Reminders

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Reminders

• Case Studies
• Due Wed., March 19- DUE TODAY
• Exam 3- Wed., March 26
• Chapters 3, 5, 6.

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Chapter 6- T Cell-Mediated Immunity

• The 3 different APCs have different roles in the
  immune response.

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Distribution of APC in the secondary lymphoid
tissue- lymph nodes
Marginal sinus where lymph collects.
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The Dendritic Cells
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The Dendritic Cells

• Dendritic Cells are derived from myeloid
  lymphoid progenitors in the bone marrow.
• (not follicular DC)
• Immature DC travel to peripheral tissues
  organs
• Surface epithelial areas gut, respiratory tract,
  skin
• Heart kidneys etc.
• Waiting for encounters with antigen!

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Migration from the peripheral site of infection
to the lymphoid tissue stimulates maturation.
Langerhans cells
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• Proteins Labeled
• MHC class II- green.
• Lysosomal protein-red

• fig 8-9, Janeway

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Mature Dendritic Cell in the Lymph Node
N
C
C
C

• Interdigitating Reticular Cells

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• MHC
• B7
• DC-SIGN CAMs to interact with naïve T cells.
• chemokine receptors (CCRs)- CCR7
• CCL18 chemokine

Immature DC express different surface molecules
as compared to the mature DC
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The Macrophage

• Resting Mf cant activate naïve T cells poorly
  activate effector T cells.
• Why?

• Requires activation
• Cytokines /or binding of pathogens or their
  products.
• Upregulates MHC class II B7.

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• Mf is best at internalizing particulate Ag
  bacteria!

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• Adjuvants-
• a substance (often microbial in origin) that will
  induce production of a costimulatory response in
  APC-
• used when making a vaccine with soluble antigen.

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• B cells are adapted to take in soluble antigen.
• Expressed on MHC that is constitutively expressed.

Naïve B cells generally require a Th2 response
before becoming activated.
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• B cells are less important for activating naïve
  T cells.

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How does the binding of TCR to MHC-Ag mediate
cell signaling?

• Signal Transduction Pathway- Common themes in
  Lymphocyte activation

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• 1. Signal Transduction requires the crosslinking
  of receptors
• Successful signal requires 100 TCR binding
  MHC-peptide _at_ a given time.
• Each MHC must carry same peptide!
• Coreceptor is required!

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Janeway

• 2. TCR complex Coreceptor must associate with
  Receptor Associated Tyrosine Kinases (RATK)
• ITAMs- Immunoreceptor tyrosine-based activation
  motifs
• AA seq in the TCR complex cytoplasmic tails that
  are bound by kinases.
• 2 tyr residues

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Who are the RATKs?

• Src Family-
• Fyn- associates with ITAM in zz chains e of
  CD3.
• Require clustering of receptors to associate.
• Lck- always associates with CD4 or CD8.
• ZAP-70- Tyr kinase responsible for signal
  cascade.
• SH2 domains- binds P-Tyr in ITAMs in the zz chains

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