Adaptive Immunity: T-Cell Response II

• What is antigen processing?

  The mechanism that breaks down proteins to peptides which may be bound by MHC molecules & exported to the surface

  
• Where are antigenic peptides presented by MHC class I derived from? What are they recognised by?

  -Derived from intracellular pathogens that synthesise or release proteins in the cytosol

  
  

  -Recognised by CTL's.
• Where are antigenic peptides presented by MHC class II derived from? What are they recognised by?

  -Derived from proteins of extracellular pathogens that are endocytosed by antigen presenting cells.

  
  

  -Recognised by Helper T cells
• What happens in the MHC class I pathway?

  1. Proteins in cytosol are broken down into peptides by proteosomes

  
  

  2. Peptides are transported into the endoplasmic reticulum by the TAP transporter

  
  

  3. In this compartment, some peptides bind to newly synthesised MHC class I proteins & the peptide-MHC complexes are transported to the cell surface in membrane vesicles

  
  

  4. At the cell surface, the peptide-MHC complex may be recognised by CD8 expressing CTLs that recognise that the peptide is pathogen-derived & kill the infected cell to eliminate the pathogen
• What are some examples of antigen presenting cells (APCs)?

  Dendritic cells, macrophages, B cells
• What happens in the MHC class II pathway?

  1.Antigens processed in class II pathway are derived from the extracellular environment & are endocytosed in membrane vesicles

  
  

  2.The endocytic vesicles fused with lysosymes contain various cellular proteases that break the protein into peptides (these are generally bit longer than the ones produced by class I pathway)

  
  

  3.The endolysosomal vesicles fuse with membrane vesicles that contain newly synthesised MHC class II proteins

  
  

  4.MHC class II complexes with extracellular peptides are transported to surface of APC where they may be recognised by antigen-specific helper T cell
• What are the MHC class II proteins synthesised together with, and what happens to this during the pathway?

  1.The class II proteins are synthesised together with a protein called the invariant chain.

  
  

  2.which blocks the antigen binding site of the MHC class II molecules so that it can't be occupied by peptides from intracellular proteins.

  
  

  3.But when the class II-containing vesicle fuses with the endolysosomal vesicle, proteases now digest the invariant chain so that the peptide binding site becomes available for binding to peptides derived from extracellular proteins
• What does it mean to say MHC peptide binding is highly promiscuous?

  Individual MHC molecules must be able to bind to an enormous number of different peptides so as to alert the immune system to a large range of different pathogens- promiscuous binding
• How is promiscuous binding possible?

  
• What do some of the smaller populations of T cells have?

  They express γẟ (gamma delta) T cell receptors, which can recognise other antigens such as pathogen-derived metabolites & lipids

  
  

  These antigens don't require processing & is displayed on the target cell bound to MHC class I-like molecules that are expressed from entirely separate gene loci

  
• What are naive T cells?

  Resting T cells that have not previously encountered antigens before
• What are naive T cells activated by and where does it occur?

  Specialised antigen presenting cells (APCs): dendritic cells (DC), macrophages

  
  

  APC's express both MHC class I and MHC class II proteins, so bind to and activate both CD4 Th and CD8 Tc lymphocytes

  
  

  Activation occurs in lymph nodes
• What 3 signals are needed for Th cell activation?

  1. T cell receptor recognises MHC class I or II with the loaded antigen. CD3 is recruited to the TCR and can be phosphorylated and transmit the signal.

  
  

  2. Signal given by co-stimulatory proteins, expresses 2 CD28 on the T cell. This is important to strengthen the first signal given by the TCR, the first signal alone is not enough as the T cell will become anergic.

  
  

  3. Signal given by cytokines secreted by the antigen presenting cell. These cytokines determine what type of immune response is going to be produced.

  
  

  The T cell is now activated

  
• What can activated Th cells proliferate and give rise to?

  T effector cells

  
  

  T memory cells

  
• Induction of what expression on Th cells is needed for the cell to become fully activated and produce cytotoxic T cells?

  CD40

  
  

  CD40L

  
• What signals are required for a T cell to become activated?

  
• What signals are involved in cytotoxic T cell activation?

  
• What do cytokines determine?

  The type of immune response.

  
• How and why is the immune response switched off?

  -Inhibitory receptors = CTLA-4, LAG3 = replace activatory signals

  
  

  -Express apoptotic receptors = FAS

  
  

  - leads to reduction of immune cells as they've proliferated massively upon activation but once the pathogen is no longer there, we do not need so many immune cells anymore.

  
  

  - The few cells that remain = memory cells
• Summarise the content in this lecture.