1 Humoral Immune Response Bacteria Th2 B Cell Bacteria CD4 + B - - PDF document

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1 Humoral Immune Response Bacteria Th2 B Cell Bacteria CD4 + B - - PDF document

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


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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 Cell Antibody Production Ag Th CD4+

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Humoral Immune Response

Bacteria

B Cell Ag Th2 CD4+ 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 cells and Ab producing plasma cells (Th cells)

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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 Interaction with 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

  • f 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 –IgG Fetus – IgA (dimeric): Secretions, cross epithelia –IgE Mast cells beneath epithelia

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