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 .

called primary and secondary responses. differ quantitatively and qualitatively .• 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.

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. and mucosal lymphoid tissues recognize antigens . lymph nodes.

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 .

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 . THE FUNCTION OF HELPER T LYMPHOCYTES IN HUMORAL IMMUNE RESPONSES TO PROTEIN ANTIGENS • For a protein antigen to stimulate an antibody response.

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. and display class II MHC- associated peptides for recognition by CD4+ helper T cells . process them in endosomal vesicles.

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 .

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 . 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.

Features of antibody responses to T-dependent and T-independent antigens .

but most of the activated B cells probably die by a process of programmed cell death.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. This gradual loss of the activated B cells contributes to the physiologic decline of the humoral immune response .

The mechanism of antibody feedback .

A. P.: Immunobiology.. M. 6th edn. 2005 . 3th edn.: Basic Immunology. Travers.K.A. C. Saunders Elsevier. Licthman. Walport. New York. 2009 • Janeway. M. Garland Science...H. Shlomchick.REFERENCES • Abbas. Philadelphia.J. A..

called T-dependent responses .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.

.SUMMARY • Heavy chain isotype switching (or class switching) is the process by which the isotype. 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. but not the specificity.

• Secreted antibodies form immune complexes with residual antigen and shut off B cell activation by engaging an inhibitory Fc receptor on B cells. lipids.SUMMARY • T-dependent humoral responses generate long- lived plasma cells • Polysaccharides. . and other nonprotein antigens are called T-independent antigens because they induce antibody responses without T cell help.

com .Thank You for Attention Discussion and Lecture Consultation: Biochemistry Department Faculty of Medicine UNHAS ikayustisia@yahoo.