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2/10/2005 MICR 415 / 515 / 682 1
Topics
• Humoral Immune Response Part I– Antibody effector functions– Thymus dependent and independent antigens– Linked recognition– B cell Activation, proliferation and differentiation– Isotype switching, Affinity maturation– Distribution and function of Ab– Accessory cells
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Extracellular Bacteria
•Destruction of extracellular bacteria•Neutralize the toxins•Prevents the spread of intracellular infections
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Humoral Immune Response
Bacteria APC
Cytokines
Th 2
APC
B CellAntibody Production
Ag
ThCD4+
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Humoral Immune Response
Bacteria B CellAg
Th2CD4+B Cell
Bacteria
Cytokines
B Cell
B Cell
B Cell B Cell
B Cell
Plasma Cell
–Epitope recognition–Internalization of Ag–Processing and presentation–Stimulation by armed Th2 cell–B cell proliferation–Differentiation–Production of Ab
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Antibody effector functions
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Thymus dependent antigens
–Proteins–Require T cell help
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Thymus independent antigens
–Bacterial Lipopolysaccharides (LPS)
–Do not require T cell
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Linked recognition
Fig 9.3
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• Adhesion molecules interaction• Stimulation via TCR• CD40 /CD40 ligand stimulation (Accessory signal)
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– Secretion of cytokines (IL4) by the Th2 cell
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B cell proliferation and differentiation
–IL4, CD40 lead to B cell proliferation
–IL5 and IL6 lead to B cell differentiation into plasma cells
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Isotype switching
• A variable region can be associated with the constant region of any isotype
• mRNA splicing
• IgM• IgD• IgA• IgG
– IgG1, IgG2a, IgG2b, IgG3
• IgE
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Cytokines determine Isotype
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–B cell is activated–Migrate to primary follicles of spleen and lymph nodes–Proliferates and forms germinal center (follicular dendritic cells)–Proliferating B cells are called centroblasts (random somatic Hypermutation of V region)–Produce centrocytes (positive selection by FDC)–Differentiation into memory cellsand Ab producing plasma cells (Thcells)
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Affinity maturation
Caused by:–somatic hypermutation–Selection cells with high affinity receptors
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Centrocyte selection at the germinal center
Take up foreign Ag from FDC?
No
Apoptosis
Yes
Interactionwith T cells
Differentiation
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Distribution and function of Ab
– Pathogens are can grow in all the body– Ab need to be available in all the body
• Route of entry of pathogens:• Epithelial barries:
– Mucosa of the respiratory, digestive, urogenital tract, damaged skin
• Directly to the blood– Insects, wounds, needles
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IgM
–First to be produced–Low affinity–Forms pentameres (high avidity)–Large, confined to the blood–Activates complement
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• IgG Monomeric• IgG is the most
important in the blood• IgG Opsonization,
Complement activation, neutralization
• Transported through placenta
• IgA forms dimers• IgA is most important in
secretions (epithelium of intestine and respiratory tract)
• Neutralizing antibodies• Present in mother’s milk
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IgA
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IgE
• Monomeric• Binds receptor in
mast cells beneath skin and mucosa
• Acts as a receptor• Binding causes
degranulation of mast cells
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Distribution of Igs–IgG, IgM:Plasma–IgG, IgA (monomeric):Extracellular fluid–IgGFetus– IgA (dimeric):Secretions, cross epithelia–IgEMast cells beneath epithelia
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