Immunology Model Drawing Exercise

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1. T cell activation

Include these elements in the part of your model showing T cell activation:

1. 1. APC (DC) signals given to help activate a naive CD4 T cell:
      1. MHCII/peptide Ag on a DC being bound by TCR on a naive CD4 T cell
      2. B7.1 or B7.2 on the same DC being bound by CD28 on the same CD4 T cell (costimulation signals)
      3. CD3 subunits and zeta chain homodimer within the TCR complex with ITAMs that get phosphorylated during T cell activation
      4. Kinases Lck associated with the intracellular domain of CD4 (also associates with CD8) and Zap70 that phosphorylate ITAMs
      5. The 3 transactivating transcription factors: NFAT, NFkB and AP1 that lead to IL-2 gene expression by translocating to the nucleus during T cell activation
      6. IL-2 binding the high affinity IL-2R receptor (gamma chain; beta chain and inducible alpha chain)
   2. The TH1 differentiation pathway, including:
      1. IFN-gamma, released by an activated NK cell, binding to the IFN-gamma receptor (R) on the CD4 T cell undergoing activation
      2. IL-12, released by an activated DC cells, binding to the IL-12 receptor (IL-12R) on the same CD4 T cell undergoing activation
      3. T-bet as a key transcription factor inside the CD4 T cell that drives TH1 differentiation
      4. The CD4 T cell having differentiated into a TH1 cell that is now secreting TH1 cytokines, including
         1. IFN-gamma
         2. IL-2 (high levels)
         3. TNF
      5. IFN-gamma from TH1 bound by IFN-gR on a macrophage, along with CD40L on TH1 bound by CD40 on a macrophage together lead to a fully activated macrophage with stronger capacity to kill intracellular bacteria resistant to being killed
   3. The TH2 differentiation pathway, including:

1. 1. 1. IL-4, released by an activated basophil (or mast cell, or NKT cell), binding to the IL-4 receptor (IL-4R) on a CD4 T cell undergoing activation
      2. GATA-3 as a key transcription factor inside the CD4 T cell that drives TH2 differentiation
      3. The CD4 T cell having differentiated itno a TH2 cell that is now secreting TH2 cytokines, including:
         1. IL-4 (IgE switch factor; differentiation factor leading to memory B cells; amplifyer of TH2 response by positive feedback)
         2. IL-5 (induces Eosinophil production in BM and helps to activate Eosinophils)
         3. IL-6 (B cell differentation factor promoting B cell differentiation; pro-inflammatory cytokine)
         4. IL-13 (similar functions as IL-4; binds to a receptor that shares receptor subunits with the IL-4R)
         5. IL-10 (a B cell differentiation factor leading to plasma cells and a T cell modulator that inhibits IFN-gamma production)

4. The TFH differentiation pathway, including:

1. 1. 1. IL-6, released by an activated DC, binding to the IL-6 receptor (IL-6R) on a CD4 T cell undergoing activation
      2. BCL-6 as a key transcription factor inside the CD4 T cell that drives TFH differentiation
      3. The CD4 T cell having differentiated into a TFH cell that is now secreting TFH cytokines, including:
         1. IL-21 (B cell differentiation factor promoting maturation of antibody response)
         2. IL-4, IL-5, IL-6, IL-10, etc. (B cell differentiation factors as listed above)

5. The CD8 T cell to CTL differentiation pathway, including:

1. 1. 1. MHCI/peptide Ag on a DC bound by the TCR on a naive CD8 T cell undergoing activation
      2. B7.1 or B7.2 on a DC bound by CD28 on the same CD8 T cell undergoing activation (costimulation signals)
      3. IL-2 from a TH1 cell bound by the IL-2R on the CD8 T cell to induce proliferation and differentation into a CTL
      4. CTL binding a target cell via TCR binding to MHCI/Ag peptide on the target cell (only 1 signal needed)
      5. Perforin and granzymes released from CTL granules to induce apoptosis in target cell (perforin makes hole in target cell membrane; granzymes enter target cell to induce the caspase-dependent apoptosis pathway)

2. T-cell dependent B cell activation

1. 1. 1. BCR (IgM isotype) on a naive B cell binds Ag ( its native form) from a pathogen
      2. Igalpha and Igbeta associated with the IgM transmit activation signal 1 via phosphorylation of ITAMs in intracellular domains
      3. CD81/CD19/CR2 B cell co-receptor complex binds to Ag to provide additional activation signals
      4. CD40 on B cell binds to CD40L on TFH cell (costimulation signals)
      5. IL-21 from TFH bind to the IL-21 receptor (IL-21R) on B cell to trigger proliferation and differentiation into plasma cells
      6. Plasma cells secrete Ab with same idiotype as parent B cell clone that was activated
      7. CD40-CD40L interaction and TFH cytokines together provide proliferating B cell with signals for isotype switching and somatic hypermutation to occur. Example: IL-4 bound by IL-4R on a proliferating B cell that in response will differentiate into an IgE-secreting plasma cell (since IL-4 is the switch factor for IgE production)