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Reminders. Case Studies: Due Wed., March 19- DUE TODAY Exam 3- Wed., March 26 Chapters 3, 5, & 6. Chapter 6- T Cell-Mediated Immunity. The 3 different APCs have different roles in the immune response. Distribution of APC in the secondary lymphoid tissue- lymph nodes:.
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Reminders • Case Studies: • Due Wed., March 19- DUE TODAY • Exam 3- Wed., March 26 • Chapters 3, 5, & 6.
Chapter 6- T Cell-Mediated Immunity The 3 different APCs have different roles in the immune response.
Distribution of APC in the secondary lymphoid tissue- lymph nodes: Marginal sinus where lymph collects.
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!
Migration from the peripheral site of infection to the lymphoid tissue stimulates maturation. Langerhans cells
Proteins Labeled: • MHC class II- green. • Lysosomal protein-red • fig 8-9, Janeway
Mature Dendritic Cell in the Lymph Node: N C C • “Interdigitating Reticular Cells” C
- Lectin - Induces macropinocytosis • 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:
Resting Mf can’t activate naïve T cells & poorly activate effector T cells. Why? The Macrophage • Requires activation: • Cytokines &/or binding of pathogens or their products. • Upregulates MHC class II & B7.
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.
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.
How does the binding of TCR to MHC-Ag mediate cell signaling? Signal Transduction Pathway- Common themes in Lymphocyte activation:
1. Signal Transduction requires the crosslinking of receptors: • Successful signal requires ~100 TCR binding MHC-peptide @ a given time. • Each MHC must carry same peptide! • Coreceptor is required!
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
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