Download 3. Immune Response B cells 4.10.16.ppt

CHAPTER 11
THE IMMUNE RESPONSE
B cells
Prof. Win Win Maw
MBBS, PhD(Shimane),
FACTM(Australia),
Dip MedEd
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IMMUNE RESPONSE B CELLS
• Naive B cells
• reside in and circulate through the follicles of peripheral
lymphoid organs
• ( Lymph nodes, spleen, mucosa).
• Most B cells enter follicles and are called follicular B cells.
•
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Ag, T and B cels entry into Lymph
Nodes
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IMMUNE RESPONSE B CELLS
•
• Bone marrow B cells
B cells from circulation
through High Endothelial Venue
enter paracortex
region of lymph nodes
enter follicle in cortex.
• (Follicular dendritic cells and stroma cell secrete CxCL 13
bind to receptor - CxCR5 on B cells and
• attract B cells to follicle)
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Antigen capture and delivery to B cells
• 1. Antigen from tissue sites are transported to lymphoid
organs by afferent lymphatics, drain to subcapsular sinus
and conduit.
• 2. Sub capsular sinus macrophages capture and transport
to follicle
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Antigen capture and delivery to B cells
• 3. Large antigens are captured by medullary dendritic
cells to follicles
• 4. Immune complex bind to Cr 1, 2 of merginal zone B
cells, or FDC
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Activation of B Cells
1. T-cell–dependent response
• Antigen binds to IgM or IgD on the surface of the B cell,
• is internalized within the B cell, and
• is fragmented;
• transported to the surface in association with class II MHC
molecules. Interact with TCR on T cells
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• if the costimulatory signal
• is given by the B7 protein on the B cell interacting with
CD28 protein on the helper T cell,
• the helper T cell is then stimulated to produce
interleukins (e.g., IL-2, IL4 and IL-5)
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Activation of B Cells
• 1. T-cell–dependent response
• Interleukins alone are not sufficient to activate B cells.
• CD40 ligand (CD40L), on activated helper T cells
• must interact with a protein called CD40 on the surface of
the resting B cells
A. to stimulate the differentiation of B cells into
antibody-producing plasma cells.
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“class switching”
A.
IL-4 and IL-5 induce “class switching”
from IgM,
which is the first class of immunoglobulins
produced, to other classes, namely, IgG, IgA,
and IgE.
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• The CD28-B7 interac on is required for
ac va on of the T cell to produce interleukins,
and
• the CD40L-CD40 interac on is required for
class switching from IgM to other
immunoglobulin classes, such as IgM and IgA,
to occur.
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• Furthermore, other proteins on the surface of these
cells serve to strengthen the interaction between the
helper T cell and the antigen-presenting B cell
(e.g., CD28 on the T cell interacts with B7 on the B
cell, and
LFA-1 on the T cell interacts with ICAM-1 on the B cell).
(There are also ICAM proteins on the T cell that interact
with LFA proteins on the B cell.)
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Immunoglobulin Class Switching
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2. T-cell–independent response: by Marginal zone B cells
and B1 B cell
• Antigens (e.g., polymerized [multivalent]
macromolecules such as bacterial capsular
polysaccharide) are T-cell–independent.
• consisting of repeated subunits of several sugars.
• act as a multivalent antigen that
• cross-links the IgM antigen receptors on the B cell
• Other macromolecules, such as DNA, RNA, and many
lipids, also elicit a T-cell–independent response.
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T I response - induced class switching
• In the T-cell–dependent response, all classes of antibody
are made (IgG, IgM, IgA, etc.),
• whereas in the T-cell – independent response, primarily
IgM is made.
• The T-cell–dependent response generates memory B cells,
• the T-cell–independent response does not;
• Activation -induced deaminase (AID) is responsible for
isotype switching.
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Control
Inhibi on
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Control
Ac va on
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Activation
• Extra follicular activation - at the paracortex and
medulla, low affinity Ab production
• Follicular activation - somatic hypermutation,
affinity maturation, class switching
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B cells differentiation into antibody secreting plasma cells
(cellular 263)
1. Signals from BCR and IL 21- generation of plasma cells
2. Plasmablast in the circulation and plasma cells generated
in germinal centres can go home to bone marrow where
they are maintained by the cytokines of BAFF family that
bind to BCMA on plasma cells.
3. This allow plasma cells to survive for long periods, often
as long as the life span of the host.
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B cells differentiation into antibody secreting plasma cells
(cellular 263)
4. Two to 3 weeks after immunization bone marrow becomes
a major site of antibody production.
5. Plasma cells in the bone marrow(BM) may continue to
secret Abs for months or even years after the antigen is no
longer present.
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SHORT
LIVE
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LONG LIVE BMarrow
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Structural alteration of plasma cells
• 1. The cell enlarges dramatically
• 2. the ratio of cytoplasm and nucleus increase
• 3. ER may become prominent Ig become membrane
form to secreted form
• Plasma cells produced in early phase of immune
response from marginal zone B cells or B1B cells are
short - lived.
• Plasma cells produced in germinal centre are long-lived.
IgG antibody in the circulation is derived from
long-lived plasma cells of BM.
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Humoral responses
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Memory B cells
• express high levels of anti apoptotic protein Bcl2; bear
high affinity receptor of class switching
• Hyper-IgM syndrome is caused by a mutation in the gene
encoding CD-40 L. Patients have very high IgM levels
and very little IgG, IgA and IgE because they cannot
“classswitch.”
• This syndrome is characterized by severe pyogenic
infections.
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hapten-specific antibody
• To stimulate hapten-specific antibody, the hapten must be
covalently bound to the carrier protein.
• The hapten binds to the IgM receptor on the B-cell surface.
• That IgM is specific for the hapten, not the carrier protein.
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hapten-specific antibody
• The hapten-carrier conjugate is
• internalized and the carrier protein processed into small
peptides
• that are presented in association with class II MHC proteins
to a helper T cell bearing a receptor for that peptide.
• The helper T cell then secretes lymphokines that activate
the B cell to produce antibodies to the hapten.
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