Immunology lecture 4

Question 1

Self tolerance

Answer 1

Innate = Ag receptor = germline encoded, use non-protein Ag, response inflexible 
Adaptive = receptors rearranged, response is flexible

Question 2

T cell differentiation

Answer 2

• Mature in thymus
• 4 subsets of thymocyte
• Interactions w/ stroll cell cells → thymocyte along a diff pathway

Question 3

T cell diff checkpoints

Answer 3

1. Transition from CD4-8- to CD4+8+
   - Express product of gene rearrangement expressed at surface w/ pre-TCR a antigen
   - Ligantion of pre-TCR by ligand signals to thymocyte B chain is functional → a chain rearrangement can start
2. Transition from CD4+8+ → mature CD4+8- (Th cell) or CD4-8+ (CTL)
   - Involves +ve selection
   - TCRs that complement shape of MHC molecule = +ve
   - If x fit die by neglect
   - -ve selection
   - Screen cells w/ functional TCRs for self reactivity

Paradox

• +ve selection ensures MHC-restricted recognition
• -ve selection ensures cells are self-tolerant
• Both involve ligation of TCR by complexes btw self-peptide + MHC determinant
• Same ligand recognised by same TCR but → diff outcome

Question 4

Differential affinity model

Answer 4

• Avidity of Ag recognition = to do w/ affinity for self-peptide-MHC
• x affinity = dies
• Too high = deleted by DC

Question 5

Issues w/ -ve selection

Answer 5

• Self-components may x be present (developmental Ag, immunologically-privileged sites)
• Can release sequestered self compounds
• Cross-reactivity btw self components + infectious agents → molecular mimicry

Question 6

Myasthesia Gravis

Answer 6

• Muscle weakness
• Ab for AchR
• Binding of Ab to AchR means Ab compete w/ Acc for binding → functional blockade → x open → x muscle contraction