HUMORAL IMMUNE

RESPONSES
IMMUNOLOGY
THURSDAY, JUNE 11TH 2009

Ika Yustisia
Biochemistry
Department
Faculty of Medicine
 CONTENTS (1)

Introduction
Phases and Types of Humoral Immune
Responses
Stimulation of B Lymphocytes by Antigen
Antigen-Induced Signaling in B Cells
The Role of Complement Proteins in B Cell Activation
Functional Consequences of Antigens-Mediated B
Cell Activation
 CONTENTS (2)

The Function of Helper T Lymphocytes in

Humoral Immune Responses to Protein Antigens
Activation and Migration of Helper T Cells
Presentation of Antigens by B Lymphocytes to Helper
T Cells
Mechanisms of Helper T Cells-Mediated Activation of
B Lymphocytes
Heavy Chain Isotype (Class) Switching)
Affinity Maturation
Antibody Responses to T-independent Antigens
Regulation of Humoral Immune Responses:
Antibody Feedback
 INTRODUCTION

Humoral immunity is mediated by antibodies

and is the arm of the adaptive immune
response that functions to neutralize and
eliminate extracellular microbes and
microbial toxins
Humoral immunity is more important than
cellular immunity in defending against
microbes with capsules rich in poly-
saccharides and lipids, and against
polysaccharide and lipid toxins
 How are receptor-expressing B lymphocytes
activated and converted to antibody-
secreting cells?
How is the process of B cell activation
regulated so that the most useful types of
antibodies are produced in response to
different types of microbes?
The humoral
immune
response is
mediated by
antibody
molecules
that are
secreted by
plasma cells
PHASES AND TYPES OF HUMORAL
IMMUNE RESPONSES
Naive B lymphocytes
Express two classes of membrane-bound antibodies
IgM and IgD that function as the receptors for
antigens
Activated by antigens and by other signals
Activation of B lymphocytes
Proliferation of antigen-specific cells (clonal
expansion)
Differentiation into effector cells (plasma cells) that
actively secrete antibodies
Once activated B cell may
generate up to 4000 plasma
cells, which can produce
10 antibody molecules per day

Phases of humoral immune responses

 Antibody responses to different antigens are
classified as T-dependent or T-independent,
based on the requirement for T cell help
Different subsets of B cells respond
preferentially to protein and nonprotein
antigens
Antibody responses to the first and
subsequent exposures to an antigen, called
primary and secondary responses, differ
quantitatively and qualitatively
Subsets of B cells
Features of
primary and
secondary
antibody
responses
STIMULATION OF B LYMPHOCYTES
BY ANTIGEN

Humoral immune responses are initiated

when antigen-specific B lymphocytes in the
spleen, lymph nodes, and mucosal lymphoid
tissues recognize antigens
Antigen-induced signaling in B cells

Antigen-induced clustering of membrane Ig

receptors triggers biochemical signals that
are transduced by receptor-associated
signaling molecules
Antigen receptor-mediated signal transduction in B lymphocytes
The role of complement proteins in
B cell activation

B lymphocytes express a receptor for a

protein of the complement system that
provides signals for the activation of the
cells
The role of the
complement
protein C3d in
B cell
activation
Functional consequences of antigen-
mediated B cell activation

The consequences of B cell activation by

antigen (and second signals) are to initiate
B cell proliferation and differentiation and to
prepare the B cells to interact with helper T
lymphocytes (if the antigen is a protein)
 Functional
consequences of
immunoglobulin
(Ig)-mediated B
cell activation
 THE FUNCTION OF HELPER T
LYMPHOCYTES IN HUMORAL IMMUNE
RESPONSES TO PROTEIN ANTIGENS

For a protein antigen to stimulate an

antibody response, B lymphocytes and
helper T lymphocytes specific for that
antigen must come together in lymphoid
organs and interact in a way that stimulates
B cell proliferation and differentiation
Activation and migration of helper
T cells

