone has a unique
receptor distinct from all other receptors
Clone: A parental lymphocyte and all its progeny.
Asilmi 06 - B CELLS AND ANTIBODIES
2. When adjacent antigen
receptors bind two or more
antigens the receptors are pulled
together into an aggregate.
Extracellular
BCR
Intracellular
1. Antigen receptors are noncovalently associated with
cellular signaling proteins in the
BCR or TCR complex.
BCR COMPLEX
BCR/TCR ACTIVATION
3. Cross-linking brings signaling proteins together and initiates signal
transduction.
4. As the signaling proteins are the same in each clone, the transduced
signal is also the same.
Asilmi 06 - B CELLS AND ANTIBODIES
B CELLS
1. B CELLS ARISE FROM BONE MARROW STEM CELLS.
2. MATURE B CELLS EXIT BONE MARROW AND ENTER THE CIRCULATORY SYSTEM.
3. B CELLS RECIRCULATE THROUGH LYMPHOID ORGANS IN SEARCH OF ANTIGEN.
Asilmi 06 - B CELLS AND ANTIBODIES
B CELLS
1. BCR detect three-dimensional
antigens.
2. B cell activation does not
require antigen presentation.
3. B cells are active only against
extracellular antigens.
Asilmi 06 - B CELLS AND ANTIBODIES
B CELLS AND ANTIBODIES
1. Each B cell makes One specificity of antibody (Immunoglobulin (Ig)).
The antigen receptor is membrane bound on a naïve B cell.
2. Ag plus second signal stimulate B cell.
3. Active B cell secretes antibody into the blood and lymph or patrolling
mucosal surfaces.
Asilmi 06 - B CELLS AND ANTIBODIES
B CELLS AND ANTIBODIES
Secreted
antibodies
BCR
Naive
Active
In the transition from naïve to active B cells, the B cells secrete a modified
version of the B cell receptor. This molecule is known as an antibody.
The BCR and corresponding antibody share IDENTICAL antigen
specificities.
Asilmi 06 - B CELLS AND ANTIBODIES
What are Antibodies?
Antibodies (A.K.A. Immunoglobulin) are a type of
glycoprotein produced by B lymphocytes. Antibodies bind
antigen with a high degree of specificity and affinity.
Antibodies recognize a variety of three-dimensional shapes
(amino acids, lipids, carbohydrates, etc).
Asilmi 06 - B CELLS AND ANTIBODIES
ANTIBODY STRUCTURE
An antibody consists of four
polypeptides: two identical light
chains and two identical heavy
chains form a Y-shaped molecule.
Each light chain is connected to a
heavy chain by a disulfide bond and
the two heavy chains are connected
by two disulfide bonds.
Antigen binding and effector
domains are separated by a hinge
region. The hinge region allows the
two antigen binding domains to
move, enabling them to bind
antigens that are separated by
varying distances.
LIGHT CHAIN
HEAVY CHAIN
Asilmi 06 - B CELLS AND ANTIBODIES
ANTIBODY STRUCTURE
ANTIGEN RECEPTORS HAVE
DISTINCT FUNCTIONAL DOMAINS
1. The variable (V) region varies
between clones and is involved in
antigen recognition.
2. The constant (C) region is
conserved among clones and is
required for structural integrity and
effector functions.
Asilmi 06 - B CELLS AND ANTIBODIES
ANTIBODY STRUCTURE
The unique structural architecture of antibodies allows multiple, highly
diverse antigens to induce identical effector functions.
Antigen
Variable region
Constant region
IMMUNITY
IMMUNITY
IMMUNITY
Different variable regions bind different antigens. Identical constant
regions induce identical responses.
Asilmi 06 - B CELLS AND ANTIBODIES
ANTIBODY STRUCTURE
Each Light chain contains one V
domain and one C domain.
Each Heavy chain contains one V
domain and at least three C
domains.
Each domain folds into a
characteristic 3-D shape:
The Immunoglobulin (Ig)
domain.
VL
Antibodies bind antigens through the variable
regions of the light and heavy chains.
VH
Asilmi 06 - B CELLS AND ANTIBODIES
BINDING OF ANTIGEN BY ANTIBODY - TERMS AND CONCEPTS
Epitope
Antibodies bind antigens by reversible noncovalent interactions.
