Cell Mediated Immunity

Cell Mediated Immunity

1. CD4+ T Cells (Helper T cells)

   • Main Function: secretion of cytokines that recruit and activate other leukocytes to phagocytose and destroy microbes
   • MHC-CD4+ interaction
   • Naive T cell
     • Th1 Cells
       • Differentiation stimulated by IL-12 and IFN-gamma secreted from macrophages and NK cells (respectively)
       • Secrete IFN-gamma
         • Activates macrophages to become efficient killers
         • Promotes secretion of antibodies that promote opsonisation
     • Th2 cells
       • Differentiation stimulated by IL-4 secreted from NK cells and Th2 cells
       • Secrete IL-4
         • Promotes B cell activation
           • Secretion of neutralising IgG antibodies
           • Secretion of IgE
             • Activates mast cells
       • Secrete IL-5
         • Promotes eosinophil activation
       • Cross regulation
         • Cytokines that induce differentiation of each T helper cell type also inhibit the production of the other
           • Il-12 and IFN-gamma promote Th1 differentiation and inhibit Th2 differentation
           • Il-4 promotes Th2 differentiation and inhibits Th1 differentation
     • Th17 cells
   • Internalised antigens

2. CD8+ T Cells (Cytotoxic T cells)

   • Main function: kill infected cells
   • Induce apoptosis
     • Release cytotoxic granules
       • Perforin - pokes holes in infected cell; allows granzymes to enter cell
       • Granzymes - activate target cell's apoptotic pathway; leads to cell death
   • Recognise MHC Class 1
   • Expansion promoted by cytokines released from Th1 cells
   • Cytosolic antigen

3. MHC Restriction

   • MHC Class 1
     • Presents to CD8+ T cells
   • MHC Class 2
     • Presents to CD4+ T cells
   • T cells can only recognise antigens when they're presented on MHC molecules of the surface of antigen presenting cells
     • Antigen presenting cells
       • Macrophages
       • Dendritic cells
       • B cells
     • Conditions for recognition
       • Antigen must fit MHC
       • MHC class must match T cell receptor
         • Haplotype dependent
       • Antigen must match antigen binding site of TCR
   • Maturation and selection of MHC restricted T cells
     • Stem cell
       • Double negative pro-T cell
         • Pre-T cell (with Pre-TCR complex)
           • Double positive T cell
             • Weak recognition of Class 2 MHC + peptide
               • Positive selection - CD4+ T cells
             • Weak recognition of Class 1 MHC + peptide
               • Positive selection - CD8+ T cells
             • No recognition of MHC + peptide
               • Failure of positive selection - death by neglect
             • Strong recognition of either MHC Class 1 or 2
               • Negative selection

4. T cell activation

   • Molecular interactions
     • Adhesion
       • LFA-1/ICAM-1
       • VLA-4/VCAM-1
     • Signal transduction
       • CD4/MHC Class 2
       • CD8/MHC Class 1
       • CD3
       • zeta
       • CD28/B7-1 or B7-2
       • CTLA-4/B7-1 or B7-2 (negative regulation)
   • The process: Antigen recognition > Activation > Clonal Expansion > Differentiation > Effector Functions

Imagens e arquivos do mapa