Down regulation of effector Cell

Down regulation of effector Cell

1. Passive Cell Death

   • Lack of antigen stimulation
   • Mito releases cytochorme C leading to activation of caspase 9 leading to apoptosis

2. Activation induced cell death (AICD)

   • Activated Cells are more prone to apoptosis
     • Contain Pro-aptotoic proteins
       • Bax, Bad, Bad, Bak, Bik, Bok
     • Increased expression of Fas and FASL
       • APC - T cell interaction willl lead to expresion of FAS/FASL, this interaction is TCR - MHC
       • Other circumstances of increased expression of FAS/FASL
         • Tumor cells increase expression of FASL, leading to death of T cells
         • Immune privleged sites have constitutively expresssed FasL
   • Gets rid of T cells that have been repeatedly activated

3. Regulation via B7 ligands / receptors

   • Positive
     • ICOS / ICOSL (APC)
     • CD28 / B7 (APC)
   • Negative
     • CTLA4 / B7
       • Expression of CTLA4 increases in activated T cell, CTLA4 has greater affinity for B7 than CD28
     • PD1 / PDL
       • PD1 expression is upregualted when the T cell becomes activated
       • Tumor cells express PDL to deactivate T cells and NK cells

4. B cell

   • FcyRIIB negative feed back loop
     • The FcyRIIB has ITIM regions where phosphorylation will induce signals resulting in inhibition of B cell function

5. Regulatory T cells

   • iTreg
     • Releases IL10 and TGFbeta
       • IL 10 Inhibits APC Function specifically DC : inhibit cytokine release, MHC and costimulatry molecules expression, maturation and inhibit the release of IL12 which is related to proliferation and differentation of T cells
       • TGFBeta
         • DC: increased langerhans cell development, decreased maturation and decreased antigen presentation
         • Macrophages: increased chemotaxis, decreased phagocyte function , decreased antigen presentation
         • Regulatory T cells: increased generation and maintaince in periphery and increased suppresive function