T cell activation

• T cells


  - thymus selected lymphocytes

  - required for cell mediated immunity

  - remove intracellular pathogens by killing infected cells

  - respond to antigenic fragments presented by MHC molecules on APCs

  - required to help B cells to become activated and produce ABs
• Th cells (CD4+)


  - recognise fragments presented on class 2 MHC

  - differentiation regulated by cytokine production (Il-4 promotes Th1, IL-4 promoted Th2)

  - usually sign of bacterial infection

  
• Th1

  - innate immunity

  - activate macrophages and cytotoxic T cells (IFNy,TNFa)

  
• Th2

  - AB production

  - provides costimulatory help to B cells (IL-4,5,10)

  
• cytotoxic T cells (CD8+)


  - recognise fragments presented on class 1 MHC

  - kill infected cells

  - usually sign of viral infection

  
• TCR

  - T cell receptor

  - similar structure and assembly as ABs

  - associated with CD3 signalling chains and CD4/8

  - undergo thymic selection for self tolerance

  - no somatic hypermutation - so affinity stays low

  
• Major Histocompatibility Complex (MHC)

  - group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances

  - 2 classes

  
• antigen recognition

  - only recognise small fragment of antigen

  - requires endocytosis, processing and presentation by APc in conjunction with MHC molecule

  - peptide fragments bind in groove of MHC

  - TCR binds across peptide and MHC residues

  - CD4/8 bind MHC to prevent T cells killing self-cells

  
• thymic selection

  - developing T cells encounter self antigen presented on self MHC found on thymic epithelial cells

  - if T cell doesn't recognise/bind to MHC - signalled to die by apoptosis (positive selection)

  - if T cell binds strongly and is activated - signalled to die by apoptosis (negative selection)

  - surviving T cells are kept alive in peripheral lymphoid organs by continual interaction with self peptide/MHC

  - become activated only when encountering foreign antigen presented on self MHC

  
• co-stimulation

  - T cells don't activate to antigen alone

  - require 2nd signal generated by co-stimulatory molecules

  - TCR engagement w/o co-stimulation causes T cell to become unresponsive (anergic) and probably undergo apoptosis

  - CD28 expressed on resting T cells

  - B7-2 expressed on resting APCs

  - antigenic engagement of TCR leads to activation of CD28 by binding B7-2 and followed by upregulation of CTLA-4 & B7-1

  
• Th1 effector cells

  - migrate to infection site

  - release IFNy to activate macrophages

  - stimulate production of monocytes in bone marrow

  - increase expression of adhesion molecules on endothelium

  - induce leucocyte migration via chemokine release

  - components of acute inflammation

  
• Th2 effector cells

  provides signal 2 to B cells

  
• 2 mechanisms of cytotoxic T cells and NK cells

  1. perforin-dependent killing = secretes perforin molecules creating channels in target cell decreasing membrane integrity. Enzymes injected in cause apoptosis

  2. fas-dependent receptor killing = enzyme cascade - apoptosis