Epitope
Epitope: The parts of an antigen recognized
by an antibody are called epitopes. Epitopes
can be recognized on the basis of sequence
or shape.
Affinity: The strength with which one
antigen-binding surface of an antibody binds
an antigen.
Avidity: Each Isotype has between 2 and 10 antigen binding sites. Therefore, each antibody
can bind 2 to 10 epitopes of an antigen, as long as identical epitopes are sufficiently close
together, e.g. microbial cell surface proteins. In this case the binding is much greater than
the affinity of a single antibody-antigen bond and is called the avidity.
Asilmi 06 - B CELLS AND ANTIBODIES
Specific Antibody (Ig) Molecules Are Tailored to Exactly Fit A
3 D Surface Site On An Antigen.
Epitope
Influenza coat protein
Ig
Asilmi 06 - B CELLS AND ANTIBODIES
FEATURES OF ANITBODY-MEDIATED
ANTIGEN RECOGNITION
1. Antibodies recognize a large array of 3-D structures.
2. Each clone is specific for a single antigen.
3. Antigen recognition is mediated by specific domains of the
antibody.
4. Signaling triggers B lymphocyte activation.
Asilmi 06 - B CELLS AND ANTIBODIES
B CELL ACTIVATION
B cell activation requires two signals
1. Antigen
A. T Cell-independent.
1st signal: BCR detects Ag.
1. Antigen
2. PAMP
PRR
BCR
2. PAMP
PRR
BCR
2nd signal: PRR detects PAMP.
B cell
B. T Cell-dependent.
Active B cell
Cytokines
1. Ag
CD4+ T cell
1st signal: BCR detects Ag.
B cell internalizes Ag and
presents to CD4+ T cell (B cell as
APC).
2nd signal: T cell produces
cytokines that activate B cell.
BCR
MHC II/Ag
B cell
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
There are five types of heavy chain that differ in
their C region. Each class is an Isotype. Each
Isotype differs in their physical/biological
properties and effector functions.
IgA. Two IgA
molecules joined
by J chain.
The J chain facilitates transport of IgA
across mucosal epithelia. The J chain
also facilitates transfer of IgA to
newborns to confer neonatal passive
immunity.
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
IgD. Function unknown. Restricted to
membrane and not expressed on active B
lymphocytes. IgD knock-out mice do not have
any apparent defects.
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
Antigen
IgE
Fc Receptor
Secreted as a
monomer.
MAST
CELL
IgE binds the Fc receptors of mast cells.
When IgE is cross-linked by
antigen, it triggers mast cell
degranulation - allergic
response.
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
Secreted as
monomer
IgG can bind
and neutralize
toxins.
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
Opsonization: IgG coats pathogens and
prevents them from entering host cells.
Infectious pathogen
entering host cell
to propagate
Pathogen cannot
enter cell
when coated
(“opsonized”) with
antibody
Asilmi 06 - B CELLS AND ANTIBODIES
Ag
IMMUNOGLOBULIN ISOTYPES
Phagolysosme
IgG
FcR
Macrophage
MHC II/peptide
1. IgG-Ag binds the Fc receptor of
macrophages.
2. Ag is internalized through phagocytosis.
3. Microbe is degraded in the phagolysosome.
4. Microbial peptides are presented on Class II
MHC molecules - CD4 T cell activation!
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
Fc receptors also mediate Antibody-Dependent
Cellular Cytotoxicity (ADCC)
Natural Killer Cells
Ig
Target
Ag
1. Ig binds Ag on surface of target cell.
2. Fc Receptors on Natural Killer cells bind Fc
of Ig.
3. Cross-linking of Fc receptors signals to the
NK cell to kill the target.
4. Target cell dies by apoptosis
Asilmi 06 - B CELLS AND ANTIBODIES
IMMUNOGLOBULIN ISOTYPES
IgM exists as pentamers
10 different Ag binding
sites - very high avidity!
As with IgA, it has a J
chain for secretion.
IgM is the first antibody expressed in mature B
cells.
Important for activation of the complement
pathway. Appears early after infection and
usually not seen upon re-infection.
Asilmi 06 - B CELLS AND ANTIBODIES