Helper T cells that have been activated to

differentiate into effector cells interact with
antigen-stimulated B lymphocytes at the
edges of lymphoid follicles in the peripheral
lymphoid organs
The interactions of helper T cells and B cells in lymphoid tissues
Presentation of antigens by
B lymphocytes to helper Tcells

B lymphocytes that bind protein antigens by

their specific antigen receptors endocytose
these antigens, process them in endosomal
vesicles, and display class II MHC-
associated peptides for recognition by
CD4+ helper T cells
 Antigen
presentation by B
lymphocytes to
helper T cells
Mechanisms of helper T cell-mediated
activation of B lymphocytes

Helper T lymphocytes that recognize

antigen presented by B cells activate the B
cells by expressing CD40 ligand (CD40L)
and by secreting cytokines
Mechanisms of helper T cell-mediated activation of B lymphocytes
Heavy chain isotype (class) switching

Helper T cells stimulate the progeny of IgM and

IgD-expressing B lymphocytes to produce
antibodies of different heavy chain isotypes
(classes)
Heavy chain isotype switching is induced by a
combination of CD40L-mediated signals and
cytokines
Cytokines produced by helper T cells determine
which heavy chain isotype is produced by
influencing which heavy chain constant region
gene participates in switch recombination
Immunoglobulin (Ig) heavy chain isotype (class) switching
 Mechanism of
immunoglobulin
(Ig) heavy chain
isotype
switching
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
Affinity maturation in antibody responses
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
 Selection of
high-affinity B
cells in germinal
centers
Affinity maturation

The various stages of antibody responses to

T cell-dependent protein antigens occur
sequentially and in different anatomic
compartments of lymphoid organs
The anatomy of humoral immune responses
Germinal Centers
Animation
Plasma cells secrete antibody at high rate but can no longer
respond to antigen or helper Tcells
 ANTIBODY RESPONSES TO
T-INDEPENDENT ANTIGENS
Polysaccharides, lipids, and other nonprotein
antigens elicit antibody responses without the
participation of helper T cells
The nonprotein antigens cannot bind to MHC
molecules, so they cannot be seen by T cells
Polysaccharide and lipid antigens are able to
cross-link many antigen receptors on a
specific B cell
Features of antibody responses to T-dependent and
T-independent antigens
REGULATION OF HUMORAL IMMUNE
RESPONSES:
ANTIBODY FEEDBACK
After B lymphocytes differentiate into
antibody-secreting cells and memory cells, a
fraction of these cells survive for long
periods, but most of the activated B cells
probably die by a process of programmed
cell death. This gradual loss of the activated
B cells contributes to the physiologic decline
of the humoral immune response
The mechanism
of antibody
feedback
REFERENCES

Abbas, A.K., Licthman, A.H.: Basic Immunology,

3th edn. Philadelphia, Saunders Elsevier, 2009
Janeway, C.A., Travers, P., Walport, M.,
Shlomchick, M.J.: Immunobiology, 6th edn. New
York, Garland Science, 2005
SUMMARY

Humoral immunity is mediated by antibodies

Humoral immune responses to nonprotein
antigens are initiated by the recognition of the
antigens by specific Ig receptors of naive B cells.
Humoral immune responses to a protein antigen,
called T-dependent responses
SUMMARY

Heavy chain isotype switching (or class switching)

is the process by which the isotype, but not the
specificity, of the antibodies produced in response
to an antigen changes as the humoral response
proceeds
Affinity maturation is the process by which the
affinity of antibodies for protein antigens
increases with prolonged or repeated exposure to
the antigens.
SUMMARY

T-dependent humoral responses generate long-

lived plasma cells
Polysaccharides, lipids, and other nonprotein
antigens are called T-independent antigens
because they induce antibody responses without
T cell help.
Secreted antibodies form immune complexes with
residual antigen and shut off B cell activation by
engaging an inhibitory Fc receptor on B cells.
Thank You
for Attention

Discussion and Lecture Consultation:

Biochemistry Department
Faculty of Medicine UNHAS
ikayustisia@yahoo.com