Mechanisms of Auto-Immunity & Hypersensitivity II

• What is molecular mimicry?

  Antigens of infectious agent may resemble self antigens & stimulate cross-reactive B- & T-cells

  
  

  (Cross-react = immune system might mistakenly target and attack hosts tissues that share similarities with the microbial molecules)
• How else might the effects of regulatory T cells be bypassed?

  -In SLE,

  
  

  -for example, innate immune receptors such as Toll like receptors can provide an alternative means of activating B cells

  
  

  -This mechanism removes the need for T cell help & therefore bypasses the effects of Treg cells
• What is SLE characterised by?

  Production of antibodies that recognise nucleic acid.
• What is the role of innate immune receptors (TLRs) in B cell activation in SLE?

  1. Binding to slg (signal lymphocyte activation) induces 1st signal

  
  

  2.slg traffics to endosome

  
  

  3.Nucleic acid complex binds to TLR7, 9

  
  

  4.TLR signal via nucleus triggers production of type 1 interferon

  
  

  5.IFN binding to receptor provides second signal

  
  

  6.B cell proliferates - plasma cells producing autoantibody + memory cells

  
• How do activated B cells act as antigen presenting cells to T cells in SLE?

  
• What are hypersensitivity reactions?

  Exaggerated immune mechanisms that damage host tissue

  
  

  Requires previous exposure to antigens
• What are the 4 types of hypersensitivity reactions?

  Types I-III (antibody-mediated) & produce relatively fast responses & they're known as immediate hypersensitivity reactions

  
  

  Type IV is a slower, T-cell mediated response & is known as delayed type hypersensitivity
• Describe a Type I hypersensitivity reaction.

  
• Have Type I reactions been considered likely to contribute to autoimmune damage?

  No, not really

  
• Describe a Type II hypersensitivity reaction.

  
• Describe a Type III hypersensitivity reaction.

  
• Describe a Type IV hypersensitivity reaction.

  Multiple granulomas = excessive tissue damage

  
• What are the key points to take away from this lecture?

  Molecular mimicry whereby antibodies produced in response to pathogen-derived antigens that partially resemble host components may overcome self-tolerance and mediate autoimmune tissue damage

  
  

  Innate immune receptors (TLRs) may contribute to initiation of autoimmune response

  
  

  Tissue damage in autoimmune disease is mediated by hypersensitivity reactions