1. Chapter 9 Immunity Mediated by B Cells and Antibodies

3. RECALL Pathogens extracellular Antibodies secreted in 2 ND LT & Bone Marrow B cell function extracellular spaces Other Pathogens fluids B cell PM cell virus ~~~~~~ ~~~ Next cell bacteria Y Y Y intracellular virus

6. Antibody production by B lymphocytes

7. The Development Of B Cells Can Be Divided Into six Broad Phases

13. 7-1 B-cell activation requires cross-linking of surface immunoglobulin

14. Protein or carbohydrate epitopes Bacterial cell Naïve Mature B cell IgM’s  X-linked by repetitive Ag epitopes Ig  Ig  IgM Ig  Ig  Note that BCR signal transduction resembles that of TCR Signal transduction extracellular  intracellular

31. 9-4: Activation of naïve B cells by most antigens requires help from CD4 T cells

37. Two signals  B cell proliferation & differentiation into plasma cell B-cell activation in response to TD-Ag requires T cell help

43. 9-7 Activated B cells undergo somatic hypermutation and isotype switching in the specialized microenvironment of the B-cell zone

44. Common theme of lymphocyte development B cell maturation in germinal center Activation proliferation selection Activation proliferation selection

45. Proliferation in the GC, Okay What about hypermutation and affinity maturation in the GC? centroblasts dividing in germinal center somatic hypermutation & isotype switching T-cell cytokines Nondividing centrocytes Mutated surface Ig Post hypermutation Surface Ig of centrocyte Affinity for a specific antigen higher lower equal

47. Mutated centrocytes compete! To engage a helper T cell Centrocyte  bind Ag  process antigen  surface = MHCII + Ag Mutated centrocytes now compete! Access of Ag on FDC’s Ag-specific helper T cells MHCII 1 2 Follicular dendritic cells provide a source of intact Ag Mutated centrocyte

55. Chapter 9 – Lecture Notes Immunity Mediated by B Cells and Antibodies

56. Chapter 9 continued

57. 9-9: Interactions with T cells are required for isotype switching in B cells

64. Hyper-IgM syndrome No GC in Lymph Nodes GC in Lymph nodes

68. 9-11 IgM, IgG and IgA Abs protect the blood and extracellular fluids

74. How are IgA & IgG transported across epithelial barriers? Apical surface Basolateral surface Receptor mediated endocytosis Transcytosis

76. Brambell receptor (FcRB)

81. High-affinity neutralizing Ab’s prevent viruses and bacteria from infecting cells

84. Fc of Ab and Fc  receptor of effector cell

98. The complement component C1

100. Cleavage of C4 exposes a reactive thioester bond that covalently attaches the C4b fragment to the pathogen surface

101. Activated C1s cleaves C4 and C2 to produce C4b and C2a, which associate to form the classical C3 Convertase

102. Formation of the alternative C3 convertase

103. The two types of C3 convertase have similar structures and functions

104. C3 activation by the alternative C3 convertase is a process analogous to C3 activation by the classical C3 convertase

117. MAC