Immunology

Question 1

State the similarities and differences between how peptide binds to MHC class 1 molecules and MHC class II molecules.( anchor residues, size of peptide , way it interacts with peptides)

Answer 1

S - Interacts with peptide backbone via hydrogen bonds and ionic interactions

D. 1 - MHC molecule interacts with peptide backbone at their ends
2 - extend along their lengths
1 - size of peptide - 8 to 10 AA
2 - size of peptide - 13 to 17 AA
1 - anchor residues at ends - bulging
2 - anchor residues along the length- held in a flat elevation
D - differentially express on different tissues( class 2 - more abundant in APC, class 2 - mostly in all cells)

Question 2

State how variable region genes are constructed by separate gene segments.

Answer 2

• Main key word - somatic recombination( gene segments randomly recombined together)
  Light chain - V,J,C (V+J , V+J+C and heavy chain- V,D,J,C ( D+J first and V+D+J )
• genes transcribed to give primary transcript RNA
• splicing event to produce mRNA for constant and variable domains of heavy and light chains

Question 3

How combinatorial diversity of immunoglobin is generated?

Answer 3

different families of light chain - lama, kappa

• many copies of variable region segments in the heavy chain
• any combination of V , J and C from different families

Question 4

State the comparison of diversity between B cell and T cell receptors.

Answer 4

-greater diversity in TCR because of extra requirement to recognise peptide and MHC molecule

Question 5

State similarities in how B cell and T cell receptors generate diversity by somatic recombination .

Answer 5

• rearranged by same enzymes and arranged in a similar pattern to immunoglobin gene segments
• Recombinational signal sequences also flank T-cell receptor gene segments and recombination obeys 23/12 rule

Question 6

Compare the antigen binding of T cell receptor, B cell receptor and MHC receptor.

Answer 6

T cell receptor : recognise linear peptide
B cell receptor : recognise 3D shape
MHC receptor : recognise repertoire of antigen

Question 7

Why MHC receptor can recognise wide repertoire of antigens?

Answer 7

• contains allelic specific binding motifs in the binding groove to be able to let them bind so each MHC molecule can bind 1000 different peptides or more as long as they share the same anchor residues.

Question 8

State how MHC diversity is generated?

Answer 8

- protein products of MHC class I and Class II genes are polymorphic 
( for instance, 3 classes of alleles for MHC class I, can have any one of these alleles at each gene loci and high variation at loci DRB of MHC class II)
- MHC repertoire is multiple genes
- MHC gene variants are highly variable among the population
codominant expression ( heterozygous, express all the alleles you have on both chromosome- protein products of each allele will be present)

Question 9

State MHC restriction

Answer 9

• T cell only recognise self MHC molecules

- no recognition by MHC molecules if its not its cognate antigen and T cell receptor

Question 10

How MHC polymorphism affects antigen recognition

Answer 10

• By influencing the contact between T cell receptor and MHC molecule and peptide binding
  (- variation in peptide binding grooves due to polymorphism accounts for variation in peptides which can be held .
• hyper variability regions at the antigen binding groove

Question 11

State a way of how normal recognition process can be circumvented.

Answer 11

• super antigen can recognise any TCR and MHC molecule

- activate a large number of cells and can give dangerous immune responses to super antigens

Question 12

State the function of adhesion molecules

Answer 12

• T cell crossing into lymph node

- interactions between T cell and APC

Question 13

State the process of CD8 T cell requiring help from T cell.

Answer 13

-Interaction between a CD4+ T cell and an APC activates the T cell to produce CD40 Ligand and IL-2.
- 1st - CD40L binds to CD40 on th APC
2nd - in APC increase levels of 4-IBBL and B7
3rd - 4-IBBL binds to 4-IBB on CD8 T cell & B7 binding to CD28 - signals to produce IL-2

Question 14

State the B cell development in bone marrow

Answer 14

• pre B cell - surrogate light chain and pre B receptor
• firstly heavy chain rearrangement and then light chain gene rearrangement starts at small pre B cell
• incorporate light chain and heavy chain to form B cell receptor ( immunoglobulin)