Ch. 9 Immunologic Tolerance and Autoimmunity

Question 1

Immunologic tolerance

Answer 1

• unresponsiveness to self-antigens

Question 2

Negative Tolerance

Answer 2

• principle mechanism of central tolerance
• if a T-cell strongly interacts a self-peptide presented by MHC it dies
  
  • could be because lots of the peptide present or high affinity
  • peptides that induce negative selection generally present at larger conc. than pos. selection
• some T-cells that recognize self-antigens in central will go on to be regulatory T-cells in periphery instead of dying

Question 3

AIRE

Answer 3

• Autoimmune regulator

- it produces the self-peptides in the thymus to test developing T-cells to induce tolerance

Question 4

peripheral tolerance

Answer 4

• Mature T-cells recognize self antigen in periphery
• leads to:
  
  • anergy
  • death
  • suppression by regulatory T-cells

Question 5

Anergy

Answer 5

• part of peripheral tolerance
• functional inactivation of T-cells
• occurs when they recognize an antigen but didn’t get the secondary signal that is induced when microbes are present

Question 6

CTLA-4

Answer 6

• molecules that can bind to co-stim B7 from APC cells

- This interation inhibits T-cells instead and creates anergy.

Question 7

Activation induced cell death

Answer 7

• repeated activation of CD4 cells leads them to express both Fas and FasL
  
  • they then bind to themselves or adjacent cells
  • Fas is a death receptor and activates caspase pathway
• Pro-apoptotic proteins - produced in cell when antigen binds
  
  • with microbes, these proteins are counter-acted by anti-apoptotic proteins from co-stimulation
  • with self-antigens, no co-stim - so pro-apoptotic proteins lead to cell death

Question 8

B-cell central tolerance

Answer 8

• when B-cells recognize self antigen either - die (neg. selection)
• or make a new light chain so they then have a different Ig that recognizes a different antigen
  = Receptor Editing

Question 9

regulatory T-cells

Answer 9

• can result when T-cells respond to self- antigen - then go control other self-reactive T-cells
• most are Cd4+
• express lots of IL-2 receptor alpha chains - so leads to their proliferation which inhibits other t-cells-
• they release TGF-beta and IL-10 which inhibit leukocytes
• their development depends on transcription factor Foxp3

Question 10

Infections increase chance of autoimmune response:

Answer 10

• damage tissue, exposing some self-antigens that immune system doesn’t normally see
• Molecular mimicry
  
  • microbes can be very similar to self antigens - so microbes present, leads to an immune response specific to that microbe and co-stimulation. so now these T-cells upregulated and the microbe was so similar in structure that t-cells also recognize self antigens - they were suppressed before b/c no co-stim but now they have it
• local immune response
  
  • leads to increase in co-stimulation and cytokines, the APCs present self-antigens like normal, but may have co-stim now too - overcome anergy of self-reactive t-cells