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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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