Adaptive Immunity: T-Cell Response III

• What does each T cell have an antigen receptor of?

  Unique specificity
• How is diversity of a T cell receptor generated?

  ALPHA CHAIN: One of each region (variable and joining) has to be brought together to form an exon that encodes the function and complete variable antigen binding domain.

  
  

  Requires rearrangement of chromosome at this locus mediated by RAG 1 and 2.

  
  

  Looping off DNA randomly aligns one of the v and j segments

  
  

  Addition or elimination of nucleotides increases diversity further.

  
  

  Same for Beta but BETA needs the recombination of V,D and J.

  
  

  Any beta chain can joint with any alpha chain, increasing diversity further.

  
• How does recombination & nucleotide addition affect diversity?

  
• What happens after T cells mature in the thymus?

  They undergo positive and then negative selection.

  
  

  The purpose of selection is to retain only T and B cells that recognise foreign antigens but not self antigens (or they will attack the body's own tissues)
• What do immature T cells express?

  TCR as well as CD4 and CD8 (double positive, DP)
• What happens to T cells that don't bind self to MHC, that bind to MHC class II & those that bind to MHC class I?

  T cells that do not bind self MHC undergo apoptosis

  T cells that bind to self MHC II (on epithelial cells or dendritic cells) in thymus cortex become CD4 single positive (SP) cells

  T cells that bind to MHC I become CD8 SP cells

  This is positive selection of T cells in the thymus
• What is negative selection of T cells in the thymus?

  The T cells that survived positive selection now have to go through negative selection:

  
  

  Surviving SP T cells migrate to medulla

  
  

  SP T cells that bind weakly/moderately to self antigens associated with MHC, survive

  
  

  SP T cells that bind strongly to self antigens/MHC undergo apoptosis or become Treg cells

  
• What are the sequence of events during selection?

  1. Thymocytes express CD4 and CD8 becoming double positive cells.

  
  

  2. Double positive cells bind to MHC I or MHC II

  
  

  3. Cells become CD4 single positive or CD8 single positive

  
  

  4. Double positive cells in the Cortex which do not bind MHC undergo apoptosis.
• What is peripheral tolerance?

  Peripheral tolerance mechanisms are crucial for preventing autoimmune reactions, where the immune system attacks its own cells and tissues.
• What are the 2 key mechanisms of peripheral tolerance?

  Regulatory T cells (Tregs) : Suppress activity of other immune cells e.g self reactive T and B cells, preventing harmful immune responses against body's own tissues.

  
  

  Anergy: Immune cells become inactive when they encounter self-antigens without proper signals, reducing damage to healthy tissues.
• Summarise the content in this lecture.