Immunology

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Immunology

• Chapter 12
• B-Cell Activation and Differentiation
• Dr. Capers

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B cell activation

• B cell encounters specific antigen
• B cell presents to T helper cell
• Cytokines are released for full B cell activation
• Proliferation, some of the B cells become plasma
  cells
• Some of the B cell clones move to germinal
  centers of lymph nodes, somatic hypermutation can
  occur
• Class switching occurs

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• The tiny region of the antigen that BCR actually
  binds to is called its epitope.
• The epitope will be the part of that protein
  (usually 6 12 amino acids) to which the BCR
  receptor binds.

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• When the BCR recognizes the epitope, for which it
  is matched, it must signal this recognition to
  the nucleus of the B cell, where genes involved
  in activating the B cell can be turned on or off.
  

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B cell Activation

• Thymus-dependent (TD) antigens
• B cell required direct contact with TH cell
• B-2 B cells, majority of B cells
• Thymus-independent antigens (TI)
• These antigens activate B cells by pattern
  recognition receptors (bacteria that might be in
  high amount)
• Type I (TI-1) lipopolysaccharide
• Type 2 (TI-2) highly repititous molecules
  (bacterial flagella)

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B cell Activation

• Membrane bound antibody have short cytoplasmic
  tails
• Too short to generate signal by associating with
  tyrosine kinases and G proteins

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• So that the external part of the BCR can signal
  what it has seen, B cell are equipped with two
  accessory proteins
• Membrane Ig must be associated with B-cell
  receptor
• Ig-a/Ig-ß

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ITAMS

• ITAMs are important for signal transduction in
  immune cells. An ITAM is a specific sequence of
  amino acids occurring twice in close succession
  in the intracellular tail of a receptor

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• They are found in the tails of important cell
  signaling molecules such as the CD3 and ?-chains
  of the T cell receptor complex, the CD79-alpha
  and -beta chains of the B cell receptor complex,
  and certain Fc receptors.

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• The tyrosine residues within these motifs become
  phosphorylated following interaction of the
  receptor molecules with their ligands and form
  docking sites for other proteins involved in the
  signaling pathways of the cell

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• ITIM (immunoreceptor tyrosine inhibitory motif)
• Associated with CD22
• Functions to deactivate B cells negative
  regulation
• Important in preventing autoimmunity

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• TH cells play essential role in B cell repsonses

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• Remember B cells can be t-cell independent or
  dependent!

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• TEM of interaction between B cell and T cell

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Humoral Response Primary vs Secondary
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Hapten-carrier conjugates

• Hapten low molecular weight molecule that can
  elicit an immune response only when attached to a
  large carrier such as a protein.

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In vivo sites for induction of humoral responses

• Bloodborne antigen is filtered by spleen
• Antigen from tissue spaces filtered by lymph
  nodes
• Antigen either enters alone or with
  antigen-transporting cells
• Langerhans cells (antigen-presenting immune
  cells) of the skin and mucosa
• Dendritic cells
• Encounters antigen-presenting cells
• Dendritic cells
• Macrophages
• Follicular dendritic in follicles and germinal
  centers

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T cells are green and B cells are red
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• Germinal centers arise within 7-10 days after
  initial exposure to thymus-dependent antigen in
  lymph node
• 3 events in germinal centers
• Affinity maturation
• Result of somatic hypermutation
• Class switching
• Formation of plasma and memory B cells

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Cellular events in germinal centers
Dendritic cell presents antigen to developing B
cells to see which B cells are producing antibody
with high-affinity for that antigen
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Class Switching

• Dependent on cytokines to switch from IgM to
  other isotype
• Thymus-dependent antigens
• Interaction of CD40 on B cell and CD40L on T cell
• X-linked hyper-M syndrome
• TH cells dont express CD40L, patients only
  produce IgM
• No memory cell populations, no germinal centers

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Regulation

• Humoral and cell-mediated branches must be
  heavily regulated
• Cytokines play important role
• Antigenic competition
• Previous encounter with antigen can render animal
  tolerant or may result in formation of memory
  cells
• Presence of antibody can suppress response to
  antigen
• Some vaccines are given to babies after maternal
  IgG (that was transferred across placenta) has
  left system
• Vaccination before this will prevent proper
  response and development of long-lasting memory
  cells