Immunology lecture Extra

Question 1

Antigen presentation (extra)

Answer 1

MHC I

• Peptide translocated to ER by TAP
• Peptides bind MHC I, chaperone are released, MHCI leaves ER

MHC II

• Cathepsin S + L are activated + digest MHC Class Ii → CLIP
• CLIP exchanged for antigenic peptide derived from protein in eadosomal pathway

Question 2

NK vs CD8 cell

Answer 2

1. Recognition
   - CD8 = single TCR, NK = several (inhibitory + activator)
   - Missing self recognition (MHC I switches off NK cell)
   - CD8 needs CD80/86 or CD28
   - CD28 needed for cytokine secretion + proliferation in NK cells
   - T cells also need pro-inflam. cytokines
2. Destroying cells
   - Perforin + granzymes
   - Both have FasL
   - CTL = stable contact w/ target, NK forms transient
   - NK have more perform, CD8 have more granzyme B
   - NK have cytotoxic granules already, CD8 x (memory do)
3. Memory
   - CD8 undergo contraction, 5% remain → memory T
   - Faster 2o response
   - NK cells undergo contraction
   - NK memory x as stable, NK cells decay at same rate

Question 3

How ‘self’ Ag arise

Answer 3

• Body needs ↑ diverse immune
• Random re-arrangement
• Random → specificities that recog. own

Question 4

Central tolerance (T cell)

Answer 4

• 1o lymph tissues
• T cells / low affinity for self MHC → diff to CD4 or CD8 single +ve (+ve selection)
• High affinity TCR for self-MHC die
• If x bind die
• Zipper model (zipper btw membrane-proximal domain of CD8B + peptide of a chain of TCR)

Question 5

Central tolerance (Aire)

Answer 5

• Some peptides expressed in other cells
• AIRE in thymic medulla induces expression of ↑
• ↑ efficiency of -ve selection
• APECED

Question 6

Central tolerance (B cell)

Answer 6

• Auto-reactive → auto-Ab → autoimmune
• Strength of BCR to Ag
• If weak leave bone marrow
• Tolerance x as strong, help from T helpers

Question 7

Clonal deletion

Answer 7

• 2/3 of T cell
• Fas-FasL apoptosis
• Nur77 + Bim

Question 8

Peripheral tolerance

Answer 8

• Some Ag are seen w/ inadequate affinity or have too ↓ conc
• Tolerance needs to be incomplete

Question 9

Peripheral tolerance (T cell)

Answer 9

• Intrinsic = T cell anergy, phenotype skewing

- Extrinsic = reg. by Treg cells

Question 10

Peripheral tolerance (B cell)

Answer 10

• Somatic mutation → B cell w/ new Ag specificities

- Th for activation

Question 11

Anergy

Answer 11

• Cells x killed but inactive
• Following peptide + MHC engagement for T cell or free epitope engagement for B cell
• Absence of co-stim receptor activates NFAT, w/o APA-1

Question 12

Tregs

Answer 12

• FoxP3
• Natural / induced Tregs
• Regulate effector T by ↑ mechanisms
• Tregs down-reg. APC function by CTLA-4-dependent mechanism
• Secrete immunosuppressor molecules
• Maintain population