Section 17 B cell recognition and response of antigens B cell response to T cell-dependent antigen B cell response to T cell-independent-antigen Rules of antibody production Mucosal immune response

B1 CD5+ B2 CD5-

B cell surface marker BCR FcR CR MHC-II CKR CD40 MR （Mitogens recepter） CD28 IL-5 IgM B7-2 FcμR C3b,C4b IL-2 CD40 CD23 CD40-L CD32 IgE IgG CD21 antigen IL-4 C3bi

Phytohemagglutinin PHA Lipopolysaccharide LPS Pokeweed mitogen PWM

TI or TD antigen CD40/CD40L B1 cell B2 cell Th cell TI-1 antigen

TI-Ag induced humoral responses TD-Ag induced humoral responese Effect of humoral immune responese Features of primary and secondary response Regulation of humoral immune response Theories of antibody formation

TI-1 and TI-2 antigens LPS B cell TI-1 antigen LPS recepter Signal transduction B cell Signal transduction

Features of response to TI-Ag No requirement of involvement of Th cell No memory B cell are formed IgM is the predominant，no class switch and no affinty matuation

The humoral immune response to TI antigens Antibody concentration in serum,（Log） primary secondary 100000 10000 1000 100 10 1 IgM 0 7 14 21 28 35 42 days

The humoral immune response to TD antigens Th cell activation Th1 Bm B7 CD28 Th CD4 Plasmacyte MHC-II TCR B ICAM LFA-1 APC secreting cytokins B B Th2 CD40L CD40 B BCR antigen B cell expansion

antibody class switching and affinity maturation Plasmacyte IgG2a or IgG3 g Activited B cell IFN- IgA or IgG 2b TGF- β IL-2 IL-4 IgE IL-5 IL-4 IL-2 IgM IL-4 IL-5

Somatic hypermutation of Ig genes roles in Ab Affinity maturation)

Affinity of Ag-Ab binding

Avidity of Ag-Ab binding

Non-covalent bonds essential for Ag-Ab binding antibody O H = – ionic bond –C –O – + H –N – – Van der Waals forces H antigen hydrogen bond –C=O……………H –N – hydrophobic bond H2O

Effect of humoral immune response Pathway : Neutralizing toxin & virus fixation of complement opsonization mediating ADCC Effect ： preventing infections（extracellular） —anti-bacterial , anti-viral anti-toxic mediating hypersensitivity I II,III mediating autoimmunity

1 2 3 4 5 6

Primary and Secondary Humoral Response Antibody concentration in serum,（Log） First immunization Second immunization 100000 10000 1000 100 10 1 primary secondary IgG IgM 0 7 14 21 28 35 42 days

The humoral immune response to TI antigens Antibody concentration in serum,（Log） primary secondary 100000 10000 1000 100 10 1 IgM 0 7 14 21 28 35 42 days

Features of primary and secondary response primary response secondary response Responding B cell naive B cell Bm Ag TI-Ag or TD-Ag TD-Ag Lag period 4-7days 1-3days lower higher Peak concentration of antibody Isotype produced IgM IgG、IgA etc Antibody affinity lower higher

Regulation of humoral immune response

Antiboy-mediated suppression antigen IgG BCR FcgRII suppression Igα Igβ phosphorylase B cell

Theories of Ab Formation Side chain theory Template theory Clonal selection theory

Side chain theory

Template theory Ab Ag

Clonal selection theory Frank Burnet 1900--1990 Nobel Prize 1960

antigen-A Lag period ：T / B cell clonal to antigen A

The Clonal Selection Theory 1 2 The Clonal Selection Theory 3 n

Lymphocytes 1 2 3 n Antigen

? Lymphocytes Plasma cells 1 3 3 3 2 3 3 3 3 3 3 3 n 3 (? How large is “n”?) Plasma cells 1 3 3 3 2 3 3 3 3 3 3 3 n 3

1. Master the humoral immune response （the features of response to TI-Ag ,the features of Interaction of the cells during the response ） 2. Master the principle of antibody formation（Comparison of primary and secondary response ）

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