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HUMORAL IMMUNE
RESPONSE
Tran Thi Thu Phuong, PhD, PharmD
Email: [email protected]
Humoral immunity
Activation of B cell by antigen
Mechanisms antibodies participate in clearance of antigens
Antibody class switching and affinity maturation-Phase of
humoral immune responses
Regulation of humoral immune response: antibody feed
back
Primary and secondary responses to the same antigen
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B cell activation
B cell development in bone marrow
Stem cell Pro-B Pre-B Immature B Mature B
Peripheral lymphoid organs (lymph nodes, spleen etc.)
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
Microbes enter body,
get captured,
processed and
presented their
antigens to the
immune system
Naïve B cells
contact with Ag
and then get
activated at
peripheral lymphoid
tissues (lymph
nodes or spleen)
Abbas A. K and Lichtman A. H
Basic Immunology 3nd Ed
© Saunders 2011
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B cell proliferation and
B cell selection (by Ag) differentiation
Progeny cell have
the same
specificity (BCR
and secrete Ab) as
mother cell
B Plasma
cell cell
Each B cell has (pre-made) receptors that can
bind only to ONE epitope Binding to
epitope is signal to activate the cell.
The ONE (B cell) that can bind to epitope is
“SELECTED” for activation Antige
n Antibod
y
Changes in B cell upon activation
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
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Changes in B cell upon activation
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
T cell-dependent and T cell-independent antigens
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Production of Abs to
T cell-dependent antigens
B cell captures, processes and then
presents antigen to TH cell or recognition
and analyze information about the antigen
Base on the nature of antigen, TH cell will
give B cell appropriate help in order to
produce best protection against the
pathogen
Abbas A. K, Lichtman A. H, and Pillai S.
Basic Immunology 6th Ed © Saunders 2020
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TH cell activates B cell
B cell presents Ag to TH cell; TH cell recognizes Ag then secretes cytokine to stimulate B
cell. Upon stimulation by Ag and cytokine produced by TH cell, B cell proliferates and
differentiates to plasma cell which secrete Abs
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Mechanisms by which antibodies clear out antigens
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
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Antibodies neutralize microbes and toxins
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
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Antibody blocks virus, does not allow the virus to
infect to the cell
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Antibody blocks does not allow them to infect to the cell
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Opsonization of microbe for phagocytosis by phagocytes
Abbas A. K, Lichtman A. H, and Pillai S.
Basic Immunology 6th Ed © Saunders 2020
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Opsonization of microbe for phagocytosis by phagocytes
By opsonization with specific Ab the adaptive immune response (HI)
has utilize and “arm” a non-specific mechanism of innate immunity
to become more effective and powerfull one (strong and specific)
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Antibody-dependent Cellular Cytotoxicity (ADCC)
NK cell and IgG work together to remove cancer cell and virus-
infected cell
Abbas A. K, Lichtman A. H, and Pillai S.
Basic Immunology 6th Ed © Saunders 2020
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Antibody-dependent Cellular Cytotoxicity (ADCC)
Eosinophil and IgE work together to remove worms
Abbas A. K, Lichtman A. H, and Pillai S.
Basic Immunology 6th Ed © Saunders 2020
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Ab activates complement by classical pathway to remove microbe
(adaptive immunity employs and enhances an innate immunity
mechanism – make it stronger and “specific” to microbe)
2 - Inflammation
3 – Lysis
1- Opsonization by C’ Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
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Effects of antibodies
via C’ activation
Humoral immunity
Phase of humoral immune responses
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed © Saunders 2011
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Antibody class switching
(heavy chain isotype switching)
Antibody class switching is the
phenomenon by that plasma cell
turns to produce heavy chains of
other chains - not µ nor
of IgM and IgD as SIgM & SIgD
play as BCR of the B cell originally
interact with antigen, consequently
produce new classes of Abs.
Significance: help to customize immune
Abbas A. K, Lichtman A. H, and Pillai S.
response to fight more effectively to microbe. Basic Immunology 6th Ed © Saunders 2020
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Examples of class switching
Microbes in blood or the extracellular spaces are easily achievable by
IgG turns to produce gamma chain the obtained antibody is IgG.
Microbes that attack to mucous membrane, the most powerful antibody
at mucous membrane is IgA turns to produce alpha chain obtained
antibody is IgA.
Worms are very big and can only be destroyed with toxins from
eosinophil turns to produce epsilon chain obtained antibody is IgE
that help eosinophil to approach the worms to kill them.
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Molecular mechanism of class
switching
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Switching or not, it depends on the help of TH
Which isotype (class of Ab) depends on
which cytokines the TH cell secrete
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Affinity maturation
Affinity maturation is the process by which
the affinity of antibodies produced in
response to a protein antigen increases
with prolonged or repeated exposure to
that antigen
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Affinity maturation
Affinity maturation occurs in the germinal
centers of lymphoid follicles and is the result
of somatic hypermutation of Ig genes in
dividing B cells, followed by the selection of
high-affinity B cells by antigen
Take place in germinal center of lymph node.
It is the process of selection of B cell which have
higher affinity of BCR to bind to antigen presented by
DC cell.
The winner survives, the loser is dead by apoptosis.
Significance: Having the increased
affinity help antibodies bind better to
microbes or their antigens if prolonged
infection or repeated infection happen
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Ab affinity maturation:
Binding affinity of Ab to Ag increases after long or repeated
exposure to Ag
Basic Immunology 3rd Ed © Saunders 2011
Abbas A. K and Lichtman A. H
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Production of Abs
to T cell-independent
antigens
oOften weak respond Janeway’s Immunology, 9/e. (®Garland Science 2017)
oCan produce IgM only
o Still need TH help for
production of IgG
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Regulation of humoral immune
response: antibody feed back
FcγRIIB receptor (a special type of Fc
receptor expressed on B cells ) delivers
inhibitory signals that shut off antigen
receptor–induced signals, thereby
terminating B cell responses. This process,
in which antibody bound to antigen inhibits
further antibody production, is called
antibody feedback
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Primary and secondary (2nd, 3rd, 4th etc.) Ab
production to the same Ag
Primary response is the response to the Ag for the first time that Ag enters
body; secondary response is response after the same Ag enter body
from second time onwards.
Different profiles of Abs produce in the primary and
secondary responses
Lag duration is shorter in 2nd response (faster)
Amount of Ab produced in 2nd response is higher (stronger)
🗸 The existance of Abs in 2nd response is longer (longer)
🗸 More IgM in 1st response, more IgG in 2nd response (wiser)
More effective
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Primary and Secondary Responses Differ Significantly
Kuby Immunology 5th Ed ©Freeman and Company 2003
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Different populations of B cells are responsible in
1st and 2nd reponse that make the differencies
Basic Immunology 3rd Ed © Saunders 2011
Abbas A. K and Lichtman A. H
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Practical implications
Repeat vaccination.
One vaccination can produce memory cells, these cells may reduce the
number as time pass.
Repeating vaccination to maintain necessary number of memory cells
for effective 2nd response.
Analyse the contain of specific IgM and IgG to know:
an individual who has infection, it is the first time (primary, IgM) or repeated
infection (secondary, IgG).
a population having a pandemic, it is the first time the disease hit that
population (primary, IgM) or the outbreak of an old pandemic (secondary,
IgG).
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Practical implications
Repeated immunization is required for
IgG production.
Vaccination need to be done long enough
before coming to the pandemic area.
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